Critical Path IND-enabling Studies, Regulatory, and Product Development

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The goal of the this project (Project 6) is to perform the critical IND-directed path activities necessary to advance two novel dual compartment topical microbicide gels that are suitable for use in either the vaginal or rectal compartments to the IND stage in preparation for pre-Phase 1 clinical testing. The active pharmaceutical ingredient (API) will be IQP-0528, a potent, small molecular weight antiviral compound that has been shown to completely sterilize an in vitro HIV infection model, blocking the establishment and spread of infection in the culture. IQP-0528 is unique in that it possesses two distinct mechanisms of anti-HIV action; blockade of viral entry and inhibition of the viral polymerase through interaction with a non-nucleoside binding site, in principle, constituting a combination of drugs in a single API. One of the gels being developed will contain IQP-0528 as the only API, the second gel, which will be developed in a sequential fashion, will contain both IQP-0528 and tenofovir (TFV), a well characterized anti-retroviral compound that is approved for systemic control of HIV replication in infected individuals that has also been used with some success as a single agent in the topical microbicide setting. The critical path IND-enabling studies proposed in this project that will be executed for two topical microbicide gel are (1) synthesis, release and stability testing of GMP IQP-0528 API, (2) GMP production, release and stability of the candidate dual compartment gel developed at ImQuest as part of the proposal, (3) production of non-GMP dual compartment gel products for use in nonclinical safety and toxicology studies, (4) conduct of the appropriate nonclinical GLP and non-GLP safety and toxicological studies, (5) submission of a approvable IND package for the clinical study of the each gel in both the vaginal and rectal compartments, and (6) manufacturing filling support for the evaluation of over-the-counter gels for the purpose of defining user acceptability parameters for gels deployed in the rectal compartment.