In recent years, most venture capital firms have focused on investing in companies with well-developed product pipelines. In this issue of START-UP, we profile two trendsetters: Fred Cohen, managing director at Texas Pacific Group Ventures; and Christoph Westphal, formerly a partner at Polaris Ventures and now vice chairman and CEO of Sirtris Pharmaceuticals. Both men are physician scientists turned investors, who have tapped into their scientific and clinical knowledge to make investments in "high concept" discovery stage companies. And although the investments are intriguing, it's too early to say whether or not the strategies adopted by these two men will yield returns for their backers.

By the end of this year, three major US venture firms---JP Morgan Partners, the American affiliate of Apax, and MPM Capital--will be transformed. Their partners are leaving; their strategies are changing. And their stories are all marked by their common failure to combine early-stage biopharmaceutical venture capital with later-stay growth capital and buyouts into so-called "balanced funds."

VCs worried about depressed financial markets and demanding Big Pharma customers are being tough on almost all start-ups seeking funding-but no tougher than on their existing portfolio companies. For some, hard times are creating opportunities. The circumstances of companies that raised money in the past few years are impacting newer firms now. Even organizations that met their milestones have seen valuations plummet, and are struggling to get financing. The down market is making it more desirable and easier for VCs to invest in late-stage start-ups. In-licensing has been popular, but investors are increasingly seeking value-priced components to fill out existing firms or launch new ones. Investors haven't stopped doing early-stage deals, but they're looking for firms with advantages that can reduce risk or cost, or speed a company to market. Drugmakers that used to sign big-money deals are now demanding that start-ups prove their technologies' merits through short-term, inexpensive pilot programs. Some firms aren't so pressed by hard times. VCs are promising stellar founders lots of support and time to take big risks they bet will pay off handsomely.

Start-Up showcases the following recently launched companies: Acceleration bioPharmaceuticals Inc., Appro Healthcare Inc., HaptoGuard Ltd. and Kemia Inc.