Aravive Announces AVB-500 Improves Anti-Tumor Effects When Combined With Anti-Angiogenic Bevacizumab or PARP Inhibitor Olaparib

Aravive, Inc. recently announced that AVB-500 improves anti-tumor effects when combined with the anti-angiogenic bevacizumab or the PARP inhibitor olaparib in preclinical uterine cancer models. Additional research also showed that inhibition of GAS6/AXL signaling with AVB-500 induces BRCA-ness, increasing response to platinum and PARPi in a preclinical model of ovarian cancer. Taken together, these research findings suggest the potential for AVB-500 to be used in combination with existing therapies to address multiple gynecologic cancers.

The data were to be presented at the Society of Gynecologic Oncology (SGO) 2020 Annual Meeting on Women’s Cancer which has been cancelled due to the ongoing COVID-19 pandemic. The following abstracts were published Saturday March 28, 2020 on the SGO meeting website, and a recorded webcast of the oral plenary presentation as well as the posters will be made available on the Aravive website in the coming weeks.

-Oral Plenary: Abstract 15271, “AVB500, a receptor tyrosine kinase AXL inhibitor, has improved therapeutic efficacy in combination with bevacizumab compared to bevacizumab alone in uterine serous cancer mouse model,” Michael Toboni, M.D., et al.

-Poster: Abstract 15964, “Inducing ‘BRCAness’ by inhibiting the GAS6/AXL pathway in high-grade serous ovarian cancer,” Maggie Mullen, M.D., et al.

-Poster: Abstract 15185, “Improving response to olaparib in uterine serous cancer through treatment with AVB a receptor tyrosine kinase AXL inhibitor,” Michael Toboni, M.D., et al.

“We are excited to share our findings that the combination of AVB-500 with either platinum chemotherapy or with an anti-angiogenic agent, bevacizumab, or a PARP inhibitor, olaparib, can decrease tumor burden to a greater degree than with the single agent alone in ovarian and uterine serous cancer models,” said Katherine Fuh, MD, PhD, Assistant Professor, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Center for Reproductive Health Sciences, Washington University School of Medicine, St. Louis, MO. “Combining AVB-500 with standard of care chemotherapies and targeted therapies may potentially make these therapies more effective against aggressive cancers without adding a treatment burden to patients.”

AVB-500 is a therapeutic recombinant fusion protein that has been shown to neutralize GAS6 activity by binding to GAS6 with very high affinity. In doing so, AVB-500 selectively inhibits the GAS6-AXL signaling pathway. In preclinical studies, GAS6-AXL inhibition has shown anti-tumor activity, both as a single agent and in combination with a variety of anticancer therapies including radiation therapy, immuno-oncology agents and chemotherapeutic drugs that affect DNA replication and repair. Increased expression of AXL and GAS6 in tumors is correlated to poor prognosis and survival, and has been implicated in therapeutic resistance to conventional chemotherapeutics and targeted therapies.

Aravive reported positive data from the first 31 patients enrolled in the Phase 1b portion of a Phase 1b/2 clinical trial of AVB-500 in platinum-resistant recurrent ovarian cancer. AVB-500 continues to be well tolerated. Investigator-sponsored Phase 1/2 trials of AVB-500, in combination with durvalumab in patients with platinum-resistant recurrent epithelial ovarian cancer and with avelumab in patients with advanced urothelial Carcinoma (COAXIN), are also ongoing. Based on AVB-500’s safety profile and specifically targeted mechanism of action, this drug candidate has the potential to be used both in combination with existing therapies, as well as a maintenance drug. The US FDA granted Fast Track Designation to AVB-500 in platinum-resistant recurrent ovarian cancer.

Aravive, Inc. is a clinical-stage biopharmaceutical company developing treatments designed to halt the progression of life-threatening diseases, including cancer and fibrosis. Aravive’s lead product candidate, AVB-500, is an ultra-high affinity decoy protein that targets the GAS6-AXL signaling pathway. By capturing serum GAS6, AVB-500 starves the AXL pathway of its signal, potentially halting the biological programming that promotes disease progression. AXL receptor signaling plays an important role in multiple types of malignancies by promoting metastasis, cancer cell survival, resistance to treatments, and immune suppression. The GAS6-AXL signaling pathway also plays a significant role in fibrogenesis. Aravive is evaluating AVB-500 in platinum-resistant ovarian cancer, clear cell renal cell carcinoma and kidney fibrosis and intends to expand development into additional oncology and fibrotic indications. Aravive is based in Houston, Texas and received a Product Development Award from the Cancer Prevention & Research Institute of Texas (CPRIT) in 2016. For more information, visit www.aravive.com.