Napo Pharmaceuticals Inc. is developing its lead product crofelemer--a refined version of a natural extract from a South American tree-as a treatment for treating irritable bowel syndrome and other gastrointestinal indications including chronic diarrhea,. Napo plans to market medicines to developing countries before testing the waters back home.

Nabi with PhosLo and Genzyme with Renagel now split the market for dialysis patients requiring treatment for high phosphate levels. Soon a third firm will enter the fray--the UK's Shire. Thus far, the marketing battle has been fought with nitty-gritty clinical data. But now Genzyme is raising the notion of "accumulation" to stigmatize competitors, while Nabi emphasizes the issue of cost. The competitive stakes are rising because Medicare changes in 2006 will dramatically expand the market.

Microbial drug resistance is a real and growing problem, but drugmakers face disincentives: a plethora of products already on the market, the difficulty of differentiating drugs, and the habit of reserving truly new drugs for emergencies. Big Pharmas are backing out, creating opportunities for small companies who feel they can play successfully. But lack of interest from large partners means biotechs can't access the assets those firms hold, so many start-ups are pairing up with peers. Some firms are building businesses around an abundance of targets derived through genomics. But others are deliberately avoiding working with novel genetic code and instead studying whole cells and physiological changes in organisms. Many firms are addressing the lack of chemical diversity against targets. Some of these are pursuing diversity through natural products like marine microbes, insisting they'll fare better than earlier firms did, in part because of technological advances. Others are trying to create diversity synthetically, by taking structural approaches to understanding targets new and old, as well as compounds. Crystallography, in silico libraries, computational models and mass spectroscopy are key tools in iterative development processes that remain unproven in the anti-infectives field. Some firms are seeking to minimize the risks of novelty, by putting their efforts into developing new versions of antibiotics that worked well before resistance grew. No matter what technological approach start-ups take to developing antibiotics, all face similar challenges external to themselves-primarily in regulatory affairs and funding, but also in hunting Big Pharma partnerships.

GeneSoft Inc., a company founded to commercialize technology for interfering with gene expression using compounds that bind to grooves on DNA sequences has a wide scope of potential applications before it, but it has chosen to position itself as an anti-infective specialty pharmaceuticals company. Its direction stems not merely from unpopularity of platform models, but because it believes it's learned the lessons of its in-licensing anti-infective forebears and can pursue the strategy with lower risk.