Therapy and Prophylaxis for Genital Tract Infection - ABSTRACT GneX12 is a patented therapeutic vaccine in development specifically for women with Neisseria gonorrhoeae (gonorrhea) infection. It is a novel formulation of recombinant human interleukin-12 (IL-12) encapsulated in biodegradable sustained release micro-particles. It is meant to be given in conjunction with standard of care antibiotics to turn infections into live vaccines that generate protective immunity against re-infection. It is also an immune therapy-based failsafe treatment against emerging multi-drug resistant gonorrhea strains. In our SBIR phase I proof of concept studies in mice, we showed that GneX12 induces anti-gonococcal T-cell and antibody responses against existing gonococcal infections, accelerates bacterial clearance and generates protection against re-infection. Protection was broad, against both homologous and heterologous strains and lasted for at least six months. Such protection had never been observed. In our subsequent SBIR phase II award, GneX12 dose and regimen were optimized, and initial pharmacokinetics parameters determined after intravaginal administration. The mechanisms of cross-protection against diverse strains of naturally occurring N. gonorrhoeae were elucidated, substantiating the scientific basis for the treatment and identifying parameters of protective immunity for testing in humans. Scaled-up methods for drug product production were developed, and batch-to- batch consistency, uniformity and stability demonstrated. Finally, a briefing package and set of interrogatives were prepared and a type C meeting held with the FDA. In our SBIR phase IIb work, FDA-recommended toxicity studies, including reproductive toxicity, were conducted in rodents. Scaled-up manufacturing methods were transferred to commercial GMP facilities at Ascendia Pharmaceuticals, along with development and qualification of analytical methods. GMP drug substance (rhIL-12), suitable for human use, was produced under a co- development agreement with Akron Biotech, securing for Therapyx an exclusive source of API not otherwise available on the open market. Finally, we prepared a briefing package and set of interrogatives and conducted a type B meeting with the FDA in preparation for submission of an IND application. Funds are herein requested to manufacture and validate cGMP drug product, perform agency-required toxicity studies in monkeys, and finally, for IND submission. In the future, with separate company funds, we will conduct a phase I/II trial with GneX12 in women with Neisseria gonorrhoeae. The trial will be conducted in collaboration with our partners at the University of Louisville.
