Compugen Ltd. has announced that the first patient has been dosed in a Phase 1 clinical trial evaluating COM503, a potential first-in-class antibody targeting IL-18 binding protein, in patients with advanced solid tumors. This trial marks a significant step in harnessing cytokine biology for cancer therapeutics. The Phase 1 study, managed by Compugen, will assess COM503 both as a monotherapy and in combination with zimberelimab, Gilead's anti-PD1 antibody.
The multi-center, dose-escalation, and dose-expansion trial aims to determine the safety, tolerability, and pharmacokinetics of COM503. The trial was initiated in the fourth quarter of 2024. The primary objectives include identifying the maximum tolerated dose and/or the recommended dose of COM503, both as a monotherapy and in combination with zimberelimab. For additional details, the trial is listed on clinicaltrials.gov under the identifier NCT06759649.
Novel Approach to IL-18 Inhibition
According to Anat Cohen-Dayag, Ph.D., President, and CEO of Compugen, the company's Unigen discovery engine identified high levels of IL-18 expression in tumors. However, an endogenous IL-18-binding protein blocks the anti-tumor activity of IL-18, rendering it ineffective. COM503 is designed to block this binding protein, releasing naturally occurring IL-18 locally within tumors, which can then potentiate anti-tumor immune responses. This approach aims to overcome the limitations of systemically administered cytokines.
Collaboration and Licensing Agreement
Gilead Sciences, Inc. holds exclusive rights to develop and commercialize anti-IL-18 binding protein antibodies, including COM503, under a license agreement established in December 2023. Compugen is responsible for the Phase 1 trial, after which Gilead will assume sole responsibility for further development and commercialization. The agreement included an upfront payment of $60 million and a $30 million milestone payment to Compugen. Compugen is eligible for up to an additional $758 million in future development, regulatory, and commercial milestone payments, potentially reaching a total deal value of $848 million, plus royalties on worldwide net sales.
Expert Commentary
Manish Sharma, M.D., Co-Director of Clinical Research at the START Center for Cancer Research-Midwest (START Midwest), expressed enthusiasm for the trial, stating, "Having COM503 as an additional novel investigational treatment option with a unique mechanism of action to offer our cancer patients is exciting...we were delighted to be the first to dose a patient with COM503 and look forward to swiftly enrolling additional patients in this first dose escalation part of the trial with a focus on evaluating the safety and pharmacokinetics of COM503 monotherapy."
