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.