OncoC4, Inc. has received FDA clearance for its Investigational New Drug (IND) application for AI-081, a bispecific antibody targeting both PD-1 and VEGF, for the treatment of advanced solid tumors. This clearance paves the way for the initiation of the BIPAVE-001 Phase 1/2 clinical trial, anticipated to begin in the first quarter of 2025.
AI-081: A Novel Bispecific Antibody
AI-081 is engineered with high-affinity anti-PD1 (AI-025) and anti-VEGF (AI-011) antibodies. The bispecific design aims to enhance checkpoint therapy by leveraging cooperative interactions between PD-1 and VEGF blockade. Preclinical studies have demonstrated that AI-081 exhibits superior PD-1 blockade in the presence of VEGF, leading to robust anti-tumor activities in multiple preclinical models.
Yang Liu, PhD, Co-Founder, CEO and CSO of OncoC4, stated, "Through optimal cooperative interactions, AI-081 has displayed superior PD-1 blockade in the presence of VEGF which translates into robust, superior anti-tumor activities in multiple preclinical studies. We look forward to initiating clinical development of AI-081 with the dosing of the first patient in our BIPAVE-001 Phase 1/2 trial in early 2025."
BIPAVE-001: Phase 1/2 Trial Design
The BIPAVE-001 trial is a Phase 1/2 study designed to evaluate the safety, pharmacokinetic profile, and efficacy of AI-081 in patients with advanced solid tumors. Part A of the trial will focus on dose escalation to determine the recommended Phase 2 dose of AI-081 as a monotherapy.
Preclinical Evidence and Mechanism of Action
AI-081 incorporates a head-and-tail bispecific configuration and Fc silencing mutations to preserve immune effector cells. Preclinical studies have shown that AI-081 has higher affinity for both PD-1 and VEGF targets, improved cooperative interactions, and enhanced in vivo activity compared to other drug candidates in the same class. These findings suggest that AI-081 has the potential to be a best-in-class therapeutic due to its high affinity and cooperative interactions, which enable synergistic anti-tumor activities with enhanced PD-1 blockade in the presence of VEGF.
