Carcinoma in Situ of the Bladder

High-grade NMIBC is a highly aggressive form of bladder cancer. TURBT is the initial treatment of choice for high grade NMIBC; however, the high rates of recurrence and significant risk of progression to muscle-invasive tumors are particularly dangerous. Bladder removal can be the first treatment of choice for young, otherwise healthy patients with high-grade disease or for patients who cannot tolerate BCG. BCG, an immunotherapy-based drug, is the current standard of care as an adjuvant therapy post-resection in high-grade tumors. However, treatment with BCG is associated with severe side effects, as evidenced by a Black Box warning on the label.

UroGen are developing VESIMUNE™ (imiquimod) , an immune-modulation product candidate, for the treatment of high-grade NMIBC.  VESIMUNE™ could represent a valid alternative to the current standard of care for the BCG adjuvant, post TURBT treatment of high-grade NMIBC. VESIMUNE™ ’s active ingredient is Imiquimod, an imidazoquinoline, synthetic immune modulator, which specifically targets TLR7, which is expressed in bladder cancer cells. Toll-like receptors are pattern recognition receptors whose importance in stimulating innate and adaptive immunity has been established by recent studies and approval by the FDA of various cancer immunotherapies. Toll-like receptors are able to sense microbial components as well as host-derived endogenous molecules released by injured tissues and play a critical role in defending against invading pathogens.

Imiquimod, in its topical formulation, is FDA approved for several indications, including superficial basal cell carcinoma. Vesimune is a liquid formulation of Imiquimod for intravesical administration that has been optimized for delivery in the urinary tract. Vesimune does not use our RTGel technology. The Company believes that VESIMUNE™ may elicit an adaptive immune response in the presence of released bladder cancer antigens, which may translate into a long lasting acquired immune response. The Company also believes the combination of VESIMUNE™ with immune checkpoint inhibitors could further increase the adaptive immune response and potentially represent a viable alternative to BCG for the adjuvant treatment of high-grade NMIBC or UTUC.

The Company obtained Orphan Drug Designation for VESIMUNE™ for the treatment of CIS in the bladder. UroGen has an active IND for VESIMUNE™, which has been effective since 2013.