PROJECT SUMMARY Unintended pregnancies, which are unwanted or mistimed pregnancies, result from either not using contraception or improper use of available contraceptives. These pregnancies have a significant impact on healthcare costs and the families in which the unintended pregnancies occur. A promising strategy to reduce unintended pregnancies and subsequent costs is to increase the contraceptive options available to men. Contraline has developed an injectable, long-lasting, vas-occlusive hydrogel called ADAM. ADAM is injected into the vas deferens to block sperm from traveling from the testicles to the ejaculatory duct. Although ADAM has shown safety and efficacy in a First-in-Human trial, initial studies have shown that the next generation of ADAM (ADAM Air) can reduce manufacturing and procedural complexities, and enable on-demand reversibility should a patient desire their fertility be restored. ADAM Air is an aerogel, or dehydrated version of the ADAM hydrogel. As a result, ADAM Air is implanted into the vas deferens, rather than injected; however, within minutes, the aerogel absorbs fluid and swells to become a highly effective occlusive hydrogel. The initial formulation of ADAM Air displays >20% terminal swelling and >200% swelling force than ADAM, all while maintaining ideal mechanical properties for vas occlusion. Moreover, the first generation of ADAM induces azoospermia at implant lengths of ≥ 15 cm, making on-demand reversal prior to implant degradation difficult. ADAM Air can be manufactured at a variety of diameters and lengths (i.e., <5 cm) making on-demand reversal safer and more reliable. In this SBIR proposal, we will develop three optimized formulations of ADAM Air to screen for enhanced occlusive performance and commercial potential. The ADAM Air formulation that demonstrates superior physicochemical properties will be selected and undergo preliminary biocompatibility studies in vitro and in vivo (rabbit model). After establishing initial biocompatibility, implant delivery and reversal feasibility will be tested and optimized in a human cadaver model. After completion of Phase I, Contraline will perform GLP compliant FDA IDE-enabling, starting with detailed mechanical and chemical characterization of ADAM Air. Next, the full suite of biocompatibility studies will be executed based on FDA requirements. Finally, in vivo canine studies will be performed to evaluate ADAM Air implantation and reversal safety and efficacy. Upon completion of these aims, Contraline will have demonstrated the overall feasibility of using an aerogel for male contraception, the first product of its kind. ADAM Air will be shown to be safe, effective, and reversible across a variety of benchtop, ex vivo, and in vivo models. This will allow Contraline to submit an IDE application to pursue a First-in-Human clinical trial for ADAM Air. Following completion of the First-in-Human trial, a pivotal trial will be initiated to support FDA approval. These aims will lead to the development and FDA approval of the first long-acting, reversible contraceptive for men, which will significantly reduce unintended pregnancies and provide men and couples with more contraceptive options.

PROJECT NARRATIVE There are no effective, long-acting reversible male contraceptives commercially available. Contraline has developed a long-lasting, non-permanent, injectable hydrogel (ADAM) to occlude sperm transport in the vas deferens, which has demonstrated safety and efficacy in a First-in-Human clinical study. This SBIR proposal focuses on the development of a next-generation implantable male contraceptive (ADAM Air) that is simpler to implant and reverse than previous vas-occlusive contraceptives, and demonstration of its safety and efficacy via GLP studies to allow Contraline to pursue future clinical trials.