DEVELOPMENT OF A UC-781 COMBINATION MICROBICIDE

DESCRIPTION (provided by applicant): Despite significant advances in the treatment of HIV-1 infection, the epidemic continues to expand at an alarming rate. It is estimated that 36 million people are currently infected with HIV-1, and that there are over 5 million new cases each year. The vast majority of these new infections occur through sexual transmission. Other sexually transmitted diseases (STD) are also transmitted at very high rates. Approximately 15 million new cases of STD occur each year in the U.S., and there are over 400 million cases of STD world-wide. Clearly, the conventional approaches of counseling and condom use are not sufficient to stem the increase in these infections. As vaccines continue to be lacking for these infections, alternative means of prevention need to be developed. Thus, a vaginal microbicide with a broad spectrum of activity against sexually transmitted bacteria and viruses (including HIV-1) would be an extremely important advancement in the prevention of STD transmission. Moreover, such a microbicide would be particularly important for women, who would gain some level of control in the use of appropriate preventive measures. Unfortunately, there is no single agent available that has the ability to protect against all of the relevant types of sexually transmitted pathogens. Therefore, Biosyn, Inc. proposes to determine the feasibility of combining C31 G, a surface active, broad spectrum anti-bacterial agent which also has anti-enveloped virus activity, with UC-781, an extremely potent inhibitor of HIV-1 reverse transcriptase. Specifically, the objectives of this Phase I SBlR project are: (1) to determine the activities of these two drugs in the presence of the other, and correlate these activities with their physical state, (2) to produce candidate vaginal microbicide formulations that combine these two drugs, (3) to develop analytical methods that can subsequently be used to evaluate formulations that include both drugs, and (4) develop functional assays for such formulations that can discriminate between the activities of each drug in a formulation. At the completion of this effort, we expect to have a set of candidate formulations that can be progressed into a Phase II SBlR project that will involve comprehensive evaluation and appropriate pre-clinical development.