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.

Grant Number: 5SB1AI104067-09
NIH Institute/Center: NIH
Principal Investigator: DOMINICK AUCI