AVB-500 is a clinical stage therapeutic recombinant decoy fusion protein that has been shown to neutralize GAS6/TAM pathway activity by binding to GAS6 with very high affinity. In November, 2020, 3D Medicines acquired the exclusive license for development and commercialization of AVB-500 in Greater China, from NASDAQ-listed Aravive, the developer of AVB-500. AVB-500 is currently being evaluated in clinical trials and has been granted Fast Track Designation by the U.S. Food and Drug Administration in platinum resistant recurrent ovarian cancer (PROC). Besides, the pivot trial of AVB-500 for PROC will be initiated shortly.
Function of GAS6/TAM (AXL) pathway
The GAS6-AXL signaling pathway is key to tumor cell growth, cancer metastasis, immune escape and drug tolerance. AXL is reported to be up-regulated in multiple cancer types including acute myeloid leukemia (AML), kidney cancer, pancreatic cancer, breast cancer, lung cancer, ovarian cancer and prostate cancer. Increased expression of AXL and GAS6 in tumors has been correlated with poor prognosis and decreased survival and has been implicated in therapeutic resistance to conventional chemotherapeutics and targeted therapies. Preclinical studies have proved the anti-tumor activity of GAS6-AXL inhibition, either alone or its combination with a variety of antie-cancer therapies, including radiation therapy, immuno-oncology agents, and chemotherapeutic drugs. As a result, GAS6-AXL has attracted wide attention as a new target for cancer treatment.
Current clinical trials of 3D-229
The Phase 1b trial of 3D-229 in platinum resistant ovarian cancer has been successfully completed in the U.S., and 3D-229 is also being evaluated in clinical trials for clear cell renal cell carcinoma, as well as other indications.
Potential combination of 3D-229 with immune checkpoint inhibitors
The current combination trials of 3D-229 with immune checkpoint inhibitor include the combination with Durvalumab in PROC and the combination with Avelumab in advanced urothelial cancer. 3D Medicines will continue to investigate the combination therapy of 3D-229 and Envafolimab in other indications, according to the medical needs of Chinese patients.