— HMPL-A83 is the thirteenth innovative oncology drug candidate discovered in-house by HUTCHMED and its second large molecule drug candidate to enter clinical studies —

Hong Kong, Shanghai & Florham Park, NJ — Friday, July 15, 2022: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM; HKEX:​13) today announces that it has initiated a Phase I trial in China of HMPL-A83, an investigational novel IgG4-type humanized anti-CD47 monoclonal antibody. The first patient received their first dose on July 15, 2022.

The Phase I trial is a multicenter, open-label study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of HMPL-A83 in patients with advanced malignant neoplasms. The primary endpoints are dose-limiting toxicity (DLT), safety, tolerability, recommended phase II dose (RP2D) and maximum tolerated dose (MTD). The secondary endpoints include pharmacokinetics, pharmacodynamics, immunogenicity and preliminary efficacy profile. The lead principal investigators are Dr Ye Guo of Shanghai East Hospital and Dr Yuping Sun of Shandong Cancer Hospital. Additional details may be found at clinicaltrials.gov, using identifier NCT05429008.

Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, said: “HMPL-A83 marks a new chapter in our large molecule and immunotherapy exploration. It is our thirteenth oncology drug candidate to emerge from our innovative in-house discovery platform and it has significant potential to offer new combination therapy opportunities with our existing small molecule portfolio. This approach forms a key part of our multi-pronged strategy to treat cancer and immunological diseases and we are very excited to advance HMPL-A83’s development.”

About HMPL-A83 and CD47

CD47 is a cell surface transmembrane protein that is ubiquitously expressed on virtually all human cells. The overexpression of CD47 is reported in a variety of tumors and is believed to be associated with immune escape from macrophage-mediated phagocytosis.

HMPL-A83 is an investigational IgG4-type humanized anti-CD47 monoclonal antibody that exhibits high affinity for CD47. HMPL-A83 blocks CD47 binding to Signal regulatory protein (SIRP) α and disrupts the “do not eat me” signal that cancer cells use to shield themselves from the immune system.

In preclinical studies, HMPL-A83 demonstrated weak affinity for red blood cells and no induction of hemagglutination, implying low risk of anemia. HMPL-A83 also demonstrated a high affinity for CD47 antigen on tumor cells and strong phagocytosis induction of multiple tumor cells. HMPL-A83 has also demonstrated strong anti-tumor activity in multiple animal models.

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 more than 4,900 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception it has advanced 13 cancer drug candidates from in-house discovery into clinical studies around the world, with its first three oncology drugs now approved and marketed. 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-A83 for patients, its expectations as to whether any studies on HMPL-A83 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 HMPL-A83, 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 HMPL-A83 for a targeted indication; the sufficiency of funding; 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 press release, whether as a result of new information, future events or circumstances or otherwise.

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— 49% ORR amongst SAVANNAH patients with higher MET levels —

Hong Kong, Shanghai & Florham Park, NJ — Wednesday, July 13, 2022: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces the first presentation of results from the ongoing SAVANNAH global Phase II trial at the upcoming International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer (“WCLC”), taking place August 6-9 in Vienna, Austria.

SAVANNAH is a global Phase II study of HUTCHMED and AstraZeneca’s (LSE/​STO/​Nasdaq:​AZN) savolitinib in combination with AstraZeneca’s TAGRISSO^® (osimertinib) in epidermal growth factor receptor (“EGFR”)-mutated non-small cell lung cancer (“NSCLC”) patients with mesenchymal epithelial transition receptor (“MET”) driven tumors, following disease progression on treatment with TAGRISSO^®. In addition to continuing TAGRISSO^® treatment, patients received savolitinib 300mg once daily, 300mg twice daily, or 600mg once daily. A total of 294 patients are enrolled in the study.

The abstract presents results from an analysis of 193 efficacy evaluable patients who received savolitinib 300mg once daily plus TAGRISSO^® 80mg once daily at data cut-off date of August 27, 2021. Qualifying MET aberrations are MET amplification as detected by FISH (MET copy number ≥ 5 and/or MET: CEP signal ratio ≥ 2 [FISH5+]) or MET overexpression as detected by IHC (3+ in ≥ 50% tumor cells [IHC50+]). Additional analysis using an exploratory, higher cut-off level of MET aberration are presented. The higher cut-off levels for MET aberration are MET copy number ≥ 10 (FISH10+) and/or 3+ staining ≥ 90% tumor cells (IHC90+). The prevalence of this higher cut-off levels of MET aberration was 34% of patients centrally tested for enrollment in this study.

Results showed a trend toward improved response rates with increasing level of MET aberration. Across all patients in this analysis, objective response rate (“ORR”) was 32% [95% confidence interval (“CI”): 26-39%], median duration of response (“DoR”) was 8.3 months [95% CI: 6.9-9.7 months], and median progression-free survival (“PFS”) was 5.3 months [95% CI: 4.2- 5.8 months]. These results are consistent with the previously presented results from the TATTON global exploratory study in over 220 EGFR mutation positive NSCLC patients with MET amplified tumors following progression after treatment with any EGFR TKI.

Among the SAVANNAH patients who met the criteria for higher cut-off levels of MET aberration (n=108), ORR was 49% [95% CI: 39-59%], median DoR was 9.3 months [95% CI: 7.6-10.6 months], and mPFS was 7.1 months [95% CI: 5.3-8.0 months]. The safety profile of savolitinib plus TAGRISSO^® was consistent with the known profiles of the combination and each treatment alone.

Findings based on the ongoing SAVANNAH study, and the previously presented TATTON Phase Ib/II study, supported the initiation of the SAFFRON global Phase III study in patients with EGFR-mutated, MET-driven, locally advanced or metastatic NSCLC whose disease progressed on first- or second-line treatment with TAGRISSO^® as the most recent therapy. Patients will be prospectively selected for the higher level of MET aberration. The SAFFRON study will evaluate the efficacy and safety of savolitinib in combination with TAGRISSO^® compared to pemetrexed plus platinum doublet-chemotherapy, the current standard-of-care treatment in this setting. Approximately 324 patients are planned to be randomized. If successful, the multi-regional clinical trial (“MRCT”) may support registration for this combination globally. Two registrational studies are ongoing in China in EGFR mutation positive NSCLC with MET aberrations: the SANOVO study in treatment naïve patients, and SACHI study in patients whose disease progressed following treatment with any EGFR tyrosine kinase inhibitor (“TKI”).

Further details from SAVANNAH will be available at WCLC. Further details of the savolitinib WCLC updates are as follows:

About NSCLC, EGFR and MET Aberrations

Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.^[1] More than a third of the world’s lung cancer patients are in China.^[2] Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.^[3] The majority of NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.^[4],[5]

Approximately 10-25% of NSCLC patients in the U.S. and Europe and 30-40% of patients in Asia have EGFR-mutated NSCLC.^[6],[7],[8] These patients are particularly sensitive to treatment with an EGFR TKI which blocks the cell-signaling pathways that drive the growth of tumor cells.^[9] While an EGFR TKI can provide a durable survival benefit to most patients, the majority will ultimately develop resistance to their first-line treatment, underscoring a great unmet need to tackle acquired resistance in this patient population.^[10]

MET is a tyrosine kinase receptor.^[11] Aberration of MET (amplification or overexpression) is present in both treatment naïve patients as well as being one of the primary mechanisms of acquired resistance to EGFR TKIs for metastatic EGFR-mutated NSCLC.^[12],[13] Approximately 2-3% of NSCLC patients have tumors with MET exon 14 skipping alterations, a targetable mutation in the MET gene.^[14] Among patients who experience disease progression post-osimertinib treatment, approximately 15-50% present with MET aberration.^{[15],[16],[17],[18],[19]} The prevalence of MET amplification and overexpression may differ depending on the sample type, detection method and assay cut-off used.

About Savolitinib (ORPATHYS^® in China)

Savolitinib is an oral, potent, and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations) or gene amplification.

Savolitinib is marketed in China under the brand name ORPATHYS^® for the treatment of patients with NSCLC with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy. 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.

In 2011, following its discovery and initial development by HUTCHMED, 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.

Savolitinib development in NSCLC

Phase II study of savolitinib monotherapy in MET Exon 14 skipping alteration NSCLC (NCT02897479) – The conditional approval in China for MET Exon 14 skipping alteration NSCLC was based on the results of a Phase II study that were published in The Lancet Respiratory Medicine[20]. At a median follow up of 17.6 months, savolitinib demonstrated an ORR of 42.9% (95% confidence interval [CI] 31.1-55.3) and median PFS of 6.8 months (95% CI 4.2-9.6) in the overall trial population. Disease control rate (“DCR”) in the overall trial population was 82.9% (95% CI 72.0-90.8). The safety and tolerability profile of savolitinib was consistent with previous trials, and no new safety signals were identified. Continued approval is contingent upon the successful completion of a confirmatory trial in this patient population (NCT04923945).

Based on results of the TATTON and SAVANNAH studies below, several Phase III studies of savolitinib in combination with TAGRISSO^® have been initiated, including SACHI, SANOVO and SAFFRON.

• SACHI Phase III study of savolitinib in combination with TAGRISSO^® in patients who have progressed following EGFR TKI treatment due to MET amplification (NCT05015608)– Initiated in the second half of 2021, this is a randomized, open-label study in China in EGFR mutated NSCLC patients with MET amplified tumors following progression after treatment with any EGFR TKI.

• SANOVO Phase III study of savolitinib in combination with TAGRISSO^® in treatment-naïve patients with EGFR mutant positive NSCLC with MET overexpression (NCT05009836)– Initiated in the second half of 2021, this is a randomized, double-blinded study in China in untreated, unresectable or metastatic patients with EGFR mutated NSCLC with MET overexpressed tumors.

• SAVANNAH Phase II study of savolitinib in combination with TAGRISSO^® in patients who have progressed following TAGRISSO^® due to MET amplification or overexpression (NCT03778229)– This is an open-label, global study in EGFR mutated NSCLC patients with MET amplified/overexpressed tumors following progression after treatment with TAGRISSO^®. Results were accepted for presentation at the upcoming WCLC annual meeting.

• SAFFRON Phase III study of savolitinib in combination with TAGRISSO^® in patients who have progressed following TAGRISSO^® due to MET amplification or overexpression (NCT05261399) – This is a global Phase III study in patients with EGFR mutated, MET-driven, locally advanced or metastatic NSCLC whose disease progressed on first- or second-line treatment with TAGRISSO^® as the most recent therapy. Patients will be prospectively selected for the higher level of MET aberration. The SAFFRON study will evaluate the efficacy and safety of savolitinib in combination with TAGRISSO^® compared to pemetrexed plus platinum doublet-chemotherapy, the current standard-of-care treatment in this setting. Approximately 324 patients are planned to be randomized. If successful, the MRCT may support registration for this combination globally.

• TATTON Phase Ib/II studies of savolitinib in combination with TAGRISSO^® in patients who have progressed following EGFR TKI treatment due to MET amplification (NCT02143466)– This global exploratory study included over 220 EGFR mutated NSCLC patients with MET amplified tumors following progression after treatment with any EGFR TKI. Results were published in Lancet Oncology^[21] and final analysis was presented at the 2021 World Conference on Lung Cancer^[22]. Three cohorts with patients treated following progression on first- or second-generation EGFR TKI demonstrated an ORR of 64.7-66.7% and a median PFS of 9.0-11.1 months. The cohort of patients treated following progression on a first- and third-generation EGFR TKI demonstrated an ORR of 33.3% (95% CI 22.4-45.7), with a median PFS of 5.5 months (95% CI 4.1-7.7). The combination demonstrated encouraging anti-tumor activity and an acceptable risk-benefit profile.

Savolitinib development in kidney cancer

SAMETA Phase III study in combination with IMFINZI^® PD-L1 inhibitor in MET-driven, unresectable and locally advanced or metastatic papillary renal cell carcinoma (“RCC”) (NCT05043090) – Based on the encouraging results of the SAVOIR monotherapy and CALYPSO combination therapy studies below, we initiated SAMETA, a global Phase III, open-label, randomized, controlled study of savolitinib plus IMFINZI^® versus sunitinib monotherapy versus IMFINZI^® monotherapy in patients with MET-driven, unresectable and locally advanced or metastatic papillary RCC.

SAVOIR randomized, controlled study of savolitinib monotherapy in MET-driven locally advanced or metastatic PRCC (NCT03091192) – Data from 60 patients in this global study of savolitinib monotherapy compared with sunitinib monotherapy in MET-driven papillary RCC was presented at the American Society of Clinical Oncology (“ASCO”) 2020 Program and published simultaneously in JAMA Oncology^[23]. Savolitinib demonstrated encouraging activity, including an ORR of 27% versus 7% for sunitinib, with no savolitinib responding patients experiencing disease progression at data cut-off, and an encouraging OS hazard ratio of 0.51 (95% CI: 0.21–1.17; p=0.110) with the median not reached at data cut-off.

CALYPSO study of savolitinib in combination with IMFINZI^® PD-L1 inhibitor in RCC (NCT02819596) – This investigator initiated open-label Phase I/II study of savolitinib in combination with IMFINZI^®, a PD-L1 antibody owned by AstraZeneca, evaluated the safety and efficacy of the savolitinib/IMFINZI^® combination in patients with RCC. An analysis of 41 papillary RCC patients was presented at the 2021 ASCO Annual Meeting^[24], showing a confirmed response rate in 8 out of the 14 MET-driven patients, or 57%, with a median DoR of 9.4 months, median PFS of 10.5 months and median OS of 27.4 months. No new safety signals were seen.

Savolitinib development in gastric cancer and other cancer indications

Phase II study of savolitinib monotherapy in advanced or metastatic MET amplified gastric cancer (“GC”) or adenocarcinoma of the gastroesophageal junction (“GEJ”) (NCT04923932) – This is an open-label, two-cohort, multi-center study to evaluate the efficacy, safety and pharmacokinetics of savolitinib in locally advanced or metastatic GC or GEJ patients whose disease progressed after at least one line of standard therapy.

This trial follows multiple Phase II studies that have been conducted in Asia to study savolitinib in MET-driven GC patients, including VIKTORY^[25]. VIKTORY is an investigator-initiated Phase II umbrella study in GC in South Korea in which a total of 715 patients were successfully sequenced into molecular-driven patient groups, including those with MET amplified GC. Patients whose tumors harbor MET amplification were treated with savolitinib monotherapy, reporting an ORR of 50% (10/20, 95% CI: 28.0, 71.9).

Savolitinib opportunities are also continuing to be explored in multiple other MET-driven tumor settings via investigator-initiated studies including colorectal cancer.

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 more than 4,900 personnel across all its companies, at the center of which is a team of over 1,800 in oncology/immunology. Since inception it has advanced 12 cancer drug candidates from in-house discovery into clinical studies around the world, with its first three oncology drugs now approved and marketed. 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 patients with NSCLC, the further clinical development of savolitinib in this and other indications, its expectations as to whether clinical studies of 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 the sufficiency of HUTCHMED’s data to support New Drug Application approval of savolitinib for the treatment of patients with NSCLC in China, the U.S., E.U., Japan or other jurisdictions, the safety profile of savolitinib, the potential for savolitinib to become a new standard of care for patients with NSCLC and other types of cancer, its ability to implement and complete its further clinical development plans for savolitinib, the potential commercial launch of savolitinib in the U.S., E.U., Japan, China and other jurisdictions, the timing of these events, and the impact of the COVID-19 pandemic on general economic, regulatory and political conditions. In addition, as certain studies rely on the use of TAGRISSO^® and IMFINZI^® as combination therapeutics with savolitinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of TAGRISSO^® and IMFINZI^®. 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 with 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.

[1]  World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at gco.iarc.fr/​today/​data/​factsheets/​cancers/​15-Lung-fact-sheet.pdf. Accessed June 2021.
[2] World Health Organization. International Agency for Research on Cancer. Globocan China Fact Sheet 2020. Available at gco.iarc.fr/​today/​data/​factsheets/​populations/160-china-fact-sheets.pdf. Accessed June 2021.
[3]  LUNGevity Foundation. Types of Lung Cancer. Available at lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer. Accessed June 2021.
[4]  Cagle PT, Allen TC, Olsen RJ. Lung Cancer Biomarkers: Present Status and Future Developments. Arch Pathol Lab Med. 2013;​137(9):​1191-1198. doi: 10.5858/arpa.2013-0319-CR.
[5]  Le Chevalier T, et al. Adjuvant Chemotherapy for Resectable Non-Small Cell Lung Cancer: Where is it Going? Ann Oncol. 2010;21:vii196-vii198. doi: 10.1093/annonc/mdq376.
[6]  Zhang YL, 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):78985-78993. doi: 10.18632/oncotarget.12587.
[7]  Keedy V.L., 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.
[8] Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol. 2013:66;79-89. doi: 10.1136/jclinpath-2012-201194.
[9] Cross DA, et al. AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer. Cancer Discov. 2014;4(9):1046-1061. doi: 10.1158/2159-8290.CD-14-0337.
[10] Soria JC, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(2):113-125. doi:10.1056/NEJMoa1713137
[11] Organ SL, Tsao MS. An overview of the c-MET signaling pathway. Ther Adv Med Oncol 2011; 3(1 Suppl):S7-S19. doi: 10.1177/​1758834011422556.
[12] Ramalingham SS, et al. Mechanisms of acquired resistance to first-line osimertinib: Preliminary data from the phase III FLAURA study.  Ann Oncol. 2018; 29, SUPPLEMENT 8, VIII740. doi: 10.1093/annonc/mdy424.063.
[13] Sterlacci W, et al. MET overexpression and gene amplification: prevalence, clinico-pathological characteristics and prognostic signific­ance in a large cohort of patients with surgically resected NSCLC. Virchows Arch. 2017;471(1):49-55. doi:10.1007/s00428-017-2131-1.
[14] Vuong 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.
[15] Soria JC, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(2):113-125. doi:10.1056/NEJMoa1713137.
[16] Mok TS, et al. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017;376(7):629-640. doi:10.1056/NEJMoa1612674.
[17] Hartmaier R, et al. Tumor genomics in patients (pts) with advanced epidermal growth factor receptor mutant (EGFRm) non-small cell lung cancer (NSCLC) whose disease has progressed on first-line (1L) osimertinib therapy in the Phase II ORCHARD study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; Abstract nr LB078 / 3.
[18] Piotrowska, et al.  MET amplification (amp) as a resistance mechanism to osimertinib. Journal of Clinical Oncology 2017 35:15_suppl, 9020-9020
[19] Hartmaier, et al. Detection of MET-mediated EGFR tyrosine kinase inhibitor (TKI) resistance in advanced non-small cell lung cancer (NSCLC): biomarker analysis of the TATTON study. Cancer Res (2019) 79 (13_Supplement): 4897.doi: 10.1158/1538-7445.AM2019-4897.
[20] Lu S, et al. Once-daily savolitinib in Chinese patients with pulmonary sarcomatoid carcinomas and other non-small-cell lung cancers harbouring MET exon 14 skipping alterations: a multicentre, single-arm, open-label, phase 2 study. Lancet Respir Med. 2021 Jun 21:S2213-2600(21)00084-9. doi: 10.1016/S2213-2600(21)00084-9.
[21] Sequist LV, et al. Osimertinib plus savolitinib in patients with EGFR mutation-positive, MET-amplified, non-small-cell lung cancer after progression on EGFR tyrosine kinase inhibitors: interim results from a multicentre, open-label, phase 1b study. Lancet Oncol. 2020;21(3):373-386. doi:10.1016/S1470-2045(19)30785-5.
[22] Han JY, et al. Osimertinib + savolitinib in patients with EGFRm MET-amplified/overexpressed NSCLC: Phase Ib TATTON Parts B and D final analysis.  WCLC January 2021 #FP14.03. doi: 10.1016/j.jtho.2021.01.146.
[23] Choueiri TK, et al. Efficacy of Savolitinib vs Sunitinib in Patients With MET-Driven Papillary Renal Cell Carcinoma: The SAVOIR Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Aug 1;6(8):1247-1255. doi: 10.1001/jamaoncol.2020.2218.
[24] Suarez C, et al. Clinical activity of durvalumab and savolitinib in MET-driven, metastatic papillary renal cancer. J Clin Oncol 39, no. 15_suppl (May 20, 2021) 4511-4511. doi: 10.1200/JCO.2021.39.15_suppl.4511.
[25] Lee J, 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-19-0442.

CONTACTS

San Diego, Shanghai, Hong Kong and Sydney — Wednesday, July 6, 2022: Inmagene Biopharmaceuticals (“Inmagene“) and HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM; HKEX:​13) announce today that the first participant, based in Australia, was dosed in a global Phase I trial of IMG-007, an investigational OX40 antagonistic monoclonal antibody.

The Phase I study is a multi-stage, double-blind, randomized, placebo-controlled, dose-escalation study in healthy volunteers, and a dose-escalation and parallel design, multiple-dose study in adult patients with moderate to severe atopic dermatitis. The study will be used to evaluate the safety, tolerability and efficacy of IMG-007 in patients with atopic dermatitis. Additional details will be found at clinicaltrials.gov, using identifier NCT05353972.

“Dosing the first participant is an important milestone for the IMG-007 program,” said Dr Jonathan Wang, Chairman and Chief Executive Officer of Inmagene. “We hope the data will help us demonstrate that IMG-007 is one of the strongest OX40 antagonist drug candidates worldwide.”

Dr Jean-Louis Saillot, Chief Development Officer of Inmagene, said, “IMG-007 blocks the OX40 activity and has demonstrated high potency in preclinical studies, indicating a best-in-class potential. We welcome the start of the IMG-007 clinical program with the hope of developing an innovative, safe and effective treatment option for patients with atopic dermatitis and other immunological diseases.”

Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, said: “This is an exciting step towards taking our novel drug candidates into immunological diseases, where Inmagene has significant expertise, as we work to maximize the impact of our drug discovery engine.”

About IMG-007

IMG-007 is a novel antagonistic monoclonal antibody targeting the OX40 receptor. It was originally discovered by HUTCHMED, with Inmagene assuming development responsibility at the candidate stage. Inmagene has an exclusive option to in-license IMG-007’s global rights.

About OX-40 and Atopic Dermatitis

OX40 is a costimulatory receptor member of the tumor necrosis factor receptor (TNFR) superfamily expressed predominantly on activated T cells. The ligation of OX40 by its ligand OX40L leads to enhanced T cell survival, proliferation, and effector functions. Preclinical research results show that IMG-007 can bind to human OX40 receptor with high affinity, thereby inhibit the binding of OX40 to OX40L, reducing OX40L-dependent downstream signaling and cytokine release by OX40+ T cells. By selectively shutting down OX40+ T cell function, IMG-007 may provide a treatment option for pathological OX40+ T cell-mediated immune diseases, such as atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin condition that is estimated to affect 8-19% of children and 2-5% of adults in US, Europe, and East Asia.^[1],[2],[3]

About Inmagene

Inmagene is a global clinical-stage biotechnology company focused on developing novel therapeutics for immunology-related diseases. The company is building a robust pipeline of nearly twenty drug development programs.

Inmagene’s most advanced drug candidate is IMG-020 (izokibep), which has successfully met the endpoints in global phase II studies for both psoriasis and psoriatic arthritis (“PsA”). It has received the IND approval from the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) for phase III studies in plaque psoriasis. Inmagene is working with its partners to conduct global phase II studies for multiple autoimmune diseases, including PsA, ankylosing spondylitis (AS) and uveitis. In addition, IMG-004 and IMG-007, both of which with global rights, are in global phase I studies.

Believing in “Borderless Innovation”, the Inmagene team strives to integrate efficient resources worldwide to develop novel therapeutics for global patients. Based on its proprietary QuadraTek™ drug discovery platform, Inmagene is operating 12 “Smart Innovation” programs to create and develop drug candidates with global rights. Inmagene also in-licenses drug candidates and, together with its partners, carries out global development activities, including global multi-center clinical trials. Inmagene has formed strategic partnerships with multiple partners, such as HUTCHMED and Affibody AB, to develop highly innovative drug candidates. For more information, please visit: www.inmagenebio.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 more than 4,900 personnel across all its companies, at the center of which is a team of over 1,800 in oncology/immunology. Since its inception, 13 drug candidates from in-house discovery have entered into clinical studies around the world, with the 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 Inmagene’s and/or HUTCHMED’s current expectations regarding future events, including expectations regarding the therapeutic potential of IMG-007 for the treatment of patients with atopic dermatitis and other immunological diseases, the further clinical development of IMG-007, expectations as to whether clinical studies of IMG-007 would meet their primary or secondary endpoints, and 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 IMG-007 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 IMG-007 for a targeted indication; the sufficiency of funding; 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 various risks applicable to HUTCHMED, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, on AIM and with The Stock Exchange of Hong Kong Limited. Neither Inmagene nor HUTCHMED undertakes to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

[1] Silverberg JI, Barbarot S, Gadkari A, et al. Atopic dermatitis in the pediatric population: A cross-sectional, international epidemiologic study. Ann Allergy Asthma Immunol. 2021;126(4):417-428.e2. doi:10.1016/j.anai.2020.12.020
[2] Barbarot S, Auziere S, Gadkari A, et al. Epidemiology of atopic dermatitis in adults: Results from an international survey. Allergy. 2018;73(6):1284-1293. doi:10.1111/all.13401
[3] Stander S. Atopic Dermatitis. N Engl J Med. 2021;384(12):1136-1143. doi:10.1056/NEJMra2023911

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