Aravive Biologics, a clinical-stage biotechnology company focused on development of treatments for cancer and fibrotic diseases, announced the initiation of a phase 1 clinical trial of AVB-S6-500 (previously referred to as Aravive-S6).  The study is being conducted in the United States and will evaluate safety, pharmacokinetics and pharmacodynamics in approximately 40 healthy volunteers and is designed to demonstrate proof-of-mechanism for the company’s lead drug candidate.

“We are very pleased to achieve this key development milestone for AVB-S6-500, which in preclinical testing has shown potential in a variety of solid tumors and acute myeloid leukemia (AML),” said Gail McIntyre, senior vice president of R&D at Aravive. “Extensive research by Aravive and others has shown the GAS6-AXL signaling pathway to be an important target in oncology, whose inhibition has the potential to overcome tumor resistance and increase the efficacy of a variety of anticancer agents.”

“AVB-S6-500 is unique as an inhibitor of the GAS6-AXL pathway in its high affinity for GAS6 and the high selectivity with which it inhibits AXL signaling,” said Stephen L. Eck M.D. Ph.D, chief executive officer of Aravive. “Given the availability of our proprietary biomarker, the company hopes to establish the proof-of-mechanism for this first-in-class drug candidate as well as safety in phase 1 clinical studies by demonstrating full target engagement and inhibition of GAS6 in the clinic.”

AVB-S6-500 is a novel biologic that is designed to bind GAS6 with high affinity and neutralize its activity. Research has shown GAS6-AXL signaling to be a key molecular pathway that scientists believe promotes tumor growth and metastasis, as well as tumor immune evasion and resistance to other anticancer agents. AXL and GAS6 expression correlate with poor prognosis in cancer and are thought by many experts to be attractive targets for cancer therapy. In preclinical studies, GAS6-AXL inhibition has shown activity, whether achieved by a single agent (including AVB-S6-500) or through combinations of a variety of anticancer therapies including radiation therapy, immuno-oncology agents, and drugs that affect DNA replication and repair. GAS6/AXL inhibition has also shown potential as a strategy for the treatment of certain fibrotic diseases.