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.