High Grade NMIBC is defined as high-grade papillary stage, Ta or T1 tumors and any patient with carcinoma in situ (CIS), and makes up 15 to 44% of patients with non-muscle-invasive cancer in some series. The probability of progression to muscle-invasive cancer within 5 years of diagnosis is highest for this group of patients, and ranges from 25% to 50%. Radical cystectomy can be the first treatment of choice for young, otherwise healthy patients with high-grade T1 disease, or for patients with multifocal CIS who cannot tolerate BCG. Possible indications for cystectomy include multifocal disease, deep involvement of the lamina propria, and associated CIS. For patients with BCG failure, radical cystectomy remains the gold standard treatment.
Treatment of CIS differs from Ta, T1 papillary tumors. Endoscopic surgery, which is the initial treatment of papillary cancers, is not effective for CIS because the disease is often so diffuse and difficult to visualize that surgical removal is not feasible. When a combination of papillary tumor and CIS is present, the papillary tumor is removed before treatment of the CIS is initiated.
Vesimune is a clinical-stage targeted small molecule drug candidate being developed for the treatment of non-muscle invasive carcinoma in situ or CIS, a form of high-grade bladder cancer. The active ingredient in Vesimune is Imiquimod, an FDA approved immunostimulatory small molecule (in a topical formulation) with a highly selective mechanism of action of Toll-like receptor 7 (TLR7) positive cells. Vesimune is a novel, liquid formulation of imiquimod, specifically optimized for delivery into the urinary bladder.
Vesimune has received Orphan Drug Designation from the FDA for the treatment CIS. We have an active IND for Vesimmune, which has been effective since 2013. Vesimune has been shown, in multiple animal models, to produce anti-tumor effects and to activate the immune system in bladder tissue. .
Vesimune was evaluated in a Phase 1 dose escalation study that enrolled 23 patients diagnosed with NMIBC. Vesimune was well-tolerated at the doses used. Subsequently, a Phase 1b study of Vesimune was conducted under an IND in patients with CIS bladder cancer in the United States. The Phase 1b study was commenced in April 2013 and completed in February 2014. Patients were dosed with Vesimune 0.4% weekly for six weeks. The study was designed to evaluate the safety and preliminary efficacy of Vesimune in CIS patients. The primary efficacy endpoint for observational purposes only was the rate of complete response at five to seven weeks after the sixth weekly instillation. Twelve patients were enrolled into the pilot study, of which 10 patients were evaluable for response. Four of the 10 patients, or 40%, achieved a complete response. Vesimune was observed to be well tolerated in this trial. The most common AEs related to Vesimune were urination urgency, dysuria, fatigue, urinary tract infections and hematuria. One SAE, a urinary tract infection, was observed and was resolved. For observational purposes, patients were followed for an additional six month period beyond the completion of the study, referred to as the Post- Study Follow Up. Of the four patients who had achieved a complete response with Vesimune in the study, two patients remained disease free at the end of the Post-Study Follow Up while receiving no additional therapy. The two other patients who had achieved a complete response with Vesimune in the study also remained disease free at the end of the Post-Study Follow Up while receiving BCG therapy during this period.