CASI Pharmaceuticals, Inc. announced that the China National Medical Products Administration (NMPA) has approved the Company's Clinical Trial Application (CTA) for CB-5339, a first-in-class VCP/p97 inhibitor from Cleave Therapeutics. CASI is planning a Phase 1 development program in China of CB-5339 as a single agent to evaluate the PK/safety profile, select the Recommended Phase 2 Dose, and assess early signs of clinical efficacy. The Phase 1 development program is expected to start in 2023.

CB-5339 is an oral second-generation, small molecule VCP/p97 inhibitor, and is currently being evaluated by Cleave Therapeutics in a Phase 1 clinical trial in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (NCT04402541). VCP/p97 inhibitors exploit molecular features that define cancer cell growth and metabolism. VCP/p97 plays a critical role in protein homeostasis processes such as endoplasmic reticulum associated degradation (ERAD) and chromatin-associated degradation (CAD), as well as the DNA damage response (DDR).

These key cellular stress pathways are known to represent sensitivities critical to cancer cell survival. Cellular stress provides an attractive means of targeting non-oncogene addiction as a way to combat tumor heterogeneity and emerging resistance to targeted therapies. Such an approach has the added benefit of broad applicability, not dependent on a single driver mutation and potential efficacy across cancer types.