A Multicenter, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HMPL-523, a Syk Inhibitor, in Adult Subjects With Immune Thrombocytopenia

This is an open-label, multicenter study to evaluate the safety, tolerability, and efficacy of HMPL-523 in adult subjects with ITP.

Start Date02 Apr 2024

Sponsor / Collaborator

HUTCHMED (China) Ltd.

CTR20223101 / CompletedPhase 1

单中心、开放、多剂量设计，研究中国成年男性健康受试者多次口服 HMPL-523 片随后单次口服 300 mg/150 μCi [14C]HMPL-523 混悬液后人体内物质平衡的 I 期临床试验

[Translation] A single-center, open-label, multiple-dose phase I clinical trial to investigate the balance of substances in healthy Chinese adult male subjects after multiple oral administration of HMPL-523 tablets followed by a single oral administration of 300 mg/150 μCi [14C]HMPL-523 suspension

主要研究目的：评价中国成年男性健康受试者多次口服 HMPL-523 片、随后单次口服[14C]HMPL-523 混悬液后体内的吸收、代谢和排泄次要研究目的：评价多次口服 HMPL-523 片、随后单次口服[14C]HMPL-523 混悬液在中国成年男性健康受试者中的安全性和耐受性

[Translation]

Primary study objective: To evaluate the absorption, metabolism and excretion of HMPL-523 tablets followed by a single oral dose of [14C]HMPL-523 suspension in healthy Chinese adult male subjects Secondary study objective: To evaluate the safety and tolerability of HMPL-523 tablets followed by a single oral dose of [14C]HMPL-523 suspension in healthy Chinese adult male subjects

Start Date09 Feb 2023

Sponsor / Collaborator

Hutchison MediPharma Ltd.

NCT05781906 / Active, not recruitingPhase 1

Single-center, Open-label, Multi-dose Study to Investigate the Human Mass Balance in Healthy Adult Male Following Multiple Oral Doses of HMPL-523 Tablets Followed by a Single Oral Dose of 300 mg/150 µCi [14C]HMPL-523 Suspension

To evaluate the absorption, metabolism and excretion of HMPL-523 in healthy male Chinese subjects following multiple oral doses of HMPL-523 tablets followed by a single oral dose of [14C]HMPL-523 suspension

Start Date08 Feb 2023

Sponsor / Collaborator

HUTCHMED (China) Ltd.

100 Clinical Results associated with Sovleplenib

100 Translational Medicine associated with Sovleplenib

100 Patents (Medical) associated with Sovleplenib

Literatures (Medical) associated with Sovleplenib

01 Jan 2024·The Journal of pharmacology and experimental therapeutics

Preclinical Pharmacology Characterization of Sovleplenib (HMPL-523), an Orally Available Syk Inhibitor

Article

Author: Sai, Yang ; Cheng, Min ; Xu, Yan ; Dai, Xiaoming ; Li, Xiong ; Cai, Yu ; Jia, Hong ; Ren, Yongxin ; He, Jianlin ; Wang, Jian ; Wu, Zhipeng ; He, Weigang ; Su, Weiguo ; Wang, Guanglin ; Yang, Na ; Dai, Guangxiu

Spleen tyrosine kinase (Syk) is an intracellular tyrosine kinase involved in the signal transduction in immune cells mainly. Its aberrant regulation is associated with diversified allergic disorders, autoimmune diseases and B cell malignancies. Therefore, inhibition of Syk is considered a reasonable approach to treat autoimmune/inflammatory diseases and B cell malignancies. Here we described the preclinical characterization of sovleplenib, a novel, highly potent and selective, oral Syk inhibitor, in several rodent autoimmune disease models. Sovleplenib potently inhibited Syk activity in a recombinant enzymatic assay and Syk-dependent cellular functions in various immune cell lines and human whole blood in vitro. Furthermore, sovleplenib, by oral administration, demonstrated strong in vivo efficacies in murine models of immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and chronic graft-versus-host disease (cGVHD), and a rat model of collagen induced arthritis (CIA) respectively, in a dose-dependent manner. Collectively, these results clearly supported sovleplenib as a therapeutic agent in the treatment of autoimmune diseases. Sovleplenib is being globally developed for ITP (Phase III, NCT05029635, Phase Ib/II, NCT03951623), wAIHA (Phase II/III, NCT05535933) and B-cell lymphoma (Phase I, NCT02857998, NCT03779113). SIGNIFICANCE STATEMENT: Syk is a key mediator of signaling pathways downstream of a wide array of receptors important for immune functions, including the B cell receptor, immunoglobulin receptors bearing Fc receptors. Inhibition of Syk could provide a novel therapeutic approach for autoimmune diseases and hematologic malignancies. The manuscript describes the preclinical pharmacology characterization of sovleplenib, a novel Syk inhibitor, in enzymatic and cellular assays in vitro and several murine autoimmune disease models in vivo.

01 Jun 2023·The Lancet. Haematology

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.

Article

Author: Zhou, Hu ; Leng, Yun ; Yin, Hongyan ; Su, Weiguo ; Yang, Renchi ; Yin, Jie ; Ding, Bingjie ; Shi, Haiyan ; Gong, Yuping ; Luo, Chengwei ; Chen, Wenming ; Wang, Jian ; Liu, Xiaofan ; Hu, Yu ; Mei, Heng ; Li, Yan ; Li, Junmin ; Fan, Songhua ; Ji, Dexiang ; Chen, Keyan ; Gu, Chengyuan ; Sun, Huiping ; Huang, Ruibin

BACKGROUND:

Spleen tyrosine kinase (Syk) inhibitor is a treatment option for primary immune thrombocytopenia. We aimed to evaluate the safety, tolerability, pharmacokinetics, preliminary activity, and recommended phase 2 dose of sovleplenib in patients with primary immune thrombocytopenia.

METHODS:

This randomised, double-blind, placebo-controlled, phase 1b/2 study was conducted at nine hospitals in China. Eligible patients were aged 18-75 years, had an ECOG performance score of 0-1, had primary immune thrombocytopenia for more than 6 months, and did not respond or relapsed after previous first-line treatment or had poor response or postoperative relapse after a splenectomy. Dose-escalation (100 mg, 200 mg, or 300 mg given orally once a day) and dose-expansion phases (recommended phase 2 dose) each consisted of an 8-week, double-blind, placebo-controlled period in which patients were randomly assigned (3:1) to receive sovleplenib or placebo with an interactive web response system followed by a 16-week, open-label period with sovleplenib. Patients, investigators, and the sponsor were masked to treatment allocation during the first 8 weeks. The main efficacy endpoint was the proportion of patients whose platelet count reached 30 × 10⁹ platelets per L or higher and was double of the baseline at two consecutive visits during 0-8 weeks without rescue therapy. Efficacy was evaluated by intention-to-treat. This study is registered with ClinicalTrials.gov, NCT03951623.

FINDINGS:

Between May 30, 2019, and April 22, 2021, 62 patients were assessed for eligibility and 45 (73%) were randomly assigned. Patients received at least one dose of the study drug during the 8-week double-blind period (placebo [n=11] and sovleplenib 100 mg [n=6], 200 mg [n=6], 300 mg [n=16], and 400 mg [n=6]; this group was added following the observation of no protocol-specified safety events at the previous doses). All participants were Asian; 18 (40%) of 45 were male and 27 (60%) were female. The median age was 40·0 years (IQR 33·0-50·0). Ten (29%) of 34 patients in sovleplenib groups versus five (45%) of 11 in the placebo group received concomitant anti-primary immune thrombocytopenia therapy. The recommended phase 2 dose was determined as 300 mg once a day. The proportion of patients who met the main efficacy endpoint were three (50%; 95% CI 12-88) in the 100 mg group, three (50%; 12-88) in the 200 mg group, ten (63%; 35-85) in the 300 mg group, and two (33%; 4-78) in the 400 mg group compared with one (9%; 0-41) in the placebo group. The overall response rate in the 300 mg group was 80% (16 of 20 who received continuous sovleplenib plus those who crossed over from placebo) and the durable response rate was 31% (11-59; five of 16) in the continuous sovleplenib 300 mg and 75% (19-99; three of four) crossed from placebo to sovleplenib during 0-24 weeks. During the 28-day safety evaluation period, two grade 2 or worse treatment-related treatment-emergent adverse events occurred in the sovleplenib groups (hypertriglyceridaemia and anaemia). During 0-8 weeks, the most frequent treatment-emergent adverse events were an increase in blood lactate dehydrogenase, haematuria, and urinary tract infection (seven [21%] of 34 in sovleplenib groups vs one [9%] of 11 in the placebo group); and occult blood-positive and hyperuricaemia (four [12%] vs three [27%] for each). No fatal treatment-emergent adverse events were recorded.

INTERPRETATION:

Sovleplenib was well tolerated, and the recommended phase 2 dose showed a promising durable response in patients with primary immune thrombocytopenia, which provides evidence for future investigations. A phase 3 trial is ongoing (NCT05029635) to confirm the efficacy and safety of sovleplenib in patients with primary immune thrombocytopenia.

FUNDING:

HUTCHMED.

Journal of xenobiotics

Safety and Efficacy of Tyrosine Kinase Inhibitors in Immune Thrombocytopenic Purpura: A Systematic Review of Clinical Trials

Review

Author: Rengarajan, Harish Kumar ; Dhanesar, Gurneel ; Anwar, Muhammad Yasir ; Maroules, Michael ; Hamza, Mohammad ; Ali, Muhammad Ashar ; Aiman, Wajeeha ; Zafar, Maha ; Omar, Zainab

Immune thrombocytopenic purpura (ITP) is an acquired antibody or cell-mediated platelet damage or decreased platelet production. Steroids, IV immunoglobulins (IVIG), and Rho-anti-D antibodies are the commonly used initial treatments for ITP. However, many ITP patients either do not respond or do not maintain a response to initial therapy. Splenectomy, rituximab, and thrombomimetics are the commonly used second-line treatment. More treatment options include tyrosine kinases inhibitors (TKI), including spleen tyrosine kinase (Syk) and Bruton’s tyrosine kinase (BTK) inhibitors. This review aims to assess the safety and efficacy of TKIs. Methods: Literature was searched on PubMed, Embase, WOS, and clinicaltrials.gov using keywords, “tyrosine kinase” and “idiopathic thrombocytopenic purpura”. PRISMA guidelines were followed. Results: In total, 4 clinical trials were included with 255 adult patients with relapsed/refractory ITP. In all, 101 (39.6%) patients were treated with fostamatinib, 60 (23%) patients with rilzabrutinib, and 34 (13%) with HMPL-523. Patients treated with fostamatinib achieved a stable response (SR) and overall response (OR) in 18/101 (17.8%) and 43/101 (42.5%) of the patients, respectively, while SR and OR were achieved in 1/49 (2%) and 7/49 (14%) of the patients, respectively, in the placebo group. Patients treated with HMPL-523 (300 mg dose expansion) achieved an SR and OR in 5/20 (25%) and 11/20 (55%) of the patients, respectively, while SR and OR were achieved in 1/11 (9%) of the patients treated with the placebo. Patients treated with rilzabrutinib achieved an SR in 17/60 (28%) patients. Dizziness (1%), hypertension (2%), diarrhea (1%), and neutropenia (1%) were serious adverse events in fostamatinib patients. Rilzabrutinib or HMPL-523 patients did not require a dose reduction due to drug-related adverse effects. Conclusions: Rilzabrutinib, fostamatinib, and HMPL-523 were safe and effective in the treatment of relapsed/refractory ITP.

News (Medical) associated with Sovleplenib

17 Jun 2024

·www.globenewswire.com

HUTCHMED Highlights Publication of Phase III ESLIM-01 Results in The Lancet Haematology

— 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-RA1 exposure — — Data supported regulatory submission in China accepted in January 2024 — HONG KONG and SHANGHAI and FLORHAM PARK, N.J., June 17, 2024 (GLOBE NEWSWIRE) -- 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 Investor Enquiries+852 2121 8200 / ir@hutch-med.com Media Enquiries Ben Atwell / Alex Shaw, FTI Consulting+44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) / HUTCHMED@fticonsulting.comZhou Yi, Brunswick+852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com Nominated Advisor Atholl Tweedie / Freddy Crossley / Rupert Dearden, Panmure Gordon+44 (20) 7886 2500 _____________________ 1TPO = Thrombopoietin; TPO-RAs = Thrombopoietin receptor agonists.2Hu 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. 2024.3Zufferey A, et al. Pathogenesis and Therapeutic Mechanisms in Immune Thrombocytopenia (ITP). J. Clin. Med. 2017, 6(2), 16.4McMillan R, et al. Self-reported health-related quality of life in adults with chronic immune thrombocytopenic purpura. Am J Hematol. 2008 Feb;83(2):150-4.5Snyder 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):2767-76.6Doobaree IU, et al. Thromboembolism in adults with primary immune thrombocytopenia: a systematic literature review and meta-analysis. Eur J Haematol. 2016 Oct;97(4):321-30.7Sarpatwari 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):1167-75.8Sarpatwari A, et al. Health-related lifestyle in adults and children with primary immune thrombocytopenia (ITP). Br J Haematol. 2010 Oct;151(2):189-91.9Lambert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood. 2017 May 25;129(21):2829-2835.10Clarivate Landscape & Forecast for Immune Thrombocytopenic Purpura, 2018.11Provan D, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780-3817.12Crowley 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).

Phase 3Clinical ResultImmunotherapyBreakthrough TherapyPriority Review

17 May 2024

·www.globenewswire.com

HUTCHMED Highlights Sovleplenib Phase III ESLIM-01 Study and Hematological Malignancy Programs Data to be Presented at the upcoming EHA2024 Congress

May 17, 2024 -- HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that topline and subgroup results from the ESLIM-01 Phase III study of sovleplenib, as well as new and updated data related to novel investigational hematological malignancy therapies HMPL-306, HMPL-760 and tazemetostat, will be presented at the upcoming European Hematology Association (“EHA”) Hybrid Congress, taking place on June 13-16, 2024 in Madrid, Spain and online. ESLIM-01 is a randomized, double-blinded, placebo-controlled Phase III trial in China of sovleplenib in adult patients with primary Immune Thrombocytopenia (“ITP”) who have received at least one prior line of standard therapy (NCT05029635). In 188 patients randomized to receive oral sovleplenib or placebo, sovleplenib demonstrated a clinically meaningful early and sustained durable platelet response in patients with primary ITP with durable response rate of 48.4% compared to zero with placebo (p Most patients were heavily pretreated with a median of four prior lines of ITP therapy and a majority (71.3%) of the patients had received prior TPO/TPO-RA1 treatment. 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, regardless of TPO/TPO-RA treatment types and number of prior regimens. In addition to the promising data in ITP, results from Phase II part of the ongoing ESLIM-02 Phase II/III study (NCT05535933) of sovleplenib for warm antibody autoimmune hemolytic anemia (wAIHA) will also be presented at the congress demonstrating encouraging hemoglobin (Hb) benefit compared with placebo, with overall response rate of 43.8% vs. 0% in the first 8 weeks, and overall response rate of 66.7% during the 24 weeks of sovleplenib treatment (including patients that crossed over from placebo). A favorable safety profile was also demonstrated. Details of the presentations are as follows: 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 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. The content above comes from the network. if any infringement, please contact us to modify.

Clinical ResultImmunotherapy

05 Apr 2024

·www.biospace.com

HUTCHMED Highlights Data to be Presented at AACR Congress 2024

HONG KONG and SHANGHAI, China and FLORHAM PARK, N.J., April 05, 2024 (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 will be presented at the upcoming American Association of Cancer Research (“AACR”) Annual Meeting 2024, taking place on April 5-10, 2024 in San Diego, California. Initial preclinical data will be presented for HMPL-506, a novel, highly potent and differentiated menin-MLL inhibitor for the treatment of certain types of acute leukemia. Compared with five other menin inhibitors in clinical development, HMPL-506 showed the stronger inhibitory potency in MLL-rearranged and NPM1 mutant leukemia cell line models. Furthermore, HMPL-506 in combination with azacytidine, venetoclax or gilteritinib synergistically improved the anti-tumor effect against MLL-rearranged leukemias both in vitro and in vivo. The investigational drug candidate displayed favorable pharmacokinetic pro high selectivity and low risk of cardiac toxicity. A Phase I study of HMPL-506 is planned for the second half of 2024. Initial preclinical data will also be presented for HMPL-A067 (HMA800067), a novel CD38-targeting antibody-drug conjugate (ADC) in which daratumumab was conjugated with cytotoxic payload Monomethyl auristatin E (MMAE) via a novel linker. It demonstrated significant superior anti-tumor activity to daratumumab, including in several B-cell malignancies models with resistance to daratumumab treatment. Other presentations include preclinical data on the ERK 1/2 inhibitor, HMPL-295; early clinical data on the Syk inhibitor, sovleplenib, in lymphoma patients; additional clinical data from global studies of VEGFR inhibitor, fruquintinib, and MET inhibitor, savolitinib; and several investigator-initiated studies of fruquintinib and VEGFR/CSF-1R/FGFR inhibitor, surufatinib. Details of the presentations are as follows: Abstract title Presenter / Lead author Presentation details SPONSORED STUDIES HMPL-506, a novel, highly potent and differentiated menin-MLL inhibitor for the treatment of MLL-rearranged and NPM1mutant acute leukemia in preclinical models Min Cheng, HUTCHMED, Shanghai, China #2113 Poster Session (PO.ET07.02 - Pharmacodynamic Biomarkers of Drug Response) Monday, April 8, 2024 HMPL-A067 (HMA800067), a novel CD38-targeting antibody-drug conjugate (ADC), demonstrated superior anti-tumor activity to daratumumab in preclinical B-cell malignancies models Yan Xu, HUTCHMED, Shanghai, China #1890 Poster Session (PO.ET01.02 - Antibody-Drug Conjugates and Bispectific Antibodies) Monday, April 8, 2024 Preclinical characterization of HMPL-295, a potent and selective ERK1/2 inhibitor Jia Hu, HUTCHMED, Shanghai, China #1661 Poster Session (PO.MCB03.01 - Cell Signaling Components as Therapeutic Targets) Monday, April 8, 2024 Targeting YAP1/TEAD signaling re-sensitizes MAPK/ERK pathway inhibitors in KRAS-driven cancer cells Xianwen Yang, HUTCHMED, Shanghai, China #1931 Poster Session (PO.ET03.04 - Drug Resistance 2: Ras GTPase) Monday, April 8, 2024 Safety and Efficacy of Sovleplenib (HMPL-523), a Syk Inhibitor, in Patients with Relapsed or Refractory Lymphoma Paolo Strati, The University of Texas MD Anderson Cancer Center, USA #CT144 Poster Session (PO.CT01.03 - Phase 0 and Phase I Clinical Trials) Monday, April 8, 2024 Early carcinoembryonic antigen (CEA) dynamics to predict the efficacy of fruquintinib (F) + best supportive care (BSC) in patients with metastatic colorectal cancer (mCRC) enrolled in FRESCO-2 Stefano Lonardi, Veneto Institute of Oncology IOV-IRCCS Padua, Italy #6408 Poster Session (PO.CL01.10 - Predictive Biomarkers 5) Tuesday, April 9, 2024 Savolitinib (savo) + osimertinib (osi) vs savo + placebo (PBO) in patients (pts) with EGFR-mutated (EGFRm), MET-amplified advanced NSCLC with progression on osi James Chih-Hsin Yang, National Taiwan University Hospital and National Taiwan University Cancer Centre, Taipei, Taiwan #CT251 Poster Session (PO.CL01.10 - Predictive Biomarkers 5) Tuesday, April 9, 2024 INVESTIGATOR-INITIATED STUDIES Enhanced anticancer efficacy via ROS-dependent ferroptosis: synergy between surufatinib and cisplatin in small cell lung cancer Xiaolin Li, First Affiliated Hospital of Nanjing Medical University, Nanjing, China #2122 Poster Session (PO.ET07.02 - Pharmacodynamic Biomarkers of Drug Response) Monday, April 8, 2024 Efficacy and underlying mechanisms of surufatinib in non-small cell lung cancer treatment Yanfang Zheng, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China #2126 Poster Session (PO.ET07.02 - Pharmacodynamic Biomarkers of Drug Response) Monday, April 8, 2024 Enhancing Radiosensitivity in Biliary Tract Cancer: The Dual Role of Surufatinib in Tumor Suppression and Macrophage Reprogramming Hong Ma, Wuhan Union Hospital, Wuhan, China #2127 Poster Session (PO.ET07.02 - Pharmacodynamic Biomarkers of Drug Response) Monday, April 8, 2024 Surufatinib treatment in pancreatic cancer: unveiling the role of GPR34 in TAMs and enhancing immunotherapy efficacy Jihui Hao / Song Gao, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China #2128 Poster Session (PO.ET07.02 - Pharmacodynamic Biomarkers of Drug Response) Monday, April 8, 2024 Efficacy and Underlying Mechanisms of Surufatinib Combined with PD-1 Monoclonal Antibody and Chemotherapy in Pancreatic Cancer Guanghai Dai / Ru Jia, Chinese PLA General Hospital (CPLAGH), Beijing, China #2129 Poster Session (PO.ET07.02 - Pharmacodynamic Biomarkers of Drug Response) Monday, April 8, 2024 Optimizing the treatment schedule of radiotherapy combined with VEGFR-TKIs and PD-(L) 1 inhibitors in metastatic colorectal cancer Tao Zhang / Zhenyu Lin, Cancer Center, Union Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China #3827 Poster Session (PO.CL10.04 - Outcome Investigation with Real World Data) Monday, April 8, 2024 Clinical and epidemiological pro neuroendocrine differentiation- A hospital-based retrospective study Susheng Shi / Yaru Wen, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China #4630 Poster Session (PO.ET06.04 - Molecular Classification of Tumors for Diagnostics, Prognostics, and Therapeutic Outcomes) Tuesday, April 9, 2024 Epidemiological characteristics and treatment strategies of gastric cancer with neuroendocrine differentiation (NED) Jun Zhang, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China #4864 Poster Session (PO.PS01.08 - Descriptive Epidemiology and Statistical and Epidemiological Methodology) Tuesday, April 9, 2024 Initial efficacy of surufatinib plus sintilimab and IBI310 for patients with high-grade advanced-neuroendocrine neoplasm: A multicenter, single arm phase 2 study Lin Shen / Ming Lu, Peking University Cancer Hospital and Institute, Beijing, China #CT266 Poster Session (PO.CT02.02 - Phase II Clinical Trials 2) Tuesday, April 9, 2024 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 medicines marketed in China, the first of which is also marketed in the U.S. For more information, please visit: 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 but not limited to its expectations regarding the therapeutic potential of fruquintinib, savolitinib, surufatinib, sovleplenib, HMPL-295, HMPL-506 and HMA800067, the further clinical development for fruquintinib, savolitinib, surufatinib, sovleplenib, HMPL-295, HMPL-506 and HMA800067, its expectations as to whether any studies on fruquintinib, savolitinib, surufatinib, sovleplenib, HMPL-295, HMPL-506 and HMA800067 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, surufatinib, sovleplenib, HMPL-295, HMPL-506 and HMA800067, 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, surufatinib, sovleplenib, HMPL-295, HMPL-506 and HMA800067 for a targeted indication, and the sufficiency of funding. In addition, as certain studies rely on the use of nab-paclitaxel, sintilimab, toripalimab, pemetrexed, platinum, etoposide or cisplatin 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 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 Investor Enquiries +852 2121 8200 / ir@hutch-med.com Media Enquiries Ben Atwell / Alex Shaw, FTI Consulting +44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) / HUTCHMED@fticonsulting.com Zhou Yi, Brunswick +852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com Nominated Advisor Atholl Tweedie / Freddy Crossley / Daphne Zhang, Panmure Gordon +44 (20) 7886 2500

Phase 1ImmunotherapyAACRPhase 2

100 Deals associated with Sovleplenib

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Purpura, Thrombocytopenic, Idiopathic	NDA/BLA	CN	Hutchison MediPharma Ltd.	11 Jan 2024
Autoimmune Haemolytic Anaemias	Phase 3	CN	Hutchison MediPharma Ltd.	26 Sep 2022
Hemorrhage	Phase 1	US	HUTCHMED (China) Ltd.	02 Apr 2024
Hemorrhage	Phase 1	AU	HUTCHMED (China) Ltd.	02 Apr 2024
Hemorrhage	Phase 1	DE	HUTCHMED (China) Ltd.	02 Apr 2024
Hemorrhage	Phase 1	NO	HUTCHMED (China) Ltd.	02 Apr 2024
Hemorrhage	Phase 1	ES	HUTCHMED (China) Ltd.	02 Apr 2024
Skin Manifestations	Phase 1	US	HUTCHMED (China) Ltd.	02 Apr 2024
Skin Manifestations	Phase 1	AU	HUTCHMED (China) Ltd.	02 Apr 2024
Skin Manifestations	Phase 1	DE	HUTCHMED (China) Ltd.	02 Apr 2024

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05029635 (ESLIM-01, EHA2024) Manual	Phase 3	Purpura, Thrombocytopenic, Idiopathic	188	sovleplenib	glhhxxonaz(ydbatokhzq) = tjardxogcc crrcktklig (iqihkfltnj ) View more	Positive	14 May 2024
				Placebo	glhhxxonaz(ydbatokhzq) = jwfdyblpyk crrcktklig (iqihkfltnj ) View more
NCT05535933 (EHA2024) Manual	Phase 2	Autoimmune Haemolytic Anaemias	21	SOVLEPLENIB	txlgwrhnif(vokqkailid) = auldtrnlsb wzgcncckes (cykizbzrjl ) View more	Positive	14 May 2024
				Placebo	txlgwrhnif(vokqkailid) = muepylokjb wzgcncckes (cykizbzrjl ) View more
NCT03779113 (Part 2 of NCT03779113, EHA2024)	Phase 2	Hodgkin's Lymphoma	25	Sovleplenib 700 mg QD	zqsbgpqzrn(ywybwatams) = wbfhdbpqsy sjemkcmnzp (rgaflwbvun ) View more	Positive	14 May 2024
NCT05029635 (ESLIM-01, EHA2024)	Phase 3	Purpura, Thrombocytopenic, Idiopathic	188	Sovleplenib 300 mg	dhohonpbjf(hlapgobpsh) = phldnmqlro odhpqavlfk (ecedxewzmg ) View more	Positive	14 May 2024
				Placebo	cqlssvdwwl(zgvuvsgtua) = rtzvyxglvn jnpaauymbe (yvfuueilfe ) View more
NCT03779113 (AACR2024) Manual	Phase 1	Lymphoma	47	HMPL-523 700 mg QD	zlakxteixx(bhotwgkunh) = alngwjehzt gdddivzeur (vdoznathqa ) View more	Positive	05 Apr 2024
NCT05029635 (ESLIM-01, Corporate Publications) Manual	Phase 3	Purpura, Thrombocytopenic, Idiopathic	188	索乐匹尼布	kmvfjqdgqp(htrbjzdayb) = 该试验成功达到了其主要终点，即与接受安慰剂治疗的患者相比，接受索乐匹尼布治疗的患者的持续应答率取得了具有临床意义和统计学意义的显著改善。 dypkgpqbfr (qvfsnxxaxe ) Met View more	Positive	21 Aug 2023
				安慰剂
NCT03951623 (Pubmed)	Phase 1/2	Purpura, Thrombocytopenic, Idiopathic First line	45	Sovleplenib 300 mg	qskpxeohti(bvpyqhrjlr) = two grade 2 or worse treatment-related treatment-emergent adverse events occurred in the sovleplenib groups ikfoggbpeu (vtrtzwzgjm ) View more	Positive	04 Apr 2023
				Placebo
NCT02857998 (GlobeNewswire) Manual	Phase 1	Purpura, Thrombocytopenic, Idiopathic	45	HMPL-523	yqhkeekdpi(onwnwsvkmd) = No patients discontinued treatment due to treatment-related adverse events wykdykmuks (szwapijawz ) View more	Positive	14 Dec 2021
				Placebo
NCT03779113 (GlobeNewswire) Manual	Phase 1	Lymphoma	21	HMPL-523	icnifnulgw(lvoqdgyebs) = erpcfodrhn xjqcynujnx (xkbtrmjnfr ) View more	Positive	14 Dec 2021
NCT03951623 (ASH2021) Manual	Phase 1	Purpura, Thrombocytopenic, Idiopathic	45	HMPL-523	kcydvzmbjw(yeccetafwk) = leljautnmk ngrghyorem (jukkedlvae )	Positive	05 Nov 2021
				Placebo	zyptkuhkrd(qitxzgwscs) = cdnsxqwvwg vhcackdfqw (pxhwtplyul )

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