Today (February 9), InnoCare announced that ICP-538, its internally discovered VAV1-targeted molecular glue degrader, has been officially approved by the National Medical Products Administration (NMPA) to initiate clinical trials. It is the first VAV1 molecular glue degrader to enter clinical development in China, and the second worldwide.
ICP-538 is a novel, oral, potent and highly selective VAV1-targeted molecular glue degrader. Its mechanism of action is highly innovative: it selectively mediates the formation of a ternary complex between CRBN E3 ubiquitin ligase and VAV1 protein, thereby inducing rapid, dose-dependent degradation of VAV1.

ICP-538 drug list
Picture source: Yaozhi Data-Global Drugs Analysis System
As a key protein in the downstream signaling pathways of T-cell and B-cell receptors, VAV1 plays a central role in immune cell activation, proliferation and cytokine release. By degrading VAV1, ICP-538 effectively inhibits T-cell proliferation, differentiation and activation, while suppressing B-cell activation and inflammatory cytokine secretion. These actions confer anti-inflammatory and immunomodulatory effects, and may alleviate the pathological processes of autoimmune and inflammatory diseases.
Preclinical data strongly support this mechanism: ICP-538 induces robust degradation of VAV1, leading to marked reductions in cytokines linked to immune-mediated disorders, with no detectable effects on other proteins, demonstrating excellent selectivity.
ICP-538 is being developed for multiple refractory autoimmune diseases, including inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE) and multiple sclerosis (MS). These indications affect large patient populations with limited treatment options, representing a substantial unmet medical need.
Notably, no VAV1-targeted therapies have been approved globally to date. With this clinical approval, InnoCare has gained a strong position in the global race for VAV1-targeted drugs. According to public information, the world’s first VAV1 molecular glue degrader to enter the clinic is MRT-6160 from Monte Rosa Therapeutics, which entered into a global exclusive license and commercialization agreement with Novartis worth over $2 billion in October 2024.
Conclusion:
As the first VAV1 molecular glue degrader approved for clinical use in China, ICP-538 represents not only the latest application of targeted protein degradation technology in China’s innovative drug R&D, but also demonstrates the ability of Chinese biopharmaceutical companies to catch up and break through in cutting-edge global therapeutic areas. As clinical trials advance, this innovative therapy is expected to deliver a new treatment option for numerous patients with autoimmune diseases.