UroGen Terminates Anti-CTLA-4 Drug License with Agenus, Citing Underwhelming Phase 1 Results

UroGen Pharmaceuticals has announced the termination of its license agreement with Agenus for the anti-CTLA-4 antibody zalifrelimab (UGN-301), following disappointing results from a phase 1 dose-escalation study in bladder cancer. The decision marks a setback for both companies and highlights the challenges faced in developing novel immunotherapies for urinary tract cancers.

Phase 1 Study Outcomes and Decision to Terminate

UroGen, a New Jersey-based pharmaceutical company, initially acquired the rights to zalifrelimab in 2019 for $10 million upfront. The company's strategy involved combining the anti-CTLA-4 antibody with its proprietary TLR7/8 agonist UGN-201 for the treatment of urinary tract cancers. Additionally, the program aimed to showcase the potential of UroGen's RTGel technology, a sustained-release hydrogel platform designed to enhance existing drug therapies.

However, in its recent third-quarter earnings release, UroGen revealed that the phase 1 study results failed to meet the company's internal benchmarks for advancement to phase 2. While the study confirmed the viability of RTGel for local delivery of complex immunotherapies, the overall clinical profile of UGN-301 fell short of expectations.

Implications for Agenus and Industry Trends

The termination of the license agreement represents a significant loss for Agenus, as the company will now forfeit potential milestone payments totaling $200 million. This amount included $115 million tied to clinical development and regulatory milestones, as well as $85 million in commercial milestone payouts.

This setback for Agenus follows a series of recent challenges in the immuno-oncology space. In the past year, the company has faced the termination of partnerships with other major pharmaceutical players, including Bristol Myers Squibb's decision to axe a TIGIT bispecific antibody collaboration and Incyte's withdrawal from an immuno-oncology deal.

Broader Context in Immuno-Oncology

Despite the setback for zalifrelimab, anti-CTLA-4 checkpoint inhibitors have demonstrated significant value in oncology. Notable examples include Bristol Myers Squibb's Yervoy and AstraZeneca's Imjudo, both of which have achieved blockbuster status.

The termination of the UroGen-Agenus agreement underscores the ongoing challenges and high stakes in the development of novel cancer immunotherapies. As companies continue to explore new approaches and combinations, the industry remains focused on identifying effective treatments that can meet rigorous clinical benchmarks and improve patient outcomes.