Advancing SRX246 to Commericialization

PROJECT SUMMARY/ABSTRACTSRX246, a first-in-class, orally bioavailable, CNS-active vasopressin 1a receptor antagonist, recently was tested in an Exploratory Phase 2 clinical trial, “Safety, Tolerability, and Activity of SRX246 in Irritable Subjects with Huntingtonandapos;s Disease (STAIR),” with support from an SBIR Fast Track award (5U44NS090616). The trial, conducted in collaboration with the NINDS NeuroNext Network, met the primary, secondary, and exploratory objectives. The data demonstrated that in HD patients, SRX246 was well tolerated, safe, and provided clinical benefit by decreasing aggressive behavior and reducing caregiver burden in comparison to placebo. The data support the continued development of SRX246 to address the significant unmet need for a pharmaceutical treatment for the irritability and aggressive behavior seen in HD that are among the leading causes of institutionalization and where there are no approved drugs. The clinical findings were the basis for our FDA filing that recently led to an Orphan Drug designation for the treatment of HD. The development of SRX246, which also includes a Phase 2 trial in Intermittent Explosive Disorder and an in-progress trial for the treatment of PTSD, has been supported by grants from the NIH, the DoD, and private venture capital.In accord with Commercialization Readiness Pilot Program requirements under PAR 19-333, this proposal requests funds to accelerate commercialization by engaging in late-stage Randamp;D activities that build on the recent Exploratory Phase 2 clinical trial results in HD patients. Support is requested to meet three objectives that address key questions the Company recently has encountered in partnering discussions with pharmaceutical companies and private venture capital investors. The objectives are to 1) optimize a pilot plant scale method and use it to produce a cGMP lot for Phase 3 clinical trials; 2) conduct two chronic toxicology studies, 26 week in rat and 39 week in dog, to provide initial tests that determine whether long-term treatment will be safe in accord with earlier 13-week toxicology and clinical studies that included up to 12 weeks of treatment; and 3) undertake an in-Depth Market Overview and Product Positioning analysis that includes developing a full Target Product Profile, payer discussions, and revenue forecasts as well as defining follow-on market opportunities in one additional neurodegenerative disease where agitation, anger, excessive irritability, and inappropriate aggression are significant problems (Alzheimer’s Disease).Achieving these 3 objectives will further de-risk investment in SRX246 and add value, putting Azevan Pharmaceuticals in a stronger position to accelerate commercialization of SRX246 as a treatment for Huntington’s Disease and potentially other indications through partnering or additional venture capital investment.PROJECT NARRATIVE In patients with Huntington’s Disease (HD), irritability and aggression are among the first and most distressing symptoms, they commonly lead to institutionalization, and there are no approved drugs to treat these problematic behaviors. In a recent Phase 2 clinical trial in HD patients, we showed that SRX246, a first- in-class, orally bioavailable vasopressin 1a receptor antagonist, was well tolerated, safe, and clinically beneficial. The proposed studies--synthesis of additional drug at andquot;pilotandquot; scale, chronic toxicology studies in two species, and characterization of the market potential of the compound in HD and other neurodegenerative diseases--will further de-risk SRX246 and enhance positioning for a partnership or additional private investment that will accelerate commercialization.