ABBISKO-B(02256): A new type of PRMT5*MTA inhibitor ABSK131 has received approval for an IND application from the China CDE.

ABBISKO-B (02256) announced on March 6, 2025, that Shanghai Heyu Biomedical Technology Co., Ltd. today announced that the clinical study application for the highly selective small molecule PRMT5*MTA inhibitor ABSK131 has been approved by the China National Medical Products Administration Drug Evaluation Center. In early December 2024, its IND application was approved by the US FDA. The Phase I clinical study, titled "A Phase I, First-in-Human, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABSK131 in Patients with Advanced/Metastatic Solid Tumors", will be conducted in late-stage solid tumor patients. The study population mainly consists of patients with a gene deletion in methylthioadenosine phosphorylase ("MTAP"). Approximately 15% of solid tumors lack expression of the tumor suppressor gene MTAP. Solid tumors with a high incidence of MTAP loss include non-small cell lung cancer (NSCLC) (15.7%), pancreatic cancer (21.7%), esophageal cancer (28.4%), mesothelioma (32.2%), and gastrointestinal cancer (10.4% gastric cancer and 1% colorectal cancer), with mesothelioma and pancreatic cancer lacking approved targeted therapies. MTAP is involved in coding key rate-limiting enzymes in polyamine and purine metabolism, playing an important role in purine and methionine salvage pathways. MTAP loss leads to the accumulation of its substrate methylthioadenosine (MTA), which then inhibits protein arginine methyltransferase 5 (PRMT5). PRMT5, as an enzyme, catalyzes the transfer of two methyl groups from S-adenosylmethionine (SAM) symmetrically onto arginine residues on proteins, impacting various physiological processes including transcription, RNA splicing, ribosome biogenesis, and cell cycle regulation. PRMT5 exhibits a "synthetic lethality" effect in MTAP-deficient tumors. Recent studies have shown that selectively targeting PRMT5*MTA inhibition may represent a novel therapeutic strategy for MTAP-deficient tumors.