PRINCETON, N.J.– UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, today announced the submission of an Investigational New Drug application (IND) for UGN-301 (zalifrelimab) to the U.S. Food and Drug Administration (FDA) in support of the planned initiation of a multi-arm, Phase I clinical study for its anti-CTLA4 antibody. The study is expected to begin in the second quarter of 2022 and will evaluate the safety and tolerability of UGN-301 as monotherapy and in combination with other immunomodulators and chemotherapies in recurrent non-muscle invasive bladder cancer (NMIBC). This clinical program builds on encouraging preclinical data showing that intravesical administration of anti-CTLA4 and a TLR agonist leveraging the RTGel™ platform can produce clinical benefit in the setting of high-grade bladder cancer. It will take approximately 12 months to complete the monotherapy arm of the study.
“UroGen has shown that combination immunotherapy, when delivered intravesically, is potentially synergistic. While CTLA-4 has long been considered a good target for overcoming the immune suppression produced by tumor cells, anti-CTLA4 antibodies are associated with toxicities when administered systemically,” said Mark Schoenberg, Chief Medical Officer, UroGen Pharma. “Local delivery using our RTGel™ proprietary technology may permit us to leverage the power of a potent antibody while avoiding the toxicity associated with intravenous administration. This is critical because anti-CTLA4 antibodies stimulate cytotoxic T cells while inhibiting suppressive T-regulatory cells, making this class a potentially more comprehensively acting immunomodulator than antibodies to PD-1 and PD-L1.”
In the nonclinical study of UGN-301 in cynomolgus monkeys, UroGen assessed the potential toxicity via instillation into the urinary bladder delivered with RTGel reverse thermal hydrogel. The results showed that instillation of UGN-301 at different dose concentrations for a pre-defined period was not associated with mortality, changes in body weights, organ weight differences or meaningful changes among other endpoints, or macroscopic or microscopic findings following a specified recovery period.
According to Dr. Schoenberg, “We view intravesical delivery of our anti-CTLA4 antibody UGN-301 as a cornerstone of the urologic cancers program that we are pursuing in collaboration with MD Anderson Cancer Center, and we are thrilled at the prospect of advancing this program in the form of a multi-arm, Phase 1 study of UGN-301 in combination with other agents. We believe that this approach is unique and leverages our proprietary drug delivery technology and provides an opportunity to evaluate a variety of novel immunomodulatory drug combinations.”
