c-Met

EpiTAC platform can also combine with drug payload delivery to deepen anti-tumor activity and reach broader tumor indications, supporting first-in-class potential SAN MATEO, CA, USA I April 28, 2025 I EpiBiologics , a leader in tissue-selective extracellular protein degradation, today presented the first preclinical data on its EpiTAC bispecific antibody degrader of c-Met, a potential first-in-class therapy for a range of cancers driven by mutated, amplified, or overexpressed c-Met signaling. The data, which were presented in a poster at the American Association for Cancer Research (AACR) Annual Meeting, show that c-Met degrading EpiTACs demonstrate strong anti-tumor activity in vivo and as ADCs, combining c-Met degradation with payload-dependent cell killing to broaden the clinical opportunity into tumors that are not solely dependent on c-Met signaling for survival. c-Met is a receptor tyrosine kinase that acts as both a pathogenic driver and disease marker in multiple tumor types, including non-small cell lung cancer (NSCLC), gastric cancer, colorectal cancer and renal cancer. While tyrosine kinase inhibitors are approved for tumors with c-Met mutations, targeted therapies for c-Met-amplified or -overexpressed tumors are lacking, hampered by the need for high levels of c-Met expression and variable dependency on c-Met for tumor cell survival and proliferation. Key highlights of EpiBiologics’ data include: “We’re pleased to share data from our c-Met EpiTAC program, confirming our platform’s ability to drive deep and durable degradation with therapeutically relevant impact. These data underscore how we can flexibly tune EpiTACs to have specific characteristics that solve the limitations of current clinical therapies,” said Shyra Gardai, Ph.D., Chief Scientific Officer of EpiBiologics. “Additionally, this dataset showed that there is exciting potential, in certain therapeutic settings, for augmenting our bispecific antibodies with a cytotoxic payload to drive even broader patient benefit.” “c-Met represents one of several important targets in our pipeline of EpiTAC bispecific antibodies,” said Ann Lee-Karlon, Ph.D., Chief Executive Officer of EpiBiologics. “As our lead tissue-selective EGFR degrader moves rapidly toward the clinic, we are also advancing EpiTACs for membrane, soluble, and GPCR targets. We have demonstrated strong single-agent activity and can successfully combine with current standards-of-care, paving the way for future therapies.” The poster, entitled “Discovery of c-MET degrading bispecific antibodies (EpiTACs) for NSCLC and other c-MET driven tumors,” will be available on the company’s website here when presentation concludes. About EpiBiologics EpiBiologics is advancing a next-generation protein degradation pipeline and platform that targets membrane and extracellular proteins. EpiBiologics was founded on pioneering work from scientific founder Dr. Jim Wells of the University of California, San Francisco (UCSF). The Company’s proprietary EpiTAC platform is a modular bispecific antibody system that enables targeted degradation of disease-driving membrane and extracellular proteins in a tissue-specific manner. Preclinical anti-tumor data support the innovative EpiTAC approach to extracellular protein degradation as the company advances toward the clinic. Headquartered in the San Francisco Bay Area, EpiBiologics is backed by leading healthcare investors and aims to develop first-in-class and best-in-class targeted therapies across multiple therapeutic areas, including oncology and immunology. For more information, please visit epibiologics.com and follow us on LinkedIn . SOURCE: EpiBiologics

HONG KONG and SHANGHAI and FLORHAM PARK, N.J., April 24, 2025 (GLOBE NEWSWIRE) -- HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM; HKEX:​13) today announces that new and updated data from several studies of compounds discovered by HUTCHMED including savolitinib, fruquintinib and surufatinib, which will be presented at the upcoming American Association of Cancer Research (AACR) Annual Meeting 2025, taking place on April 25-30, 2025 in Chicago, Illinois. Details of the presentations are as follows: Abstract titlePresenter / Lead authorPresentation detailsSPONSORED STUDIESTargeting KEAP1/NRF2 signaling sensitizes KRAS-driven NSCLC to KRAS inhibitorsXianwen Yang, HUTCHMED, Shanghai, China4450Poster Session (PO.ET03.04)Tuesday, April 29, 2025SAVANNAH: Clearance of plasma EGFRm in patients with EGFRm MET-overexpressed (OverExp) and/or -amplified (Amp) NSCLC post-osimertinib (osi) treated with savolitinib (savo) + osiJonathan W. Riess, University of California, UC Davis Comprehensive Cancer Center, CA, USLB416Late-Breaking Poster Session(LBPO.CL04)Wednesday, April 30, 2025A phase I open-label positron-emission tomography study to determine brain exposure of [11C]savolitinib in healthy volunteersKowser Miah, AstraZeneca, Waltham, MA, US4353Poster Session (PO.ET07.01)Tuesday, April 29, 2025 INVESTIGATOR-INITIATED STUDIESA multi-cohort study of treatment regimens for metastatic colorectal cancer (mCRC): Subgroup analysis of sequential therapy between fruquintinib and regorafenibWangxia Lv, Cancer Hospital of the University of Chinese Academy of Sciences/ Zhejiang Cancer Hospital, Hangzhou, ChinaCT085Poster Session (PO.CT02.03)Monday, April 28, 2025Phase Ib/II study of fruquintinib (F) combined with capecitabine (C) as maintenance therapy (MT) for RAS/BRAF wild-type metastatic colorectal cancer (mCRC) after first-line treatment with cetuximab combined with chemotherapyLin Yang/ Kai Ou, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaCT222Poster Session (PO.CT02.02)Tuesday, April 29, 2025Tyrosine kinase inhibitor (TKI) plus PD-1 blockade in TKI-responsive MSS/pMMR metastatic colorectal adenocarcinoma (mCRC): Results of a multicenter, phase II trial (TRAP)Jingdong Zhang/ Qian Dong, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology, Shenyang, China6002Poster Session (PO.CL08.03)Tuesday, April 29, 2025Efficacy and mechanism of radiotherapy combined with fruquintinib and tislelizumab in mCRCXianglin Yuan, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China1828Poster Session (PO.ET08.02)Monday, April 28, 2025Prediction of surufatinib treatment outcome in advanced grade 3 neuroendocrine tumors (NET G3) patientsJing Hao, Qilu Hospital of Shandong University, Jinan, ChinaCT084Poster Session (PO.CT02.03)Monday, April 28, 2025Surufatinib and sintilimab in combination with capecitabine for previously treated metastatic small bowel adenocarcinoma or appendiceal carcinoma: A single-arm, single-center, phase Ib/II trialYanhong Deng/ Xiaoyu Xie, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaCT033Poster Session (PO.CT01.03)Monday, April 28, 2025GPR34-driven damage-response macrophages underlie therapeutic resistance to surufatinibSong Gao, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China6818Poster Session (PO.ET07.02)Wednesday, April 30, 2025Efficacy and mechanism of surufatinib combination with PD-1 monoclonal antibody and chemotherapy for the treatment of pancreatic cancer with liver metastasis in animal modelsGuanghai Dai/ Ru Jia, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China6824Poster Session (PO.ET07.02)Wednesday, April 30, 2025Efficacy and mechanistic insights of Shengyang Qushi Decoction in managing surufatinib-associated diarrheaHuangying Tan, China-Japan Friendship Hospital, Beijing, China1043Poster Session (PO.PR02.03)Sunday, April 27, 2025 About Lung Cancer Lung cancer is the leading cause of cancer death, accounting for about one-fifth of all cancer deaths.1 More than a third of the world’s lung cancer patients are in China. Lung cancer is broadly split into non-small cell lung cancer (“NSCLC”) and small cell lung cancer, with NSCLC accounting for about 80% of cases.2 Approximately 10-15% of NSCLC patients in the US and Europe and 30-40% of patients in Asia have an epidermal growth factor receptor (“EGFR”) mutation (“EGFRm”).3,4,5,6 Approximately 2-3% of NSCLC patients have tumors with MET exon 14 skipping alterations, a targetable mutation in the MET gene.7 About Savolitinib and MET Aberrations in Lung Cancer Savolitinib is an oral, potent, and highly selective MET tyrosine kinase inhibitor (“TKI”) being jointly developed by AstraZeneca and HUTCHMED and commercialized by AstraZeneca. MET is a tyrosine kinase receptor that has an essential role in normal cell development.8 Savolitinib 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. MET overexpression and/or amplification can lead to tumor growth and the metastatic progression of cancer cells, and is a known mechanism of acquired resistance to EGFR TKIs.8,9 The prevalence of MET depends on the sample type, detection method and assay cut-off used. Savolitinib is approved in China and is marketed under the brand name ORPATHYS® by AstraZeneca for the treatment of adult patients with locally advanced or metastatic NSCLC with MET exon 14 skipping alteration, representing the first selective MET inhibitor approved in China. It is currently under clinical development for multiple tumor types, including lung, kidney, and gastric cancers as a single treatment and in combination with other medicines. About Savolitinib in combination with TAGRISSO® (osimertinib) Among patients who experience disease progression following treatment with a third-generation EGFR TKI, approximately 15-50% present with MET aberration, depending on the sample type, detection method and assay cut-off used. TAGRISSO® is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system metastases. Treatment with savolitinib in combination with TAGRISSO® has been studied extensively in these patients in the TATTON (NCT02143466) and SAVANNAH (NCT03778229) studies. The encouraging results led to the initiation of several Phase III trials in this setting including the SACHI trial in China (NCT05015608) and the global SAFFRON trial (NCT05261399), as well as the SANOVO trial in China (NCT05009836). This combination represents a promising chemo-free oral treatment strategy to address mechanisms of resistance in this advanced setting. Positive data from the SACHI randomized Phase III trial has led to the filing of a second New Drug Application (“NDA”) in China. Strong data from the SAVANNAH single-arm Phase II study was recently presented at the European Lung Cancer Congress (ELCC) in March 2025 demonstrated high, clinically meaningful and durable objective response rate (ORR), with consistent safety results. The SAFFRON randomized Phase III trial is progressing. Following AstraZeneca’s consultation with the US Food and Drug Administration (“FDA”), we look forward to completing the SAFFRON trial as soon as possible to support potential US and other global registration filings. SACHI: The SACHI China Phase III trial met the primary endpoint of progression free survival (PFS) during its interim analysis towards the end of 2024 and a NDA was accepted and granted Breakthrough Therapy Designation and Priority Review status in China in December 2024. SACHI evaluated the combination of savolitinib and TAGRISSO® for the treatment of patients with EGFRm, MET-amplified locally advanced or metastatic NSCLC after progression on EGFR TKI compared to platinum-based doublet chemotherapy. Results will be presented at an upcoming scientific conference. SAFFRON: In 2023, savolitinib and TAGRISSO® received Fast Track Designation from the US FDA in this setting. The global SAFFRON Phase III trial is currently ongoing to assess the savolitinib plus TAGRISSO® combination versus platinum-based doublet chemotherapy in patients with EGFRm, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following progression on treatment with TAGRISSO®. Patients are being prospectively selected using the high MET level cut-off identified in SAVANNAH. 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. Since inception it 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 around the world including in the US, Europe and Japan. 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 US Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including but not limited to its expectations regarding the therapeutic potential of fruquintinib, savolitinib and surufatinib, the further clinical development for fruquintinib, savolitinib and surufatinib, its expectations as to whether any studies on fruquintinib, savolitinib and surufatinib would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates and the timing and availability of subjects meeting a study’s inclusion and exclusion criteria; changes to clinical protocols or regulatory requirements; unexpected adverse events or safety issues; the ability of fruquintinib, savolitinib and surufatinib, including as combination therapies, to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions and to gain commercial acceptance after obtaining regulatory approval; the potential markets of fruquintinib, savolitinib and surufatinib for a targeted indication, and the sufficiency of funding. In addition, as certain studies rely on the use of osimertinib, capecitabine, sintilimab or tislelizumab, as combination therapeutics, such risks and uncertainties include assumptions regarding their safety, efficacy, supply and continued regulatory approval. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the US 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 Investor Enquiries+852 2121 8200 / ir@hutch-med.com Media Enquiries FTI Consulting –+44 20 3727 1030 / HUTCHMED@fticonsulting.comBen Atwell / Alex Shaw+44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile)Brunswick – Zhou Yi+852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com Panmure LiberumNominated Advisor and Joint BrokerAtholl Tweedie / Freddy Crossley / Rupert Dearden+44 20 7886 2500 HSBCJoint BrokerSimon Alexander / Alina Vaskina / Arnav Kapoor+44 20 7991 8888 CavendishJoint BrokerGeoff Nash / Nigel Birks+44 20 7220 0500 ________________________REFERENCES 1World Health Organization. International Agency for Research on Cancer. All cancers fact sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/39-all-cancers-fact-sheet.pdf. Accessed November 2022.2American Cancer Society. What is Lung Cancer? Available at: https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html. Accessed November 2022.3Knight SB, et al. Progress and prospects of early detection in lung cancer. Open Biol. 2017;7(9): 170070. DOI: 10.1098/RSOB.170070.4Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011:29;2121-27. DOI: 10.1200/JCO.2010.31.8923.5Zhang Y, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(48). DOI: 10.18632/oncotarget.12587.6Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in 11. Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol. 2013:6;2800-12. PMID: 24294366.7Vuong HG, et al. Clinicopathological implications of MET exon 14 mutations in non-small cell lung cancer – A systematic review and meta-analysis. Lung Cancer. 2018; 123: 76-82. DOI: 10.1016/j.lungcan.2018.07.006.8Uchikawa E, et al. Structural basis of the activation of c-MET receptor. Nat Commun. 2021;12(4074). DOI: 10.1038/s41467-021-24367-3.9Wang Q, et al. MET inhibitors for targeted therapy of EGFR TKI-resistant lung cancer. Journal of Hematology & Oncology. 2019;63. DOI: 10.1186/s13045-019-0759-9.

HONG KONG and FLORHAM PARK, N.J., April 22, 2025 (GLOBE NEWSWIRE) -- HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM; HKEX:​13) today announces that it has completed enrollment of the registration phase of its Phase II trial of savolitinib in gastric cancer patients with MET amplification. This clinical trial 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 gastroesophageal junction (“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. A total of 64 patients have been enrolled in the study. Further details may be found at clinicaltrials.gov using identifier NCT04923932. As reported at the American Association for Cancer Research Annual Meeting, interim results from the study showed a 45% ORR confirmed by IRC and a 50% ORR in patients with high MET gene copy number. 4-month duration of response (DOR) rate was 85.7% with median follow up time of 5.5 months. The most common grade 3 or higher treatment-related adverse events (“TRAE”) (≥ 5%) were platelet count decreased, hypersensitivity, anemia, neutropenia and hepatic function abnormal. Only one patient discontinued treatment due to grade 4 liver function abnormal (TRAE) and no patient died due to TRAE. The China’s National Medical Products Administration (“NMPA”) has granted Breakthrough Therapy Designation to savolitinib for the treatment of locally advanced or metastatic gastric cancer or GEJ adenocarcinoma patients with MET amplification who have failed at least two lines of standard therapies. If positive, HUTCHMED may initiate plans to apply for marketing authorization of savolitinib for gastric cancer in China in late 2025. About Gastric Cancer with MET Amplification MET-driven gastric cancer has a very poor prognosis.1 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 18,000 in China.4 The ongoing registration trial follows multiple Phase II studies conducted in Asia to study savolitinib in MET-driven gastric cancer patients, including VIKTORY.3 The VIKTORY study reported a 50% ORR in patients whose tumors harbored MET amplification and were treated with savolitinib monotherapy. About Savolitinib Savolitinib is an oral, potent, and highly selective MET tyrosine kinase inhibitor (“TKI”) being jointly developed by AstraZeneca and HUTCHMED and commercialized by AstraZeneca. MET is a tyrosine kinase receptor that has an essential role in normal cell development.5 Savolitinib 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 approved in China and is marketed under the brand name ORPATHYS® by our partner, AstraZeneca, for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping alteration, representing the first selective MET inhibitor approved in China. It has been included in the National Reimbursement Drug List of China (NRDL) since March 2023. It is currently under clinical development for multiple tumor types, including lung, kidney, and gastric cancers as a single treatment and in combination with other medicines. About HUTCHMED HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. Since inception it 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 around the world including in the US, Europe and Japan. 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 US Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of savolitinib, the further clinical development for savolitinib, its expectations as to whether any studies on savolitinib would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates and the timing and availability of subjects meeting a study’s inclusion and exclusion criteria; changes to clinical protocols or regulatory requirements; unexpected adverse events or safety issues; the ability of savolitinib, including as a combination therapy, to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions and to gain commercial acceptance after obtaining regulatory approval; the potential market of savolitinib for a targeted indication and the sufficiency of funding. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the US 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 Investor Enquiries+852 2121 8200 / ir@hutch-med.com Media Enquiries FTI Consulting –+44 20 3727 1030 / HUTCHMED@fticonsulting.comBen Atwell / Alex Shaw +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile)Brunswick – Zhou Yi+852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com Panmure LiberumNominated Advisor and Joint BrokerAtholl Tweedie / Freddy Crossley / Rupert Dearden+44 20 7886 2500 HSBCJoint BrokerSimon Alexander / Alina Vaskina / Arnav Kapoor+44 20 7991 8888 CavendishJoint BrokerGeoff Nash / Nigel Birks+44 20 7220 0500 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.304372 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-19-0443 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-18-13374 Global Cancer Observatory. China Fact Sheet. https://gco.iarc.who.int/media/globocan/factsheets/populations/160-china-fact-sheet.pdf. Accessed April 7, 2025.5 Uchikawa E, et al. Structural basis of the activation of c-MET receptor. Nat Commun. 2021;12(4074).