Hong Kong, Shanghai & Florham Park, NJ — Tuesday, August 29, 2023: 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 savolitinib for the treatment of locally advanced or metastatic gastric cancer or gastroesophageal junction (“GEJ”) adenocarcinoma patients with mesenchymal epithelial transition factor (“MET”) amplification who have failed at least two lines of standard therapies.

The study of savolitinib is a single-arm, multi-center, open-label, Phase II registration study to evaluate the efficacy, safety and tolerability of savolitinib in treating gastric cancer or GEJ adenocarcinoma patients with MET amplification. Primary endpoint is objective response rate (“ORR”) evaluated by the Independent Review Committee (“IRC”) (RECIST 1.1). Secondary endpoints include progression free survival (PFS) and incidence of various adverse events (AE), among others.  The study is expected to enroll approximately 60 patients. Further details may be found at clinicaltrials.gov using identifier NCT04923932.

About Breakthrough Therapy Designation in China

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 a New Drug Application (“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 Gastric Cancer with MET Amplification

MET-driven gastric cancer has a very poor prognosis.¹ The ongoing registration trial follows multiple Phase II studies that have been conducted in Asia to study ORPATHYS^® in MET-driven gastric cancer patients, including VIKTORY.³ VIKTORY is an investigator initiated Phase II umbrella study in gastric cancer in South Korea in which a total of 715 patients were successfully sequenced into molecular-driven patient groups, including those with MET amplified gastric cancer. Patients whose tumors harbor MET amplification were treated with ORPATHYS^® monotherapy. The VIKTORY study reported a 50% ORR.

At American Association for Cancer Research Annual Meeting 2023 (AACR 2023), it was reported that the interim results from a China Phase II study of savolitinib in patients with MET-amplified GEJ adenocarcinomas or gastric cancer showed a 45% ORR confirmed by IRC and a 50% ORR in patients with high MET gene copy number.  Duration of response (DOR) rate at 4-month was 85.7% with median follow up time of 5.5 months. The most common grade≥3 treatment-related adverse events (“TRAE”) (≥5%) were platelet count decreased, hypersensitivity, anemia, neutropenia and hepatic function abnormal. Only 1 patient discontinued treatment due to grade 4 liver function abnormal (TRAE) and no patient died due to TRAE.

It is estimated that MET amplification accounts for approximately 4-6% of gastric cancer patients.^2,3 The annual incidence of MET amplification gastric cancer is estimated to be approximately 24,000 in China.⁴

About Savolitinib

Savolitinib is an oral, potent and highly selective MET tyrosine kinase inhibitor that has demonstrated clinical activity in advanced solid tumors. Іt 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.

Savolitinib is marketed in China under the brand name ORPATHYS^® for the treatment of patients with non-small cell lung cancer (“NSCLC”) with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy. Іt 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.  Starting on March 1, 2023, ORPATHYS^® was included in the National Reimbursement Drug List (NRDL) for the treatment of locally advanced or metastatic NSCLC adult patients with MET exon 14-skipping alterations who have progressed after or unable to tolerate platinum-based chemotherapy.

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

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 now approved and marketed in China. 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 savolitinib for the treatment of gastric cancer and the further clinical development of savolitinib 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 savolitinib for the treatment of 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 savolitinib, HUTCHMED’s ability to fund, implement and complete its further clinical development and commercialization plans for savolitinib, the timing of these events, and the impact of COVID-19 on general economic, regulatory and political conditions. 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.

Reference

[1] Catenacci DV, Ang A, Liao WL, et al. MET tyrosine kinase receptor expression and amplification as prognostic biomarkers of survival in gastroesophageal adenocarcinoma. Cancer. 2017;123(6):1061-1070. doi:10.1002/cncr.30437

[2] Lee J, Kim ST, Kim K, et al. Tumor Genomic Profiling Guides Patients with Metastatic Gastric Cancer to Targeted Treatment: The VIKTORY Umbrella Trial. Cancer Discov. 2019;9(10):1388-1405. doi:10.1158/2159-8290.CD-19-044

[3] Van Cutsem E, Karaszewska B, Kang YK, et al. A Multicenter Phase II Study of AMG 337 in Patients with MET-Amplified Gastric/Gastroesophageal Junction/Esophageal Adenocarcinoma and Other MET-Amplified Solid Tumors. Clin Cancer Res. 2019;25(8):2414-2423. doi:10.1158/1078-0432.CCR-18-1337

[4] Global Cancer Observatory. China Fact Sheet. gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf.  Accessed March 20, 2023.

Contacts

— Randomized, double-blind, controlled trial met primary endpoint of durable response rate and all secondary endpoints —

— Overall safety consistent with sovleplenib known profile —

— Plans for regulatory submission underway in China, where it was designated a Breakthrough Therapy —

— Results to be submitted to an upcoming medical meeting —

Hong Kong, Shanghai & Florham Park, NJ — Monday, August 21, 2023: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM; HKEX:​13) today announces that the pivotal Phase III trial ESLIM-01 evaluating the investigational use of sovleplenib met its primary endpoint of durable response rate and all secondary endpoints in adult patients with primary immune thrombocytopenia (“ITP”) in China. HUTCHMED plans to submit the New Drug Application (“NDA”) around the end of 2023.

The National Medical Products Administration of China (“NMPA”) granted Breakthrough Therapy designation (“BTD”) to sovleplenib for the indication studied in ESLIM-01 in January 2022. The NMPA granted this designation to sovleplenib as a new drug that could treat a serious condition for which there are no effective treatment options, and where clinical evidence demonstrates significant advantages over existing therapies. As such, the sovleplenib NDA may be considered for priority review for its use in ITP.

ESLIM-01 is a randomized, double-blinded, placebo-controlled Phase III trial in China of sovleplenib in 188 adult patients with primary ITP who have received at least one prior line of standard therapy. Enrollment was completed in December 2022. The trial met its primary endpoint of demonstrating a clinically meaningful and a statistically significant increase in durable response rate in patients treated with sovleplenib as compared to patients treated with placebo. Secondary endpoints including response rate and safety were also met. Full results will be submitted for presentation at an upcoming scientific conference.

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 an autoimmune disorder that can lead to increased risk of bleeding. Encouraging proof of concept data was presented at ASH^[1] 2021 and published in The Lancet Haematology in June 2023.^[2]

“Sovleplenib offers a potential new treatment for patients with chronic adult primary ITP who have received at least one prior therapy, a heterogeneous disease that can persist for years and where there remains a significant need for new treatments,” said Dr Michael Shi, Chief Medical Officer of HUTCHMED. “We are very pleased to see the positive outcomes of the ESLIM-01 study and would like to thank the patients, their families, and the healthcare professionals who participated in this study and helped reach this achievement.”

Professor Ren-Chi Yang, MD, of the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, who served as the ESLIM-01 co-Leading Principal Investigator (“PI”) and Steering Committee (“SC”) member, said, “By meeting the primary and all the secondary endpoints in this study while demonstrating a good level of tolerability and once daily oral dosing, I am optimistic that sovleplenib may be a potential choice to help ITP patients.”

Professor Yu Hu, MD, at the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, co-Leading PI and SC member commented, “Many patients with recurrent or refractory ITP feel burdened by their disease in their daily lives and by the management of their current medications. I welcome the opportunity to offer my patients another treatment option to live better with their disease.”

About Sovleplenib

Sovleplenib is a novel, selective inhibitor of Syk for once daily oral administration. Syk 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.

Results from the Phase I/II study in China study published in The Lancet Haematology showed a rapid and durable increase in platelet counts in previously treated patients with ITP. Among the 20 patients who received the recommend Phase II dose of 300mg once daily (“RP2D”), 8 (40%) patients experienced durable response, as defined by platelet count equal to or exceeding 50×10⁹/L in four out of six visits during week 14 to 24 of the study. All 20 patients had been previously treated with glucocorticoid steroid, and 15 previously treated with thrombopoietin or thrombopoietin receptor agonists. Median time to response to treatment was 1.1 weeks for the 16 patients who received the RP2D during the first 8 weeks of the study, as defined by first platelet count equal to or exceeding 30×10⁹/L. Among the 41 patients who received treatment at all doses through week 24 of the study, treatment-emergent adverse events (“TEAE”) led to dose reduction or interruption in three (7%) patients, and no dose discontinuation. No TEAEs of grade 3 or above occurred in more than one patient through week 24 of the study.

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

HUTCHMED currently 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 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 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 oncology medicines now approved and marketed in China. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

Forward-Looking Statements

This announcement contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of sovleplenib for the treatment of patients with ITP and the further development 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, the timing of these events, and the impact of the COVID-19 pandemic on general economic, regulatory and political conditions. 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 announcement, whether as a result of new information, future events or circumstances or otherwise.

Inside Information

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

[1] ASH = American Society of Hematology.

[2] Liu X, Zhou H, Hu Y, et al. Sovleplenib (HMPL-523), a novel Syk inhibitor, for patients with primary immune thrombocytopenia in China: a randomised, double-blind, placebo-controlled, phase 1b/2 study. Lancet Haematol. 2023;10(6):e406-e418. doi:10.1016/S2352-3026(23)00034-0.

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

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

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

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

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

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

[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, Arnold DM, Bussel JB, 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, Costello PS, Fitzer-Attas CJ 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 — Monday, August 7, 2023: HUTCHMED (China) Limited (“HUTCHMED” or the “Company”) (Nasdaq/AIM:​HCM, HKEX:​13) today announces that it has issued a total of 3,000,000 ordinary shares of US$0.10 each (“Ordinary Shares”) following the exercise of share options by Dr Weiguo Su, Executive Director, Chief Executive Officer and Chief Scientific Officer, at an exercise price of GBP1.97 per Ordinary Share on August 7, 2023 (the “Exercise of Options”).

Following the Exercise of Options, Dr Su is beneficially interested in 5,000,000 Ordinary Shares ^{Note 1} and 632,505 American Depositary Shares (“ADSs”) ^{Note 2}, representing 0.94% of the current issued share capital of the Company.

Notes:

1. 5,000,000 Ordinary Shares included (i) 3,000,000 Ordinary Shares currently held by Dr Su, and (ii) share options for 2,000,000 Ordinary Shares granted under Share Option Scheme
2. 632,505 ADSs included (i) 143,518 ADSs currently held by Dr Su, (ii) share options for 395,442 ADSs granted under Share Option Scheme and (iii) 93,545 ADSs as beneficiary of a trust under long term incentive plan.

The notification set out below is provided in accordance with the requirements of the EU Market Abuse Regulation.

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 oncology medicines now approved and marketed in China. For more information, please visit: www.hutch‑med.com or follow us on LinkedIn.

Forward-Looking Statements

This announcement contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. 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, on AIM and on HKEX. HUTCHMED undertakes no obligation to update or revise the information contained in this announcement, whether as a result of new information, future events or circumstances or otherwise.

Contacts