UroGen Terminates Anti-CTLA-4 Partnership with Agenus Following Disappointing Phase 1 Results

In a significant setback for both companies, UroGen Pharmaceuticals has announced the termination of its license agreement with Agenus for the development of zalifrelimab (UGN-301), an anti-CTLA-4 antibody intended for the treatment of urinary tract cancers. The decision comes after phase 1 data failed to meet UroGen's internal benchmarks for advancement to phase 2 trials.

Zalifrelimab's Journey: From Promise to Disappointment

UroGen initially acquired the rights to zalifrelimab in 2019, paying Agenus $10 million upfront. The New Jersey-based company had planned to develop the drug in combination with its TLR7/8 agonist UGN-201, leveraging its proprietary RTGel technology. This hydrogel-based platform was designed to improve the therapeutic profiles of existing drugs through sustained release.

Despite confirming the viability of RTGel for local delivery of complex immunotherapies, UroGen's phase 1 dose-escalation study revealed that zalifrelimab's overall clinical profile fell short of expectations. As a result, UroGen has opted to return the rights to Agenus, forfeiting potential milestone payments that could have totaled $200 million - $115 million for clinical development and regulatory milestones, and $85 million for commercial achievements.

Implications for Agenus and the Broader Immuno-Oncology Landscape

This setback is the latest in a series of challenges for Agenus. The Massachusetts-based biotech has faced multiple partnership dissolutions in recent years, including Bristol Myers Squibb's termination of a TIGIT bispecific antibody collaboration in 2024 and Incyte's withdrawal from an immuno-oncology deal earlier this year.

The termination of the zalifrelimab program also raises questions about the future of anti-CTLA-4 therapies in bladder cancer treatment. While checkpoint inhibitors targeting CTLA-4 have proven successful in other oncology indications - as evidenced by Bristol Myers Squibb's Yervoy and AstraZeneca's Imjudo - their efficacy in urinary tract cancers remains uncertain.

The Road Ahead for UroGen and RTGel Technology

Despite this setback, UroGen remains committed to advancing its RTGel platform. The company's statement emphasized that the phase 1 study did confirm proof of concept for RTGel as a viable platform for local delivery of complex immunotherapies. This suggests that UroGen may continue to explore applications of its technology with other potential drug candidates or partnerships in the future.