生物科技公司初期投资实战宝典

    • 生物科技行业不会经常出现快车道，除非它通向垃圾堆。迅速获得美国食品药品监督管理局（FDA）批准或短期内实现并购利益的承诺大多都是空头支票。我们曾听到过的类似承诺包括“这是退出前的最后一次融资”或者“二期临床进展顺利”，目的是在我们知晓结果前筹集到资金。2005年前后，这种后半程宣传让我们蒙受了两次损失，那就是Ivrea和Proprius。它们的产品均已进入二期临床，但受试验方案等令人困惑的变量影响，二者的结果都变得完全无法解读。迅速进入三期临床的道路至此戛然而止。现在我们更愿意把重点放在可持续的价值创造上，因为这个主题要可靠得多。

    • 通过吸收带有各类风险或处于各种临床阶段的资产来实现多元化往往会破坏价值（这个主题以前我也提到过）。用处于二期临床的授权资产和一个临床前项目组建一家公司并不明智，因为产品所处的阶段与其价值并不对称：二期临床项目需要消耗资金并且预示着公司的未来，而临床前资产的价值可能随之上升，也可能随之下降。

    此外，即使资产处于类似阶段，它的价值一般也会存在差异。如果所加入的第二项资产没有第一项资产那么吸引人，而仅仅是为了让管理团队派上用场，那就会让人觉得是滥用资金；应当通过其他途径来使用管理团队（比如在其他所投资的公司担任兼职）并将摊薄资产的门槛保持在非常高的水平。这是我们在5年多前得出的结论，它促成了我们的投资模式，即针对单一项目，以资产为中心，比如Stromedix的单克隆抗体STX-100。这一结论和医药行业的外部化趋势造就了我们的Atlas Venture Development Corp。

    • 超薄虚拟模式（ultra-lean virtual model）非常好，但有局限性。比如，如果没有自己的生物实验室来进行特定工作，就难以组建大型生物科技公司（不过也可以说在这方面我们还没有真正犯过错误）。给我们带来教训的是虚拟模式在其他经营领域的局限性。如果初创型公司的核心创业者很少，那么在不停止或放缓研发的情况下进行融资或业务开发就会非常困难。对于一个人员较少的管理团队来说，配合多家医药公司或多名潜在投资人派来的大量专家进行全面尽职调查所牵扯的精力让人难以置信。迅速找到把精力集中在业务开发方面的办法很关键。如果能通过业内人士组建一个强大的财团从而无须融资，由此产生的益处也会让人不敢相信。在那些较倾向于虚拟模式的投资中，我们当然很注意这一点。

    5. 律师是必要的反派。我们还回顾了在法律、知识产权和签署协议方面的经验，目的是看一看是否能从中吸取教训。要成功完成投资，好的法律建议显然非常重要，特别是在防止不利态势恶化方面。

    • 专利对生物科技行业来说很关键，所以要在投资前对知识产权进行深入的尽职调查，不可草率。它帮助我们避免了一些投资失误。我们在知识产权方面只出过一次大的纰漏，它改变了一家公司的发展轨迹。那是2004年，Dynogen还有几个月就可完成规模为5,000万美元（约3.11625亿元人民币）的第二轮融资（未分批进行！），这时出现了一项意料之外的专利，使该公司的主打产品——用于治疗膀胱过动症的复方制剂DDP200项目受到了影响。从某种角度来说我们还是幸运的。但在投资前，知识产权尽职调查应排在首位。我们发现，拥有最佳知识产权实践策略的生物科技公司通常每过几年就会聘用外部公司来进行知识产权审计，以确保自身经营没有缺陷。

    • 对关键投资，投资者应详细阅读合同。和上述尽职调查类似，盲目相信董事会其他成员已经读过关键的投资文件，这不是什么好的策略。事后才发现意外之处会让人很痛苦。我们曾多次遇到这种情况，结果也让人不舒服。

    • Quick flips in biotech don't happen often, unless it's a flip to the trashcan. Promises of quick FDA approvals or near term M&A interest are most often empty claims. We've all heard the "this is the last financing before an exit" pitch, or "the ongoing Phase 2 is going well" in order to close a financing before opening the envelope. This latter pitch burnt us twice in the mid-2000s: Ivrea and Proprius both had inherited ongoing Phase 2s, both of which readout as completely uninterpretable due to protocol issues among other confounding variables. So much for the quick path to Phase 3. We'd prefer to focus on sustainable value creation as the thesis is much more credible.

    • Company diversification by adding assets across risk or clinical stage often destroys value (another theme I've mentioned before). Forming a company with a Phase 2 in-licensed asset and a preclinical program isn't smart due to the stage and value asymmetry: the Phase 2 program consumes the capital and dictates the future of the company, dragging the preclinical asset either up or down.

    Furthermore, even if the assets are of similar stage, they typically aren't of similar merit. Adding a second asset to a story that's not quite as compelling to the first just to make use of a management team feels like the wrong use of capital; figure out other ways of leveraging a team (e.g., part-time roles at other portfolio companies) and keep the bar for asset dilution very high. These observations 5+ years ago led to our asset-centric investment model around single program entities, like Stromedix's STX-100 focus. Our AVDC initiative was born out of this observation in conjunction with Pharma's externalization trend.

    • Ultra-lean virtual models are great, but they have their limitations. For instance, big biology plays are hard to do without your own wet lab to do the bespoke work (though it’s fair to say we haven't really gotten that wrong yet). Where we've felt some pain is around the constraints of the virtual model on other operational elements: when you have only a few key entrepreneurs in a startup, it’s very hard to go on the road for fundraising or BD without stalling or slowing the work on the R&D front. It can be incredibly distracting for a lean team to enter full due diligence with an army of experts from multiple pharmas or potential investors. Figuring out how to focus the BD campaign quickly is essential, and if one can avoid fundraising by having a strong insider syndicate that's incredibly helpful. This is certainly something we are mindful of in our more virtual plays.

    5. Lawyers are a necessary evil. We also looked at our legal, IP and deal-making experiences to see if there were lessons here. Getting good legal advice is clearly very important to successfully navigating deals, especially in preventing bad outcomes from becoming worse.

    • Patents are critical to biotech, so don't skimp on doing deep IP diligence before investing. This has helped prevent us from doing some bad deals. We've only really had one big IP blow-up that changed a company's trajectory: within months of the Dynogen $50 million Series B closing in 2004 (no tranching!), a unexpected patent appeared that impaired the lead DDP200 program. So in some ways we've been lucky. But IP diligence goes beyond doing work before an investment; we've found that biotechs with best practice IP strategies often have an IP audit by an outside firm every couple years to ensure they are on strong ground.

    • For critical deals, investors should read the contract details. Similar to the diligence point above, trusting that others in the boardroom have read the critical deal documents isn't always a great strategy. Having a surprise appear after the fact can be a painful realization. We had this happen multiple times with uncomfortable outcomes.