SBIR-STTR Award

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.

Thesaurus Terms:
antibacterial agent, antiviral agent, chemoprevention, combination chemotherapy, drug administration route, drug design /synthesis /production, drug screening /evaluation, reverse transcriptase inhibitor, sexually transmitted disease analytical method, antiAIDS agent, antifungal agent, chemical structure function, human immunodeficiency virus 1, topical drug application, vagina

The worldwide incidence of new HIV infecti ons remains at a desperately high level. Although more effective treatments continue to be developed, they remain costly and are not readily available in those regions of the world most severely effected by the epidemic. For physiological reasons, women are disproportionately at risk for transmission of HIV infection. There has been great focus in recent years on the development of effective means of preventing new infections. Unfortunately, successful development of a vaccine has yet to be achieved. Although barrier methods can be effective, their use is not controlled by the women at risk. Great attention is now being devoted to the development of women controlled microbicide products that can be applied for the prevention of HIV transmission and other sexually transmitted diseases. All of the most clinically advanced first generation microbicide products involve the formulation of a single active drug compound in a gel or cream dosage form for vaginal use. However, the long term success of microbicides will depend on the availability of such formulations with combinations of active agents that have independent mechanisms of action, and are broad spectrum in terms of target pathogens. This will protect women from other STD that could function as cofactors in HIV infection, and will also reduce or prevent the emergence of resistant virus. Thus, Biosyn proposed a Phase I SBIR program for the development of a combination microbicide containing the broad spectrum surface active agent C31G with the highly potent HIV NNRTI, UC-781. This combination formulation would prevent the emergence of resistance and provide broad spectrum protection. During the Phase I SBIR effort, we demonstrated that these drugs do not interfere with the intrinsic activities of each other. Moreover, it was possible to develop early stage analytical methods that could readily be applied to combinations containing both actives. Finally, a set of candidate gel formulations were developed, which will serve as the basis for additional formulation development and optimization in the Phase II SBIR effort. The combination development proposed here benefits from the fact that Biosyn has independent development programs for UC-781 and C31G. Thus, GMP manufacture of API, acute and chronic toxicology studies, as well as clinical data are all available at no additional cost to the combination program. Therefore, Biosyn is proposing the continued development of a U C-781/C31G combination microbicide in a Phase II SBIR. The overall objective is to develop a combination formulation that can serve as the basis for an INDsubmission to the FDA. This will be achieved by means of expanded study of the physical and chemical nature of this combination, and using this characterization to design and optimize an appropriate formulation. There will be specific investigation of the potential use of C31G as both an active agent and a delivery agent in the combination formulation, which potentially enhances the activity of the product.

Thesaurus Terms:
antiinfective agent, chemoprevention, combination chemotherapy, drug design /synthesis /production, drug screening /evaluation, reverse transcriptase inhibitor, sexually transmitted disease AIDS education /prevention, analytical method, antiAIDS agent, antibacterial agent, antifungal agent, antiviral agent, chemical property, chemical structure function, dosage forms, human immunodeficiency virus 1, method development, micelle, physical property, topical drug application, vagina clinical research, human tissue, patient oriented research, tissue /cell culture