VOLUNTARY ANNOUNCEMENT - HUTCHMED Initiates Phase I Trial of Menin Inhibitor HMPL-506 in Patients with Hematological Malignancies in China

Hong Kong Exchanges and Clearing Limited and The Stock Exchange of Hong Kong Limited take no responsibility for the contents of this announcement make no representation as to its accuracy or completeness and expressly disclaim any liability whatsoever for any loss howsoever arising from or in reliance upon the whole or any part of the contents of this announcement.HUTCHMED (China) Limited 和黄医药（中国）有限公司 (?ncorporated in the Cayman ?slands with limited liability) (Stock Code: ??) VOLUNTARY ANNOUNCEMENT HUTCHMED Initiates Phase I Trial of Menin Inhibitor HMPL-506 in Patients with Hematological Malignancies in China HUTCHMED (China) Limited (“HUTCHMED”) today announces that it has initiated Phase ? 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 ? 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.123 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 ?nstitute (NC?) there will be approximately 20380 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 19700 new cases of AML in China in 2018 and is estimated to reach 24200 in China in 2030.9 About HUTCHMED HUTCHMED (Nasdaq/A?M:HCM; HKEX:13) is an innovative commercial-stage biopharmaceutical company. ?t is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. ?t has approximately 5000 personnel across all its companies at the center of which is a team of about 1800 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 Linked?n. 1Forward-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 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 A?M. 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. 1 ?brahim 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 2010116(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 ?nhibitor ?nduces 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 M?-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia. J Clin ?nvest 2020;130:981–97. 8 National Cancer ?nstitute – seer.cancer.gov/statfacts/html/amyl.html. 9 Lin J Yao D Qian J et al. ?DH1 and ?DH2 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.By Order of the Board Edith Shih Non-executive Director and Company Secretary Hong Kong June 7 2024 As at the date of this announcement the Directors of the Company are: Chairman and Non-executive Director: Non-executive Directors: Dr Dan ELDAR Ms Edith SH?H Ms Ling YANG Executive Directors: Dr Weiguo SU Independent Non-executive Directors: (Chief Executive Officer and Mr Paul Rutherford CARTER Chief Scientific Officer) (Senior ?ndependent Director) Mr CHENG Chig Fung Johnny Dr Renu BHAT?A (Chief Financial Officer) Mr Graeme Allan JACK Professor MOK Shu Kam Tony 2