Advancing a novel on-demand non-hormonal male contraceptive to IND enablement

PROJECT SUMMARY With global unintended pregnancy rates at nearly 50%, and even higher rates among adolescents in the United States, there is a profound unmet need for reliable and convenient to use contraceptive options. While multiple contraceptive alternatives exist for women, condoms, with a 13% yearly average failure rate, and surgical vasectomy are the sole contraceptive options available to men. The global contraceptive market was $22.5 billion in 2021 and is expected to grow to over $31 billion by 2026. Recent multi-country market research indicates that over half of all men of reproductive age would try a new male contraceptive, with a new contraceptive option for men likely to grow this market considerably as well as have the greatest impact towards reducing unintended pregnancies. In the United States, men favor an on-demand, nonhormonal, orally available option. To meet this demand, Sacyl Pharmaceuticals, Inc (SACYL) is developing small molecules that will provide innovative first-in- class, nonhormonal, reversible, pre-coital, on-demand contraception for men via inhibition of soluble adenylyl cyclase (ADCY10; sAC) in sperm. sAC is genetically and pharmacologically validated as a target for male contraception in both mice and men. SACYL has licensed the exclusive worldwide rights for systemic delivery of a series of drug-like sAC inhibitors, which impede progressive motility of human and mouse sperm and demonstrated 100% contraceptive efficacy in preclinical mouse mating studies. In this phase 1 SBIR application, we request funding to advance our sAC inhibitor leads towards preclinical development. On-demand male contraception is a novel concept which (to our knowledge) has never been evaluated by the FDA; therefore, in Aim 1, we will develop the new strategy needed to hold an initial meeting with the FDA to progress our advanced candidates to an Investigational New Drug (IND). Because the sAC inhibitor used to successfully demonstrate proof-of-concept for on-demand contraception in male mice still has liabilities which limit its utility as a clinical asset, we have developed a series of advanced leads with improved efficacy-defining features. In Aim 2, we will assess metabolic stability and oral bioavailability to identify the lead and backup preclinical compounds to advance into IND enablement. Upon completion of this phase 1 award, we will present a clinical lead (and backup) compound and a development strategy to the FDA in a pre-IND meeting.