Initiation of Registration Stage of P2/3 Trial

HUTCHMED Initiates Registration Stage of the ESLIM-02 Phase II/III Trial of Sovleplenib for Warm Antibody Autoimmune Hemolytic Anemia in China

Hong Kong, Shanghai & Florham Park, NJ - Friday, March 22, 2024: HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) today announces that it has 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.

This follows positive data from the proof-of-concept Phase II stage of the trial and subsequent consultation with the China National Medical Products Administration ("NMPA"). If positive, the data from the trial may be used to support a future New Drug Application ("NDA") filing. wAIHA is an autoimmune disorder that can lead to anemia and has limited treatment options. The first Phase III patient received their initial dose on March 20, 2024.

ESLIM-02 is a randomized, double blind, placebo-controlled Phase II/III clinical trial. The objective of the registration stage of the study is to confirm the safety and efficacy of sovleplenib in adult patients with wAIHA. The primary endpoint for the study is the proportion of patients who achieve a durable hemoglobin (Hb) response by Week 24. 21 patients have been enrolled in the study so far and approximately 90 more patients are expected to be enrolled to this registration stage. The lead principal investigators are Dr. Fengkui Zhang of Chinese Academy of Medical Sciences Blood Diseases Hospital, Dr. Bing Han of Chinese Academy of Medical Sciences Peking Union Medical College Hospital and Dr. Liansheng Zhang of Lanzhou University Second Hospital. Additional details may be found at clinicaltrials.gov, using identifier NCT05535933.

About Sovleplenib

Sovleplenib is a novel, investigational, selective small molecule inhibitor for oral administration targeting the spleen tyrosine kinase, also known as Syk. Syk is a major component in B-cell receptor and Fc receptor signaling and is an established target for the treatment of multiple subtypes of B-cell lymphomas and autoimmune disorders. HUTCHMED currently retains all rights to sovleplenib worldwide.

In addition to wAIHA, sovleplenib is also being studied in immune thrombocytopenia ("ITP"). ESLIM-01 (NCT05029635) is a randomized, double-blinded, placebo-controlled Phase III trial in China of sovleplenib in patients with primary ITP that met all its endpoints. ITP is an autoimmune disorder that can lead to increased risk of bleeding. The 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 in planning (NCT06291415).

About wAIHA and Syk

AIHA is an autoimmune disorder characterized by the destruction of red blood cells ("RBCs") due to the production of antibodies against RBC. The incidence of AIHA is estimated to be 0.8-3.0/100,000 adults per year with an estimated prevalence of 17 per 100,000 adults and a death rate of 8%-11%.[1],[2] wAIHA is the most common form of the autoimmune hemolytic diseases,[3] accounting for about 75-80% of all adult AIHA cases.[4]

The accelerated clearance of antibody-coated RBCs by immunoglobulin Fc receptor ("FcR") bearing macrophages is thought to be the pathogenic mechanism in wAIHA.[5] Activation of the FcR is associated with a signaling subunit, FcRγ, whose phosphorylation subsequent to receptor binding results in the recruitment and activation of Syk.[6] Activated Syk mediates downstream signaling of the activated FcRs in phagocytic cells, resulting in phagocytosis of RBCs.[7] In addition, activation of Syk through the B-cell receptor mediates activation and differentiation of B-lymphocytes into antibody secreting plasma cells.[8] Therefore, inhibition of Syk may have potential effects in the treatment of wAIHA through inhibition of phagocytosis and reduction of antibody production.

Medical Information

[1] Eaton WW, Rose NR, Kalaydjian A, Pedersen MG, Mortensen PB. Epidemiology of autoimmune diseases in Denmark. J Autoimmun. 2007; 29 (1):1-9. doi: 10.1016/j.jaut.2007.05.002.

[2] Roumier M, Loustau V, Guillaud C, et al. Characteristics and outcome of warm autoimmune hemolytic anemia in adults: new insights based on a single-center experience with 60 patients. Am J Hematol. 2014; 89 (9):E150-5. doi: 10.1002/ajh.23767.

[3] Cotran Ramzi S, Kumar Vinay, Fausto Nelson, Nelso Fausto, Robbins Stanley L, Abbas Abul K. Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders; 2005. p. 637.

[4] Gehrs BC, Friedberg RC. Autoimmune haemolytic anemia. Am J Hematol. 2002; 69:258-271. doi: 10.1002/ajh.10062.

[6] Braselmann S, Taylor V, Zhao H, et al. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex‐mediated inflammation. J Pharmacol Exp Ther. 2006; 319(3):998‐1008. doi: 10.1124/jpet.106.109058.