Immunotherapy – locally triggering the innate immune system via proprietary formulation of immune modulating drugs for intravesical use

UroGen Pharma Immunotherapy - Urogenis developing a unique immune-modulation drug candidate, Vesimune (imiquimod), based on Toll like receptors (TLR) stimulators. TLRs are pattern recognition receptors (PRRs) and their importance in stimulating innate and adaptive immunity is well established. TLRs are sensors of microbial components as well as host-derived endogenous molecules released by injured tissues. TLRs play a critical role in defense against invading pathogens but are also involved in other serious pathological processes, such as tumorigenesis. TLR can be expressed on members of the innate and adaptive immune system as well as by endothelial and epithelial cells. More recently, TLR have been found on tumor cells. Growing evidence is being collected of TLRs activation efficacy in arming the immune system against cancer cells.

Imiquimod is approved in the US in a topical formulation for genital warts, superficial basal cell carcinoma, and actinic keratosis.   Imiquimod is an imidazoquinoline, synthetic immune modulator which target TLR7 and a potent inducer of immune stimulatory cytokines –including Interferon-alpha (IFNα), TNFα, interleukin IL-1β and IL-6, and exerts consistent antitumor effects in animal models.  TLR7 expression on bladder cancer cells has been reported. Imiquimod is believed to also adjuvant properties, eliciting an adaptive immune response in the presence of released bladder cancer antigens that translate into a long lasting acquire immune response. Imiquimod is the active ingredient of Vesimune.

BCG, an immunotherapy agent, is the current standard of care for adjuvant treatment of high-grade bladder cancer tumors, including CIS.  However, BCG is associated with a high rate of tolerability issues.  UroGen Pharma’s Vesimune is a reformulation of imiquimod specifically optimized for intravesical delivery in the urinary bladder.