On December 18, 2023 Avstera Therapeutics Corp, an oncology-focused biotech dedicated to addressing the large disease burden and significant unmet need of cancer patients, reported the U.S. FDA clearance of its Investigational New Drug application (IND) for AVS100, a novel highly selective oral HDAC6 inhibitor intended to treat locally advanced or metastatic solid tumors in a Phase I clinical study (Press release, Avstera Therapeutics, DEC 18, 2023, View Source [SID1234638662]).
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"The FDA clearance of our IND for AVS100 marks an amazing step for our company towards the fulfillment of our mission. We are excited to advance this promising new therapy into the clinic to address the disease burden for the benefit of patients, and our transition to a viable clinical stage biotech. AVS100 has demonstrated significant preclinical efficacy, remarkable safety, and durability in numerous in-vivo studies." said Karthik Musunuri, CEO & Co-Founder, Director of Avstera Therapeutics.
AVS100 is a highly selective, orally bioavailable, isoxazole-3-hydroxamate based HDAC6 inhibitor. AVS100 demonstrated unique ability in its class preclinically in suppressing the polarization of macrophages toward pro-tumoral phenotypic pathways. This immunomodulatory function is both pivotal and of keen interest as tumor associated macrophages can constitute up to 50% or more of solid tumor cell mass. AVS100 is AMES negative and demonstrated a strong safety profile in animals, including GLP toxicology studies in dogs and rats with no major adverse events.
"FDA clearance of our IND for AVS100 represents a significant milestone for Avstera’s mission in providing state of the art oncological agents to tackle solid tumors. I am proud of our team’s efficiency as drug developers in advancing to FIH trials in a just over a year since our seed round." said Ajay Raju, Co-Founder & Director of Avstera Therapeutics.
"New findings demonstrating a critical role of tumor-associated macrophages in resistance to immunotherapy suggest that targeting this cell population could both effectively reverse and/or avoid resistance to existing ICB. Therefore, an emerging interest is in developing new immunotherapies targeting this immune population, including selective HDAC6 inhibitors, which have been proven effective modulators of immunosuppressive macrophages. Undoubtedly, the IND approval of AVS100 selective HDAC6 inhibitor will open new opportunities to potentially enhance response rates for patients." said Alejandro Villagra, PhD, Georgetown University Associate Professor and Co-Inventor of AVS100 who also serves on Avstera’s Scientific Advisory Board (SAB).
More About the Phase I Clinical Study
The Phase Ia/b clinical trial for AVS100 is targeting locally advanced or metastatic solid tumors. This trial is an open label, dose-escalation and confirmation study to characterize the safety, tolerability, pharmacokinetics, and MTD of AVS100 when administered as a monotherapy and in combination with pembrolizumab. The primary endpoints are to evaluate the incidence of adverse events including DLTs in monotherapy and in combination, while secondarily assessing the PK, Objective Response Rate (ORR) using RECIST v1.1, and Progression Free Survival (PFS). Avstera will also assess multiple exploratory biomarkers, including conducting multi-omics analyses on patient samples.
Avstera intends to initiate the Phase Ia/b clinical trial in the first half of 2024. The principal investigator of the study is Apostolia M Tsimberidou, MD, PhD, FASCO, FAAAS, Professor of Medicine at MD Anderson Cancer Center, Houston, TX.