Hong Kong, Shanghai & Florham Park, NJ — Tuesday, December 31, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that it has appointed Cavendish Capital Markets Limited as its joint Corporate Broker in London with effect from January 1, 2025.  Panmure Liberum Limited and HSBC Bank plc will continue to act as joint Corporate Brokers in London and Panmure Liberum Limited will continue to act Nominated Advisor to HUTCHMED in London in respect of the AIM rules.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. Since inception, HUTCHMED has focused on bringing drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also approved in the US, Europe and Japan. For more information, please visit: www.hutch-med.com or follow us on LinkedIn.

CONTACTS

Hong Kong, Shanghai & Florham Park, NJ — Monday, December 30, 2024: HUTCHMED (China) Limited (“HUTCHMED” or the “Company”) (Nasdaq/AIM:​HCM; HKEX:​13) announces the following blocklisting six monthly return:

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception it has focused on bringing cancer drug candidates from in‑house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also approved in the US, Europe and Japan. For more information, please visit www.hutch-med.com or follow us on LinkedIn.

CONTACTS

— US$10 million milestone payment to HUTCHMED follows first national reimbursement in Europe —

— Follows June 2024 European approval of FRUZAQLA^® (fruquintinib), the first novel oral targeted therapy in the EU for metastatic colorectal cancer regardless of biomarker status in over a decade —

Hong Kong, Shanghai & Florham Park, NJ —  Friday, December 13, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that it will receive a US$10 million milestone payment by its partner Takeda (TSE:4502/​NYSE:TAK). Takeda received a national reimbursement recommendation for FRUZAQLA^® (fruquintinib) for patients with previously treated  metastatic colorectal cancer (“CRC”) in Spain in December 2024, the first national reimbursement recommendation in Europe. CRC is the second most common cause of cancer-related deaths in Europe.

FRUZAQLA^® was approved by the European Commission (“EC”) of the European Union (“EU”) in June 2024. Takeda has the exclusive worldwide license to further develop, commercialize and manufacture fruquintinib outside of mainland China, Hong Kong and Macau.

“We are delighted for both our partner, Takeda, and patients in Spain who will now be able to receive reimbursement for this innovative treatment. This is an important step forward in improving patient access across Europe more broadly,” said Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED. “It also underscores our ongoing collaboration with Takeda and reinforces our shared commitment to addressing the needs of patients with metastatic colorectal cancer.”

The approvals by the EC were primarily based on results from the Phase III multiregional FRESCO-2 trial. Data from FRESCO-2 were published in The Lancet in June 2023. FRUZAQLA^® was approved in the US in November 2023, in the EU in June 2024, in Switzerland in August 2024, in Canada, Japan and the United Kingdom in September 2024 and in Argentina, Australia and Singapore in October 2024. Regulatory applications are progressing in many other jurisdictions.

About CRC

CRC is a cancer that starts in either the colon or rectum. According to the International Agency for Research on Cancer/World Health Organization, CRC is the third most prevalent cancer worldwide, associated with more than 1.9 million new cases and 900,000 deaths in 2022. In Europe, CRC was the second most common cancer in 2022, with approximately 538,000 new cases and 248,000 deaths.^[1],[2] In the US, it is estimated that 153,000 patients will be diagnosed with CRC and 53,000 deaths from the disease will occur in 2024.^[3] In Japan, CRC was the most common cancer, with an estimated 146,000 new cases and 60,000 deaths, in 2022.² Although early-stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options. Some patients with metastatic CRC may benefit from personalized therapeutic strategies based on molecular characteristics; however, most patients have tumors that do not harbor actionable mutations.^{[4],[5],[6],[7],[8]}

About Fruquintinib

Fruquintinib is a selective oral inhibitor of all three VEGF receptors (VEGFR-1, -2 and -3). VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for drug exposure that achieves sustained target inhibition and flexibility for potential use as part of a combination therapy.

About Fruquintinib Approvals

Global regulatory submissions are based on data from two large, randomized, controlled Phase III trials, the global, multi-regional FRESCO-2 trial and the FRESCO trial conducted in China, showing consistent benefit among a total of 734 patients treated with fruquintinib. Safety profiles were consistent across trials. Results from the FRESCO-2 trial were published in The Lancet in June 2023, ^[9] while results from the FRESCO trial were published in The Journal of the American Medical Association, JAMA.^[10]

In mainland China, Hong Kong and Macau, fruquintinib is co-marketed by HUTCHMED and Eli Lilly and Company under the brand name ELUNATE^®. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. Since its launch in China, over 100,000 patients with colorectal cancer have been treated with fruquintinib.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial‑stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception it has focused on bringing cancer drug candidates from in‑house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also approved in the US, Europe and Japan. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

E.U. IMPORTANT SAFETY INFORMATION

Please consult the FRUZAQLA (fruquintinib) Summary of Product Characteristics (SmPC) before prescribing.

Guidance for use: FRUZAQLA should be initiated by a physician experienced in the administration of anticancer therapy. Patients should be given the package leaflet.

CONTRAINDICATIONS: Hypersensitivity to the active substance or to any of the excipients.

SPECIAL POPULATIONS: Renal impairment: No dose adjustment is required for patients with mild, moderate, or severe renal impairment; Hepatic impairment: No dose adjustment is required for patients with mild or moderate hepatic impairment. FRUZAQLA is not recommended for use in patients with severe hepatic impairment as FRUZAQLA has not been studied in this population; Elderly: No dose adjustment is required in patients aged 65 years or above; Pediatric population: There is no relevant use of FRUZAQLA in the pediatric population for the indication of metastatic colorectal cancer; Women of childbearing potential / Contraception in females: Women of childbearing potential should be advised to use highly effective contraception during treatment and for at least 2 weeks following the last dose of FRUZAQLA; Pregnancy: There are no clinical data available on the use of FRUZAQLA in pregnant women. Based on its mechanism of action, FRUZAQLA has the potential to cause fetal harm. Animal studies have shown reproductive toxicity, including fetal malformations. FRUZAQLA should not be used during pregnancy unless the clinical condition of the woman requires treatment with FRUZAQLA. If FRUZAQLA is used during pregnancy or if the patient becomes pregnant while on treatment, the patient must be informed of the potential hazard to the fetus; Breast-feeding: The safe use of FRUZAQLA during breast-feeding has not been established. It is not known whether FRUZAQLA or its metabolites are excreted in human milk. There are no animal data on the excretion of FRUZAQLA in animal milk. A risk to the breastfeeding newborns/infants cannot be excluded. Breastfeeding should be discontinued during treatment and for 2 weeks after the last dose; Fertility: There are no data on the effects of FRUZAQLA on human fertility. Results from animal studies indicate that FRUZAQLA may impair male and female fertility.

SPECIAL WARNINGS AND PRECAUTIONS FOR USE

• Hypertension: Hypertension, including hypertensive crisis, has been reported in patients treated with FRUZAQLA. Pre-existing hypertension should be monitored and adequately controlled in accordance with standard medical practices before starting FRUZAQLA treatment.
  Hypertension should be medically managed with antihypertensive medicinal products and adjustment of the FRUZAQLA dose, if necessary. FRUZAQLA should be permanently discontinued for hypertension that cannot be controlled with antihypertensive therapy or in patients with hypertensive crisis.
• Hemorrhagic events: Hemorrhagic events have been reported in patients treated with FRUZAQLA, including gastrointestinal (GI) tract events. Serious and sometimes fatal bleeding events have been reported in patients after treatment with FRUZAQLA.
  Hematologic and coagulation profiles should be monitored in accordance with standard medical practices in patients at risk for bleeding, including those treated with anticoagulants or other concomitant medicinal products that increase the risk of bleeding. In the event of severe bleeding requiring immediate medical intervention, FRUZAQLA should be permanently discontinued.
• Gastrointestinal perforation: GI perforation events, including fatal events, have been reported in patients treated with FRUZAQLA.
  Symptoms of GI perforation should be periodically monitored during treatment with FRUZAQLA.
  FRUZAQLA should be permanently discontinued in patients developing GI perforation.
• Proteinuria: Proteinuria events have occurred in patients treated with FRUZAQLA.
  Proteinuria should be monitored before initiation and during treatment with FRUZAQLA in accordance with standard medical practices. If urine dipstick proteinuria ≥ 2 g / 24 hours is detected, dose interruptions, adjustments, or discontinuation may be necessary. FRUZAQLA should be permanently discontinued in patients developing nephrotic syndrome.
• Palmar-plantar erythrodysesthesia syndrome (PPES): PPES is the most frequently reported dermato­logical adverse reaction.
  If Grade ≥2 skin reactions are detected, dose interruptions, adjustments, or discontinuation may be necessary.
• Posterior reversible encephalopathy syndrome (PRES): PRES has been reported in 1 patient (0.1%) treated with FRUZAQLA in clinical studies. PRES is a rare neurologic disorder that can present with headache, seizure, lethargy, confusion, altered mental function, blindness, and other visual or neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). In patients developing PRES, discontinuation of FRUZAQLA, along with control of hypertension and supportive medical management of other symptoms, are recommended.
• Impaired wound healing: Impaired wound healing has been reported in 1 patient (0.1%) treated with FRUZAQLA in clinical studies.
  Patients are recommended to withhold FRUZAQLA for at least 2 weeks prior to surgery. FRUZAQLA should not be resumed for at least 2 weeks after surgery, as clinically indicated when there is evidence of adequate wound healing.
• Arterial and venous thromboembolic events: It is recommended to avoid starting treatment with FRUZAQLA in patients with a history of thromboembolic events (including deep vein thrombosis and pulmonary embolism) within the past 6 months or if they have a history of stroke and/or transient ischemic attack within the last 12 months. If arterial thrombosis is suspected, FRUZAQLA should be discontinued immediately.

INTERACTIONS

Effects of other medicinal products on the pharmacokinetics of FRUZAQLA

CYP3A inducers

Co-administration of FRUZAQLA with rifampicin (a strong CYP3A inducer) 600 mg once daily decreased FRUZAQLA AUC_inf by 65% and decreased C_max by 12%. The concomitant use of FRUZAQLA with strong and moderate CYP3A inducers should be avoided.

CYP3A inhibitors

Co-administration of FRUZAQLA with itraconazole (a strong CYP3A inhibitor) 200 mg twice daily did not result in clinically meaningful changes in the area under the concentration-time curve (AUC) and C_max of FRUZAQLA. No dose adjustment of FRUZAQLA is needed during concomitant use with CYP3A inhibitors.

Gastric acid lowering agents

Co-administration of FRUZAQLA with rabeprazole (a proton pump inhibitor) 40 mg once daily did not result in clinically meaningful changes in the AUC of FRUZAQLA. No dose adjustment of FRUZAQLA is needed during concomitant use with gastric acid lowering agents.

Effect of FRUZAQLA on the pharmacokinetics of other medicinal products

Medicinal products that are substrates of P-glycoprotein (P-gp)

Co-administration of a single dose of dabigatran etexilate 150 mg (a P-gp substrate) with a single dose of FRUZAQLA 5 mg decreased AUC of dabigatran by 9%. No dose adjustment is recommended for P-gp substrates during concomitant use with FRUZAQLA.

Medicinal products that are substrates of breast cancer resistance protein (BCRP)

Co-administration of a single 10 mg dose of rosuvastatin (a BCRP substrate) with a single 5 mg dose of FRUZAQLA decreased AUC of rosuvastatin by 19%. No dose adjustment is recommended for BCRP substrates during concomitant use with FRUZAQLA.

UNDESIRABLE EFFECTS: The most commonly reported adverse reactions with FRUZAQLA are:

Very common (frequency ≥1/10): Thrombocytopenia, hypothyroidism, anorexia, hypertension, dysphonia, diarrhoea, stomatitis, aspartate aminotransferase increased, total bilirubin increased, alanine aminotransferase increased, palmar-plantar erythrodysesthesia syndrome, musculoskeletal discomfort, arthralgia, proteinuria, asthenia, and fatigue

Common (≥1/100 to <1/10): Pneumonia, upper respiratory tract infection, bacterial infections, leukopenia, neutropenia, hypokalemia, epistaxis, throat pain, gastrointestinal hemorrhage, gastrointestinal perforation, pancreatic enzymes increased, oral pain, rash, and mucosal inflammation

For US Prescribing Information:

https://www.fruzaqla.com/sites/default/files/resources/fruzaqla-prescribing-information.pdf

For Japan Prescribing Information:

https://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/400256_42910H0M1028_1_01

For EU Prescribing Information:

https://www.ema.europa.eu/en/documents/product-information/fruzaqla-epar-product-information_en.pdf

CONTACTS

Hong Kong, Shanghai & Florham Park, NJ — Thursday, December 12, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that the Center for Drug Evaluation of China’s National Medical Products Administration (“NMPA”) has granted Breakthrough Therapy Designation (“BTD”) to the combination of ORPATHYS^® (savolitinib) and TAGRISSO^® (osimertinib) for the treatment of patients with locally advanced or metastatic epidermal growth factor receptor (“EGFR”) mutation‑positive non‑small cell lung cancer (“NSCLC”) with MET amplification after disease progression on EGFR inhibitor therapy. ORPATHYS^® is an oral, potent and highly selective MET tyrosine kinase inhibitor (“TKI”). TAGRISSO^® is a third-generation, irreversible EGFR TKI.

This treatment combination is being evaluated in China in the ongoing multi-center, open-label, randomized, controlled, Phase III SACHI trial. The study is investigating the efficacy and safety of a combination of ORPATHYS^® and TAGRISSO^® compared to platinum-based doublet-chemotherapy (pemetrexed plus cisplatin or carboplatin), the standard‑of‑care treatment option, in patients with locally advanced or metastatic NSCLC with MET amplification after failure of EGFR inhibitor therapy. The primary endpoint of the study is progression-free survival (“PFS”) as assessed by investigators. Other endpoints include PFS assessed by an independent review committee, overall survival (OS), objective response rate (ORR), duration of response (DoR), disease control rate (DCR), time to response (TTR), and safety (NCT05015608).

NMPA grants BTD to new drugs that treat life-threatening diseases or serious conditions for which there are no effective treatment options, and where clinical evidence demonstrates significant advantages over existing therapies. Drug candidates with BTD may be considered for conditional approval and priority review when submitting an NDA. This indicates that the development and review of the therapy for this disease indication may be expedited, to address patients’ unmet needs more quickly.

About NSCLC and MET aberrations

Lung cancer is the leading cause of cancer death, accounting for about one-fifth of all cancer deaths.^[1] Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.^[2] The majority of NSCLC patients (approximately 75%) are diagnosed with advanced disease, and approximately 10-15% of NSCLC patients in the US and Europe and 30-40% of patients in Asia have EGFR-mutated (“EGFRm”) NSCLC. ^[3],^[4],^[5],^[6]

MET is a tyrosine kinase receptor that has an essential role in normal cell development.^[7] MET overexpression and/or amplification can lead to tumor growth and the metastatic progression of cancer cells, and is one of the mechanisms of acquired resistance to EGFR TKI for metastatic EGFR-mutated NSCLC.⁷,^[8] Approximately 2-3% of NSCLC patients have tumors with MET exon 14 skipping alterations, a targetable mutation in the MET gene.^[9] MET aberration is a major mechanism for acquired resistance to both first/second-generation EGFR TKIs as well as third-generation EGFR TKIs like osimertinib. Among patients who experience disease progression post-osimertinib treatment, approximately 15-50% present with MET aberration.^[10],^[11],^[12],^[13],^[14] The prevalence of MET aberration depends on the sample type, detection method and assay thresholds used.^[15]

About ORPATHYS^® and TAGRISSO^® Combination Development in EGFR mutation-positive NSCLC

The combination of ORPATHYS^® and TAGRISSO^® has been studied extensively in patients with EGFR mutation-positive NSCLC, including the TATTON (NCT02143466) and SAVANNAH (NCT03778229) studies. The encouraging results from these studies led to the initiation of three Phase III trials with this combination: SACHI (NCT05015608) and SANOVO (NCT05009836) were initiated in China in 2021, and the global, pivotal Phase III SAFFRON (NCT05261399) study started enrollment in 2022. In comparison to other treatment options, this combination treatment is chemotherapy-free, biomarker-specific and orally administered, aiming for a balanced efficacy, safety and quality-of-life profile for lung cancer patients.

SAVANNAH is a global Phase II study in patients who have progressed following osimertinib due to MET amplification or overexpression, and recruitment completed earlier in 2024. The evaluation of savolitinib in combination with osimertinib was designated as a Fast Track development program by the US Food and Drug Administration (FDA) in 2023.

SAFFRON is a multi-center, randomized, controlled, open-label, global Phase III trial in patients with EGFR mutation-positive NSCLC with MET overexpression and/or amplification after disease progression on osimertinib.

SACHI is a multi-center, randomized, controlled, open-label, China Phase III trial in patients with EGFR mutation-positive NSCLC with MET amplification after disease progression on any EGFR inhibitor therapy, including third-generation EGFR-TKIs such as osimertinib.

SANOVO is a multi-center, randomized, controlled, blinded, China Phase III trial in treatment-naïve patients with EGFR mutation-positive NSCLC with MET-positive tumors.

About ORPATHYS^® Approval in China

ORPATHYS^® was granted conditional approval in China for the treatment of patients with locally advanced or metastatic NSCLC with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy. ORPATHYS^® is the first selective MET inhibitor approved in China. It has been included in the National Reimbursement Drug List of China (NRDL) since March 2023. A supplementary NDA is under review which, if approved, could expand this indication to include treatment‑naïve adult patients in China. More than a third of the world’s lung cancer patients are in China and, among those with NSCLC globally, approximately 2-3% have tumors with MET exon 14 skipping alterations.

About ORPATHYS^® (savolitinib)

ORPATHYS^® is an oral, potent and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.

ORPATHYS^® is marketed in China and is currently under clinical development for multiple tumor types, including lung, kidney and gastric cancers, as a single treatment and in combination with other medicines.

In 2011, AstraZeneca and HUTCHMED entered a global licensing and collaboration agreement to jointly develop and commercialize ORPATHYS^®. Joint development of ORPATHYS^® in China is led by HUTCHMED, while AstraZeneca leads development outside of China. HUTCHMED is responsible for the marketing authorization, manufacturing and supply of ORPATHYS^® in China. AstraZeneca is responsible for the commercialization of ORPATHYS^® in China and worldwide. Sales of ORPATHYS^® are recognized by AstraZeneca.

About TAGRISSO^®

TAGRISSO^® (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system (CNS) metastases. TAGRISSO^® (40mg and 80mg once-daily oral tablets) has been used to treat nearly 800,000 patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO^® as a treatment for patients across multiple stages of EGFRm NSCLC.

There is an extensive body of evidence supporting the use of TAGRISSO^® as standard of care in EGFRm NSCLC. TAGRISSO^® improved patient outcomes in early-stage disease in the ADAURA Phase III trial, locally advanced disease in the LAURA Phase III trial, late-stage disease in the FLAURA Phase III trial, and with chemotherapy in the FLAURA2 Phase III trial.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also approved in the US, Europe and Japan. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

CONTACTS

— First regulatory approval for fruquintinib combination therapy with an immune checkpoint inhibitor —

Hong Kong, Shanghai & Florham Park, NJ — Tuesday, December 3, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM; HKEX:​13) and Innovent Biologics, Inc. (“Innovent”) (HKEX:1801) today jointly announce that the New Drug Application (“NDA”) for the combination of ELUNATE^® (fruquintinib) and TYVYT^® (sintilimab injection) has been granted conditional approval in China for the treatment of patients with advanced endometrial cancer with Mismatch Repair proficient (“pMMR”) tumors that have failed prior systemic therapy and are not candidates for curative surgery or radiation.  This approval follows the priority review status and breakthrough therapy designation by the National Medical Products Administration (“NMPA”) of China and marks the first regulatory approval for the combination of fruquintinib with a leading immune checkpoint inhibitor.

The conditional approval by the NMPA was supported by registration stage data from FRUSICA-1, the endometrial cancer registration cohort of a multi-center, open-label Phase II study investigating fruquintinib in combination with sintilimab in endometrial cancer patients who have experienced disease recurrence, disease progression or intolerable toxicity with treatment on platinum-based doublet chemotherapy. Results from FRUSICA-1 were presented at the American Society of Clinical Oncology annual meeting in June 2024.^[1] The study results showed that IRC-assessed objective response rate (ORR) and disease control rate (DCR) was 35.6% and 88.5% respectively. The combination treatment showed rapid on-set efficacy, with a median time to response (TTR) of only 1.6 months. The median progression free survival (PFS) and overall survival (OS) reached 9.5 months and 21.3 months respectively. Adverse events are consistent with those reported for similar immunotherapy and antiangiogenic agents combination treatments. Additional details can be found at clinicaltrials.gov, using identifier NCT03903705.

“This approval of fruquintinib plus sintilimab could represent a paradigm shift in managing this challenging disease. This innovative combination not only leverages the synergistic effects of targeted therapy and immunotherapy, but also addresses a critical gap in treatments available for patients with limited responses to traditional therapies,” said Prof. Xiaohua Wu, Director of the Department of Gynecologic Oncology at Fudan University Affiliated Cancer Hospital and Principal Investigator of the FRUSICA-1 study. “With the promising efficacy and manageable safety profile observed in clinical trials, we are eager to have this treatment option available to patients. It brings us closer to our goal of improving survival and enhancing quality of life for patients living with advanced endometrial cancer.”

“This NMPA approval of fruquintinib in combination with sintilimab represents a significant advancement for patients with advanced endometrial cancer who have long await more effective treatments. It underscores the potential of fruquintinib to be used with other therapeutic agents to improve patient outcomes,” said Dr. Michael Shi, Head of R&D and Chief Medical Officer of HUTCHMED. “It is also a testament to our ongoing efforts to extend the clinical benefit of fruquintinib to a broader patient population. We are eager to make this innovative treatment available to advanced endometrial cancer patients as soon as we can and will continue to explore further opportunities to bring hope to more patients battling cancer.”

Dr. Hui Zhou, Senior Vice President of Innovent, stated: “This approval of sintilimab and fruquintinib combination therapy marks a meaningful advancement in the treatment landscape for advanced endometrial cancer. Together with HUTCHMED, we aim to provide a novel treatment option that improves survival rates and quality of life for patients facing limited treatment options against this aggressive cancer. TYVYT^® (sintilimab injection), as a cornerstone in immuno-therapy, continues to be evaluated in clinical trials in combination with novel modalities. We remain steadfast in our commitment to reinforcing the leadership position of TYVYT^® (sintilimab injection) in immuno-therapy and driving forward treatment solutions through innovation and cooperation.”

In July 2023, the NMPA granted Breakthrough Therapy Designation to the combination of fruquintinib and sintilimab for this potential indication. This designation recognizes the potential of a therapy to address a severe condition with no effective treatment options, and where clinical evidence demonstrates substantial advantages over existing therapies.

A Phase III confirmatory study of the fruquintinib and sintilimab combination in this setting has been planned (NCT06584032).

About Endometrial Cancer

Endometrial cancer originates in the uterus and remains a significant global health challenge. In 2020, approximately 417,000 people were diagnosed with endometrial cancer, resulting in around 97,000 deaths.^[2] Іn China alone, an estimated 82,000 new cases and 17,000 were reported in 2020.^[3] While early-stage endometrial cancer can often be surgically resected, recurrent and/or metastatic endometrial cancer remains an area of high unmet need with poor outcomes and limited treatment options.^[4],^[5],^[6]

About Fruquintinib

Fruquintinib is a selective oral inhibitor of all three vascular endothelial growth factor (“VEGF”) receptors (VEGFR-1, -2 and -3). VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for drug exposure that achieves sustained target inhibition and flexibility for potential use as part of a combination therapy.

About Fruquintinib Approvals

Fruquintinib is approved for marketing for the treatment of patients with metastatic colorectal cancer who have previously received fluoropyrimidine, oxaliplatin and irinotecan-based chemotherapy, and those who have previously received or are not suitable for receiving anti-VEGF therapy or anti-epidermal growth factor receptor (“EGFR”) therapy (RAS wild-type) in China, where it is co-developed and co-marketed by HUTCHMED and Eli Lilly and Company under the brand name ELUNATE^®. It was included in the China National Reimbursement Drug List (“NRDL”) in January 2020. Since its launch in China, over 100,000 patients with colorectal cancer have been treated with fruquintinib.

Takeda has the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside of mainland China, Hong Kong and Macau, and markets under the FRUZAQLA^® brand name.  Fruquintinib received approval in the US in November 2023, in the EU in June 2024, in Switzerland in August 2024, in Canada, Japan and the United Kingdom in September 2024 and in Argentina, Australia and Singapore in October 2024. Regulatory applications are progressing in many other jurisdictions.

The global regulatory submissions are based on data from two large, randomized, controlled Phase III trials, the global, multi-regional FRESCO-2 trial and the FRESCO trial conducted in China, showing consistent benefit among a total of 734 patients treated with fruquintinib. Safety profiles were consistent across trials. Results from the FRESCO-2 trial were published in The Lancet in June 2023,^[7] while results from the FRESCO trial were published in The Journal of the American Medical Association, JAMA.^[8]

About Sintilimab

Sintilimab, marketed as TYVYT^® (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody co-developed by Innovent and Eli Lilly and Company. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells.^[9]

In China, sintilimab has been approved and included in the updated NRDL for seven indications. The updated NRDL reimbursement scope for TYVYT^® (sintilimab injection) includes:

• For the treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy;
• For the first-line treatment of unresectable locally advanced or metastatic non-squamous non-small cell lung cancer lacking EGFR or ALK driver gene mutations;
• For the treatment of patients with EGFR-mutated locally advanced or metastatic non-squamous non-small cell lung cancer who progressed after EGFR-TKI therapy;
• For the first-line treatment of unresectable locally advanced or metastatic squamous non-small cell lung cancer;
• For the first-line treatment of unresectable or metastatic hepatocellular carcinoma with no prior systematic treatment;
• For the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma;
• For the first-line treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.

Furthermore, sintilimab’s eighth indication, in combination with fruquintinib for the treatment of patients with advanced endometrial cancer with pMMR tumors that have failed prior systemic therapy and are not candidates for curative surgery or radiation, has been approved by the NMPA in December 2024.

In addition, two clinical studies of sintilimab have met their primary endpoints:

• Phase II study of sintilimab monotherapy as second-line treatment of esophageal squamous cell carcinoma;
• Phase III study of sintilimab monotherapy as second-line treatment for squamous non-small cell lung cancer with disease progression following platinum-based chemotherapy.

Statement: Innovent does not recommend the use of any unapproved drug(s)/indication(s).

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also approved in the US, Europe and Japan. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

About Innovent

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 11 products in the market. It has 5 new drug applications under regulatory review, 3 assets in Phase III or pivotal clinical trials and 17 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, Adimab, LG Chem and MD Anderson Cancer Center.

Guided by the motto, “Start with Integrity, Succeed through Action,” Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of the fruquintinib and sintilimab combination for the treatment of patients with advanced endometrial cancer and the further clinical development of the fruquintinib and sintilimab combination in this and other indications. Forward‑looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the sufficiency of clinical data to support NDA approval of the fruquintinib and sintilimab combination for the treatment of patients with advanced endometrial cancer in China and other jurisdictions, the safety profile of the fruquintinib and sintilimab combination, HUTCHMED’s ability to fund, implement and complete its further clinical development and commercialization plans for fruquintinib, and the timing of these events. In addition, as certain studies rely on the use of other drug products such as sintilimab as combination therapeutics with fruquintinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

Medical Information

This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

CONTACTS

[1]    Wu X, et al. Fruquintinib plus sintilimab in treated advanced endometrial cancer (EMC) patients (pts) with PMMR status: Results from a multicenter, single-arm phase 2 study. J Clin Oncol 42, 2024 (suppl 16; abstr 5619). DOI: 10.1200/JCO.2024.42.16_suppl.5619.

[2]     The Global Cancer Observatory, World Fact Sheet. Accessed June 12, 2023.

[3]     The Global Cancer Observatory, China Fact Sheet. Accessed June 12, 2023.

[4]     Yi A, et al. Real-world characteristics and treatment pattern of patients with newly diagnosed endometrial cancer in China.  J Clin Oncol. 2023;41, no. 16_suppl (June 01, 2023) e17613-e17613. DOI: 10.1200/JCO.2023.41.16_suppl.e17613.

[5]     Koppikar S, et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with endometrial cancer. ESMO Open. 2023;8(1):100774. DOI: 10.1016/j.esmoop.2022.100774.

[6]     Siegel RL, et al. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17-48. DOI:10.3322/caac.21763.

[7]     Dasari NA, et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO‑2): an international, multicentre, randomised, double‑blind, Phase III study. Lancet. 2023;402(10395):41‑53. doi:10.1016/S0140‑6736(23)00772‑9.

[8]     Li J, et al. Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018;319(24):2486-2496. DOI:10.1001/jama.2018.7855.

[9]     Wang J, et al. Durable blockade of PD-1 signaling links preclinical efficacy of sintilimab to its clinical benefit. mAbs 2019;11(8): 1443-1451. DOI: 10.1080/19420862.2019.1654303.

Hong Kong, Shanghai & Florham Park, NJ — Friday, November 29, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM; HKEX:​13) hereby notifies the market that as at November 29, 2024, the issued share capital of HUTCHMED consisted of 871,601,095 ordinary shares of US$0.10 each, with each share carrying one right to vote and with no shares held in treasury.

The above figure of 871,601,095 may be used by shareholders as the denominator for the calculations by which they could determine if they are required to notify their interest in, or a change to their interest in, HUTCHMED under the Financial Conduct Authority’s Disclosure Guidance and Transparency Rules.

For illustrative purposes only, the 871,601,095 ordinary shares would be equivalent to 871,601,095 depositary interests (each equating to one ordinary share) which are traded on AIM or, if the depositary interests were converted in their entirety, equivalent to 174,320,219 American depositary shares (each equating to five ordinary shares) which are traded on Nasdaq.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception it has focused on bringing cancer drug candidates from in‑house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also approved in the US, Europe and Japan. For more information, please visit www.hutch-med.com or follow us on LinkedIn.

CONTACTS

Hong Kong, Shanghai & Florham Park, NJ — Thursday, November 28, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM; HKEX:​13) today announces that following the contract renewal with the China National Healthcare Security Administration (“NHSA”), the updated National Reimbursement Drug List (“NRDL”) effective on January 1, 2025 will continue to include ORPATHYS^® (savolitinib) at the same terms as the current two-year agreement.

ORPATHYS^® is an oral, potent, and highly selective MET tyrosine kinase inhibitor (“TKI”). It received conditional approval in China in June 2021 for the treatment of certain patients with non-small cell lung cancer (“NSCLC”) with MET exon 14 skipping alterations. More than a third of the world’s lung cancer patients are in China and, among those with NSCLC globally, approximately 2-3% have tumors with MET exon 14 skipping alterations.

ORPATHYS^® was first included in the NRDL on March 1, 2023. The government in China has placed great importance on improving the affordability of drug treatments for the public. As of end of 2023, 1.33 billion people in China had basic medical insurance coverage, representing around 95% of the entire population. The NRDL is updated every year, and inclusion on the list is subject to renewal every two years. The NHSA annually convenes a broad network of experts in medicine, pharmacology, pharmacoeconomics and actuarial valuation to identify innovative medicines to consider for NRDL inclusion. Reimbursement of Category B medicines, including novel oncology medicines, requires varying degrees of copayment from patients, depending on their provinces or types of NHSA insurance scheme enrollment.

About ORPATHYS^®

ORPATHYS^® (savolitinib) is an oral, potent, and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.

ORPATHYS^® is jointly developed by HUTCHMED and AstraZeneca and commercialized by AstraZeneca. It is approved in China for the treatment of patients with NSCLC with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy. It is the first selective MET inhibitor approved in China and the first in the NRDL. It is currently under clinical development for multiple tumor types, including lung, kidney, and gastric cancers, as a single treatment and in combination with other medicines.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also approved in the US, Europe and Japan. For more information, please visit www.hutch-med.com or follow us on LinkedIn.

CONTACTS

— Launch follows approval by Japanese Ministry of Health, Labour and Welfare in September 2024 —

— Milestone payment to be made to HUTCHMED from Takeda —

— Fruquintinib already launched in several regions including the United States, Europe and China —

Hong Kong, Shanghai & Florham Park, NJ — Friday, November 22, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that it will receive a milestone payment following the pricing approval and launch of FRUZAQLA^® (fruquintinib) 1mg/5mg capsules in Japan by its partner Takeda (TSE:4502/​NYSE:TAK) for patients with previously treated metastatic colorectal cancer (“CRC”). This follows approval for the manufacturing and marketing of FRUZAQLA^® by the Japanese Ministry of Health, Labour and Welfare.

FRUZAQLA^® is the first novel oral targeted therapy in Japan to be approved for metastatic CRC, regardless of biomarker status, in over a decade. FRUZAQLA^® is indicated for the treatment of advanced or recurrent colorectal cancer that is neither curable nor resectable, and that has progressed after chemotherapy. CRC is the most prevalent type of cancer in Japan, with an estimated 161,000 new cases and 54,000 deaths in 2023, according to statistics from the National Cancer Center.^[1]

On the launch of FRUZAQLA^® in Japan by Takeda, Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, said: “The launch of FRUZAQLA^® in Japan highlights the continued progress of our partnership with Takeda across the globe. Takeda is well positioned to build on more than a decade of leadership in the treatment of metastatic CRC in Japan and bring a differentiated treatment option in FRUZAQLA^® to patients.”

The launch of FRUZAQLA^® in Japan follows its approval in September 2024, primarily based on results from the Phase III FRESCO-2 trial conducted in the US, Europe, Japan and Australia. Data from FRESCO-2 were published in The Lancet in June 2023. Takeda has the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside of mainland China, Hong Kong and Macau, and markets under the FRUZAQLA^® brand name. It received approval in the US in November 2023, in the EU in June 2024, in Switzerland in August 2024, in Canada, Japan and the United Kingdom in September 2024 and in Argentina, Australia and Singapore in October 2024. Regulatory applications are progressing in many other jurisdictions.

About CRC

CRC is a cancer that starts in either the colon or rectum. According to the International Agency for Research on Cancer/World Health Organization, CRC is the third most prevalent cancer worldwide, associated with more than 1.9 million new cases and 900,000 deaths in 2022. In Japan, CRC was the most common cancer, with an estimated 146,000 new cases and 60,000 deaths, in 2022. In Europe, CRC was the second most common cancer in 2022, with approximately 538,000 new cases and 248,000 deaths.^[2],^[3]In the US, it is estimated that 153,000 patients will be diagnosed with CRC and 53,000 deaths from the disease will occur in 2024.^[4] Although early-stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options. Some patients with metastatic CRC may benefit from personalized therapeutic strategies based on molecular characteristics; however, most patients have tumors that do not harbor actionable mutations.^{[5],[6],[7],[8],[9]}

About Fruquintinib

Fruquintinib is a selective oral inhibitor of all three VEGF receptors (VEGFR-1, -2 and -3). VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for drug exposure that achieves sustained target inhibition and flexibility for potential use as part of a combination therapy.

About Fruquintinib Approvals

Global regulatory submissions are based on data from two large, randomized, controlled Phase III trials, the global, multi-regional FRESCO-2 trial and the FRESCO trial conducted in China, showing consistent benefit among a total of 734 patients treated with fruquintinib. Safety profiles were consistent across trials. Results from the FRESCO-2 trial were published in The Lancet in June 2023,^[10] while results from the FRESCO trial were published in The Journal of the American Medical Association, JAMA.^[11]

In mainland China, Hong Kong and Macau, fruquintinib is co-marketed by HUTCHMED and Eli Lilly and Company under the brand name ELUNATE^®. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. Since its launch in China, over 100,000 patients with colorectal cancer have been treated with fruquintinib.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception it has focused on bringing cancer drug candidates from in‑house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also approved in the US, Europe and Japan. For more information, please visit www.hutch-med.com or follow us on LinkedIn.

JAPAN IMPORTANT SAFETY INFORMATION

Please consult the FRUZAQLA (fruquintinib) Japan package insert (J-PI) before prescribing.

WARNING: FRUZAQLA should be administered only to patients for whom the use of FRUZAQLA is considered appropriate under the supervision of a physician with sufficient knowledge of and experience in cancer chemotherapy at a medical institution where adequate emergency care can be provided. Prior to treatment initiation, the efficacy and risks should be fully explained to the patient and/or his/her family and informed consent should be obtained; Severe gastrointestinal hemorrhage, including fatal cases, has been reported. Patients should be carefully monitored, and if any abnormalities are observed, administration of FRUZAQLA should be withheld and appropriate measures should be taken. If severe hemorrhage occurs, FRUZAQLA should not be re-administered; Gastrointestinal perforation has been reported with some fatal cases. Patients should be carefully monitored, and if any abnormalities are observed, administration of FRUZAQLA should be withheld and appropriate measures should be taken. If gastrointestinal perforation occurs, FRUZAQLA should not be re-administered.

CONTRAINDICATIONS: Patients with a history of hypersensitivity to any of the ingredients of FRUZAQLA.

IMPORTANT PRECAUTIONS: Hypertension, including hypertensive crisis, may occur. Blood pressure should be measured prior to the initiation of FRUZAQLA treatment and periodically during this treatment; Proteinuria may occur. Urinary protein should be monitored prior to the initiation of FRUZAQLA treatment and periodically during this treatment; If a surgical procedure is to be performed, patients are recommended to withhold FRUZAQLA before the surgery because wound healing may be delayed. Treatment resumption after the surgical procedure should be determined depending on the patient’s condition upon confirmation of adequate wound healing.

PRECAUTIONS CONCERNING PATIENTS WITH SPECIFIC BACKGROUNDS: Patients with hyper­ten­sion: Hypertension may worsen; Patients with bleeding diathesis or abnormal coagulation system: Hemorrhagic events may occur; Patients with hemorrhage such as gastrointestinal hemorrhage: Hemorrhage may be enhanced; Patients with a complication of intra-abdominal inflammation in the gastrointestinal tract, etc.: Gastrointestinal perforation may occur; Patients with current or a history of thromboembolism: Transient ischaemic attack, thrombotic microangiopathy, pulmonary embolism, portal vein thrombosis, deep vein thrombosis, etc. may occur; Patients with severe hepatic impairment (Child-Pugh Class C): Since FRUZAQLA is metabolized mainly in the liver, blood concentrations may be increased. There have been no clinical studies conducted in patients with severe hepatic impairment; Patients with Reproductive Potential: Women of childbearing potential should be advised to use adequate contraception during treatment with FRUZAQLA and for 2 weeks after the last dose; Pregnant Women: FRUZAQLA can be administered to women who are or may be pregnant only if the expected therapeutic benefits outweigh the possible risks associated with this treatment. In a rat embryo-fetal toxicity study, fetal abnormalities and teratogenic effects consisting of fetal external, visceral, and skeletal malformations and visceral and skeletal variations were observed at exposure levels approximately 0.05 times the exposure level (AUC) of FRUZAQLA at the maximum clinical dose (5 mg/day); Breast-feeding Women: It is advisable not to breastfeed. FRUZAQLA may pass into breast milk, and infants may experience serious adverse reactions if they are ingested through breast milk; Pediatric Use: There have been no clinical studies conducted in pediatric patients.

ADVERSE REACTIONS:

Any of the adverse reactions listed below may occur. Patients should be closely monitored, and if any such abnormalities are observed, appropriate measures should be taken, including treatment discontinuation. Clinically Significant Adverse Reactions are as follows.

Hypertension: Hypertension or hypertensive crisis may occur. If an increase in blood pressure is observed, appropriate treatment such as antihypertensive drug administration should be given as necessary, and if necessary, the dose of fruquintinib should be reduced, or fruquintinib administration should be interrupted. If severe or persistent hypertension, or hypertension that cannot be controlled by routine antihypertensive therapy occurs or if a hypertensive crisis occurs, fruquintinib administration should be discontinued; Skin disorder: Skin disorder including palmar-plantar erythrodysesthesia syndrome and rash may occur; Hemorrhage: Hemorrhage including epistaxis, hematuria, gastrointestinal hemorrhage and hemoptysis may occur. Fatal outcomes have been reported; Gastrointestinal perforation: Fatal outcomes have been reported; Arterial thromboembolic events: Arterial thromboembolic events including transient ischemic attack and thrombotic microangiopathy may occur; Venous thromboembolism events: Venous thromboembolism such as pulmonary embolism, portal vein thrombosis, and deep vein thrombosis may occur; Posterior reversible encephalopathy syndrome: If headaches, convulsions, lethargy, confusion, changes in mental function, blindness or other visual disturbances, or neurological impairment are observed, fruquintinib administration should be discontinued, and appropriate measures should be taken, including blood pressure control; Arterial dissection: Arterial dissection including aortic dissection may occur.

For US Prescribing Information:
https://www.fruzaqla.com/sites/default/files/resources/fruzaqla-prescribing-information.pdf

For European Union Summary of Product Characteristics:
https://www.ema.europa.eu/en/medicines/human/EPAR/fruzaqla

CONTACTS

Hong Kong, Shanghai & Florham Park, NJ — Wednesday, November 20, 2024: HUTCHMED (China) Limited (“HUTCHMED” or the “Company”) (Nasdaq/AIM:​HCM, HKEX:​13) today announces that Dr Chaohong Hu (Dr Mary Hu) is appointed as an Independent Non-executive Director and a member of the Technical Committee of the Company with effect from November 21, 2024.

Dr Hu has over 20 years of experience in the development of therapeutic antibodies, antibody-drug conjugates, and vaccines. Throughout her career, she has demonstrated strong leadership and innovative capabilities, leading various research and development initiatives. Dr Hu’s expertise spans from early-stage discovery to clinical development and commercialization. She also has a proven track record of successful business development and strategic partnerships, including out-licensing and collaboration.

Dr Dan Eldar, Chairman of HUTCHMED, said “On behalf of the Board, I would like to extend a warm welcome to Dr Hu to the Company. We believe that her expertise in the biopharmaceutical industry will bring fresh perspective and provide constructive insight to the Board.”

Dr Hu, aged 58, is currently Chief Operating Officer of D Biotherapeutics, LLC and an owner and principal consultant of Lakebio Consulting, LLC.  She was previously executive director and co-chief executive officer of Lepu Biopharma Co., Ltd. (HKEX: 2157) from 2020 to January 2024.  She was also chief executive officer and Chairman of the Board of Shanghai Miracogen Inc., a company founded by Dr Hu, focusing on the research and development, clinical study and industrialization of new drugs for targeted cancer therapy – antibody drug conjugates, from 2014 to January 2024.  She disposed of all her interests in Shanghai Miracogen Inc. in 2020. Prior to founding Shanghai Miracogen Inc., Dr Hu served as a director of the Bioassay Development and Process Analytics department at Seagen Inc. (previously listed on the Nasdaq); director of Molecular Biology and Clinical Immunology department of GlaxoSmithKline plc (currently GSK plc) (LSE/NYSE: GSK); and research scientist and director of Molecular Biology and Clinical Immunology department of ID Biomedical Corporation (previously listed on the Nasdaq).  She was also a postdoctoral fellow of the University of Washington.

Dr Hu holds a Bachelor of Science degree in biochemistry from Wuhan University and a PhD in molecular biology from Institute of Biophysics, Chinese Academy of Sciences.

Dr Hu has broad relevant board experience, currently holding or having held in the past five years the following directorships and partnerships:

Save for the appointments listed above, Dr Hu has held no other directorships or partnerships during the period of five years prior to her appointment as a director of HUTCHMED. She does not have any relationship with any Directors, senior management or substantial or controlling shareholders of HUTCHMED. Dr Hu has confirmed (a) her independence as regards each of the factors for independence referred to in Rule 3.13(1) to (8) of the Rules Governing the Listing of Securities on The Stock Exchange of Hong Kong Limited (“HK Listing Rules”); (b) that she had no past or present financial or other interest in the business of the Company or its subsidiaries or any connection with any core connected person (as defined in the HK Listing Rules) of the Company; and (c) that there are no other factors that may affect her independence at the time of her appointment.

The initial term of the appointment of Dr Hu as an Independent Non-executive Director of the Company shall end at the next following annual general meeting of the Company, subject to retirement in accordance with the Articles of Association of the Company and applicable legal and regulatory requirements, and thereafter for successive periods of 12 months, unless she is not re-elected at the next following annual general meeting or her appointment is otherwise terminated earlier by either party in writing. The director’s fees of Dr Hu as an Independent Non-executive Director and member of the Technical Committee of the Company under her appointment letter are US$76,000 and US$8,000 per annum respectively, which were determined by the Board with reference to the director’s duties and responsibilities and prevailing market conditions. Such fees are subject to review from time to time and proration for any incomplete year of service.

Dr Hu does not have any interest in the ordinary shares of the Company within the meaning of Part XV of the Securities and Futures Ordinance (Cap. 571 of the Laws of Hong Kong).

Save for the information disclosed above, there is no other information in relation to Dr Hu that is required to be disclosed pursuant to Rule 17 and Schedule 2(g) of the AІM Rules for Companies or Rule 13.51(2) of the HK Listing Rules, and there are no other matters concerning the appointment of Dr Hu that are required to be brought to the attention of the shareholders of HUTCHMED.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the US, Europe and Japan. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

CONTACTS

Hong Kong, Shanghai & Florham Park, NJ — Wednesday, November 6, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that new and updated data from the sovleplenib ESLIM-01 Phase III trial, as well as several investigator-initiated studies of compounds discovered by HUTCHMED will be presented at the American Society of Hematology (“ASH”) Annual Meeting taking place on December 7-10, 2024 in San Diego, USA, and the European Society for Medical Oncology (“ESMO”) Asia Congress 2024, taking place on December 6-8, 2024 in Singapore.

Long-term safety and efficacy data from a follow-on, open-label sub-study of the extension stage of ESLIM-01 Phase III study of sovleplenib in adult patients with chronic primary immune thrombocytopenia (“ITP”) in China will be reported at the 2024 ASH Annual Meeting (NCT05029635). At data cut-off on January 31, 2024, a total of 179 patients were treated with at least one dose of sovleplenib. 55.3% (99/179) of the patients were still on the treatment in the sub-study, with a median duration of exposure of 56.6 weeks.

The follow-on sub-study data demonstrated that long-term treatment with sovleplenib was effective in increasing and maintaining platelet count in adults with chronic primary ITP in China. In the overall population, the overall response was achieved by 81% (145/179) of the patients, with a durable response rate of 51.4% and long-term durable response rate of 59.8%. The median cumulative duration of platelet count ≥50×10⁹/L was 38.9 weeks. The long-term treatment was well tolerated, with a safety profile consistent with previous studies and no new safety signals were identified.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also approved in the US, Europe and Japan. For more information, please visit: www.hutch-med.com or follow us on LinkedIn.

CONTACTS

Hong Kong, Shanghai, & Florham Park, NJ — Thursday, October 31, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM: HCM; HKEX: 13) hereby notifies the market that as at October 31, 2024, the issued share capital of HUTCHMED consisted of 871,561,945 ordinary shares of US$0.10 each, with each share carrying one right to vote and with no shares held in treasury.

The above figure of 871,561,945 may be used by shareholders as the denominator for the calculations by which they could determine if they are required to notify their interest in, or a change to their interest in, HUTCHMED under the Financial Conduct Authority’s Disclosure Guidance and Transparency Rules.

For illustrative purposes only, the 871,561,945 ordinary shares would be equivalent to 871,561,945 depositary interests (each equating to one ordinary share) which are traded on AIM or, if the depositary interests were converted in their entirety, equivalent to 174,312,389 American depositary shares (each equating to five ordinary shares) which are traded on Nasdaq.

About HUTCHMED

HUTCHMED (Nasdaq/AIM: HCM; HKEX: 13) is an innovative, commercial-stage, biopharmaceutical company. Іt is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. Іt has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the US and Europe. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

Contacts

— US$20 million payment based on sales of FRUZAQLA^® in metastatic colorectal cancer —

Hong Kong, Shanghai & Florham Park, NJ — Thursday, October 31, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM; HKEX:​13) today announces that it will receive a US$20 million milestone payment from its partner Takeda (TSE:​4502/​NYSE:​TAK), triggered by reaching over US$200 million in sales of FRUZAQLA^® (fruquintinib) for metastatic colorectal cancer (“CRC”). CRC is the second most common cause of cancer-related deaths in the US. There are approximately 840,000 new cases of CRC each year across the US, Europe and Japan.

Takeda delivered US$203 million in net sales of FRUZAQLA^® in the nine months ended September 2024. This US$20 million payment will be the first ever commercial milestone payment received by HUTCHMED. Takeda has the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside of mainland China, Hong Kong and Macau, and markets under the FRUZAQLA^® brand name. It received approval in the US in November 2023, in the EU in June 2024, in Switzerland in August 2024, in Canada, Japan and the United Kingdom in September 2024 and in Argentina, Australia and Singapore in October 2024. Regulatory applications are progressing in many other jurisdictions.

“The achievement of US$200 million in sales is a testament to Takeda’s commercial strength in launching global brands, the clinical benefit of fruquintinib and the success of our partnership strategy for commercializing our medicines outside of China,” said Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED. “Receiving the US$20 million milestone payment will strengthen our balance sheet as we look to expand the use of fruquintinib into new indications, and highlights our strategy of global partnerships across our broad pipeline.”

About CRC

CRC is a cancer that starts in either the colon or rectum. According to the International Agency for Research on Cancer/World Health Organization, CRC is the third most prevalent cancer worldwide, associated with more than 1.9 million new cases and 900,000 deaths in 2022. In the US, it is estimated that 153,000 patients will be diagnosed with CRC and 53,000 deaths from the disease will occur in 2024.^[1] In Europe, CRC was the second most common cancer in 2022, with approximately 538,000 new cases and 248,000 deaths. In Japan, CRC was the most common cancer, with an estimated 146,000 new cases and 60,000 deaths, in 2022.^[2],[3] Although early-stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options. Some patients with metastatic CRC may benefit from personalized therapeutic strategies based on molecular characteristics; however, most patients have tumors that do not harbor actionable mutations.^{[4],[5],[6],[7],[8]}

About Fruquintinib Approvals

Global regulatory submissions are based on data from two large, randomized, controlled Phase III trials, the global, multi-regional FRESCO-2 trial and the FRESCO trial conducted in China, showing consistent benefit among a total of 734 patients treated with fruquintinib. Safety profiles were consistent across trials. Results from the FRESCO-2 trial were published in The Lancet in June 2023,^[9] while results from the FRESCO trial were published in The Journal of the American Medical Association, JAMA.^[10]

In mainland China, Hong Kong and Macau, fruquintinib is co-marketed by HUTCHMED and Eli Lilly and Company under the brand name ELUNATE^®. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. Since its launch in China, over 100,000 patients with colorectal cancer have been treated with fruquintinib.

About Fruquintinib

Fruquintinib is a selective oral inhibitor of all three VEGF receptors (VEGFR-1, -2 and -3). VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for drug exposure that achieves sustained target inhibition and flexibility for potential use as part of a combination therapy.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception it has focused on bringing cancer drug candidates from in‑house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also approved in the US, Europe and Japan. For more information, please visit www.hutch-med.com or follow us on LinkedIn.

E.U. IMPORTANT SAFETY INFORMATION

Please consult the FRUZAQLA (fruquintinib) Summary of Product Characteristics (SmPC) before prescribing.

Guidance for use: FRUZAQLA should be initiated by a physician experienced in the administration of anticancer therapy. Patients should be given the package leaflet.

CONTRAINDICATIONS: Hypersensitivity to the active substance or to any of the excipients.

SPECIAL POPULATIONS: Renal impairment: No dose adjustment is required for patients with mild, moderate, or severe renal impairment; Hepatic impairment: No dose adjustment is required for patients with mild or moderate hepatic impairment. FRUZAQLA is not recommended for use in patients with severe hepatic impairment as FRUZAQLA has not been studied in this population; Elderly: No dose adjustment is required in patients aged 65 years or above; Pediatric population: There is no relevant use of FRUZAQLA in the pediatric population for the indication of metastatic colorectal cancer; Women of childbearing potential / Contraception in females: Women of childbearing potential should be advised to use highly effective contraception during treatment and for at least 2 weeks following the last dose of FRUZAQLA; Pregnancy: There are no clinical data available on the use of FRUZAQLA in pregnant women. Based on its mechanism of action, FRUZAQLA has the potential to cause fetal harm. Animal studies have shown reproductive toxicity, including fetal malformations. FRUZAQLA should not be used during pregnancy unless the clinical condition of the woman requires treatment with FRUZAQLA. If FRUZAQLA is used during pregnancy or if the patient becomes pregnant while on treatment, the patient must be informed of the potential hazard to the fetus; Breast-feeding: The safe use of FRUZAQLA during breast-feeding has not been established. It is not known whether FRUZAQLA or its metabolites are excreted in human milk. There are no animal data on the excretion of FRUZAQLA in animal milk. A risk to the breastfeeding newborns/infants cannot be excluded. Breastfeeding should be discontinued during treatment and for 2 weeks after the last dose; Fertility: There are no data on the effects of FRUZAQLA on human fertility. Results from animal studies indicate that FRUZAQLA may impair male and female fertility.

SPECIAL WARNINGS AND PRECAUTIONS FOR USE

• Hypertension: Hypertension, including hypertensive crisis, has been reported in patients treated with FRUZAQLA. Pre-existing hypertension should be monitored and adequately controlled in accordance with standard medical practices before starting FRUZAQLA treatment.

Hypertension should be medically managed with antihypertensive medicinal products and adjustment of the FRUZAQLA dose, if necessary. FRUZAQLA should be permanently discontinued for hypertension that cannot be controlled with antihypertensive therapy or in patients with hypertensive crisis.

• Hemorrhagic events: Hemorrhagic events have been reported in patients treated with FRUZAQLA, including gastrointestinal (GI) tract events. Serious and sometimes fatal bleeding events have been reported in patients after treatment with FRUZAQLA.

Hematologic and coagulation profiles should be monitored in accordance with standard medical practices in patients at risk for bleeding, including those treated with anticoagulants or other concomitant medicinal products that increase the risk of bleeding. In the event of severe bleeding requiring immediate medical intervention, FRUZAQLA should be permanently discontinued.

• Gastrointestinal perforation: GI perforation events, including fatal events, have been reported in patients treated with FRUZAQLA.

Symptoms of GI perforation should be periodically monitored during treatment with FRUZAQLA.

FRUZAQLA should be permanently discontinued in patients developing GI perforation.

• Proteinuria: Proteinuria events have occurred in patients treated with FRUZAQLA.

Proteinuria should be monitored before initiation and during treatment with FRUZAQLA in accordance with standard medical practices. If urine dipstick proteinuria ≥ 2 g / 24 hours is detected, dose interruptions, adjustments, or discontinuation may be necessary. FRUZAQLA should be permanently discontinued in patients developing nephrotic syndrome.

• Palmar-plantar erythrodysesthesia syndrome (PPES): PPES is the most frequently reported dermato­logical adverse reaction.

If Grade ≥2 skin reactions are detected, dose interruptions, adjustments, or discontinuation may be necessary.

• Posterior reversible encephalopathy syndrome (PRES): PRES has been reported in 1 patient (0.1%) treated with FRUZAQLA in clinical studies. PRES is a rare neurologic disorder that can present with headache, seizure, lethargy, confusion, altered mental function, blindness, and other visual or neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). In patients developing PRES, discontinuation of FRUZAQLA, along with control of hypertension and supportive medical management of other symptoms, are recommended.

• Impaired wound healing: Impaired wound healing has been reported in 1 patient (0.1%) treated with FRUZAQLA in clinical studies.

Patients are recommended to withhold FRUZAQLA for at least 2 weeks prior to surgery. FRUZAQLA should not be resumed for at least 2 weeks after surgery, as clinically indicated when there is evidence of adequate wound healing.

• Arterial and venous thromboembolic events: It is recommended to avoid starting treatment with FRUZAQLA in patients with a history of thromboembolic events (including deep vein thrombosis and pulmonary embolism) within the past 6 months or if they have a history of stroke and/or transient ischemic attack within the last 12 months. If arterial thrombosis is suspected, FRUZAQLA should be discontinued immediately.

INTERACTIONS

Effects of other medicinal products on the pharmacokinetics of FRUZAQLA

CYP3A inducers

Co-administration of FRUZAQLA with rifampicin (a strong CYP3A inducer) 600 mg once daily decreased FRUZAQLA AUC_inf by 65% and decreased C_max by 12%. The concomitant use of FRUZAQLA with strong and moderate CYP3A inducers should be avoided.

CYP3A inhibitors

Co-administration of FRUZAQLA with itraconazole (a strong CYP3A inhibitor) 200 mg twice daily did not result in clinically meaningful changes in the area under the concentration-time curve (AUC) and C_max of FRUZAQLA. No dose adjustment of FRUZAQLA is needed during concomitant use with CYP3A inhibitors.

Gastric acid lowering agents

Co-administration of FRUZAQLA with rabeprazole (a proton pump inhibitor) 40 mg once daily did not result in clinically meaningful changes in the AUC of FRUZAQLA. No dose adjustment of FRUZAQLA is needed during concomitant use with gastric acid lowering agents.

Effect of FRUZAQLA on the pharmacokinetics of other medicinal products

Medicinal products that are substrates of P-glycoprotein (P-gp)

Co-administration of a single dose of dabigatran etexilate 150 mg (a P-gp substrate) with a single dose of FRUZAQLA 5 mg decreased AUC of dabigatran by 9%. No dose adjustment is recommended for P-gp substrates during concomitant use with FRUZAQLA.

Medicinal products that are substrates of breast cancer resistance protein (BCRP)

Co-administration of a single 10 mg dose of rosuvastatin (a BCRP substrate) with a single 5 mg dose of FRUZAQLA decreased AUC of rosuvastatin by 19%. No dose adjustment is recommended for BCRP substrates during concomitant use with FRUZAQLA.

UNDESIRABLE EFFECTS: The most commonly reported adverse reactions with FRUZAQLA are:

For US Prescribing Information:

https://www.fruzaqla.com/sites/default/files/resources/fruzaqla-prescribing-information.pdf

For Japan Prescribing Information:

https://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/400256_42910H0M1028_1_01

Forward-Looking Statements

This press release contains forward‑looking statements within the meaning of the “safe harbor” provisions of the US Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including but not limited to, its expectations regarding the receipt of the milestone payment, the therapeutic potential of fruquintinib for the treatment of such patients with CRC and the further clinical development of fruquintinib in this and other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the sufficiency of clinical data to support approval of fruquintinib for the treatment of patients with CRC or other indications in other jurisdictions such as Japan, its potential to gain approvals from regulatory authorities, the safety profile of fruquintinib, HUTCHMED and/or Takeda’s ability to fund, implement and complete its further clinical development and commercialization plans for fruquintinib, the timing of these events, each party’s ability to satisfy the terms and conditions under the license agreement; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or the regulatory pathway for fruquintinib; and Takeda’s ability to successfully develop and commercialize fruquintinib. In addition, as certain studies rely on the use of other drug products as combination therapeutics with fruquintinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Existing and prospective investors are cautioned not to place undue reliance on these forward‑looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the US Securities and Exchange Commission, on AIM and on The Stock Exchange of Hong Kong Limited. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

Medical Information

This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

CONTACTS

[1]   American Cancer Society. Cancer Facts & Figures 2024. Atlanta, American Cancer Society; 2024.

[2]   Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 Countries. CA Cancer J Clin. 2024;74(3):229-263. doi:10.3322/caac.21834.

[3] Ferlay J, et al. Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.who.int/today, accessed 12 June 2024.

[4]   Bando H, et al. Therapeutic landscape and future direction of metastatic colorectal cancer. Nat Rev Gastroenterol Hepatol 2023; 20(5)306‑322. doi:10.1038/s41575‑022‑00736‑1.

[5]   D’Haene N, et al. Clinical application of targeted next‑generation sequencing for colorectal cancer patients: a multicentric Belgian experience. Oncotarget. 2018;9(29):20761‑20768. Published 2018 Apr 17. doi:10.18632/oncotarget.25099.

[6]   Venderbosch S, et al. Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: A pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS Studies. Clinical Cancer Res. 2014; 20(20):5322–5330. doi:10.1158/1078‑0432.ccr‑14‑0332.

[7]   Koopman M, et al. Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Br J Cancer. 2009;100(2), 266–273. doi:10.1038/sj.bjc.6604867.

[8]   Ahcene Djaballah S, et al. HER2 in Colorectal Cancer: The Long and Winding Road From Negative Predictive Factor to Positive Actionable Target. Am Soc Clin Oncol Educ Book. 2022;42:1‑14. doi:10.1200/EDBK_351354.

[9]   Dasari NA, et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO‑2): an international, multicentre, randomised, double‑blind, Phase III study. Lancet. 2023;402(10395):41‑53. doi:10.1016/S0140‑6736(23)00772‑9.

[10] Li J, et al. Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018;319(24):2486-2496. DOI:10.1001/jama.2018.7855.

Hong Kong, Shanghai & Florham Park, NJ — Monday, October 21, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM: HCM; SEHK:13) announces that the non-performance based awards granted under the Long Term Incentive Plan (“LTIP”) on October 20, 2021 to the following persons discharging managerial responsibilities were vested on October 20, 2024:-

Notes:

• These ADSs were not received by Ms Edith Shih, but were received by or for the account of her employer, Hutchison International Limited.
• Mr Paul Carter elected, on acceptance of the grant of his awards, to have 15% of his LTIP awards (amounting to US$9,375 with respect to his awards which vested on October 20, 2024) held on his behalf by the trustee administering the LTIP pending vesting in the form of cash, to settle his tax liabilities in respect of his awards.
• Since the vesting date is not a trading day, the relevant ADSs are scheduled to be transferred to the award holders on October 21, 2024.

The notifications set out below are provided in accordance with the requirements of the UK Market Abuse Regulation.

(a) Dr Dan Eldar

(b) Mr Paul Carter

(c) Mr Graeme Jack

(d) Professor Tony Mok

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the US and Europe. For more information, please visit: www.hutch-med.com or follow us on LinkedIn.

CONTACTS

 — New data demonstrate efficacy for the oral treatment combination to address MET-driven resistance in EGFR-mutated lung cancer —

— MET is a common biomarker in this setting for patients who develop resistance to EGFR targeted therapies —

Hong Kong, Shanghai & Florham Park, NJ — Wednesday, October 16, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM; HKEX:​13) today announces positive high-level results from the SAVANNAH Phase II trial that showed TAGRISSO^® (osimertinib) plus ORPATHYS^® (savolitinib) demonstrated a high, clinically meaningful and durable objective response rate (“ORR”) for patients with epidermal growth factor receptor-mutated (“EGFRm”) non-small cell lung cancer (“NSCLC”) with high levels of MET overexpression and/or amplification, defined as IHC90+ and/or FISH10+, whose disease progressed on treatment with TAGRISSO^®. These data will be presented at a forthcoming medical meeting and shared with global regulatory authorities. In 2023, TAGRISSO^® plus ORPATHYS^® received Fast Track designation from the US Food and Drug Administration (FDA) in this setting.

ORPATHYS^® is an oral, potent, and highly selective MET tyrosine kinase inhibitor (“TKI”) being jointly developed by AstraZeneca and HUTCHMED and commercialized by AstraZeneca. It is approved in China for the treatment of patients with NSCLC with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy.

While EGFR-targeted therapy can provide a substantial survival benefit to patients with EGFRm NSCLC, most will eventually develop resistance to their treatment, with MET being a common resistance biomarker.^[1] Among patients screened for enrollment in SAVANNAH, an estimated 62% had tumors with MET overexpression and/or amplification, and approximately 34% met the defined high MET level cut-off upon clinical progression.

Myung-Ju Ahn, MD, PhD, Professor of Hemato-Oncology at the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, and principal investigator in the SAVANNAH Phase II trial, said: “Osimertinib can provide patients with EGFR-mutated lung cancer unprecedented survival and has transformed the treatment landscape, but patients can develop resistance due to genes like MET – a common resistance biomarker. These results show that adding savolitinib, a selective MET-inhibitor, while continuing osimertinib treatment helped to deliver a meaningful response among patients whose disease progressed, providing a potential new treatment option following standard-of-care osimertinib.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “These positive SAVANNAH results show the benefit of a targeted treatment approach in EGFR-mutated lung cancer patients who experience MET-driven resistance. The improved response rates from ORPATHYS^® added to TAGRISSO^®, which is the backbone EGFR-mutated lung cancer therapy, reinforce the importance of identifying MET aberration and validate our combination strategy to address resistance while allowing continued TAGRISSO^® treatment.”

Weiguo Su, Chief Executive Officer and Chief Scientific Officer, HUTCHMED, said: “Previous results from the SAVANNAH Phase II trial provided a novel biomarker approach for identifying patients with MET overexpression and/or amplification who are most likely to benefit from a MET-directed therapy, an existing unmet need. These new, positive results affirm our selective, patient-centric approach, which could allow us to deliver the first biomarker-driven targeted therapy combination option in this setting.”

The safety and tolerability of TAGRISSO^® plus ORPATHYS^® was consistent with the known safety profiles of the combination and each treatment alone. No new safety signals were identified.

In August 2022, initial positive ORR results from the SAVANNAH trial were presented at the International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer (WCLC).

The global SAFFRON Phase III trial sponsored by AstraZeneca will further assess the TAGRISSO^® plus ORPATHYS^® combination versus platinum-based doublet chemotherapy in patients with EGFRm, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following TAGRISSO^®. Patients are being prospectively selected using the high MET level cut-off identified in SAVANNAH.

About NSCLC and MET aberrations

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.^[2],[3] Lung cancer is broadly split into NSCLC and small cell lung cancer.^[4] Each year there are an estimated 2.4 million people diagnosed with lung cancer globally, with 80-85% of patients diagnosed with NSCLC, the most common form of lung cancer.^[2],^[4],^[5] Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.^[6],[7],[8]

MET is a tyrosine kinase receptor that has an essential role in normal cell development. MET overexpression and/or amplification can lead to tumor growth and the metastatic progression of cancer cells, and is the primary mechanism of acquired resistance to EGFR TKIs for metastatic EGFRm NSCLC. Among patients who experience disease progression post-osimertinib treatment, approximately 15-50% present with MET aberration.^{[9],[10],[11],[12],[13]} The prevalence of MET depends on the sample type, detection method and assay cut-off used.^[14]

About SAVANNAH

SAVANNAH is an ongoing global, randomised, Phase II trial sponsored by AstraZeneca studying the efficacy of ORPATHYS^® added to TAGRISSO^® in patients with EGFRm, locally advanced or metastatic NSCLC with MET overexpression and/or amplification who progressed following treatment with TAGRISSO^®. Based on the original single-arm trial design, patients were treated with ORPATHYS^® 300 or 600 mg once-daily (QD) or 300 mg twice-daily, in combination with oral TAGRISSO^® 80 mg QD. In 2022, a registrational component was added to the trial that compared ORPATHYS^® 300 mg twice-daily and TAGRISSO^® 80 mg QD to ORPATHYS^® 300 mg twice-daily and placebo.

The trial enrolled over 360 patients in more than 80 centers globally, including in North America, Europe, South America and Asia. The primary endpoint is ORR and key secondary endpoints include progression-free survival and duration of response.

About TAGRISSO^®

TAGRISSO^® (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system (CNS) metastases. TAGRISSO^® (40mg and 80mg once-daily oral tablets) has been used to treat nearly 800,000 patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO^® as a treatment for patients across multiple stages of EGFRm NSCLC.

There is an extensive body of evidence supporting the use of TAGRISSO^® as standard of care in EGFRm NSCLC. TAGRISSO^® improved patient outcomes in early-stage disease in the ADAURA Phase III trial, locally advanced disease in the LAURA Phase III trial, late-stage disease in the FLAURA Phase III trial, and with chemotherapy in the FLAURA2 Phase III trial.

About ORPATHYS^®

ORPATHYS^® (savolitinib) is an oral, potent, and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.

It is approved in China for the treatment of patients with NSCLC with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy. It is the first selective MET inhibitor approved in China and the first in the National Reimbursement Drug List of China (NRDL).

It is currently under clinical development for multiple tumor types, including lung, kidney, and gastric cancers, as a single treatment and in combination with other medicines. In addition to SAVANNAH and SAFFRON, in China the combination of savolitinib and osimertinib in lung cancer is also being studied in the SACHI and SANOVO Phase III trials.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also approved in the US, Europe and Japan. For more information, please visit www.hutch‑med.com or follow us on LinkedIn.

CONTACTS

— First innovative oncology medicine ever to get enlisted in HA Drug Formulary directly under the Special Drug category —

— First new drug approved by 1+ Mechanism listed in the Hospital Authority Drug Formulary —

— Rapid enlistment and 1+ approval accelerate patient access to an important treatment option —

— ELUNATE^® is the first oral targeted therapy approved in Hong Kong for metastatic colorectal cancer regardless of biomarker status or prior types of therapies in almost a decade —

Hong Kong — Wednesday, October 3, 2024: HUTCHMED (China) Limited (“HUTCHMED”) today announced that ELUNATE^® (fruquintinib) was enlisted in the Drug Formulary of the Hong Kong Hospital Authority (“HA”), categorized as a Special Drug. Patients prescribed these new medicines under specific conditions in public hospitals and clinics are only required to pay for the standard fees and charges. ELUNATE^® was approved by the Pharmacy and Poisons Board of Hong Kong in January 2024 for the treatment of adult patients with metastatic colorectal cancer (“CRC”) who have been previously treated with available standard therapies.

“The fully subsidized enlistment in the HA’s Drug Formulary has come less than six months following ELUNATE’s approval under the new 1+ Mechanism. We can clearly see and truly appreciate the government’s efforts to accelerate the pathway for novel therapies to reach local patients and remove financial barriers in accessing this treatment option.”, said Dr Tony SK MOK, medical oncologist and Independent Non-executive Director of HUTCHMED. “The HUTCHMED story began in Hong Kong. Since the approval of ELUNATE, the HUTCHMED team has been laser-focused on bringing this innovative treatment option as quickly as possible to patients in need. We are committed to continuing our mission to bring novel therapies to more patients in Hong Kong and beyond.”

“Colorectal cancer is the second most prevalent cancer indication in Hong Kong,” said Mr Wai Kit CHAN, Chairman of the Cancer Patient Alliance. “It is very encouraging to see the first cancer drug approved under the 1+ mechanism to be enlisted and categorized as a Special Drug. Not only does it mean patients have access to a meaningful treatment option, but the enlistment will also alleviate the burden that devastating diseases like cancer impose on these patients and their family. This has become possible through the hard work and collaboration of the local government and drug developers.”

According to the HA, the enlistment is expected to take effect in mid-October, 2024. Fruquintinib was discovered and developed in-house by HUTCHMED and is marketed in Hong Kong under the brand name ELUNATE^®.

About CRC in Hong Kong

CRC is a cancer that starts in either the colon or rectum. It was the second most common cancer in Hong Kong in 2021, with about 5,900 new patients diagnosed with CRC, and associated with about 2,300 deaths.[1] Although early-stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options. Some patients with metastatic CRC may benefit from personalized therapeutic strategies based on molecular characteristics; however, most patients have tumors that do not harbor actionable mutations.[2]^{,[3],[4],[5],[6]}

About the 1+ Mechanism and Fruquintinib Approval in Hong Kong

The Government of the Hong Kong Special Administrative Region announced a new mechanism for registration of new drugs (“1+” mechanism) in October 2023. The mechanism officially commenced on November 1, 2023. It allows drugs which are beneficial for treatment of life-threatening or severely debilitating diseases to apply for registration for use in Hong Kong, if they have supporting local clinical data and recognition from relevant experts, when they have been approved by only one reference drug regulatory authority (instead of two otherwise).

ELUNATE^® was granted marketing approval by the Pharmacy and Poisons Board of Hong Kong in January 2024, for the treatment of adult patients with previously treated metastatic CRC. This marked the first medicine to be approved under the 1+ mechanism, based on its approval in mainland China, supported with local clinical data.

About Fruquintinib

Fruquintinib is a selective oral inhibitor of all three VEGF receptors (VEGFR‑1, ‑2 and ‑3). VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off‑target kinase activity, allowing for drug exposure that achieves sustained target inhibition and flexibility for potential use as part of a combination therapy. Fruquintinib has demonstrated a manageable safety profile and is being investigated in combinations with other anti‑cancer therapies.

Fruquintinib is co-marketed in China in partnership with Eli Lilly & Company under the brand name ELUNATE^®. ELUNATE^® was included in the mainland China National Reimbursement Drug List (NRDL) in January 2020. Since its launch in China, over 100,000 patients with colorectal cancer have been treated with fruquintinib. Takeda has the exclusive worldwide license to fruquintinib outside of mainland China, Hong Kong and Macau, and markets fruquintinib under the brand name FRUZAQLA^®. FRUZAQLA^® is approved in Canada, the European Union, Japan, Switzerland, the United Kingdom and the United States, with additional regulatory applications in several other jurisdictions worldwide.

About HUTCHMED

HUTCHMED is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three oncology medicines marketed in China, the first of which is also marketed in the US and Europe. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

Media Enquiries

Stacey Chan, McCann Health

+852 5167 7312 (Mobile)

stacey.chan@mccannhealth.com

Medical Information

This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of fruquintinib for the treatment of patients with CRC and the further clinical development of fruquintinib in this and other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the efficacy and safety profile of fruquintinib; HUTCHMED and/or its licensees’ ability to fund, implement and complete its further clinical development and commercialization plans for fruquintinib; the timing of these events; HUTCHMED and its licensees’ ability to satisfy their obligations; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or the regulatory pathway for fruquintinib; and HUTCHMED and its licensees’ ability to successfully develop, manufacture and commercialize fruquintinib. In addition, as certain studies rely on the use of other drug products as combination therapeutics with fruquintinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Such forward-looking statements include, without limitation, statements regarding the plan to develop, manufacture and commercialize fruquintinib; and HUTCHMED’s strategy, goals and anticipated milestones, business plans and focus. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, on AIM and on The Stock Exchange of Hong Kong Limited. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

— Approval based on results from global Phase III FRESCO-2 trial in patients with previously treated metastatic colorectal cancer —

— Fruquintinib already approved in several regions including the United States, Europe and China —

Hong Kong, Shanghai & Florham Park, NJ — Tuesday, September 24, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM; HKEX:​13) today announces that its partner Takeda (TSE:​4502/​NYSE:​TAK) has received approval from the Japanese Ministry of Health, Labour and Welfare (“MHLW”) to manufacture and market FRUZAQLA^® (fruquintinib) for previously treated metastatic colorectal cancer (“CRC”). FRUZAQLA^® is the first novel targeted therapy in Japan to be approved for metastatic CRC, regardless of biomarker status, in over a decade. CRC is the most prevalent type of cancer in Japan, with an estimated 161,000 new cases and 54,000 deaths in 2023, according to the National Cancer Center’s statistics.^[1]

FRUZAQLA^® has been approved for the treatment of advanced or recurrent CRC that is neither curable nor resectable and that has progressed after chemotherapy.

“Takeda has now obtained approval in Japan for FRUZAQLA^®, demonstrating the strength of our global data package and the potential of this novel medicine to provide a much-needed treatment option to patients with metastatic CRC,” said Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED. “Takeda has been a leader in metastatic CRC treatment in Japan for over a decade and we are confident that it is well placed to bring FRUZAQLA^® to patients in Japan.”

Dr. Takayuki Yoshino, Deputy Director of Hospital, Head, Division for the Promotion of Drug and Diagnostic Development, and Chief, Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan, added: “The approval of FRUZAQLA^® in Japan is significant news for patients with metastatic colorectal cancer, who have long needed additional effective treatment options. The global FRESCO-2 study demonstrated the impact that this treatment can have on patients in the clinic. The increasing availability of screening and effective therapies in Japan has been driving patient outcomes in colorectal cancer, and we hope the introduction of FRUZAQLA^® will offer new hope to those with the condition.”

The approval by the Japanese MHLW was primarily based on results from the Phase III FRESCO-2 trial conducted in the US, Europe, Japan and Australia. Data from FRESCO-2 were published in The Lancet in June 2023. Takeda has the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside of mainland China, Hong Kong and Macau. FRUZAQLA^® was approved in the US in November 2023 and in Europe in June 2024.

About CRC

CRC is a cancer that starts in either the colon or rectum. According to the International Agency for Research on Cancer/World Health Organization, CRC is the third most prevalent cancer worldwide, associated with more than 1.9 million new cases and 900,000 deaths in 2022. In Japan, CRC was the most common cancer, with an estimated 146,000 new cases and 60,000 deaths, in 2022.² In Europe, CRC was the second most common cancer in 2022, with approximately 538,000 new cases and 248,000 deaths.^[2],[3] In the US, it is estimated that 153,000 patients will be diagnosed with CRC and 53,000 deaths from the disease will occur in 2024.^[4] Although early-stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options. Some patients with metastatic CRC may benefit from personalized therapeutic strategies based on molecular characteristics; however, most patients have tumors that do not harbor actionable mutations.^{[5],[6],[7],[8],[9]}

About the Phase III FRESCO-2 Trial

FRESCO-2 is a multiregional clinical trial conducted in the US, Europe, Japan and Australia investigating fruquintinib plus best supportive care (“BSC”) versus placebo plus BSC in patients with previously treated metastatic CRC (NCT04322539). FRESCO-2 met all of its primary and key secondary endpoints, demonstrating statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS), with consistent benefit among patients treated with fruquintinib, regardless of the prior types of therapies they received. Fruquintinib demonstrated a manageable safety profile in FRESCO-2, consistent with previously reported fruquintinib monotherapy studies. Adverse reactions leading to treatment discontinuation occurred in 20% of patients treated with fruquintinib plus BSC versus 21% of those treated with placebo plus BSC. Results from the study were presented at the European Society for Medical Oncology Congress (ESMO) in September 2022 and subsequently published in The Lancet in June 2023.^[10],^[11]

About Takeda and FRUZAQLA^®

Takeda has the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside of mainland China, Hong Kong and Macau, and markets under the brand name FRUZAQLA^®. FRUZAQLA^® received approval in the US in November 2023, in the EU in June 2024, in Switzerland in August 2024 and in Canada, Japan and the United Kingdom in September 2024. The US approval was based on data from two large, randomized, controlled Phase III trials, the multi-regional FRESCO-2 trial and the FRESCO trial conducted in China, showing consistent benefit among a total of 734 patients treated with fruquintinib. Safety profiles were consistent across trials. Regulatory applications are progressing in many other jurisdictions.

About Fruquintinib Approval in China

Fruquintinib is approved for marketing in mainland China, Hong Kong and Macau, where it is co‑marketed by HUTCHMED and Eli Lilly and Company under the brand name ELUNATE^®. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. The approvals were based on data from the FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic colorectal cancer in China, which were published in The Journal of the American Medical Association, JAMA. Since its launch in China, over 100,000 patients with colorectal cancer have been treated with fruquintinib.

About Fruquintinib

Fruquintinib is a selective oral inhibitor of all three VEGF receptors (VEGFR‑1, ‑2 and ‑3). VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off‑target kinase activity, allowing for drug exposure that achieves sustained target inhibition and flexibility for potential use as part of a combination therapy. Fruquintinib has demonstrated a manageable safety profile and is being investigated in combinations with other anti‑cancer therapies.

JAPAN IMPORTANT SAFETY INFORMATION

Please consult the FRUZAQLA (fruquintinib) Japan package insert (J-PI) before prescribing.

WARNING: FRUZAQLA should be administered only to patients for whom the use of FRUZAQLA is considered appropriate under the supervision of a physician with sufficient knowledge of and experience in cancer chemotherapy at a medical institution where adequate emergency care can be provided. Prior to treatment initiation, the efficacy and risks should be fully explained to the patient and/or his/her family and informed consent should be obtained; Severe gastrointestinal hemorrhage, including fatal cases, has been reported. Patients should be carefully monitored, and if any abnormalities are observed, administration of FRUZAQLA should be withheld and appropriate measures should be taken. If severe hemorrhage occurs, FRUZAQLA should not be re-administered; Gastrointestinal perforation has been reported with some fatal cases. Patients should be carefully monitored, and if any abnormalities are observed, administration of FRUZAQLA should be withheld and appropriate measures should be taken. If gastrointestinal perforation occurs, FRUZAQLA should not be re-administered.

CONTRAINDICATIONS: Patients with a history of hypersensitivity to any of the ingredients of FRUZAQLA.

IMPORTANT PRECAUTIONS: Hypertension, including hypertensive crisis, may occur. Blood pressure should be measured prior to the initiation of FRUZAQLA treatment and periodically during this treatment; Proteinuria may occur. Urinary protein should be monitored prior to the initiation of FRUZAQLA treatment and periodically during this treatment; If a surgical procedure is to be performed, patients are recommended to withhold FRUZAQLA before the surgery because wound healing may be delayed. Treatment resumption after the surgical procedure should be determined depending on the patient’s condition upon confirmation of adequate wound healing.

PRECAUTIONS CONCERNING PATIENTS WITH SPECIFIC BACKGROUNDS: Patients with hyper­ten­sion: Hypertension may worsen; Patients with bleeding diathesis or abnormal coagulation system: Hemorrhagic events may occur; Patients with hemorrhage such as gastrointestinal hemorrhage: Hemorrhage may be enhanced; Patients with a complication of intra-abdominal inflammation in the gastrointestinal tract, etc.: Gastrointestinal perforation may occur; Patients with current or a history of thromboembolism: Transient ischaemic attack, thrombotic microangiopathy, pulmonary embolism, portal vein thrombosis, deep vein thrombosis, etc. may occur; Patients with severe hepatic impairment (Child-Pugh Class C): Since FRUZAQLA is metabolized mainly in the liver, blood concentrations may be increased. There have been no clinical studies conducted in patients with severe hepatic impairment; Patients with Reproductive Potential: Women of childbearing potential should be advised to use adequate contraception during treatment with FRUZAQLA and for 2 weeks after the last dose; Pregnant Women: FRUZAQLA can be administered to women who are or may be pregnant only if the expected therapeutic benefits outweigh the possible risks associated with this treatment. In a rat embryo-fetal toxicity study, fetal abnormalities and teratogenic effects consisting of fetal external, visceral, and skeletal malformations and visceral and skeletal variations were observed at exposure levels approximately 0.05 times the exposure level (AUC) of FRUZAQLA at the maximum clinical dose (5 mg/day); Breast-feeding Women: It is advisable not to breastfeed. FRUZAQLA may pass into breast milk, and infants may experience serious adverse reactions if they are ingested through breast milk; Pediatric Use: There have been no clinical studies conducted in pediatric patients.

ADVERSE REACTIONS:

Any of the adverse reactions listed below may occur. Patients should be closely monitored, and if any such abnormalities are observed, appropriate measures should be taken, including treatment discontinuation. Clinically Significant Adverse Reactions are follows.

Hypertension: Hypertension or hypertensive crisis may occur. If an increase in blood pressure is observed, appropriate treatment such as antihypertensive drug administration should be given as necessary, and if necessary, the dose of fruquintinib should be reduced, or fruquintinib administration should be interrupted. If severe or persistent hypertension, or hypertension that cannot be controlled by routine antihypertensive therapy occurs or if a hypertensive crisis occurs, fruquintinib administration should be discontinued; Skin disorder: Skin disorder including palmar-plantar erythrodysesthesia syndrome and rash may occur; Hemorrhage: Hemorrhage including epistaxis, hematuria, gastrointestinal hemorrhage and hemoptysis may occur. Fatal outcomes have been reported; Gastrointestinal perforation: Fatal outcomes have been reported; Arterial thromboembolic events: Arterial thromboembolic events including transient ischemic attack and thrombotic microangiopathy may occur; Venous thromboembolism events: Venous thromboembolism such as pulmonary embolism, portal vein thrombosis, and deep vein thrombosis may occur; Posterior reversible encephalopathy syndrome: If headaches, convulsions, lethargy, confusion, changes in mental function, blindness or other visual disturbances, or neurological impairment are observed, fruquintinib administration should be discontinued, and appropriate measures should be taken, including blood pressure control; Arterial dissection: Arterial dissection including aortic dissection may occur.

For US Prescribing Information:

https://www.fruzaqla.com/sites/default/files/resources/fruzaqla-prescribing-information.pdf

For European Union Summary of Product Characteristics:

https://www.ema.europa.eu/en/medicines/human/EPAR/fruzaqla

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial‑stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception it has focused on bringing cancer drug candidates from in‑house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the US and Europe. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

Forward‑Looking Statements

This announcement contains forward‑looking statements within the meaning of the “safe harbor” provisions of the US Private Securities Litigation Reform Act of 1995. These forward‑looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of fruquintinib for the treatment of such patients with CRC and the further clinical development of fruquintinib in this and other indications. Forward‑looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the sufficiency of clinical data to support approval of fruquintinib for the treatment of patients with CRC or other indications in other jurisdictions such as Japan, its potential to gain approvals from regulatory authorities, the safety profile of fruquintinib, HUTCHMED and/or Takeda’s ability to fund, implement and complete its further clinical development and commercialization plans for fruquintinib, the timing of these events, each party’s ability to satisfy the terms and conditions under the license agreement; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or the regulatory pathway for fruquintinib; and Takeda’s ability to successfully develop and commercialize fruquintinib. In addition, as certain studies rely on the use of other drug products as combination therapeutics with fruquintinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Existing and prospective investors are cautioned not to place undue reliance on these forward‑looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the US Securities and Exchange Commission, on AIM and on The Stock Exchange of Hong Kong Limited. HUTCHMED undertakes no obligation to update or revise the information contained in this announcement, whether as a result of new information, future events or circumstances or otherwise.

Medical Information

This announcement contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

Inside Information

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) No 596/2014 (as it forms part of retained EU law as defined in the European Union (Withdrawal) Act 2018).

CONTACTS

[1] Foundation for Promotion of Cancer Research. Cancer Statistics In Japan. Tokyo, Foundation for Promotion of Cancer Research; 2023.

[2]   Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 Countries. CA Cancer J Clin. 2024;74(3):229-263. doi:10.3322/caac.21834.

[3] Ferlay J, et al. Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.who.int/today, accessed 12 June 2024.

[4]   American Cancer Society. Cancer Facts & Figures 2024. Atlanta, American Cancer Society; 2024.

[5]   Bando H, et al. Therapeutic landscape and future direction of metastatic colorectal cancer. Nat Rev Gastroenterol Hepatol 2023; 20(5)306‑322. doi:10.1038/s41575‑022‑00736‑1.

[6]   D’Haene N, et al. Clinical application of targeted next‑generation sequencing for colorectal cancer patients: a multicentric Belgian experience. Oncotarget. 2018;9(29):20761‑20768. Published 2018 Apr 17. doi:10.18632/oncotarget.25099.

[7]   Venderbosch S, et al. Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: A pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS Studies. Clinical Cancer Res. 2014; 20(20):5322–5330. doi:10.1158/1078‑0432.ccr‑14‑0332.

[8]   Koopman M, et al. Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Br J Cancer. 2009;100(2), 266–273. doi:10.1038/sj.bjc.6604867.

[9]   Ahcene Djaballah S, et al. HER2 in Colorectal Cancer: The Long and Winding Road From Negative Predictive Factor to Positive Actionable Target. Am Soc Clin Oncol Educ Book. 2022;42:1‑14. doi:10.1200/EDBK_351354.

[10]  Dasari NA, et al. LBA25 – FRESCO‑2: A global Phase III multiregional clinical trial (MRCT) evaluating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer. Ann Oncol. 2022 Sep;33(suppl_7): S808‑S869. doi:10.1016/annonc/annonc1089.

[11]  Dasari NA, et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO‑2): an international, multicentre, randomised, double‑blind, Phase III study. Lancet. 2023;402(10395):41‑53. doi:10.1016/S0140‑6736(23)00772‑9.

Savolitinib in patients in China with locally advanced or metastatic treatment-naive non-small-cell lung cancer harbouring MET exon 14 skipping mutations: results from a single-arm, multicohort, multicentre, open-label, phase 3b confirmatory study

Yongfeng Yu, Qisen Guo, Yongchang Zhang, Jian Fang, Diansheng Zhong, Baogang Liu, Pinhua Pan, Dongqing Lv, Lin Wu, Yanqiu Zhao, Juan Li, Zhihua Liu, Chunling Liu, Haichuan Su, Yun Fan, Tongmei Zhang, Anwen Liu, Bo Jin, Ye Wang, Jianying Zhou, Zhihong Zhang, Fengming Ran, Xia Song, Michael Shi, Weiguo Su, Shun Lu, on behalf of the study group*

Summary

Background

Methods

Findings

Interpretation

Funding

Trial Registration

ClinicalTrials.gov Identifier: NCT04923945

Citations and Links

Please follow the link below to access the publication:

DOI: https://doi.org/10.1016/S2213-2600(24)00211-X

Link to article: https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(24)00211-X/abstract

Hong Kong, Shanghai & Florham Park, NJ — Monday, September 9, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that new and updated data from several studies of compounds discovered by HUTCHMED will be presented at the 2024 World Conference on Lung Cancer (“WCLC24”) in San Diego, USA, and the European Society for Medical Oncology (“ESMO”) Congress 2024, taking place in Barcelona, Spain.

Results from the FLOWERS study, a prospective, two-arm, randomized, multicenter Phase II clinical trial of osimertinib with or without savolitinib as first-line treatment in EGFRm, MET-aberrant advanced non-small cell lung cancer (“NSCLC”) patients, will be presented at WCLC24. As of May 28, 2024, the median follow-up was 8.2 months. Patients treated with osimertinib plus savolitinib (Cohort 2, N=21) showed deeper and more durable response over osimertinib monotherapy (Cohort 1, N=23) along the study follow-up. The confirmed objective response rate (ORR) in Cohort 1 and Cohort 2 were 60.9% and 90.5%, respectively, with disease control rate (DCR) of 87% and 95.2%, respectively. Immature progression-free survival (“PFS”) data also showed a positive trend in favor of the combination therapy, with median PFS of 9.3 months and 19.6 months in the cohort 1 and cohort 2 with maturity of 34.8% and 23.8%, respectively. Safety profiles of osimertinib monotherapy and osimertinib plus savolitinib were as expected, tolerable and manageable.

Further analysis of fruquintinib’s FRESCO-2 study in metastatic colorectal cancer and FRUTIGA study in gastric cancer, a biomarker study of savolitinib in gastric cancer as well as investigator-initiated studies of fruquintinib and surufatinib will be presented at the ESMO Congress 2024. Details of the presentations are as follows:

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the US and Europe. For more information, please visit: www.hutch-med.com or follow us on LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including but not limited to its expectations regarding the therapeutic potential of fruquintinib, savolitinib and surufatinib, the further clinical development for fruquintinib, savolitinib and surufatinib, its expectations as to whether any studies on fruquintinib, savolitinib and surufatinib, would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates and the timing and availability of subjects meeting a study’s inclusion and exclusion criteria; changes to clinical protocols or regulatory requirements; unexpected adverse events or safety issues; the ability of fruquintinib, savolitinib and surufatinib, including as combination therapies, to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions and to gain commercial acceptance after obtaining regulatory approval; the potential markets of fruquintinib, savolitinib and surufatinib for a targeted indication, and the sufficiency of funding. In addition, as certain studies rely on the use of CAPEOX, docetaxel, gemcitabine, nab-paclitaxel, paclitaxel, pemetrexed, platinum, sintilimab, topotecan, tislelizumab or toripalimab as combination therapeutics, such risks and uncertainties include assumptions regarding their safety, efficacy, supply and continued regulatory approval. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

Medical Information

This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

CONTACTS

Hong Kong, Shanghai, & Florham Park, NJ — Friday, August 30, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM: HCM; HKEX: 13) hereby notifies the market that as at August 30, 2024, the issued share capital of HUTCHMED consisted of 871,469,720 ordinary shares of US$0.10 each, with each share carrying one right to vote and with no shares held in treasury.

The above figure of 871,469,720 may be used by shareholders as the denominator for the calculations by which they could determine if they are required to notify their interest in, or a change to their interest in, HUTCHMED under the Financial Conduct Authority’s Disclosure Guidance and Transparency Rules.

For illustrative purposes only, the 871,469,720 ordinary shares would be equivalent to 871,469,720 depositary interests (each equating to one ordinary share) which are traded on AIM or, if the depositary interests were converted in their entirety, equivalent to 174,293,944 American depositary shares (each equating to five ordinary shares) which are traded on Nasdaq.

About HUTCHMED

HUTCHMED (Nasdaq/AIM: HCM; HKEX: 13) is an innovative, commercial-stage, biopharmaceutical company. Іt is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. Іt has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines now marketed in China, the first of which is also marketed in the US and Europe. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

Contacts

Hong Kong, Shanghai & Florham Park, NJ — Friday, August 30, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM; HKEX:​13) today announces that it has voluntarily withdrawn its supplemental New Drug Application (“NDA”) in China for fruquintinib in combination with paclitaxel for the treatment of second-line advanced gastric or gastroesophageal junction adenocarcinoma and will evaluate a new route forward. Following an additional internal review of the current data package, in light of recent discussions with the National Medical Products Administration of China (“NMPA”), HUTCHMED has determined that the submission is unlikely to support an approval in China at this time.

This supplemental NDA for fruquintinib was based on data from the Phase III FRUTIGA study, which was declared positive due to a statistically significant improvements in many clinically meaningful endpoints, including progression-free survival (“PFS”), which served as one of two primary endpoints. However, while an improvement was also observed in the second primary endpoint of median overall survival (“OS”), it was not statistically significant. Extensive subsequent analyses conducted indicate that, although the high and imbalanced proportion of patients receiving subsequent antitumor therapies confounded the OS effect, fruquintinib plus paclitaxel demonstrated meaningful clinical benefit and favorable OS trends through a variety of models. Furthermore, no new safety signals were observed, and fruquintinib plus paclitaxel showed a tolerable safety profile. However, it became clear from dialogue with the Centre for Drug Evaluation (CDE) of the NMPA and its external committee members that the current understanding and interpretation of the OS results could not serve as the basis of the supplemental NDA approval, and that further work needs to be undertaken.

Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, commented, “Whilst disappointed by this outcome, we remain optimistic about the utility of fruquintinib in the treatment of gastric cancer. The data set from FRUTIGA demonstrates that fruquintinib plus paclitaxel could offer a promising new treatment option to certain patients in future, and we are driven to investigate this possibility thoroughly. We look forward to evaluating a path forward and would like to thank both the patients and principal investigators who took part in this study for contributing to a better understanding of this devastating disease.”

Dr Rui-Hua Xu, Professor at the Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, added, “Gastric cancer is the fifth most common cancer worldwide and patients in China are currently underserved by available treatment options. Although the current data package would not support approval on this occasion, the Phase III study demonstrated clear benefits of this fruquintinib combination across many clinically meaningful endpoints and the team are committed to evaluating all options. Promising subgroup analyses are helping us to better understand how we can effectively combat this disease, and we remain hopeful that this study forms part of an important journey to a much-needed new therapy.”

Fruquintinib is approved in China, the US and Europe for the treatment of previously-treated patients with metastatic colorectal cancer (“CRC”), and regulatory applications for this indication are progressing as expected in over a dozen jurisdictions. It works as an anti-cancer therapy by blocking tumor angiogenesis, a proliferation of blood vessels that is critical for cancer growth. It is a selective oral inhibitor of vascular endothelial growth factor receptors (“VEGFRs”) 1, 2 and 3, and this pathway plays a key role in the pathogenesis of many solid tumors including gastric cancer.

An NDA in China for fruquintinib in combination with sintilimab in endometrial cancer was accepted with priority review status in April 2024, and a Phase III trial in China of fruquintinib in combination with sintilimab in renal cell carcinoma was fully enrolled in December 2023.

About the Phase III FRUTIGA Trial

FRUTIGA (NCT03223376) was a 1:1 randomized, double-blind, Phase III study conducted across 35 sites in China. It evaluated fruquintinib in combination with paclitaxel chemotherapy, compared with paclitaxel monotherapy, for second-line treatment in 703 patients with advanced gastric or gastroesophageal junction adenocarcinoma. The study was declared positive due to a statistically significant improvement in progression-free survival (“PFS”), one of two dual primary endpoints. Median PFS for patients who received fruquintinib plus paclitaxel was 5.6 months, compared to 2.7 months for those who received paclitaxel monotherapy (stratified hazard ratio [“HR”] = 0.569; p < 0.0001). An improvement was also observed in the dual primary endpoint of median overall survival (OS), (9.6 months vs. 8.4 months) but this was not statistically significant. Fruquintinib plus paclitaxel demonstrated statistically significant improvements in multiple other endpoints including objective response rate (ORR), disease control rate (DCR) and duration of response (DoR). It was well tolerated, with a safety profile consistent with expectations and previously reported studies.^[1]

Results were published in Nature Medicine and presented at the ASCO 2024 Annual Meeting, concluding that fruquintinib plus paclitaxel could be a promising second-line treatment option for patients with advanced gastric or gastro­esophageal adenocarcinoma, who have failed fluoropyrimidine- or platinum-containing chemotherapy.

About Gastric Cancer

Gastric cancer is a cancer that starts in the stomach. It is the fifth most common cancer worldwide in 2022. It was estimated to have caused approximately 660,000 deaths worldwide.^[2] In China, it was estimated that over 359,000 people were diagnosed with gastric cancer, and approximately 260,000 people died from gastric cancer.^[3]

About Fruquintinib

Fruquintinib is a selective oral inhibitor of VEGFR-1, -2 and -3. VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for high drug exposure, sustained target inhibition, and flexibility for the potential use as part of combination therapy. Fruquintinib has demonstrated a manageable safety profile and is being investigated in combinations with other anti-cancer therapies.

About Fruquintinib Approval for metastatic CRC in China

Fruquintinib is approved for marketing in China, where it is co-marketed by HUTCHMED and Lilly under the brand name ELUNATE^®. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. The approval was based on data from the FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, which were published in The Journal of the American Medical Association, JAMA. Since its launch, fruquintinib has benefited over 100,000 patients in China.

About Takeda and Fruquintinib Approval for metastatic CRC outside China

Takeda has the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside of mainland China, Hong Kong and Macau. For the treatment of metastatic CRC, fruquintinib received approval in the US in November 2023 and in Europe in June 2024, where it is marketed by Takeda under the brand name FRUZAQLA^®. The approvals were based on data from two large, randomized, controlled Phase III trials: the multi-regional FRESCO-2 trial, data from which were published in The Lancet, and the FRESCO trial conducted in China. The trials investigated fruquintinib plus best supportive care versus placebo plus best supportive care in patients with previously treated metastatic CRC. Both FRESCO and FRESCO-2 met their primary and key secondary efficacy endpoints and showed consistent benefit among a total of 734 patients treated with fruquintinib. Safety profiles were consistent across trials. Other regulatory applications for this indication are progressing as expected in Japan and in many other jurisdictions.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the US and Europe. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

Forward-Looking Statements

This announcement contains forward-looking statements within the meaning of the “safe harbor” provisions of the US Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of fruquintinib for the treatment of patients with advanced gastric cancer and the further clinical development of fruquintinib in this and other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the sufficiency of clinical data to support NDA approval of fruquintinib for the treatment of patients with advanced gastric cancer in China, the US, Europe, Japan, Australia or other jurisdictions, its potential to gain expeditious approvals from regulatory authorities, the safety profile of fruquintinib, HUTCHMED’s ability to fund, implement and complete its further clinical development and commercialization plans for fruquintinib. In addition, as certain studies rely on the use of other drug products such as paclitaxel, tislelizumab and sintilimab as combination therapeutics with fruquintinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the US Securities and Exchange Commission, on AIM and on The Stock Exchange of Hong Kong Limited. HUTCHMED undertakes no obligation to update or revise the information contained in this announcement, whether as a result of new information, future events or circumstances or otherwise.

Medical Information

This announcement contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

Inside Information

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) No 596/2014 (as it forms part of retained EU law as defined in the European Union (Withdrawal) Act 2018).

CONTACTS

[1] Wang F, et al. Fruquintinib plus paclitaxel versus placebo plus paclitaxel as second-line therapy for advanced gastric or gastro-esophageal junction adenocarcinoma (FRUTIGA): a randomized, multicenter, double-blind, placebo-controlled, phase 3 study [published online ahead of print, 2024 Jun 1]. Nat Med. 2024. DOI: 10.1038/s41591-024-02989-6.

[2] The Global Cancer Observatory, Stomach Cancer Fact Sheet.  Accessed August 14, 2024.

[3] The Global Cancer Observatory, China Fact Sheet. Accessed August 14, 2024.

 TR-1: Standard form for notification of major holdings

Hong Kong, Shanghai & Florham Park, NJ — Wednesday, August 21, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that it will host a physician expert call with a professor and key opinion leader in immune thrombocytopenia (“ITP”), to discuss the treatment landscape of ITP via webcast on Wednesday, August 28, 2024, at 7:00 p.m. HKT.

The event will be held in Chinese (Putonghua) and can be accessed via www.hutch-med.com/event. Investors interested in listening to a webcast should log on before the start time to download any software required. The transcript of the event, including an English translation, will be available shortly thereafter for approximately 90 days. This event is intended for investor audiences only.

ESLIM-01 is a Phase III trial of HUTCHMED’s novel investigational drug candidate sovleplenib in patients with primary ITP in China. The trial met all its endpoints and results were published in The Lancet Haematology and orally presented at the European Hematology Association (EHA) Hybrid Congress. HUTCHMED filed a New Drug Application in China in January 2024 for sovleplenib.

About ITP

ITP is an autoimmune disorder characterized by immunologic destruction of platelets and decreased platelet production. Patients with ITP are at increased risk of excessive bleeding and bruising.^[1] ITP is also associated with fatigue (reported in up to 39% of adults with ITP) and impaired quality of life.^{[2],[3],[4],[5],[6]} The incidence of primary ITP in adults is 3.3/100,000 adults per year with a prevalence of 9.5 per 100,000 adults.^[7] Based on this prevalence rate, approximately 110,000 patients are estimated to be living with primary ITP in China, in addition to 56,000 patients in the US, Germany, France, Italy, Spain, UK, and Japan. It has been estimated that as many as 145,000 patients are living with chronic ITP in major pharmaceutical markets excluding China.^[8]

About Sovleplenib

Sovleplenib is a novel, selective inhibitor of Syk for once daily oral administration. Syk, a non-receptor tyrosine kinase, is a major component in B-cell receptor and FcR signaling and is an established target for the treatment of multiple subtypes of B-cell lymphomas and autoimmune disorders. Sovleplenib is currently under clinical investigation and its safety and efficacy have not been approved by any regulatory authority. HUTCHMED currently retains all rights to sovleplenib worldwide.

In addition to ITP (NCT05029635), sovleplenib is also being studied in warm antibody autoimmune hemolytic anemia (NCT05535933) and indolent non-Hodgkin’s lymphoma (NCT03779113).

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines now marketed in China, the first of which is also marketed in the US and Europe. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of sovleplenib for the treatment of patients with ITP and the further development of sovleplenib in this and other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the timing and outcome of clinical studies and the sufficiency of clinical data to support an NDA submission of sovleplenib for the treatment of patients with ITP or other indications in China or other jurisdictions, its potential to gain approvals from regulatory authorities on an expedited basis or at all, the efficacy and safety profile of sovleplenib, HUTCHMED’s ability to fund, implement and complete its further clinical development and commercialization plans for sovleplenib and the timing of these events. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

Medical Information

This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

CONTACTS

References

[1] Zufferey A, Kapur R, Semple JW. Pathogenesis and Therapeutic Mechanisms in Immune Thrombocytopenia (ITP). J. Clin. Med. 2017, 6(2), 16.

[2] McMillan R, Bussel JB, et al. Self-reported health-related quality of life in adults with chronic immune thrombocytopenic purpura. Am J Hematol. 2008 Feb;83(2):150-4.

[3] Snyder CF, Mathias SD, Cella D, et al. Health-related quality of life of immune thrombocytopenic purpura patients: results from a web‑based survey. Curr Med Res Opin. 2008 Oct;24(10):2767-76.

[4] Doobaree IU, Nandigam R, Bennett D, et al. Thromboembolism in adults with primary immune thrombocytopenia: a systematic literature review and meta-analysis. Eur J Haematol. 2016 Oct;97(4):321-30.

[5] Sarpatwari A, Bennett D, Logie JW, et al. Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom General Practice Research Database. Haematologica. 2010 Jul;95(7):1167-75.

[6] Sarpatwari A, Watson S, Erqou S, et al. Health-related lifestyle in adults and children with primary immune thrombocytopenia (ITP). Br J Haematol. 2010 Oct;151(2):189-91.

[7] Lambert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood. 2017 May 25;129(21):2829-2835.

[8] Clarivate Landscape & Forecast for Immune Thrombocytopenic Purpura, 2018.

Hong Kong, Shanghai & Florham Park, NJ — Wednesday, July 31, 2024: HUTCHMED (China) Limited (“HUTCHMED”, the “Company” or “we”) (Nasdaq/AIM:​HCM; HKEX:​13) today reports its financial results for the six months ended June 30, 2024 and provides updates on key clinical and commercial developments.

HUTCHMED to host results webcasts today at 8:00 a.m. EDT / 1:00 p.m. BST / 8:00 p.m. HKT in English, and at 8:30 a.m. HKT in Chinese (Putonghua) on Thursday, August 1, 2024. After registration, investors may access the live webcast via HUTCHMED’s website at www.hutch-med.com/event.

All amounts are expressed in US dollars unless otherwise stated.

Continued revenue momentum with substantial cash balance to support growth

• Reiterate full year 2024 guidance for Oncology/Immunology consolidated revenue of $300 to $400 million, with $168.7 million in the first half of 2024, driven by 59% (64% at CER^[1]) oncology product revenue growth.
• FRUZAQLA^® US in-market sales^[2] of $130.5 million in the first half of 2024 – demonstrating strong demand and commercial traction since launch in November 2023.
• Net income of $25.8 million in the first half of 2024. Cash balance of $802.5 million as of June 30, 2024, as we continued to prioritize key R&D^[3] projects and enhance commercial efficiency.

Globalization of fruquintinib continues, broader pipeline makes strong progress

• Preparation for EU launch of FRUZAQLA^® underway led by partner Takeda^[4] after European Commission approval in June 2024 – Filings in over a dozen jurisdictions supported by FRESCO-2.
• HUTCHMED preparing for China launch of sovleplenib for ITP^[5] – potentially its first hematology medicine, after the NDA^[6] was accepted and granted Priority Review status in January 2024.
• Potential US NDA filing for savolitinib for NSCLC^[7] at year end, based on SAVANNAH trial readout.
• NDAs accepted to expand use of ORPATHYS^® and ELUNATE^®, and for TAZVERIK^® in China – for treatment-naïve METex14^[8] NSCLC, endometrial cancer and follicular lymphoma, respectively.
• Key late-stage registration trials initiated with 15 ongoing/under review – across six drug candidates: ESLIM-02 for sovleplenib in warm AIHA^[9], RAPHAEL for HMPL-306 in AML^[10], and for surufatinib in PDAC^[11].
• Growing hematology portfolio with new programs targeting Menin and CD38, joining the existing portfolio of inhibitors and antibodies targeting Syk^[12], EZH2^[13], IDH^[14], BTK^[15] and CD47.

Dr Dan Eldar, Non-executive Chairman of HUTCHMED, said, “HUTCHMED has delivered strong performance in the first half of this year. The team has made significant progress implementing our strategy in discovering and developing novel, effective medicines; conducting clinical trials in our home market and in the global markets; and rapidly advancing regulatory and commercial goals. I am very pleased with the ongoing success of our partnership with Takeda and with the growing ability of the Company to provide health benefits to patients overseas. We have grown our revenues from the US during this period and we expect to see revenue growth from many other countries in the coming months. We are also capitalizing on our proven track record of bringing new medicines and additional indications for our marketed medicines to China, with several potential NDA approvals for the next few years.”

“I would like to take this opportunity to express my appreciation to Mr Simon To, my predecessor, who has recently retired. Mr To has stood at the cradle of HUTCHMED and has made a very significant contribution to grow the Company and turn it into a global innovative player, discovering, developing and commercializing therapies for the treatment of cancer and immunological diseases, improving the quality of life of patients around the world. I look forward to guiding the Company along its next phase of growth, which is full of potential and promise.”

2024 Interim Results & Business Updates

Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, said, “The HUTCHMED team has been working tirelessly to continue the outstanding clinical and regulatory momentum that we have had in recent years, whilst importantly driving the commercial success of our approved products. I would like to extend my thanks to everyone for their hard work and commitment. Our oncology product revenue has grown 59% compared to the first half of 2023 and we are progressing a more focused R&D pipeline that has considerable potential for value creation. This year we initiated three key late-stage studies across our pipeline and are excited to be running over a dozen such studies that could support future drug approvals.”

“The partnership strategy that we adopted for globalizing our medicines is allowing us to simultaneously fuel our in-house R&D engine, drive sales in our home market, and bring our medicines to patients in new geographies. Takeda’s impressive initial sales of FRUZAQLA^® demonstrates both the quality of our medicines and their potential across the globe and our strategy of working with partners outside of our home market.”

“We expect to advance our registration trials in the second half of the year. Around year end, we anticipate the potential approval of sovleplenib in China and potential NDA filing of savolitinib in the US. We will continue to progress towards becoming a self-sustaining biopharma business.”

I. COMMERCIAL OPERATIONS

Oncology in-market sales were up 140% (145% at CER) to $243.3 million (H1-23: $101.3m), which led to strong growth in consolidated oncology product revenue of 59% (64% at CER) to $127.8 million (H1-23: $80.1m), and mainly comprised of the following:

• FRUZAQLA^® (fruquintinib ex-China) in-market sales were $130.5 million (H1-23: nil), which was launched in the US in November 2023. Its strong performance was due to rapid US patient uptake, as well as fulfilling sales channel inventory requirements;
• ELUNATE^® (fruquintinib China) in-market sales increased 8% (13% at CER) to $61.0 million (H1-23: $56.3m), in line with CRC^[16] market growth, maintaining our leading market share position while weathering greater market competition;
• SULANDA^® (surufatinib) in-market sales increased 12% (17% at CER) to $25.4 million (H1-23: $22.6m), as doctors’ awareness continues to increase, leading to greater NET patient access and market share; and
• ORPATHYS^® (savolitinib) in-market sales increased 18% (22% at CER) to $25.9 million (H1-23: $22.0m), as it benefited from improved testing and diagnosis for METex14 NSCLC and also ongoing growth momentum in the second year on the NRDL^[17].

Oncology/​Immunology consolidated revenue comprised of consolidated oncology product revenue, which included product revenue, commercial service fees and royalties, as well as R&D income from our collaboration partners, mainly as follows:

• Takeda upfront, milestones and R&D services revenue were $33.8 million (H1-23: $269.1m), which included recognition of $19.4 million of the $435.0 million upfront and milestone payments already received from Takeda in cash during 2023. This compared to recognition of $258.7 million in the first half of 2023.

As a result, total Oncology/Immunology consolidated revenue was $168.7 million (H1-23: $359.2m). Including Other Ventures revenue, total revenue was $305.7 million (H1-23: $532.9m).

II. REGULATORY UPDATES

China

• Savolitinib sNDA^[19] accepted by NMPA^[20] for first-line and second-line METex14 NSCLC in 2024;
• Fruquintinib approved in Hong Kong for third-line CRC in January 2024;
• Fruquintinib sNDA accepted by NMPA with Priority Review for second-line endometrial cancer in early 2024;
• Tazemetostat approved in Hong Kong for R/R^[21] follicular lymphoma in May 2024; and
• Tazemetostat NDA accepted by NMPA with Priority Review for R/R follicular lymphoma in July 2024.

Ex-China

• Fruquintinib approved in the EU in June 2024, following positive opinion received from the EMA^[22] Committee for Medicinal Products for Human Use for previously-treated metastatic CRC in April 2024.

III. LATE-STAGE CLINICAL DEVELOPMENT ACTIVITIES

Savolitinib (ORPATHYS^® in China), a highly selective oral inhibitor of MET^[23]

• Completed enrollment of SAVANNAH (NCT03778229), a Fast Track-designated pivotal global Phase II study for NSCLC patients who have progressed following TAGRISSO^® due to MET amplification or overexpression, which may file in the US for accelerated approval. A small parallel study (NCT04606771) in this patient population presented data at AACR^[24] also demonstrated higher clinical activity with the combination therapy, with safety consistent with the known profiles of each treatment; and
• Continued enrolling SAFFRON (NCT05261399), a global, pivotal Phase III study in this patient population of the TAGRISSO^® combination supporting SAVANNAH; SACHI (NCT05015608), a similar pivotal Phase III study for patients in China that progressed on EGFR^[25] inhibitor treatment, and SANOVO (NCT05009836), a pivotal Phase III study for first-line patients in China with EGFR mutation & MET overexpression.

Potential upcoming clinical and regulatory milestones for savolitinib:

• Complete enrollment of SACHI in late 2024; and
• File FDA^[26] NDA on SAVANNAH, subject to positive results, around year end 2024.

Fruquintinib (ELUNATE^® in China, FRUZAQLA^® outside of China), a highly selective oral inhibitor of VEGFR^[27] 1/2/3 designed to have enhanced selectivity that limits off-target kinase activity

• Presented results of FRUSICA-1, the registration Phase II study combined with sintilimab for patients with endometrial cancer with pMMR^[28] status, which showed meaningful efficacy improvements regardless of prior bevacizumab treatment and a manageable toxicity profile (NCT03903705);
• Presented FRESCO-2 subgroup analyses at ASCO^[29], biomarker analysis at AACR and quality-of-life analysis at ASCO GI^[30] (NCT04322539). Analyses showed that the treatment was effective regardless of prior therapy or sequence, that CEA^[31] response may be an early predictor of improved efficacy, and that it demonstrated clinically meaningful quality-adjusted survival benefit in patients with previously-treated CRC; and
• Published in Nature Medicine the results of FRUTIGA, the study combined with paclitaxel for gastric cancer patients in China, concurrently with ASCO and following initial presentation at ASCO Plenary (NCT03223376). PFS^[32], ORR^[33] and DCR^[34] showed statistically significant improvements, and although OS^[35] improvement was not statistically significant overall, it was statistically significant in a pre-specified analysis excluding patients taking subsequent antitumor therapy.

Potential upcoming clinical and regulatory milestones for fruquintinib:

• Complete PMDA^[36] NDA review for previously-treated metastatic CRC in late-2024; and
• Announce top-line results from the FRUSICA-2 Phase II/III registration trial in clear cell RCC^[37] around year end if the requisite number of PFS events is reached (NCT05522231).

Sovleplenib (HMPL-523), an investigative and highly selective oral inhibitor of Syk, an important component of the Fc receptor and B-cell receptor signaling pathways

• Published ESLIM-01 (NCT05029635) results in adult patients with primary ITP in China inLancet Haematology concurrently with presentations at EHA^[38]. In addition to demonstrating a clinically meaningful early and sustained durable response of 48.4% and a tolerable safety profile, it significantly improved quality of life and showed consistent clinical benefits regardless of prior lines of therapies, prior TPO/TPO-RA^[39] exposure or treatment types;
• Published results of the Phase II proof-of-concept stage of a study in patients with warm AIHA in China at EHA, demonstrating a favorable safety profile and encouraging hemoglobin benefits; and
• Initiated ESLIM-02, the Phase III stage of the study, as a result of this positive data (NCT05535933).

Potential upcoming clinical milestones for sovleplenib:

• Initiate a dose-finding study in ITP in the US/EU in mid-2024 (NCT06291415); and
• Complete ESLIM-01 NMPA NDA review around year end.

Surufatinib (SULANDA^® in China), an oral inhibitor of VEGFR, FGFR^[40] and CSF-1R^[41] designed to inhibit tumor angiogenesis and promote immune response against tumor cells via tumor associated macrophage regulation

• Initiated a Phase II/III trial for treatment-naïve metastatic PDAC in China, in combination with PD-1^[42] antibody camrelizumab, nab-paclitaxel and gemcitabine (NCT06361888). This study was informed in part by an investigator-initiated trial presented at ASCO GI 2024 of a similar combination. This highly aggressive form of cancer has an estimated 511,000 people diagnosed annually worldwide.

Tazemetostat (TAZVERIK^® in Hainan, Macau and Hong Kong), a first-in-class, oral inhibitor of EZH2

• Potential to complete China NDA review for R/R follicular lymphoma in mid-2025.

HMPL-453, a novel, highly selective and potent inhibitor targeting FGFR 1, 2 and 3

• Continued enrolling the registrational Phase II trial for IHCC^[43] with FGFR 2 fusion (NCT04353375).

HMPL-306, an investigative and highly selective oral dual-inhibitor of IDH1 and IDH2 enzymes, which have been implicated as drivers of certain hematological malignancies, gliomas and solid tumors

• Presented results from China and US/European Phase I studies at EHA, showing it as an effective treatment for IDH1 and/or IDH2-mutated R/R AML (NCT04272957, NCT04764474); and
• Initiated RAPHAEL Phase III Trial for IDH1- and/or IDH2-mutated R/R AML in China (NCT06387069).

Other early-stage investigational drug candidates

• Presented preclinical and Phase I results at AACR, ASCO and EHA for ERK1/2^[44] inhibitor HMPL-295, third-generation BTK inhibitor HMPL-760, Menin inhibitor HMPL-506, and CD38 ADC^[45] HMPL-A067; and
• Initiated Phase I trial for HMPL-506 for hematological malignancies in China (NCT06387082).

IV. COLLABORATION UPDATES

Further clinical progress by Inmagene^[46] with two candidates discovered by HUTCHMED

• Received approximately 7.5% of shares (fully diluted) in Inmagene following exercise of its option for an exclusive license to further develop, manufacture and commercialize IMG-007, a nondepleting anti-OX40 antibody, and IMG-004, a reversible, non-covalent, highly selective oral BTK inhibitor;
• Inmagene announced positive interim results from a Phase IIa trial of IMG-007 for atopic dermatitis. Treatment led to rapid, marked, and durable improvement of skin signs in patients with atopic dermatitis, while remaining well-tolerated overall. Final results are anticipated later in the third quarter of 2024. Inmagene also completed enrollment of a Phase IIa trial for alopecia areata; and
• Inmagene announced positive topline results of a multiple ascending dose study with IMG-004, indicating once daily dosing potential. It was well tolerated, without reports of liver enzyme elevation or bleeding events, across once daily doses ranges for 10 days. Preliminary modeling and data support 50mg once daily as a potential therapeutic dose and further development as a differentiated treatment for BTK-mediated immunological diseases.

V. OTHER VENTURES

• Other Ventures revenue is predominantly from our prescription drug distribution operation in China. Consolidated revenue decreased by 21% (18% at CER) to $137.0 million (H1-23: $173.7m) primarily as a result of lower COVID-related prescription drug distribution sales in 2024.
• SHPL^[47], a non-consolidated joint venture, saw revenue decrease by 4% (flat at CER) to $225.2 million (H1‑23: $235.3m) mainly due to pricing reduction in a few higher-priced provinces to standardize the pricing structure of MUSKARDIA^® in preparation for potential national implementation of volume-based procurement.
• Consolidated net income attributable to HUTCHMED from our Other Ventures decreased by 8% (4% at CER) to $34.1 million (H1-23: $37.2m), which was primarily due to decrease on the net income contributed from SHPL of $33.8 million (H1-23: $35.1m) as a result of price reduction impact from volume-based procurement, as well as increase in R&D spending.
• We continue to explore opportunities to monetize the underlying value of our SHPL joint venture including various divestment and collaboration alternatives.

VI. SUSTAINABILITY

HUTCHMED is committed to progressively embedding sustainability into all aspects of our operations and creating long-term value for our stakeholders. In April 2024, we published our 2023 Sustainability Report, which highlighted progress made in our 11 goals and targets; our enhanced climate actions including Scope 3 emissions screening and measurement and engaging with suppliers; our enhanced data quality; our strengthened alignment of our five most relevant and material sustainability pillars; and our enhanced disclosure and sector specific disclosure standards ahead of requirement.

Wider recognition of HUTCHMED’s efforts have been reflected in steady improvements in major local and international sustainability ratings including from Hang Seng, ISS, MSCI, S&P Global, Sustainalytics and Wind. Recently, HUTCHMED scored 49 for S&P Global ESG^[48] Ratings, significantly higher than the industry average of 31. HUTCHMED also received the Best ESG(E) at the Hong Kong Investor Relations Association’s 10^th Investor Relations Awards, two awards at Bloomberg Businessweek’s ESG Leading Enterprises event, five awards from Metro Finance’s GBA ESG Achievement Awards, and was listed amongst the Top 20 Chinese Pharmaceutical Listed Companies in ESG Competitiveness by Healthcare Executive.

In 2024, we continue our efforts on the above areas and further strengthening our climate action by conducting a more comprehensive climate risk assessment to quantify the impact of climate risks in our major operations; incorporate sustainability into our corporate culture; and considering future goals and targets.

Financial Highlights

Foreign exchange impact: The RMB depreciated against the US dollar on average by approximately 4% during the first half of 2024, which has impacted our consolidated financial results as highlighted below.

Cash, Cash Equivalents and Short-Term Investments were $802.5 million as of June 30, 2024 compared to $886.3 million as of December 31, 2023.

• Adjusted Group (non-GAAP^[49]) net cash flows excluding financing activities in the first half of 2024 were ‑$51.3 million (H1-23: $219.3m), mainly due to $39.8 million net cash used in operating activities and $10.1 million of capital expenditure; and
• Net cash used in financing activities in the first half of 2024 totaled $32.6 million due to purchases for equity awards of $36.1 million (H1-23: net cash generated from financing activities of $5.8m).

Revenue for the six months ended June 30, 2024 was $305.7 million compared to $532.9 million in the six months ended June 30, 2023.

• Oncology/Immunology consolidated revenue amounted to $168.7 million (H1-23: $359.2m) from:
  • FRUZAQLA^® revenue was $42.8 million, reflecting its successful US launch since early November 2023, comprising royalties and manufacturing revenue;
  • ELUNATE^® revenue increased 9% (14% at CER) to $46.0 million (H1-23: $42.0m) in its sixth year since launch, comprising of manufacturing revenue, promotion and marketing service revenue and royalties, which is in line with CRC market growth, maintaining our leading market share position while weathering greater market competition;
  • SULANDA^® revenue increased 12% (17% at CER) to $25.4 million (H1-23: $22.6m) continued sales growth after NRDL renewal as doctors’ awareness continues to increase, leading to greater NET patient access and market share;
  • ORPATHYS^® revenue decreased 14% (10% at CER) to $13.1 million (H1-23: $15.1m), due to a reduction in manufacturing revenue to $5.3 million (H1-23: $8.5m), offset by an increase in royalties to $7.8 million (H1-23: $6.6m) reflecting strong in-market sales growth of 18% (22% at CER);
  • TAZVERIK^® revenue was $0.5 million (H1-23: $0.4m) mainly from sales in the Hainan Pilot Zone^[50];
  • Takeda upfront, milestones and R&D services revenue decreased to $33.8 million (H1-23: $269.1m, of which $258.7m was the recognized portion of the $400 million upfront cash payment received from Takeda in April 2023); and
  • Other R&D services revenue of $7.1 million (H1-23: $10.0m), primarily related to fees from AstraZeneca and Lilly for the management of development and regulatory activities.
• Other Ventures consolidated revenue decreased 21% (18% at CER) to $137.0 million (H1-23: $173.7m), primarily as a result of lower COVID-related prescription drug distribution sales in 2024. This excluded non‑consolidated revenue at SHPL of $225.2 million (H1-23: $235.3m).

Net Expenses for the six months ended June 30, 2024 were $279.9 million compared to $364.3 million in the six months ended June 30, 2023, reflecting our strong efforts on cost control.

• Cost of Revenue decreased by 14% to $180.1 million (H1-23: $208.3m), which was the net result of a reduction in cost of revenue from our Other Ventures, offset by the increase in product sales of our marketed products and the cost of promotion and marketing services for ELUNATE^® resulting from the increased sales force;
• R&D Expenses reduced 34% to $95.3 million (H1-23: $144.6m), mainly due to the strategic prioritization of our pipeline, particularly outside China. Clinical and regulatory expenses in the US and Europe were $14.9 million (H1-23: $55.6m), while R&D expenses in China were $80.4 million (H1-23: $89.0m);
• S&A^[51] Expenses were $57.8 million (H1-23: $68.3m), which decreased primarily due to tighter control over our spending, while utilizing existing infrastructure to support further revenue growth; and
• Other Items mainly comprised of equity in earnings of SHPL, interest income and expense, FX and taxes, generated net income of $53.3 million (H1-23: $56.9m), which decreased primarily due to lower foreign currency exchange gains recognized in the period.

Net Income attributable to HUTCHMED for the six months ended June 30, 2024 was $25.8 million compared to $168.6 million for the six months ended June 30, 2023.

• The net income attributable to HUTCHMED for the six months ended June 30, 2024 was $0.03 per ordinary share / $0.15 per ADS^[52], (H1-23: $0.20 per ordinary share / $1.00 per ADS).

FINANCIAL GUIDANCE

We reiterate full year 2024 guidance for Oncology/Immunology consolidated revenue is $300 million to $400 million, driven by 30% to 50% growth target in oncology marketed product revenue. HUTCHMED’s work in 2024 and beyond will be supported by its strong balance sheet. The Company is thus well placed to deliver against its target to become a self-sustaining business and its goal to bring its innovative medicines to patients globally through its own sales network in China markets and through partners worldwide.

Shareholders and investors should note that:

• we do not provide any guarantee that the statements contained in the financial guidance will materialize or that the financial results contained therein will be achieved or are likely to be achieved; and
• we have in the past revised our financial guidance and reference should be made to any announcements published by us regarding any updates to the financial guidance after the date of publication of this announcement.

———

Use of Non-GAAP Financial Measures and Reconciliation – References in this announcement to adjusted Group net cash flows excluding financing activities and financial measures reported at CER are based on non-GAAP financial measures. Please see the “Use of Non-GAAP Financial Measures and Reconciliation” for further information relevant to the interpretation of these financial measures and reconciliations of these financial measures to the most comparable GAAP measures, respectively.

———

Financial Summary

Condensed Consolidated Balance Sheets Data

Condensed Consolidated Statements of Operations Data

About HUTCHMED

HUTCHMED (Nasdaq/AIM: ​HCM; HKEX: ​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three oncology medicines marketed in China, the first of which is also marketed in the US. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

Contacts

References

Unless the context requires otherwise, references in this announcement to the “Group,” the “Company,” “HUTCHMED,” “HUTCHMED Group,” “we,” “us,” and “our,” mean HUTCHMED (China) Limited and its subsidiaries unless otherwise stated or indicated by context.

Past Performance and Forward-Looking Statements

The performance and results of operations of the Group contained within this announcement are historical in nature, and past performance is no guarantee of future results of the Group. This announcement contains forward-looking statements within the meaning of the “safe harbor” provisions of the US Private Securities Litigation Reform Act of 1995. These forward-looking statements can be identified by words like “will,” “expects,” “anticipates,” “future,” “intends,” “plans,” “believes,” “estimates,” “pipeline,” “could,” “potential,” “first-in-class,” “best-in-class,” “designed to,” “objective,” “guidance,” “pursue,” or similar terms, or by express or implied discussions regarding potential drug candidates, potential indications for drug candidates or by discussions of strategy, plans, expectations or intentions. You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that any of our drug candidates will be approved for sale in any market, that any approvals which have been obtained will continue to remain valid and effective in the future, or that the sales of products marketed or otherwise commercialized by HUTCHMED and/or its collaboration partners (collectively, “HUTCHMED’s Products”) will achieve any particular revenue or net income levels. In particular, management’s expectations could be affected by, among other things: unexpected regulatory actions or delays or government regulation generally, including, among others, the risk that HUTCHMED’s ADSs could be barred from trading in the United States as a result of the Holding Foreign Companies Accountable Act and the rules promulgated thereunder; the uncertainties inherent in research and development, including the inability to meet our key study assumptions regarding enrollment rates, timing and availability of subjects meeting a study’s inclusion and exclusion criteria and funding requirements, changes to clinical protocols, unexpected adverse events or safety, quality or manufacturing issues; the inability of a drug candidate to meet the primary or secondary endpoint of a study; the inability of a drug candidate to obtain regulatory approval in different jurisdictions or the utilization, market acceptance and commercial success of HUTCHMED’s Products after obtaining regulatory approval; discovery, development and/or commercialization of competing products and drug candidates that may be superior to, or more cost effective than, HUTCHMED’s Products and drug candidates; the impact of studies (whether conducted by HUTCHMED or others and whether mandated or voluntary) or recommendations and guidelines from governmental authorities and other third parties on the commercial success of HUTCHMED’s Products and drug candidates in development; the ability of HUTCHMED to manufacture and manage supply chains for multiple products and drug candidates; the availability and extent of reimbursement of HUTCHMED’s Products from third-party payers, including private payer healthcare and insurance programs and government insurance programs; the costs of developing, producing and selling HUTCHMED’s Products; the ability of HUTCHMED to meet any of its financial projections or guidance and changes to the assumptions underlying those projections or guidance; global trends toward health care cost containment, including ongoing pricing pressures; uncertainties regarding actual or potential legal proceedings, including, among others, actual or potential product liability litigation, litigation and investigations regarding sales and marketing practices, intellectual property disputes, and government investigations generally; and general economic and industry conditions, including uncertainties regarding the effects of the persistently weak economic and financial environment in many countries, uncertainties regarding future global exchange rates and uncertainties regarding the impact of pandemics and disease outbreaks. For further discussion of these and other risks, see HUTCHMED’s filings with the US Securities and Exchange Commission, on AIM and on HKEX^[53]. HUTCHMED is providing the information in this announcement as of this date and does not undertake any obligation to update any forward-looking statements as a result of new information, future events or otherwise.

In addition, this announcement contains statistical data and estimates that HUTCHMED obtained from industry publications and reports generated by third-party market research firms. Although HUTCHMED believes that the publications, reports and surveys are reliable, HUTCHMED has not independently verified the data and cannot guarantee the accuracy or completeness of such data. You are cautioned not to give undue weight to this data. Such data involves risks and uncertainties and are subject to change based on various factors, including those discussed above.

Inside Information

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) No 596/2014 (as it forms part of retained EU law as defined in the European Union (Withdrawal) Act 2018).

Medical Information

This announcement contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

^[1] CER = Constant exchange rate. We also report changes in performance at CER which is a non-GAAP measure. Please refer to “Use of

Non-GAAP Financial Measures and Reconciliation” below for further information relevant to the interpretation of these financial

measures and reconciliations of these financial measures to the most comparable GAAP measures.

^[2]  In-market sales = total sales to third parties provided by Eli Lilly (ELUNATE^®), Takeda (FRUZAQLA^®), AstraZeneca (ORPATHYS^®) and

HUTCHMED (ELUNATE^®, SULANDA^®, ORPATHYS^® and TAZVERIK^®).

^[3]  R&D = Research and development.

^[4] Takeda = Takeda Pharmaceuticals International AG, a subsidiary of Takeda Pharmaceutical Company Limited.

^[5] ITP = immune thrombocytopenia purpura.

^[6] NDA = New Drug Application.

^[7] NSCLC = Non-small cell lung cancer.

^[8] METex14 = MET exon 14 skipping alterations.

^[9] AIHA = Autoimmune hemolytic anemia.

^[10] AML = Acute myeloid leukemia.

^[11] PDAC = Pancreatic ductal adenocarcinoma.

^[12] Syk = Spleen tyrosine kinase.

^[13] EZH2 = Enhancer of zeste homolog 2.

^[14] IDH = Isocitrate dehydrogenase.

^[15] BTK = Bruton’s tyrosine kinase.

^[16] CRC = Colorectal cancer.

^[17] NRDL = China National Reimbursement Drug List.

^[18] Lilly = Eli Lilly and Company.

^[19] sNDA = Supplemental New Drug Application.

^[20] NMPA = China National Medical Products Administration.

^[21] R/R = Relapsed and/or refractory.

^[22] EMA = European Medicines Agency.

^[23] MET = Mesenchymal epithelial transition factor.

^[24] AACR = American Association for Cancer Research Annual Meeting.

^[25] EGFR = Epidermal growth factor receptor.

^[26] FDA = Food and Drug Administration.

^[27] VEGFR = Vascular endothelial growth factor receptor.

^[28] pMMR = Proficient mismatch repair.

^[29] ASCO = American Society of Clinical Oncology Annual Meeting.

^[30] ASCO GI = ASCO Gastrointestinal Cancers Symposium.

^[31] CEA = Carcinoembryonic antigen.

^[32] PFS = Progression free survival.

^[33] ORR = Objective response rate.

^[34] DCR = Disease control rate.

^[35] OS = Overall survival.

^[36] PMDA = Pharmaceuticals and Medical Devices Agency.

^[37] RCC = Renal cell carcinoma.

^[38] EHA = European Hematology Association.

^[39] TPO/TPO-RA = Thrombopoietin and/or thrombopoietin receptor agonists.

^[40] FGFR = Fibroblast growth factor receptor.

^[41] CSF-1R = Colony-stimulating factor 1 receptor.

^[42] PD-1 = Programmed cell death protein-1.

^[43] IHCC = Intrahepatic cholangiocarcinoma.

^[44] ERK = Extracellular signal-regulated kinase.

^[45] ADC = Antibody-drug conjugate.

^[46] Inmagene = Inmagene Biopharmaceuticals.

^[47] SHPL = Shanghai Hutchison Pharmaceuticals Limited.

^[48] ESG = Environmental, Social and Governance.

^[49] GAAP = Generally Accepted Accounting Principles.

^[50] Hainan Pilot Zone = Hainan Boao Lecheng International Medical Tourism Pilot Zone.

^[51] S&A= Selling and administrative expenses.

^[52] ADS = American depositary share.

^[53] HKEX = The Main Board of The Stock Exchange of Hong Kong Limited.

Hong Kong, Shanghai & Florham Park, NJ — Thursday, July 4, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM; HKEX:​13) today announces that the New Drug Application (“NDA”) for tazemetostat for the treatment of adult patients with relapsed or refractory (“R/R”) follicular lymphoma (“FL”) has been accepted for review and granted Priority Review by the China National Medical Products Administration (“NMPA”).

Tazemetostat is a first-in-class methyltransferase inhibitor of EZH2 developed by Epizyme, Inc. (“Epizyme”), an Ipsen company. Tazemetostat is approved by the U.S. Food and Drug Administration (“FDA”) for the treatment of certain patients with R/R FL and certain patients with advanced epithelioid sarcoma (“ES”) under the FDA accelerated approval program. It is also approved by the Japan Ministry of Health, Labour and Welfare (MHLW) for certain patients with R/R FL. HUTCHMED entered into a strategic collaboration to research, develop, manufacture and commercialize tazemetostat in China, Hong Kong, Macau and Taiwan.

This China NDA is supported by results from a multicenter, open-label, Phase II bridging study in China, and clinical studies conducted by Epizyme outside China.

Tazemetostat was approved for use in the Hainan Boao Lecheng International Medical Tourism Pilot Zone (Hainan Pilot Zone) in May 2022, under the Clinically Urgently Needed Imported Drugs scheme, for the treatment of certain patients with ES and FL consistent with the label as approved by the FDA. Tazemetostat was approved in the Macau Special Administrative Region (“SAR”) in March 2023 and in the Hong Kong SAR in May 2024.

About Follicular Lymphoma

FL is a subtype of non-Hodgkin’s lymphoma (“NHL”). FL accounts for approximately 17% of NHL. In 2020, there were an estimated 16,000 and 13,000 new cases of FL in China and the U.S., respectively.^[1],[2],[3]

About Tazemetostat Clinical Development in China

Tazemetostat is a first-in-class methyltransferase inhibitor of EZH2 developed by Epizyme, an Ipsen company. HUTCHMED entered into a strategic collaboration to research, develop, manufacture and commercialize tazemetostat in China, Hong Kong, Macau and Taiwan.

42 patients were enrolled in the Phase II bridging study in China. The primary objective was to evaluate the objective response rate (“ORR”) of tazemetostat for the treatment of patients with R/R FL whose disease harbor EZH2 mutations. The secondary objectives included duration of response (“DoR”), progression-free survival (PFS), overall survival (OS), safety and pharmacokinetics of tazemetostat for the treatment of R/R FL patients whose disease do or do not harbor EZH2 mutations. Results of the study will be submitted for presentation at an upcoming medical conference (NCT05467943).

HUTCHMED is participating in Ipsen’s SYMPHONY-1 study, leading it in China. This is an international, multicenter, randomized, double-blind, active-controlled, 3-stage, biomarker-enriched, confirmatory Phase Ib/III study, which is designed to evaluate the safety and efficacy of tazemetostat in combination with rituximab and lenalidomide (R²) in patients with R/R FL after at least one prior line of therapy (NCT04224493).

About Tazemetostat approval in the United States

Tazemetostat is a methyltransferase inhibitor indicated in the United States for the treatment of:

• Adults and pediatric patients aged 16 years and older with metastatic or locally advanced ES not eligible for complete resection.
• Adult patients with R/R FL whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least two prior systemic therapies.
• Adult patients with R/R FL who have no satisfactory alternative treatment options.
• These indications are approved under accelerated approval by the U.S. FDA based on ORR and DoR. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

The most common (≥20%) adverse reactions in patients with ES are pain, fatigue, nausea, decreased appetite, vomiting and constipation. The most common (≥20%) adverse reactions in patients with FL are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea and abdominal pain.

Please see the U.S. Full Prescribing Information for TAZVERIK^® (tazemetostat).

TAZVERIK^® is approved in Japan with the indication of relapsed or refractory EZH2 gene mutation-positive FL (only when standard treatment is not applicable).

TAZVERIK^® is a registered trademark of Epizyme Inc., an Ipsen company.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the review of a NDA for tazemetostat for the treatment of FL with the NMPA and the timing of such review, therapeutic potential of tazemetostat for the treatment of patients with FL and the further development of tazemetostat in this and other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the timing and outcome of clinical studies and the sufficiency of clinical data to support NDA approval of tazemetostat for the treatment of patients with FL or other indications in China or other jurisdictions, its potential to gain approvals from regulatory authorities on an expedited basis or at all, the safety profile of tazemetostat, HUTCHMED’s ability to fund, implement and complete its further clinical development and commercialization plans for tazemetostat and the timing of these events. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

Medical Information

This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

CONTACTS

*Name changed from “Panmure Gordon (UK) Limited” to “Panmure Liberum Limited” following completion of its own corporate merger

Reference:

[1] Source: NCCN – https://www.nccn.org

[2] Source: SEER – https://seer.cancer.gov/statfacts/html/follicular.html

[3] Source: GLOBOCAN https://gco.iarc.fr/

Hong Kong, Shanghai & Florham Park, NJ: Friday, June 28, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today filed the Form F-3 Registration Statement with the U.S. Securities and Exchange Commission.  This filing follows the expiration of the previous Form F-3 Registration Statement filed in 2020. The Form F-3 is available for viewing at http://www.rns-pdf.londonstockexchange.com/rns/3865U_1-2024-6-28.pdf and also on the website of the Company at www.hutch-med.com.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

CONTACTS

Hong Kong, Shanghai, & Florham Park, NJ — Friday, June 28, 2024: HUTCHMED (China) Limited (“HUTCHMED” or the “Company”) (Nasdaq/AIM: HCM; HKEX: 13) announces the following blocklisting six monthly return:

About HUTCHMED

HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three oncology drugs marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch-med.com or follow us on LinkedIn.

CONTACTS

Hong Kong, Shanghai, & Florham Park, NJ — Friday, June 28, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM: HCM; HKEX: 13) hereby notifies the market that as at June 28, 2024, the issued share capital of HUTCHMED consisted of 871,359,720 ordinary shares of US$0.10 each, with each share carrying one right to vote and with no shares held in treasury.

The above figure of 871,359,720 may be used by shareholders as the denominator for the calculations by which they could determine if they are required to notify their interest in, or a change to their interest in, HUTCHMED under the Financial Conduct Authority’s Disclosure Guidance and Transparency Rules.

For illustrative purposes only, the 871,359,720 ordinary shares would be equivalent to 871,359,720 depositary interests (each equating to one ordinary share) which are traded on AIM or, if the depositary interests were converted in their entirety, equivalent to 174,271,944 American depositary shares (each equating to five ordinary shares) which are traded on Nasdaq.

About HUTCHMED

HUTCHMED (Nasdaq/AIM: HCM; HKEX: 13) is an innovative, commercial-stage, biopharmaceutical company. Іt is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. Іt has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch-med.com or follow us on LinkedIn.

Contacts

Hong Kong, Shanghai & Florham Park, NJ — Wednesday, June 26, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM: HCM; SEHK:13) will be announcing its interim results for the six months ended June 30, 2024 on Wednesday, July 31, 2024 at 7:00 am Eastern Daylight Time (EDT) / 12:00 noon British Summer Time (BST) / 7:00 pm Hong Kong Time (HKT).

Analysts and investors are invited to join a conference call and audio webcast presentation with Q&A, conducted by HUTCHMED management.

The English conference call and audio webcast will be held on Wednesday, July 31, 2024, at 8:00 am EDT (1:00 pm BST / 8:00 pm HKT). The Chinese (Putonghua) webcast will be held at 8:30 am HKT / 1:30 am BST on Thursday, August 1, 2024 (8:30 pm EDT on Wednesday, July 31, 2024). Both webcasts will be available live via the company website at www.hutch-med.com/event/. The presentation will be available for downloading before the conference call begins. Details of the conference call dial-in will be provided in the financial results announcement and on the company website. A replay will also be available on the website shortly after the event.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three oncology drugs marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch-med.com or follow us on LinkedIn.

CONTACTS

— HUTCHMED will host in-person presentation and online webinar on Tuesday, July 9 —

Hong Kong, Shanghai & Florham Park, NJ —  Monday, June 24, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that it will host a R&D update in Shanghai, China, and via webcast on Tuesday, July 9, 2024.

During the event, the senior management team will share insights into the Company’s R&D strategy and vision. Additionally, the team will provide updates on certain programs within HUTCHMED’s extensive and innovative pipeline. This will include updates on the Phase III ESLIM‑01 and Phase II/III ESLIM‑02 studies of our Syk inhibitor sovleplenib in immune thrombocytopenia (“ITP”) and warm antibody autoimmune hemolytic anemia, (“wAIHA”) respectively; the surufatinib Phase II/III study for metastatic pancreatic ductal adenocarcinoma (“PDAC”); and the Phase III RAPHAEL study of our IDH1/2 inhibitor HMPL-306 in acute myeloid leukemia (“AML”).

The in-person event will take place from 3:00 p.m. to 5:00 p.m. HKT in Chinese (Putonghua) in Shanghai. A live webcast will be held simultaneously. Attendance for the in-person event is by invitation only.

An English language webcast will take place from 8:30 p.m. HKT / 8:30 a.m. EDT / 1:30 p.m. BST on Tuesday, July 9, for approximately two hours.

Both webcasts will be live and can be accessed via www.hutch-med.com/event. Investors interested in listening to a webcast should log on before the start time to download any software required. A replay of the event will be available shortly thereafter for approximately 90 days.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three oncology drugs marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch-med.com or follow us on LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements involve risks and uncertainties. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

CONTACTS

— Approval for previously treated metastatic colorectal cancer based on results from positive, global, Phase III FRESCO-2 Trial —

— FRUZAQLA^® (fruquintinib) is the first novel targeted therapy in the EU for metastatic colorectal cancer regardless of biomarker status in over a decade —

Hong Kong, Shanghai & Florham Park, NJ — Friday, June 21, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that its partner Takeda (TSE:4502/​NYSE:TAK) has received notification from the European Commission (“EC”) that it has approved FRUZAQLA^® (fruquintinib) as a monotherapy indicated for the treatment of adult patients with metastatic colorectal cancer (“CRC”) who have been previously treated with available standard therapies, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents, and who have progressed on or are intolerant to treatment with either trifluridine-tipiracil or regorafenib.

“With fruquintinib being the first and only selective inhibitor of all three VEGFRs to be approved in the EU for colorectal cancer, this decision represents a significant milestone in European oncology,” added Josep Tabernero, MD, PhD, director of Vall d´Hebron Institute of Oncology (VHIO). “There is a clear need in Europe for patients and their clinicians to be able to access a new treatment option for previously treated metastatic colorectal cancer, and we are excited that this important step has been taken so that we can begin prescribing this new and differentiated medicine.”

“We are delighted to have achieved EC approval for FRUZAQLA^® and that we can now offer a new therapeutic option for patients with previously treated metastatic colorectal cancer, regardless of their biomarker status,” said Teresa Bitetti, President of the Global Oncology Business Unit at Takeda. “Patients in Europe with metastatic colorectal cancer have long needed additional treatment options, and we are grateful to be able to meet that need thanks to our partnership with HUTCHMED.”

“This is a significant milestone for HUTCHMED, as it is the first product from our research and discovery engine to be approved in Europe, achieved through our partnership with Takeda to make this possible in such a short period of time,” added Weiguo Su, PhD, Chief Executive Officer and Chief Scientific Officer of HUTCHMED. “This novel oncology medicine is currently improving the treatment outlook in the U.S. and China, and we look forward to seeing its impact for patients across Europe.”

The EC’s approval has been granted following a positive opinion from the Committee for Medicinal Products for Human Use (“CHMP”) in April 2024. The CHMP’s opinion was primarily based on results from the Phase III multiregional FRESCO-2 trial, which supported the Marketing Authorisation Application (“MAA”) that was validated and accepted for review in June 2023. Data from FRESCO-2 were published in The Lancet in June 2023.

About CRC

CRC is a cancer that starts in either the colon or rectum. According to the International Agency for Research on Cancer/World Health Organization, CRC is the third most prevalent cancer worldwide, associated with more than 1.9 million new cases and 900,000 deaths in 2022. In Europe, CRC was the second most common cancer in 2022, with approximately 538,000 new cases and 248,000 deaths.^[1],[2] In the U.S., it is estimated that 153,000 patients will be diagnosed with CRC and 53,000 deaths from the disease will occur in 2024.^[3] In Japan, CRC was the most common cancer, with an estimated 146,000 new cases and 60,000 deaths, in 2022.^[2] Although early-stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options. Some patients with metastatic CRC may benefit from personalized therapeutic strategies based on molecular characteristics; however, most patients have tumors that do not harbor actionable mutations.^{[4],[5],[6],[7],[8]}

About the Phase III FRESCO-2 Trial

FRESCO-2 is a multiregional clinical trial conducted in the U.S., Europe, Japan and Australia investigating fruquintinib plus best supportive care (“BSC”) versus placebo plus BSC in patients with previously treated metastatic CRC (NCT04322539). FRESCO-2 met all of its primary and key secondary endpoints, demonstrating statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS), with consistent benefit among patients treated with fruquintinib, regardless of the prior types of therapies they received. Fruquintinib demonstrated a manageable safety profile in FRESCO-2, consistent with previously reported fruquintinib monotherapy studies. Adverse reactions leading to treatment discontinuation occurred in 20% of patients treated with fruquintinib plus BSC versus 21% of those treated with placebo plus BSC. Results from the study were presented at the European Society for Medical Oncology Congress (ESMO) in September 2022 and subsequently published in The Lancet in June 2023.^[9],[10]

About Fruquintinib

Fruquintinib is a selective oral inhibitor of all three VEG receptors (VEGFR‑1, ‑2 and ‑3). VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off‑target kinase activity, allowing for high drug exposure, sustained target inhibition, and flexibility for its potential use as part of a combination therapy. Fruquintinib has demonstrated a manageable safety profile and is being investigated in combinations with other anti‑cancer therapies.

About Takeda and FRUZAQLA^®

Takeda has the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside of mainland China, Hong Kong and Macau. Fruquintinib received approval in the U.S. in November 2023, where it is marketed by Takeda under the brand name FRUZAQLA^®. The U.S. approval was based on data from two large, randomized, controlled Phase III trials, the multi-regional FRESCO-2 trial and the FRESCO trial conducted in China, showing consistent benefit among a total of 734 patients treated with fruquintinib. Safety profiles were consistent across trials.

In addition to the submission to the EMA, a submission to the Japan Pharmaceuticals and Medical Devices Agency (PMDA) took place in September 2023.

About Fruquintinib Approval in China

Fruquintinib is approved for marketing in China, where it is co‑marketed by HUTCHMED and Eli Lilly and Company under the brand name ELUNATE^®. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. The approval was based on data from the FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic colorectal cancer in China, which were published in The Journal of the American Medical Association, JAMA. Since its launch in China and as of mid‑2023, more than 80,000 patients with colorectal cancer have been treated with fruquintinib.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial‑stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception it has focused on bringing cancer drug candidates from in‑house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

E.U. IMPORTANT SAFETY INFORMATION

Please consult the FRUZAQLA (fruquintinib) Summary of Product Characteristics (SmPC) before prescribing.

Guidance for use: FRUZAQLA should be initiated by a physician experienced in the administration of anticancer therapy. Patients should be given the package leaflet.

CONTRAINDICATIONS: Hypersensitivity to the active substance or to any of the excipients.

SPECIAL POPULATIONS: Renal impairment: No dose adjustment is required for patients with mild, moderate, or severe renal impairment; Hepatic impairment: No dose adjustment is required for patients with mild or moderate hepatic impairment. FRUZAQLA is not recommended for use in patients with severe hepatic impairment as FRUZAQLA has not been studied in this population; Elderly: No dose adjustment is required in patients aged 65 years or above; Paediatric population: There is no relevant use of FRUZAQLA in the paediatric population for the indication of metastatic colorectal cancer; Women of childbearing potential/Contraception in females: Women of childbearing potential should be advised to use highly effective contraception during treatment and for at least 2 weeks following the last dose of FRUZAQLA; Pregnancy: There are no clinical data available on the use of FRUZAQLA in pregnant women. Based on its mechanism of action, FRUZAQLA has the potential to cause foetal harm. Animal studies have shown reproductive toxicity, including foetal malformations. FRUZAQLA should not be used during pregnancy unless the clinical condition of the woman requires treatment with FRUZAQLA. If FRUZAQLA is used during pregnancy or if the patient becomes pregnant while on treatment, the patient must be informed of the potential hazard to the foetus; Breast-feeding: The safe use of FRUZAQLA during breast-feeding has not been established. It is not known whether FRUZAQLA or its metabolites are excreted in human milk. There are no animal data on the excretion of FRUZAQLA in animal milk. A risk to the breastfeeding newborns/infants cannot be excluded. Breastfeeding should be discontinued during treatment and for 2 weeks after the last dose; Fertility: There are no data on the effects of FRUZAQLA on human fertility. Results from animal studies indicate that FRUZAQLA may impair male and female fertility.

SPECIAL WARNINGS AND PRECAUTIONS FOR USE

●  Hypertension: Hypertension, including hypertensive crisis, has been reported in patients treated with FRUZAQLA. Pre-existing hypertension should be monitored and adequately controlled in accordance with standard medical practices before starting FRUZAQLA treatment.

Hypertension should be medically managed with antihypertensive medicinal products and adjustment of the FRUZAQLA dose, if necessary. FRUZAQLA should be permanently discontinued for hypertension that cannot be controlled with antihypertensive therapy or in patients with hypertensive crisis.

●  Haemorrhagic events: Haemorrhagic events have been reported in patients treated with FRUZAQLA, including gastrointestinal (GI) tract events. Serious and sometimes fatal bleeding events have been reported in patients after treatment with FRUZAQLA.

Haematologic and coagulation profiles should be monitored in accordance with standard medical practices in patients at risk for bleeding, including those treated with anticoagulants or other concomitant medicinal products that increase the risk of bleeding. In the event of severe bleeding requiring immediate medical intervention, FRUZAQLA should be permanently discontinued.

●  Gastrointestinal perforation: GI perforation events, including fatal events, have been reported in patients treated with FRUZAQLA.

Symptoms of GI perforation should be periodically monitored during treatment with FRUZAQLA.

FRUZAQLA should be permanently discontinued in patients developing GI perforation.

●  Proteinuria: Proteinuria events have occurred in patients treated with FRUZAQLA.

Proteinuria should be monitored before initiation and during treatment with FRUZAQLA in accordance with standard medical practices. If urine dipstick proteinuria ≥ 2 g / 24 hours is detected, dose interruptions, adjustments, or discontinuation may be necessary. FRUZAQLA should be permanently discontinued in patients developing nephrotic syndrome.

●  Palmar-plantar erythrodysaesthesia syndrome (PPES): PPES is the most frequently reported dermatological adverse reaction.

If Grade ≥2 skin reactions are detected, dose interruptions, adjustments, or discontinuation may be necessary.

●  Posterior reversible encephalopathy syndrome (PRES): PRES has been reported in 1 patient (0.1%) treated with FRUZAQLA in clinical studies. PRES is a rare neurologic disorder that can present with headache, seizure, lethargy, confusion, altered mental function, blindness, and other visual or neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). In patients developing PRES, discontinuation of FRUZAQLA, along with control of hypertension and supportive medical management of other symptoms, are recommended.

●  Impaired wound healing: Impaired wound healing has been reported in 1 patient (0.1%) treated with FRUZAQLA in clinical studies.

Patients are recommended to withhold FRUZAQLA for at least 2 weeks prior to surgery. FRUZAQLA should not be resumed for at least 2 weeks after surgery, as clinically indicated when there is evidence of adequate wound healing.

●  Arterial and venous thromboembolic events: It is recommended to avoid starting treatment with FRUZAQLA in patients with a history of thromboembolic events (including deep vein thrombosis and pulmonary embolism) within the past 6 months or if they have a history of stroke and/or transient ischemic attack within the last 12 months. If arterial thrombosis is suspected, FRUZAQLA should be discontinued immediately.

INTERACTIONS

Effects of other medicinal products on the pharmacokinetics of FRUZAQLA

CYP3A inducers

Co-administration of FRUZAQLA with rifampicin (a strong CYP3A inducer) 600 mg once daily decreased FRUZAQLA AUC_inf by 65% and decreased C_max by 12%. The concomitant use of FRUZAQLA with strong and moderate CYP3A inducers should be avoided.

CYP3A inhibitors

Co-administration of FRUZAQLA with itraconazole (a strong CYP3A inhibitor) 200 mg twice daily did not result in clinically meaningful changes in the area under the concentration-time curve (AUC) and C_max of FRUZAQLA. No dose adjustment of FRUZAQLA is needed during concomitant use with CYP3A inhibitors.

Gastric acid lowering agents

Co-administration of FRUZAQLA with rabeprazole (a proton pump inhibitor) 40 mg once daily did not result in clinically meaningful changes in the AUC of FRUZAQLA. No dose adjustment of FRUZAQLA is needed during concomitant use with gastric acid lowering agents.

Effect of FRUZAQLA on the pharmacokinetics of other medicinal products

Medicinal products that are substrates of P-glycoprotein (P-gp)

Co-administration of a single dose of dabigatran etexilate 150 mg (a P-gp substrate) with a single dose of FRUZAQLA 5 mg decreased AUC of dabigatran by 9%. No dose adjustment is recommended for P-gp substrates during concomitant use with FRUZAQLA.

Medicinal products that are substrates of breast cancer resistance protein (BCRP)

Co-administration of a single 10 mg dose of rosuvastatin (a BCRP substrate) with a single 5 mg dose of FRUZAQLA decreased AUC of rosuvastatin by 19%. No dose adjustment is recommended for BCRP substrates during concomitant use with FRUZAQLA.

UNDESIRABLE EFFECTS: The most commonly reported adverse reactions with FRUZAQLA are:

• Very common (frequency ≥1/10): Thrombocytopenia, hypothyroidism, anorexia, hypertension, dysphonia, diarrhoea, stomatitis, aspartate aminotransferase increased, total bilirubin increased, alanine aminotransferase increased, palmar-plantar erythrodysaesthesia syndrome, musculoskeletal discomfort, arthralgia, proteinuria, asthenia, and fatigue
• Common (≥1/100 to <1/10):Pneumonia, upper respiratory tract infection, bacterial infections, leukopenia, neutropenia, hypokalemia, epistaxis, throat pain, gastrointestinal haemorrhage, gastrointestinal perforation, pancreatic enzymes increased, oral pain, rash, and mucosal inflammation

REFERENCES
[1]   Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 Countries. CA Cancer J Clin. 2024;74(3):229-263. doi:10.3322/caac.21834.
[2]   Ferlay J, et al. Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.who.int/today, accessed 12 June 2024.
[3]  American Cancer Society. Cancer Facts & Figures 2024. Atlanta, American Cancer Society; 2024.
[4]  Bando H, et al. Therapeutic landscape and future direction of metastatic colorectal cancer. Nat Rev Gastroenterol Hepatol 2023; 20(5)306‑322. doi:10.1038/s41575‑022‑00736‑1.
[5]   D’Haene N, et al. Clinical application of targeted next‑generation sequencing for colorectal cancer patients: a multicentric Belgian experience. Oncotarget. 2018;9(29):20761‑20768. Published 2018 Apr 17. doi:10.18632/oncotarget.25099.
[6]  Venderbosch S, et al. Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: A pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS Studies. Clinical Cancer Res. 2014; 20(20):5322–5330. doi:10.1158/1078‑0432.ccr‑14‑0332.
[7] Koopman M, et al. Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Br J Cancer. 2009;100(2), 266–273. doi:10.1038/sj.bjc.6604867.
[8] Ahcene Djaballah S, et al. HER2 in Colorectal Cancer: The Long and Winding Road From Negative Predictive Factor to Positive Actionable Target. Am Soc Clin Oncol Educ Book. 2022;42:1‑14. doi:10.1200/EDBK_351354.
[9]  Dasari NA, et al. LBA25 – FRESCO‑2: A global Phase III multiregional clinical trial (MRCT) evaluating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer. Ann Oncol. 2022 Sep;33(suppl_7): S808‑S869. doi:10.1016/annonc/annonc1089.
[10]   Dasari NA, et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO‑2): an international, multicentre, randomised, double‑blind, Phase III study. Lancet. 2023;402(10395):41‑53. doi:10.1016/S0140‑6736(23)00772‑9.

CONTACTS

Efficacy and safety of sovleplenib (HMPL-523) in adult patients with chronic primary immune thrombocytopenia in China (ESLIM-01): a randomised, double-blind, placebo-controlled, phase 3 study

Yu Hu*, Xiaofan Liu*, Hu Zhou*, Shujie Wang, Ruibin Huang, Yi Wang, Xin Du, Jing Sun, Zeping Zhou, Zhenyu Yan, Wenming Chen, Wei Wang, Qingchi Liu, Qingshu Zeng, Yuping Gong, Jie Yin, Xuliang Shen, Baodong Ye, Yun Chen, Yajing Xu, Huiping Sun, Yunfeng Cheng, Zhuogang Liu, Chunling Wang, Guolin Yuan, Xiaohui Zhang, Xin Li, Peng Cheng, Xinhong Guo, Zhongxing Jiang, Feng’e Yang, Linhua Yang, Chengwei Luo, Taiwu Xiao, Sisi Fu, Hongyan Yin, Xiaojun Guo, Qian Xu, Songhua Fan, Michael M Shi, Weiguo Su, Heng Mei†, Renchi Yang†

Summary

Background

Methods

Findings

Interpretation

Funding

Trial Registration

ClinicalTrials.gov Identifier: NCT05029635

Citations and Links

Please follow the link below to access the publication:

DOI: https://doi.org/10.1016/S2352-3026(24)00139-X

Link to article: https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00139-X/abstract

— Publication shows treatment demonstrated durable response rate of 48.4% vs. 0% with placebo —

— Presentations at EHA showcased subgroup analyses demonstrating consistent benefits regardless of prior lines of therapies or prior TPO/TPO-RA^[1] exposure —

— Data supported regulatory submission in China accepted in January 2024 —

Hong Kong, Shanghai & Florham Park, NJ — Monday, June 17, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM; HKEX:​13) today announces that results from ESLIM-01, HUTCHMED’s Phase III trial of sovleplenib (HMPL-523), in adult patients with primary immune thrombocytopenia (“ITP”) in China, were published in The Lancet Haematology. Additional details and subgroup results of the study were also presented on June 14 at the European Hematology Association (“EHA”) 2024 Hybrid Congress as an oral and two poster presentations.

Sovleplenib is a novel, selective, oral inhibitor targeting spleen tyrosine kinase (“Syk”) for the treatment of hematological malignancies and immune diseases. Syk is a component in Fc receptor (“FcR”) and B-cell receptor signaling pathway. ITP is a complex autoimmune bleeding disorder, leading to a reduced platelet level in the peripheral blood. ITP can also impact on patients’ quality of life due to fatigue, restrictions on activities and anxiety. The ESLIM-01 trial results published by The Lancet Haematology suggest that sovleplenib could be a potential treatment option for patients with ITP who received at least one prior therapy.

ESLIM-01 is a 2:1 randomized, double-blind, Phase III study conducted in 188 adult patients with primary ITP who had received at least one previous anti-ITP treatment (NCT05029635). The study demonstrated a clinically meaningful early and sustained durable platelet response in patients with primary ITP, with a tolerable safety profile and improvement in quality of life. The primary endpoint was met, with durable response rate of 48.4% (61/126) with sovleplenib compared to zero with placebo (p<0.0001), which was consistent across most pre‑defined subgroups. In addition, overall response rates were 68.3% at 0–12 weeks and 70.6% at 0–24 weeks with sovleplenib, compared to 14.5% and 16.1% with placebo (p<0.0001). The median time to response was 8 days with sovleplenib compared to 30 days with placebo.

Further post-hoc subgroup analysis of the study demonstrated consistent clinical benefits across ITP patients regardless of prior lines of ITP therapies or prior TPO/TPO-RA exposure, including TPO/TPO-RA treatment types and number of prior regimens. Most patients were heavily pretreated with a median of four prior lines of ITP therapy. In patients who received four or more prior lines of therapy, the durable response rate was 47.7% with sovleplenib compared to 0% with placebo (p<0.0001). In addition, a majority of the patients had received prior TPO/TPO-RA. 74.6% of patients in the sovleplenib group had received prior treatment with TPO/TPO-RA, and analysis in this subgroup also demonstrated a significantly higher durable response rate of 46.8% with sovleplenib compared to zero with placebo (p<0.0001).

The safety profile of sovleplenib in ESLIM-01 was consistent with previously reported studies. The majority of treatment-emergent adverse events (“TEAEs”) were mild or moderate in severity (grade 1 or 2). Grade 3 or above TEAEs were reported in 25.4% of patients with sovleplenib and 24.2% with placebo. Sovleplenib also significantly improved quality of life in physical functioning and energy/fatigue (p<0.05).^[2]

The China National Medical Products Administration (“NMPA”) granted Breakthrough Therapy designation for this indication and accepted the New Drug Application (“NDA”) for review with Priority Review in January 2024. A dose-finding study in the U.S. is being planned (NCT06291415). HUTCHMED also initiated the registration stage of the Phase II/III clinical trial of sovleplenib in adult patients with warm antibody autoimmune hemolytic anemia (“wAIHA”) in China in March 2024 (NCT05535933). HUTCHMED retains all rights to sovleplenib worldwide.

About ITP

ITP is an autoimmune disorder characterized by immunologic destruction of platelets and decreased platelet production. Patients with ITP are at increased risk of excessive bleeding and bruising.^[3] ITP is also associated with fatigue (reported in up to 39% of adults with ITP) and impaired quality of life.^{[4],[5],[6],[7],[8]} The incidence of primary ITP in adults is 3.3/100,000 adults per year with a prevalence of 9.5 per 100,000 adults.^[9] Based on this prevalence rate, approximately 110,000 patients are estimated to be living with primary ITP in China, in addition to 56,000 patients in the U.S., Germany, France, Italy, Spain, UK, and Japan. It has been estimated that as many as 145,000 patients are living with chronic ITP in major pharmaceutical markets excluding China.^[10]

Adult ITP is a heterogeneous disease that can persist for years, even with best available care, and treatments are infrequently curative. Despite availability of several treatments with differing mechanisms of action, chronicity of disease continues to be a problem. Many patients develop resistance to treatment and thereby are prone to relapse.^[11] Thus, there remains a significant population of patients who have limited sensitivity to currently available agents and are in need of new treatments.

As platelet destruction in ITP is mediated by Syk-dependent phagocytosis of FcγR-bound platelets, Syk inhibition represents a promising approach to management of ITP.^[12]

About Sovleplenib

Sovleplenib is a novel, selective inhibitor of Syk for once daily oral administration. Syk, a non-receptor tyrosine kinase, is a major component in B-cell receptor and FcR signaling and is an established target for the treatment of multiple subtypes of B-cell lymphomas and autoimmune disorders.

Sovleplenib is currently under clinical investigation and its safety and efficacy have not been approved by any regulatory authority.

HUTCHMED retains all rights to sovleplenib worldwide. In addition to ITP, sovleplenib is also being studied in warm antibody autoimmune hemolytic anemia (NCT05535933) and indolent non-Hodgkin’s lymphoma (NCT03779113).

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three oncology medicines marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of sovleplenib for the treatment of patients with ITP and the further development of sovleplenib in this and other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the timing and outcome of clinical studies and the sufficiency of clinical data to support NDA approval of sovleplenib for the treatment of patients with ITP or other indications in China or other jurisdictions, its potential to gain approvals from regulatory authorities on an expedited basis or at all, the safety profile of sovleplenib, HUTCHMED’s ability to fund, implement and complete its further clinical development and commercialization plans for sovleplenib, and the timing of these events. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

Medical Information

This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

CONTACTS

[1]   TPO = Thrombopoietin; TPO-RAs = Thrombopoietin receptor agonists.

[2] Hu Y, et al. Efficacy and safety of the Syk inhibitor sovleplenib (HMPL-523) in adult patients with primary immune thrombocytopenia in China (ESLIM-01): a randomized, double-blind, placebo-controlled phase 3 study [published online ahead of print, 2024 Jun 14]. Lancet Haematol. 2024.

[3]  Zufferey A, et al. Pathogenesis and Therapeutic Mechanisms in Immune Thrombocytopenia (ITP). J. Clin. Med. 2017, 6(2), 16.

[4]  McMillan R, et al. Self-reported health-related quality of life in adults with chronic immune thrombocytopenic purpura. Am J Hematol. 2008 Feb;83(2):150-4.

[5]   Snyder CF, et al. Health-related quality of life of immune thrombocytopenic purpura patients: results from a web‑based survey. Curr Med Res Opin. 2008 Oct;24(10):2767-76.

[6]  Doobaree IU, et al. Thromboembolism in adults with primary immune thrombocytopenia: a systematic literature review and meta-analysis. Eur J Haematol. 2016 Oct;97(4):321-30.

[7]  Sarpatwari A, et al. Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom General Practice Research Database. Haematologica. 2010 Jul;95(7):1167-75.

[8] Sarpatwari A, et al. Health-related lifestyle in adults and children with primary immune thrombocytopenia (ITP). Br J Haematol. 2010 Oct;151(2):189-91.

[9]  Lambert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood. 2017 May 25;129(21):2829-2835.

[10]   Clarivate Landscape & Forecast for Immune Thrombocytopenic Purpura, 2018.

[11]  Provan D, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780-3817.

[12]  Crowley MT, et al. A critical role for Syk in signal transduction and phagocytosis mediated by Fcγ receptors on macrophages. J. Exp. Med. 186(7), 1027–1039 (1997).

Hong Kong, Shanghai & Florham Park, NJ — Friday, June 7, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that it has initiated Phase I clinical trial of its menin inhibitor HMPL-506 in patients with hematological malignancies in China. The first patient received their first dose on May 31, 2024.

This is a Phase I, multicenter, open-label clinical study to evaluate the safety, pharmacokinetics and efficacy of HMPL-506 in patients with hematological malignancies. The study is divided into two phases, a dose escalation phase and a dose expansion phase. The study is expected to enroll at least 60 patients. The lead principal investigators are Dr. Jianxiang Wang and Dr. Hui Wei of Chinese Academy of Medical Sciences Blood Diseases Hospital. Additional details may be found at clinicaltrials.gov, using identifier NCT06387082.

About HMPL-506 and Menin

HMPL-506 is a novel, investigational, selective small molecule inhibitor for oral administration targeting the menin protein. The menin protein is a scaffold protein that controls gene expression and cell signaling. Mixed-lineage leukemia (“MLL”, also known as KMT2A) rearrangement and nucleophosmin 1 (“NPM1”) mutation play key roles in acute myeloid leukemia (“AML”). MLL-rearranged AML accounts for approximately 5% of adult AML and NPM1-mutant AML accounts for approximately 30% of AML.^[1],[2],[3] Current research has demonstrated that the inhibition of menin-MLL interaction is a feasible therapeutic strategy in MLL-rearranged and/or NPM1-mutant AML.^{[4],[5],[6],[7]} Currently there is no menin inhibitor approved worldwide. HUTCHMED currently retains all rights to HMPL-506 worldwide.

According to the National Cancer Institute (NCІ), there will be approximately 20,380 new cases of AML in the U.S. in 2023 and the five-year relative survival rate is 31.7%.^[8] There were an estimated 19,700 new cases of AML in China in 2018 and is estimated to reach 24,200 in China in 2030.^[9]

About HUTCHMED

HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three oncology drugs marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch-med.com or follow us on LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of HMPL-506 for the treatment of patients with hematological malignancies  and the further development of HMPL-506 in this and other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the timing and outcome of clinical studies and the sufficiency of clinical data to support an NDA submission of HMPL-506 for the treatment of patients with hematological malignancies or other indications in China or other jurisdictions, its potential to gain approvals from regulatory authorities on an expedited basis or at all, the efficacy and safety profile of HMPL-506, HUTCHMED’s ability to fund, implement and complete its further clinical development and commercialization plans for HMPL-506 and the timing of these events. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

REFERENCES

[1] Ibrahim S, Estey EH, Pierce S, et al. 11q23 abnormalities in patients with acute myelogenous leukemia and myelodysplastic syndrome as detected by molecular and cytogenetic analyses. Am J Clin Pathol, 2000, 114(5):793-7.

[2] Grimwade D, Hills RK, Moorman AV, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood, 2010,116(3):354-65.

[3] Falini B, Mecucci C, Tiacci E, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005;352(3):254-66.

[4] Krivtsov AV, Evans K, Gadrey JY, et al. A Menin-MLL Inhibitor Induces Specific Chromatin Changes and Eradicates Disease in Models of MLL-Rearranged Leukemia. Cancer Cell 2019;36:660–73 e11.

[5] Uckelmann HJ, Kim SM, Wong EM, et al. Therapeutic targeting of preleukemia cells in a mouse model of NPM1 mutant acute myeloid leukemia. Science 2020;367:586–90.

[6] Borkin D, He S, Miao H, et al. Pharmacologic inhibition of the Menin-MLL interaction blocks progression of MLL leukemia in vivo. Cancer Cell 2015;27:589–602.

[7] Klossowski S, Miao H, Kempinska K, et al. Menin inhibitor MI-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia. J Clin Invest 2020;130:981–97.

[8] National Cancer Institute – seer.cancer.gov/statfacts/html/amyl.html.

[9] Lin J, Yao D, Qian J, et al. ІDH1 and ІDH2 mutation analysis in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome. Ann Hematol. 2012;91(4):519-525. doi:10.1007/s00277-011-1352-7.

Fruquintinib plus paclitaxel versus placebo plus paclitaxel for gastric or gastroesophageal junction adenocarcinoma: the randomized phase 3 FRUTIGA trial

Feng Wang, Lin Shen, Weijian Guo, Tianshu Liu, Jin Li, Shukui Qin, Yuxian Bai, Zhendong Chen, Jufeng Wang, Yueyin Pan, Yongqian Shu, Fuyou Zhao, Ying Cheng, Feng Ye, Kangsheng Gu, Tao Zhang, Hongming Pan, Haijun Zhong, Fuxiang Zhou, Yanru Qin, Lei Yang, Weidong Mao, Qiu Li, Wenxiang Dai, Wei Li, Shubin Wang, Yong Tang, Dong Ma, Xianli Yin, Yanhong Deng, Ying Yuan, Man Li, Wenwei Hu, Donghui Chen, Guoxin Li, Qiqi Liu, Panfeng Tan, Songhua Fan, Michael Shi, Weiguo Su & Rui-Hua Xu

Abstract

The vascular endothelial growth factor pathway plays a key role in the pathogenesis of gastric cancer. In the multicenter, double-blind phase 3 FRUTIGA trial, 703 patients with advanced gastric or gastroesophageal junction adenocarcinoma who progressed on fluorouracil- and platinum-containing chemotherapy were randomized (1:1) to receive fruquintinib (an inhibitor of vascular endothelial growth factor receptor-1/2/3; 4 mg orally, once daily) or placebo for 3 weeks, followed by 1 week off, plus paclitaxel (80 mg/m² intravenously on days 1/8/15 per cycle). The study results were positive as one of the dual primary endpoints, progression-free survival (PFS), was met (median PFS, 5.6 months in the fruquintinib arm versus 2.7 months in the placebo arm; hazard ratio 0.57; 95% confidence interval 0.48–0.68; P < 0.0001). The other dual primary endpoint, overall survival (OS), was not met (median OS, 9.6 months versus 8.4 months; hazard ratio 0.96, 95% confidence interval 0.81–1.13; P = 0.6064). The most common grade ≥3 adverse events were neutropenia, leukopenia and anemia. Fruquintinib plus paclitaxel as a second-line treatment significantly improved PFS, but not OS, in Chinese patients with advanced gastric or gastroesophageal junction adenocarcinoma and could potentially be another treatment option for these patients. ClinicalTrials.gov registration: NCT03223376.

Citations and Links

Please follow the link below to access the publication:

Wang, F., Shen, L., Guo, W. et al. Fruquintinib plus paclitaxel versus placebo plus paclitaxel for gastric or gastroesophageal junction adenocarcinoma: the randomized phase 3 FRUTIGA trial. Nat Med (2024). https://doi.org/10.1038/s41591-024-02989-6

DOI: https://doi.org/10.1038/s41591-024-02989-6

Link to article: https://www.nature.com/articles/s41591-024-02989-6

Updated subgroup efficacy and quality of life data were also presented on June 1 at ASCO 2024

Hong Kong, Shanghai & Florham Park, NJ — Monday, June 3, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM; HKEX:​13) today announces that results from FRUTIGA, HUTCHMED’s Phase III trial of fruquintinib in combination with paclitaxel for the treatment of second-line advanced gastric cancer in China, were published in Nature Medicine. Updated efficacy data in key subgroups and data on quality of life (QoL) within this publication were also presented on June 1 at the American Society of Clinical Oncology (“ASCO”) 2024 Annual Meeting.

Fruquintinib is a selective oral inhibitor of vascular endothelial growth factor receptors (“VEGFRs”) 1, 2 and 3. It works as an anti-cancer therapy by blocking tumor angiogenesis, a proliferation of blood vessels that is critical for cancer growth. The VEGFR pathway plays a key role in the pathogenesis of gastric cancer, which is the fifth most common malignant cancer worldwide, with 1.1 million new cases per year^[1]. The FRUTIGA trial results published by Nature Medicine suggest that fruquintinib could be another effective treatment option for gastric cancer patients.

FRUTIGA was a 1:1 randomized, double-blind, Phase III study conducted across 35 sites in China (NCT03223376). It evaluated fruquintinib in combination with paclitaxel chemotherapy, compared with paclitaxel monotherapy, for second-line treatment in 703 patients with advanced gastric or gastroesophageal junction adenocarcinoma. The study was declared positive due to a statistically significant improvement in progression-free survival (“PFS”), one of two dual primary endpoints. Median PFS for patients who received fruquintinib plus paclitaxel was 5.6 months, compared to 2.7 months for those who received paclitaxel monotherapy (stratified hazard ratio [“HR”] = 0.569; p < 0.0001). An improvement was also observed in the dual primary endpoint of median overall survival (“OS”), (9.6 months vs. 8.4 months) but this was not statistically significant. Fruquintinib plus paclitaxel demonstrated statistically significant improvements in multiple other endpoints including objective response rate (“ORR”), disease control rate (DCR) and duration of response (DoR). It was well tolerated, with a safety profile consistent with expectations and previously reported studies.^[2]

In further analysis of key subgroups presented at ASCO, PFS and OS results were consistent with the primary analysis compared to the intention-to-treat (ITT) population. There was a clear PFS benefit observed for fruquintinib plus paclitaxel in the majority of subgroups, with particular benefit in both PFS and OS in the intestinal-type and lymph node metastasis subgroups. An exploratory post-hoc analysis for patients with lymph node metastasis revealed superior benefits of fruquintinib versus placebo in PFS, OS, ORR, disease control rate and duration of response. A possible mechanism for this effect is fruquintinib’s potent inhibition of VEGFR­‑3, which is closely linked to lymph node metastasis and tumor invasion. Further analysis of patient-reported quality of life (“QoL”) revealed no adverse impact on QoL at end of treatment compared to current standard of care. Together, these additional findings, alongside previously reported results, support fruquintinib plus paclitaxel as another treatment option in this indication.

Key results from FRUTIGA were previously disclosed at the American Society of Clinical Oncology (ASCO) Plenary Series Session on February 6, 2024, with the full presentation available here.^[3]

Fruquintinib is approved in China and the United States for the treatment of certain patients with metastatic colorectal cancer (“CRC”). A New Drug Application (“NDA”) for fruquintinib in combination with paclitaxel for the treatment of second-line advanced gastric or gastroesophageal junction adenocarcinoma in China was accepted for review by the China National Medical Products Administration (NMPA) in April 2023.

About Gastric Cancer

Gastric cancer is a cancer that starts in the stomach. It is the fifth most common cancer worldwide in 2020. It was estimated to have caused approximately 770,000 deaths worldwide.^[4] In China, it was estimated that over 478,000 people were diagnosed with gastric cancer, and approximately 374,000 people died from gastric cancer.^[5]

About Fruquintinib

Fruquintinib is a selective oral inhibitor of VEGFR-1, -2 and -3. VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for high drug exposure, sustained target inhibition, and flexibility for its potential use as part of combination therapy. Fruquintinib has demonstrated a manageable safety profile and is being investigated in combinations with other anti-cancer therapies.

About Fruquintinib Approval in China

In China, fruquintinib is co-developed and co-marketed by HUTCHMED and Eli Lilly and Company under the brand name ELUNATE^®. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. The approval was based on data from the FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, which were published in the Journal of the American Medical Association, JAMA. Since its launch in China and as of mid‑2023, more than 80,000 colorectal cancer patients have been treated with fruquintinib.

About Fruquintinib Approval in the U.S.

Takeda has the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside of mainland China, Hong Kong and Macau. Fruquintinib received approval in the U.S. in November 2023, where it is marketed by Takeda under the brand name FRUZAQLA^®. The approval was based on data from two large, randomized, controlled Phase III trials: the multi-regional FRESCO-2 trial, data from which were published in The Lancet, along with the FRESCO trial conducted in China, showing consistent benefit among a total of 734 patients treated with fruquintinib. Safety profiles were consistent across trials. Please see FRUZAQLA^® full Prescribing Information here.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of fruquintinib for the treatment of patients with advanced gastric cancer and the further clinical development of fruquintinib in this and other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the sufficiency of clinical data to support NDA approval of fruquintinib for the treatment of patients with advanced gastric cancer in China, the U.S., Europe, Japan, Australia or other jurisdictions, its potential to gain expeditious approvals from regulatory authorities, the safety profile of fruquintinib, HUTCHMED’s ability to fund, implement and complete its further clinical development and commercialization plans for fruquintinib, and the timing of these events. In addition, as certain studies rely on the use of other drug products such as paclitaxel, tislelizumab and sintilimab as combination therapeutics with fruquintinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, on AIM and on The Stock Exchange of Hong Kong Limited. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

Medical Information

This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

CONTACTS

Reference:

[1] World Health Organization. GLOBOCAN 2020. Population fact sheets. China, https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf (2020).

[2] Wang F, et al. Fruquintinib plus paclitaxel versus placebo plus paclitaxel as second-line therapy for advanced gastric or gastro-esophageal junction adenocarcinoma (FRUTIGA): a randomized, multicenter, double-blind, placebo-controlled, phase 3 study [published online ahead of print, 2024 Jun 1]. Nat Med. 2024. DOI: 10.1038/s41591-024-02989-6.

[3] Xu RH, et al., Fruquintinib plus paclitaxel versus paclitaxel as second-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma (FRUTIGA): A randomized, multicenter, double-blind, placebo-controlled, phase 3 study. J Clin Oncol. 2024;42, 438780-438780. DOI: 10.1200/JCO.2024.42.36_suppl.438780.

[4] The Global Cancer Observatory, Stomach Cancer Fact Sheet.  Accessed April 6, 2023.

[5] The Global Cancer Observatory, China Fact Sheet. Accessed April 6, 2023.

Hong Kong, Shanghai, & Florham Park, NJ — Friday, May 31, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM: HCM; HKEX: 13) hereby notifies the market that as at May 31, 2024, the issued share capital of HUTCHMED consisted of 871,264,820 ordinary shares of US$0.10 each, with each share carrying one right to vote and with no shares held in treasury.

The above figure of 871,264,820 may be used by shareholders as the denominator for the calculations by which they could determine if they are required to notify their interest in, or a change to their interest in, HUTCHMED under the Financial Conduct Authority’s Disclosure Guidance and Transparency Rules.

For illustrative purposes only, the 871,264,820 ordinary shares would be equivalent to 871,264,820 depositary interests (each equating to one ordinary share) which are traded on AIM or, if the depositary interests were converted in their entirety, equivalent to 174,252,964 American depositary shares (each equating to five ordinary shares) which are traded on Nasdaq.

About HUTCHMED

HUTCHMED (Nasdaq/AIM: HCM; HKEX: 13) is an innovative, commercial-stage, biopharmaceutical company. Іt is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. Іt has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

Contacts

Hong Kong, Shanghai & Florham Park, NJ — Friday, May 24, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that new and updated data from several studies of compounds discovered by HUTCHMED will be presented at the upcoming American Society of Clinical Oncology (“ASCO”) Annual Meeting, taking place May 31 – June 4, 2024 in Chicago, IL and online.

Results will be presented from the registration Phase II study of fruquintinib combined with sintilimab in 98 second-line or above patients with endometrial cancer (“EMC”) with pMMR status by central laboratory analysis, which supported the New Drug Application (NDA) filed in China. The primary endpoint was objective response rate (“ORR”) per RECIST v1.1, assessed by an independent review committee. The combination showed meaningful efficacy improvements in advanced EMC patients with pMMR status, regardless of prior bevacizumab treatment, with a manageable safety profile. The median follow-up time was 15.7 months. The ORR in 87 efficacy evaluable patients was 35.6% including two complete responses. Disease control rate (“DCR”) was 88.5%, and duration of response was not reached, with 80.7% remaining in response after nine months. Amongst the 98 patients, median progression-free survival (PFS) was 9.5 months, and median overall survival (OS) was 21.3 months. Further details are available in the abstract link below.

Following the initial data of the FRUTIGA Phase III study of fruquintinib in second-line gastric cancer published during the February 2024 ASCO Plenary Series session, further updated efficacy data in key subgroups, and quality of life data will be presented at this year’s ASCO annual meeting. In addition, further data from the FRESCO and FRESCO-2 Phase III colorectal cancer studies, the study of surufatinib combinations in small cell lung cancer, and initial clinical data for the ERK1/2 inhibitor HMPL-295 will be presented.

Details of the presentations, including links to available abstracts, are as follows:

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch-med.com or follow us on LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including but not limited to its expectations regarding the therapeutic potential of fruquintinib, surufatinib and HMPL-295, the further clinical development for fruquintinib, surufatinib and HMPL-295, its expectations as to whether any studies on fruquintinib, surufatinib and HMPL-295, would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates and the timing and availability of subjects meeting a study’s inclusion and exclusion criteria; changes to clinical protocols or regulatory requirements; unexpected adverse events or safety issues; the ability of fruquintinib, surufatinib and HMPL-295, including as combination therapies, to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions and to gain commercial acceptance after obtaining regulatory approval; the potential markets of fruquintinib, surufatinib and HMPL-295 for a targeted indication, and the sufficiency of funding. In addition, as certain studies rely on the use of nab-paclitaxel, sintilimab, toripalimab, pemetrexed, platinum, etoposide or cisplatin as combination therapeutics, such risks and uncertainties include assumptions regarding their safety, efficacy, supply and continued regulatory approval. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

Medical Information

This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

CONTACTS

Hong Kong, Shanghai & Florham Park, NJ  — Friday, May 17, 2024: HUTCHMED (China) Limited (“HUTCHMED” or the “Company”) (Nasdaq/AIM:​HCM, HKEX:​13) today announces:-

• the retirement of Mr Simon To from the position as Chairman and Executive Director, after 23 years with the Company; and
• the appointment of Dr Dan Eldar as the new Chairman.

Dr Eldar has been a Non-executive Director of the Company since 2016. He has more than 30 years of experience as a senior executive, leading global operations in biotechnology, healthcare, telecommunications and water. He is an executive director of Hutchison Water Israel E.P.C Ltd, an associate of CK Hutchison group, which focuses on large scale desalination and hydro-electric projects.

Dr Eldar received a Doctor of Philosophy degree in Government from Harvard University, Master of Arts degree in Government from Harvard University, Master of Arts degree in Political Science and Public Administration from the Hebrew University of Jerusalem and a Bachelor of Arts degree in Political Science from the Hebrew University of Jerusalem.

Mr Simon To, retiring Chairman of HUTCHMED, said “After nearly a quarter of a century with HUTCHMED, I have decided to retire to attend to my personal affairs and address my health issues, which will enable me to spend more cherished time with my family. It has been an absolute privilege to lead such an exceptional team and to be a part of HUTCHMED’s journey to becoming a commercial-stage biopharmaceutical company.”

“I am confident that Dr Eldar’s appointment will further strengthen HUTCHMED’s position as a pioneer in the development of novel therapies for oncology and autoimmune diseases. We look forward to his leadership and contributions to the Company’s continued success.”

The appointment of Dr Eldar as Chairman will take effect on May 17, 2024. He will remain as a Non-executive Director of the Company.  Additionally, from the same date, Mr To will cease his membership of the Nomination Committee, Remuneration Committee, and Technical Committee of the Company, with Dr Eldar being appointed as a member of the Nomination Committee and Technical Committee in his place and Ms Edith Shih, Non-executive Director, being appointed as a member of the Remuneration Committee in his place.

Pursuant to the requirements of Rule 13.51(2) of the Rules Governing the Listing of Securities on The Stock Exchange of Hong Kong Limited (“HK Listing Rules”), Mr To has confirmed that he has no disagreement with the Board, and that there are no other matters that need to be brought to the attention of the shareholders of the Company in connection with his retirement.

The Board would like to express its sincere gratitude to Mr To, who was instrumental in the founding of HUTCHMED, for his invaluable contributions to the Company. His strategic vision has led to the establishment of HUTCHMED as a company committed to the discovery, global development, and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases for patients around the world.

The Board has requested and Mr To has agreed to serve as Strategic Advisor of the Company and in that capacity to continue to contribute to the Company on significant matters.

Further information about Dr Eldar and his appointment

Dr Eldar, aged 70, is a director of certain companies controlled by substantial shareholders (for the purpose of Part XV of the Securities and Futures Ordinance) of the Company.  Save as disclosed above, Dr Eldar does not have any relationship with any other Directors, senior management, substantial or controlling shareholders of the Company. As at the date of this announcement, Dr Eldar had a personal interest in 150,660 ordinary shares in the Company (“Shares”), representing approximately 0.02% of the number of Shares in issue, within the meaning of Part XV of the Securities and Futures Ordinance. The term of Dr Eldar’s service as a Non-executive Director of the Company is subject to retirement by rotation and re-election at the annual general meeting of the Company. The director’s fees of Dr Eldar as the Chairman and a member of the Nomination Committee and Technical Committee of the Company under his appointment letter are US$70,000, US$5,000 and US$5,000 per annum respectively. Such amounts are subject to review from time to time and proration for an incomplete year of service.

There are no other matters concerning Dr Eldar that are required to be brought to the attention of the shareholders, nor is there other information that is required to be disclosed pursuant to the requirements of Rule 13.51(2) of the HK Listing Rules and Rule 17 of the AIM Rules for Companies.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

Forward-Looking Statements

This announcement contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, the risk that current or future appointees to HUTCHMED’s board of directors are not effective in their respective positions, the difficulty in locating and recruiting suitable candidates for its board of directors and the management difficulties which may arise from changes in HUTCHMED’s board of directors. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, on AІM and with The Stock Exchange of Hong Kong Limited. HUTCHMED undertakes no obligation to update or revise the information contained in this announcement, whether as a result of new information, future events or circumstances or otherwise.

Inside Information

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) No 596/2014 (as it forms part of retained EU law as defined in the European Union (Withdrawal) Act 2018).

CONTACTS

Hong Kong, Shanghai & Florham Park, NJ — Friday, May 17, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that topline and subgroup results from the ESLIM‑01 Phase III study of sovleplenib, as well as new and updated data related to novel investigational hematological malignancy therapies HMPL-306, HMPL-760 and tazemetostat, will be presented at the upcoming European Hematology Association (“EHA”) Hybrid Congress, taking place on June 13-16, 2024 in Madrid, Spain and online.

ESLIM-01 is a randomized, double-blinded, placebo-controlled Phase III trial in China of sovleplenib in adult patients with primary Immune Thrombocytopenia (“ITP”) who have received at least one prior line of standard therapy (NCT05029635). In 188 patients randomized to receive oral sovleplenib or placebo, sovleplenib demonstrated a clinically meaningful early and sustained durable platelet response in patients with primary ITP with durable response rate of 48.4% compared to zero with placebo (p<0.0001). The median time to response was 1.1 weeks with sovleplenib. It demonstrated a tolerable safety profile with grade 3 or above treatment-emergent adverse events (TEAEs) in 25.4% of patients with sovleplenib and 24.2% with placebo. Sovleplenib also significantly improved quality of life in physical functioning and energy/fatigue (p<0.05).

Most patients were heavily pretreated with a median of four prior lines of ITP therapy and a majority (71.3%) of the patients had received prior TPO/TPO-RA[i] treatment. Further post-hoc subgroup analysis of the study demonstrated consistent clinical benefits across ITP patients regardless of prior lines of ITP therapies or prior TPO/TPO-RA exposure, regardless of TPO/TPO-RA treatment types and number of prior regimens.

In addition to the promising data in ITP, results from Phase II part of the ongoing ESLIM-02 Phase II/III study (NCT05535933) of sovleplenib for warm antibody autoimmune hemolytic anemia (wAIHA) will also be presented at the congress demonstrating encouraging hemoglobin (Hb) benefit compared with placebo, with overall response rate of 43.8% vs. 0% in the first 8 weeks, and overall response rate of 66.7% during the 24 weeks of sovleplenib treatment (including patients that crossed over from placebo). A favorable safety profile was also demonstrated.

Details of the presentations are as follows:

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including but not limited to its expectations regarding the therapeutic potential of sovleplenib, HMPL-306, HMPL-760 and tazemetostat, the further clinical development for sovleplenib, HMPL-306, HMPL-760, tazemetostat and amdizalisib, its expectations as to whether any studies on sovleplenib, HMPL-306, HMPL-760, tazemetostat and amdizalisib would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates and the timing and availability of subjects meeting a study’s inclusion and exclusion criteria; changes to clinical protocols or regulatory requirements; unexpected adverse events or safety issues; the ability of sovleplenib, HMPL-306, HMPL-760, tazemetostat and amdizalisib, including as combination therapies, to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions and to gain commercial acceptance after obtaining regulatory approval; the potential markets of sovleplenib, HMPL-306, HMPL-760 and tazemetostat for a targeted indication, and the sufficiency of funding. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

Medical Information

This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

[i] TPO = Thrombopoietin; TPO-RAs = Thrombopoietin receptor agonists.

CONTACTS

— Almost half a million people diagnosed each year across the globe —

— Collaboration based on synergistic potential of inhibiting angiogenesis and tumor-associated macrophages with HUTCHMED’s surufatinib and anti-PD-1 activity with Hengrui’s camrelizumab, promoting the immune response against tumor cells —

Hong Kong, Shanghai & Florham Park, NJ —  Tuesday, May 14, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces the initiation of a Phase II/III trial to evaluate the efficacy of a combination of the HUTCHMED drug candidate surufatinib, the Jiangsu Hengrui Pharmaceuticals Co., Ltd (“Hengrui Pharma”) PD-1 antibody camrelizumab, nab-paclitaxel and gemcitabine as a first-line treatment for patients with metastatic pancreatic ductal adenocarcinoma (“PDAC”) in China. PDAC is an exocrine tumor and the most common form of pancreatic cancer. The first patient received the first dose on May 8, 2024.

PDAC is a highly aggressive form of cancer, representing over 90% of pancreatic cancer cases. Globally, an estimated 511,000 people were diagnosed with pancreatic cancer, leading to approximately 467,000 deaths in 2022, with an average five-year survival rate of less than 10%. In China, an estimated 119,000 people were diagnosed with pancreatic cancer, causing approximately 106,000 deaths in 2022.^[1] Treatments such as chemotherapy, surgery and radiation are commonly employed, but have not shown significant improvement in patient outcomes. Under 20% of metastatic pancreatic cancer patients survive more than a year.^[ii]

The trial is a multicenter, randomized, open-label, active-controlled, Phase II/III trial to evaluate the efficacy and safety of surufatinib combined with camrelizumab, nab-paclitaxel, and gemcitabine versus nab-paclitaxel plus gemcitabine as a treatment for adults with metastatic pancreatic cancer who have not been previously treated with a systemic anti-tumor therapy. After an initial safety run-in stage, the Phase II/III stage of the study may enroll a further 500 patients, with a primary endpoint of overall survival (OS). Other endpoints include objective response rate (ORR), progression free survival (PFS), disease control rate (DCR), safety, quality of life, duration of response and time to response. Additional details may be found at clinicaltrials.gov, using identifier NCT06361888.

Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, said, “Emerging data including those from an investigator-initiated study presented at the ASCO Gastrointestinal Cancers Symposium, demonstrated that combinations of surufatinib, camrelizumab and chemotherapy have promising efficacy in comparison with existing chemotherapy-based treatments in metastatic PDAC.^[3] We hope that this partnership will enable us to bring new, potentially life-changing treatment options to patients.”

About Surufatinib

Surufatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptor (FGFR), which both inhibit angiogenesis, and colony stimulating factor-1 receptor (CSF-1R), which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies, where there may be synergistic anti-tumor effects.

Surufatinib is marketed in China by HUTCHMED under the brand name SULANDA^®, and was first included in the China National Reimbursement Drug List (NRDL) in January 2022 for the treatment of non-pancreatic and pancreatic neuroendocrine tumors (NETs).

About Camrelizumab

Camrelizumab (SHR-1210) is a humanized monoclonal antibody targeting the programmed death-1 (PD-1) receptor. Blockade of the PD-1/PD-L1 signaling pathway is a therapeutic strategy showing success in a wide variety of solid and hematological cancers. Currently, more than 10 clinical trials are underway worldwide in a broad range of tumors  and treatment settings.

Camrelizumab, under the brand name AiRuiKa^®, is currently approved for nine indications in China, including hepatocellular carcinoma (“HCC”) (second-line and first-line), relapsed/refractory classic Hodgkin’s lymphoma (third-line), esophageal squamous cell carcinoma (second-line) and nasopharyngeal carcinoma (third-line or further) and in combination with chemotherapy for the treatment of non-small cell lung cancer (non-squamous and squamous), esophageal squamous cell carcinoma, and nasopharyngeal carcinoma in the first-line setting. All indications have been included in China’s national medical insurance catalog, making it the leading domestic PD-1 product in terms of approved indications and tumor types covered. The U.S. Food and Drug Administration (“FDA”) granted Orphan Drug Designation to camrelizumab for advanced HCC in April 2021, and accepted a New Drug Application (NDA) for camrelizumab and rivoceranib as a first-line therapy for unresectable HCC, with FDA Prescription Drug User Fee Act (PDUFA) dates in May 2024.

About Hengrui Pharma

Hengrui Pharma is a leading global pharmaceutical company headquartered in China with a focus on research, development, manufacturing, and commercialization of innovative and high-quality healthcare products. Innovation is the core development strategy. Hengrui Pharma ranked 24^th among top 1,000 global pharmaceutical companies in 2021. Hengrui Pharma has been on the Pharma Exec’s annual listing of the top 50 global pharmaceutical companies for the fifth consecutive year.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world. Its first three medicines are marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of surufatinib for the treatment of patients with PDAC and the further development of surufatinib in this and other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the timing and outcome of clinical studies and the sufficiency of clinical data to support an NDA submission of surufatinib for the treatment of patients with PDAC or other indications in China or other jurisdictions, its potential to gain approvals from regulatory authorities on an expedited basis or at all, the efficacy and safety profile of surufatinib, HUTCHMED’s ability to fund, implement and complete its further clinical development and commercialization plans for surufatinib and the timing of these events. In addition, as certain studies rely on the use of other drug products such as camrelizumab as combination therapeutics with surufatinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

Medical Information

This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

REFERENCES

[1]   The Global Cancer Observatory, World Fact Sheets. Accessed April 9, 2024.

[2]   Sarantis P et al. Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy. World J Gastrointest Oncol. 2020;12(2):173-181. DOI:10.4251/wjgo.v12.i2.173

[3] Jia R et al. Updated results of a phase 1b/2 study of surufatinib plus camrelizumab, nab-paclitaxel and S-1 (NASCA) as first-line therapy for metastatic pancreatic adenocarcinoma (mPDAC). JCO 42, 671-671(2024). DOI:10.1200/JCO.2024.42.3_suppl.671

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Hong Kong, Shanghai & Florham Park, NJ — Tuesday, May 14, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that it has initiated a registrational Phase III clinical trial of HMPL-306 in patients with mutated isocitrate dehydrogenase (“IDH”) 1 or 2 relapsed / refractory acute myeloid leukemia (“AML”) in China. The first patient received their first dose on May 11, 2024.

HMPL-306 is a novel dual-inhibitor of IDH1 and IDH2 enzymes. Mutations of IDH1 and IDH2 have been implicated as drivers of certain hematological malignancies, gliomas and solid tumors, particularly among AML patients. Although some IDH inhibitors have been approved in certain markets for AML, isoform switching between the cytoplasmic mutant IDH1 and mitochondrial mutant IDH2 often leads to acquired resistance to single inhibitors of IDH1 or IDH2. Targeting both IDH1 and IDH2 mutations may provide therapeutic benefits in cancer patients by overcoming this acquired resistance.

RAPHAEL is a multicenter, randomized, open-label, registrational Phase III clinical trial designed to evaluate the safety and efficacy of HMPL-306 as a monotherapy in patients with relapsed or refractory AML harboring IDH1 and/or IDH2 mutations. The primary endpoint of overall survival (OS) and the secondary endpoints, including event-free survival (EFS) and complete remission (“CR”) rate, will be tested in comparison with current salvage chemotherapy regimens. The Company is looking to enroll approximately 320 patients for this registrational study, which is being led by principal investigator Prof Xiaojun Huang of Peking University People’s Hospital. Additional details may be found at clinicaltrials.gov, using identifier NCT06387069.

The study follows positive data from a two-stage, open-label Phase I study evaluating the safety, pharmacokinetics, pharmacodynamics and efficacy of HMPL-306 in this indication (NCT04272957). The first-in-human dose-escalation stage data was presented at the European Hematology Association Congress (“EHA”) in June 2023.^[1] Results of the dose expansion stage of the study in over 50 patients demonstrated promising CR rates at the recommended Phase II dose are expected to be presented at the EHA Congress in June 2024.

About IDH and Hematological Malignancies

IDHs are critical metabolic enzymes that help to break down nutrients and generate energy for cells. When mutated, IDH creates a molecule that alters the cell’s genetic programming and prevents cells from maturing. IDH1 or IDH2 mutations are common genetic alterations in various types of blood and solid tumors, including AML with approximately 14-20% of patients having mutant IDH genes, myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), low-grade glioma and intrahepatic cholangiocarcinoma. Mutant IDH isoform switching, either from cytoplasmic mutant IDH1 to mitochondrial mutant IDH2, or vice versa, is a mechanism of acquired resistance to IDH inhibition in AML and cholangiocarcinoma.^[2],[3],[4]

According to the National Cancer Institute (NCI), there will be approximately 20,380 new cases of AML in the U.S. in 2023 and the five-year relative survival rate is 31.7%^[5]. Currently, the U.S. Food and Drug Administration (FDA) has approved two drugs for IDH1 mutation and one drug for IDH2 mutation, but no dual inhibitor targeting both IDH1 and IDH2 mutants has been approved. There were an estimated 19,700 new cases of AML in China in 2018 and is estimated to reach 24,200 in China in 2030.^[6]  In China one IDH1 inhibitor was approved in 2022.

About HUTCHMED

HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines now marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of HMPL-306 for the treatment of patients with relapsed or refractory AML and the further development of HMPL-306 in this and other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the timing and outcome of clinical studies and the sufficiency of clinical data to support an NDA submission of HMPL-306 for the treatment of patients with relapsed or refractory AML or other indications in China or other jurisdictions, its potential to gain approvals from regulatory authorities on an expedited basis or at all, the efficacy and safety profile of HMPL-306, HUTCHMED’s ability to fund, implement and complete its further clinical development and commercialization plans for HMPL-306 and the timing of these events. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

Medical Information

This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

REFERENCES

[1]   Hu L et al. P539: A Phase 1 Study of HMPL-306, a Dual Inhibitor of Mutant Isocitrate Dehydrogenase (IDH) 1 and 2, in Patients with Relapsed/Refractory Myeloid Hematological Malignancies Harboring IDH1 and/or 2 Mutations. Hemasphere. 2023;7(Suppl):e86312d3. Published 2023 Aug 8. doi:10.1097/01.HS9.0000969064.86312.d3.

[2]   S Choe S et al. Blood 2019;134(Supplement_1):545. doi:10.1182/blood-2019-122671.

[3] Harding JJ et al. Isoform Switching as a Mechanism of Acquired Resistance to Mutant Isocitrate Dehydrogenase Inhibition. Cancer Discov. 2018;8(12):1540-1547. doi:10.1158/2159-8290.CD-18-0877.

[4] Delahousse J et al. Circulating oncometabolite D-2-hydroxyglutarate enantiomer is a surrogate marker of isocitrate dehydrogenase-mutated intrahepatic cholangiocarcinomas. Eur J Cancer. 2018;90:83-91. doi:10.1016/j.ejca.2017.11.024.

[5]   Source: National Cancer Institute – seer.cancer.gov/statfacts/html/amyl.html.

[6] Lin J et al. IDH1 and IDH2 mutation analysis in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome. Ann Hematol. 2012;91(4):519-525. doi:10.1007/s00277-011-1352-7.

CONTACTS

Hong Kong, Shanghai, & Florham Park, NJ: Friday, May 10, 2024: HUTCHMED (China) Limited (“HUTCHMED” or the “Company”) (Nasdaq/AIM: HCM; HKEX:13) today announces that all ordinary resolutions and the special resolution put to its Annual General Meeting (“AGM”) held on May 10, 2024 were duly passed.  The poll results of the resolutions were as follows:

*  Percentages rounded to 4 decimal places.

^# A vote withheld is not a vote in law and is not counted in the calculation of the proportion of the votes for and against a resolution.

^ The full text of Resolutions 4 and 5 are set out in the Notice of AGM.

Notes:

• All directors of the Company, namely Mr TO Chi Keung, Simon, Dr Weiguo SU, Mr CHENG Chig Fung, Johnny, Dr Dan ELDAR, Ms Edith SHIH, Ms Ling YANG, Mr Paul Rutherford CARTER, Mr Graeme Allan JACK and Professor MOK Shu Kam, Tony, attended the AGM, either in person or by means of electronic facilities.
• Number of shares entitling the holders to attend and vote on all the resolutions at the AGM: 871,264,820 shares.
• Number of shares entitling the holders to attend and abstain from voting in favour as set out in Rule 13.40 of the Rules Governing the Listing of Securities on The Stock Exchange of Hong Kong Limited (the “Listing Rules”) at the AGM: Nil.
• Number of shares for holders required under the Listing Rules to abstain from voting at the AGM: Nil.
• The scrutineer for the poll at the AGM was Computershare Investor Services (Jersey) Limited, the Principal Share Registrar of the Company.

About HUTCHMED

HUTCHMED (Nasdaq/AIM: HCM; HKEX: 13) is an innovative, commercial-stage, biopharmaceutical company. Іt is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. Іt has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

CONTACTS

Hong Kong, Shanghai & Florham Park, NJ  — Wednesday, May 8, 2024: HUTCHMED (China) Limited (“HUTCHMED” or the “Company”) (Nasdaq/AIM:​HCM, HKEX:​13) today announces that Dr Renu Bhatia is appointed as an Independent Non-executive Director and a member of Technical Committee of the Company with effect from May 13, 2024.

Dr Bhatia, a licensed physician, has over 25 years of experience in the healthcare, finance and fintech, and regulatory sectors.  She is an experienced board director and chair, with a healthcare and financial services background in investment banking, asset management, venture capital and compliance.  The Board of HUTCHMED is of the view that Dr Bhatia will further enhance the skill set, expertise and knowledge base of the Board as a whole.

Mr Simon To, Chairman of HUTCHMED, said “On behalf of the Board, I would like to extend a warm welcome to Dr Bhatia to the Company.  We believe that her expertise in the healthcare, finance and fintech sectors will bring fresh perspective and provide constructive insight to the Board.”

Dr Bhatia, aged 65, is the chairman and co-founder of Opharmic Technology (HK) Ltd, a company focusing on the development of ultrasound technology for non-invasive drug delivery to the eyes.  She is also co-founder of Asia Fintech Angels which invested in early stage fintech companies. In addition, Dr Bhatia is an independent non-executive director of Overstone Associates Limited, a leading UK based data science provider to financial institutions focused on the art industry.

Dr Bhatia is the chairman of the Listing Committee of The Stock Exchange of Hong Kong Limited.  She also holds positions in public service including membership of the Business Professional Federation Healthcare Committee and the Cyberport Entrepreneurship Centre Advisory Group, and acting as an assessor for the Hong Kong Enterprise Support Scheme Assessment Panel of the Innovation and Technology Fund. Dr Bhatia started her career in finance at Goldman Sachs and HSBC Asset Management.

Dr Bhatia is a Doctor of Medicine (MBBS) from the University of London and holds a Master of Business Administration degree from Yale University, and a Postgraduate Diploma in Therapeutics and Medicine from The University of Hong Kong.

Dr Bhatia has relevant board experience with the following private companies, currently holding or having held in the past five years the following directorships:

Save for the appointments listed above, Dr Bhatia has held no other directorships or partnerships during the period of five years prior to her appointment as a director of HUTCHMED. She does not have any relationship with any Directors, senior management or substantial or controlling shareholders of HUTCHMED. Dr Bhatia has confirmed that (a) she has satisfied all the criteria for independence set out in Rule 3.13(1) to (8) of the Rules Governing the Listing of Securities on The Stock Exchange of Hong Kong Limited (“HK Listing Rules”); (b) she had no past or present financial or other interest in the business of the Company or its subsidiaries or any connection with any core connected person (as defined in the HK Listing Rules) of the Company; and (c) there are no other factors that may affect her independence at the time of her appointment.

The initial term of the appointment of Dr Bhatia as an Independent Non-executive Director of the Company shall end at the next following annual general meeting of the Company, subject to retirement in accordance with the Articles of Association of the Company and applicable legal and regulatory requirements, and thereafter for successive periods of 12 months, unless she is not re-elected at the next following annual general meeting or her appointment is otherwise terminated earlier by either party in writing. The director’s fees of Dr Bhatia as an Independent Non-executive Director and member of the Technical Committee of the Company under her appointment letter are US$76,000 and US$8,000 per annum respectively.  Such fees are subject to review from time to time and proration for any incomplete year of service.

Dr Bhatia is interested in 16,000 ordinary shares with par value US$0.10 each in the share capital of the Company, representing approximately 0.002% of its issued share capital.

Save for the information disclosed above, there is no other information in relation to Dr Bhatia that is required to be disclosed pursuant to Rule 17 and Schedule 2(g) of the AІM Rules for Companies or Rule 13.51(2) of the HK Listing Rules and there are no other matters concerning the appointment of Dr Bhatia that are required to be brought to the attention of the shareholders of HUTCHMED.

About HUTCHMED

HUTCHMED (Nasdaq/AIM: HCM; HKEX: 13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

Forward-Looking Statements

This announcement contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, the risk that current or future appointees to HUTCHMED’s board of directors are not effective in their respective positions, the difficulty in locating and recruiting suitable candidates for its board of directors and the management difficulties which may arise from changes in HUTCHMED’s board of directors. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, on AІM and with The Stock Exchange of Hong Kong Limited. HUTCHMED undertakes no obligation to update or revise the information contained in this announcement, whether as a result of new information, future events or circumstances or otherwise.

CONTACTS