The goal of our drug discovery program for acne treatment and prevention is to develop a novel therapeutic regimen that addresses both the bacterial and inflammatory components of this disease. Our approach involves screening and evaluating a focused series of newly patented 5-naphthoylsalicylanildes in biological systems predictive of clinical anti-acne activity (this Phase 1), choosing the best compound from these studies for progression to pre-clinical pharmaceutical development (Phase 2), and into clinical trials in humans (Phase 3). The combined biological and physico-chemcial properties of the 5- naphtholysalicylanilides gives them a competitive advantage over other drugs and formulations currently used in the treatment of this disorder. The advantages include: 1) a broad spectrum of antibacterial activity, with excellent activity against Propionibacterium acnes, as well as other secondary dermal pathogens such as diphtheroids, Staphylococcus aureus, and other staphylococcal species; 2) potent dermal antiinflammatory activity, that apparently occurs via inhibition of COX isozymes and reduction in the levels of PGE2; 3) inhibitory activity against certain tissue destructive enzymes such as the matrix-metalloproteases 2 and 9 that are activated in response to infection; and 4) high lipophilicity which makes them suitable for use in topically administered treatments for conditions where they can partition and act in lipid rich components of the affected sites. These qualities, plus the patent status of the technology, make an optimized 5- naphthoylsalicylanilide an excellent candidate for development as an active anti-acne agent. From this Phase 1 study we will choose the most promising candidates for scale up synthesis and preliminary in vivo pharmacology and safety evaluation in several test systems. Based upon the results of these studies we will choose one "optimized" 5-naphthoylsalicylanilide for progression to Phase 2. We expect the success of these studies will entice a major pharmaceutical partner to pursue the continued development of our optimized 5-naphthoylsalicyanilide (Phase 3) as an active ingredient. The average growth rate for anti-acne treatments in the US over the past five years was approximately 5.0%. In 2002 the total US OTC market alone for anti-acne remedies was approximately $700 million
