Crescent Biopharma announced promising preclinical data for CR-001, its lead tetravalent bispecific antibody targeting both PD-1 and VEGF pathways for solid tumor treatment. The data will be presented at the Society for Immunotherapy of Cancer's 40th Annual Meeting in National Harbor, Maryland, from November 7-9, 2025.
Novel Cooperative Mechanism Enhances Therapeutic Activity
CR-001 demonstrated cooperative pharmacology in vitro, showing increased binding to PD-1 in the presence of VEGF. This enhanced binding augments PD-1/PD-L1 signaling blockade and enhances T-cell activation, representing a potentially superior approach to current checkpoint inhibitor monotherapies.
The cooperative mechanism observed with CR-001 aligns with preclinical evaluation of ivonescimab, another tetravalent PD-1 x VEGF bispecific antibody. Ivonescimab demonstrated superior efficacy compared to pembrolizumab, the current market leader, in a large third-party Phase 3 trial in non-small cell lung cancer.
Robust Preclinical Efficacy and Safety Profile
In preclinical studies, CR-001 showed potent anti-tumor activity in xenograft mouse models. The therapy was well-tolerated in non-human primates after a single intravenous dose, achieving robust PD-1 receptor occupancy without significant adverse effects.
"These data highlight the cooperative mechanism of CR-001 and its ability to reduce tumor growth in vivo, reinforcing its potential as a next generation immuno-oncology therapy," said Jan Pinkas, Ph.D., chief scientific officer of Crescent.
Clinical Development Timeline
Crescent remains on track to submit an Investigational New Drug (IND) application for CR-001 in the fourth quarter of 2025. The company plans to initiate a global Phase 1 trial in patients with solid tumors in the first quarter of 2026.
The poster presentation, titled "Preclinical development of CR-001, a novel tetravalent PD-1 x VEGF bispecific antibody with cooperative pharmacology and potent anti-tumor activity," will be presented on Friday, November 7, 2025, at the Prince George ABC Exhibit Halls.
Dual-Target Approach for Enhanced Efficacy
CR-001 combines two complementary, validated mechanisms in oncology through simultaneous blockade of PD-1 and VEGF. PD-1 checkpoint inhibition aims to restore T cells' ability to recognize and destroy tumor cells, while VEGF blockade reduces blood supply to tumor cells and inhibits tumor growth.
The anti-VEGF activity of CR-001 may also normalize vasculature at the tumor site, potentially improving localization and effectiveness of combination therapies. This includes potential combinations with Crescent's antibody-drug conjugates (ADCs) currently in development.
