????? 大多數(shù)藥物探索公司最初的首輪融資計(jì)劃都過(guò)于樂(lè)觀，而且都未能實(shí)現(xiàn)，因此融資要體現(xiàn)出這個(gè)因素。幾乎所有處于探索階段的初創(chuàng)型公司在設(shè)立之初都會(huì)在宣傳時(shí)說(shuō)：“30個(gè)月后我們將推出一種研究型新藥（IND）”。根據(jù)我們的經(jīng)驗(yàn)，將計(jì)劃付諸實(shí)施后，采用新的化學(xué)方法研制IND需要36-48個(gè)月。就連完美執(zhí)行的計(jì)劃也可能無(wú)法實(shí)現(xiàn)預(yù)定目標(biāo)：制藥公司Avila的BTK項(xiàng)目在該公司設(shè)立42個(gè)月后才提出IND申請(qǐng)，比首輪融資計(jì)劃預(yù)計(jì)的時(shí)間晚了12個(gè)月。考慮資金和時(shí)間要求時(shí)，將幾乎必然出現(xiàn)的耽擱和失誤包括在內(nèi)很重要。這里的第22條軍規(guī)是，如果一名創(chuàng)業(yè)者宣傳說(shuō)在48個(gè)月內(nèi)可推出IND，投資者就會(huì)反應(yīng)平平，甚至是Atlas這樣的初級(jí)投資者。這就造成大家都提出過(guò)于樂(lè)觀的計(jì)劃并將這個(gè)期限定為30個(gè)月。在盡職調(diào)查初期坦誠(chéng)這一悖論及其周圍的問(wèn)題是一個(gè)非常好的選擇。

????? 自行展開(kāi)一手資料盡職調(diào)查。針對(duì)一項(xiàng)新投資建立財(cái)團(tuán)后往往會(huì)出現(xiàn)所謂的泳池效應(yīng)，即每位家長(zhǎng)都認(rèn)為其他家長(zhǎng)會(huì)小心照看孩子，結(jié)果造成沒(méi)有人這樣做從而出現(xiàn)不好的情況。偉大的風(fēng)投公司XYZ承諾實(shí)施投資并不意味著它進(jìn)行了完善的盡職調(diào)查。我們經(jīng)歷一番波折后發(fā)現(xiàn)，不同的公司以及同一公司的不同合伙人往往會(huì)進(jìn)行程度不同的盡職調(diào)查。共享顧問(wèn)和專家沒(méi)問(wèn)題，重要的是直接和他們進(jìn)行對(duì)話，只聽(tīng)一位風(fēng)投伙伴說(shuō)“那個(gè)叫約翰什么的前研發(fā)負(fù)責(zé)人認(rèn)為這是有史以來(lái)最熱門的項(xiàng)目”還遠(yuǎn)遠(yuǎn)不夠。

????4. 超模和投資模式：情人眼里出西施。生物科技領(lǐng)域有許多不同的投資模式，而大多數(shù)公司都有自己的首選。一些公司善于進(jìn)行上市后私募投資（PIPE）和使用后期資產(chǎn)，但這不是我們所涉獵的領(lǐng)域，因?yàn)槲覀儍A向于早期創(chuàng)新，同時(shí)渴望一直從事能給我們帶來(lái)回報(bào)的工作。十年來(lái)我們采用過(guò)多種模式，并從中吸取了一些教訓(xùn)：

????? 盡早介入讓我們能塑造目標(biāo)公司的DNA。無(wú)論是最前沿還是最尖端，我們實(shí)施過(guò)的一些最佳投資都來(lái)自親自動(dòng)手來(lái)創(chuàng)建合資公司的模式。這是本博客一再提到的主題，因此暫不累述。

????? 如果可以按重大里程碑事件為界分批投入資金，那就應(yīng)該這么做。通過(guò)節(jié)流資金，投資者不僅可以監(jiān)督科技的去風(fēng)險(xiǎn)過(guò)程，還可以觀察管理團(tuán)隊(duì)的執(zhí)行情況以及如何實(shí)現(xiàn)其提出的目標(biāo)，這和前者同樣重要。以前，未分批的大規(guī)模融資曾多次燙了我們的手。我們無(wú)法很頻繁地將資金劃分為很小的批次，最理想的情況是恰當(dāng)?shù)匕阉O(shè)計(jì)為9-18個(gè)月為一個(gè)投資批次。

????? 后期“機(jī)會(huì)主義型”或投機(jī)型醫(yī)藥投資的風(fēng)險(xiǎn)往往比看上去要大得多。之前我曾更籠統(tǒng)地談到過(guò)這個(gè)主題（見(jiàn)此處）。我們對(duì)此有親身體驗(yàn)，因?yàn)槲覀円郧霸贿@種投資的美麗表象所吸引。從2003-2005年，我們一直沒(méi)有處理好風(fēng)險(xiǎn)較低、經(jīng)過(guò)重新配置的后期資產(chǎn)，比如Ivrea、ARCA、照隅（Shogoo）、Newron、Xytis和Nitec。我們從中得到的主要教訓(xùn)是避開(kāi)這樣的公司。從2007年初開(kāi)始，這些公司已經(jīng)在我們所有的新投資中銷聲匿跡了。

????? Most drug discovery companies fail to deliver on their overly-optimistic initial Series A plan, so factor that into the financing. Almost every new discovery-stage startup comes in with a pitch that says "in 30 months we'll have an IND." Unless you have your lead scaffold in hand now, you're not likely to get there in 30 months. In our experience, it takes between 36-48 months to get to an IND around novel chemistry when the plan hits reality. Even a superbly executed plan can fall short: Avila's BTK program filed its IND 42 months from the start of the company, 12 months later than forecast in the Series A plan. Factoring in the almost certain delay and slippage is important when thinking through capital and time requirements. The Catch-22 here is that if an entrepreneur pitches a plan for 48 months to an IND, even to an early stage investor like Atlas, it's likely to receive a lukewarm reception. This leads to overly optimistic plans from everyone that 30 months can do it. It's very healthy to have a frank conversation about this paradox and the issues around it early in a diligence process.

????? Do your own primary diligence. Often when syndicates form around a new deal, the proverbial summer pool effect happens: Since every parent thinks other parents are diligently watching the kids, no one does and bad things happen. Just because great VC firm XYZ is committing to do the deal doesn't mean they did great diligence. We've learned the hard way that different firms, and different partners in the same firm, often do varying degrees of diligence. Sharing consultants and experts is fine, but having a direct dialogue with them is important: taking a fellow VC's word for it that "former head of R&D John Doe thinks this is the hottest program ever" is simply not sufficient.

????4. Super models and investment models: Beauty is in the eye of the beholder. Lots of different investment models work in biotech, and most firms have their favorite. Some firms have done well with PIPEs and later-stage assets, but it's just not a space we've engaged in given our early stage innovation bias and the desire to keep doing what works for generating returns for us. Our experience with different models over the past decade has led to a few lessons for us:

????? Going in early allows us to shape the DNA of the company. Whether it turns out to be the bleeding edge or leading edge, some of the best deals in our portfolio over time have come from the roll-up-your-sleeves model of venture creation. This is a recurrent theme on this blog, so I'll leave it at that.

????? If you can tranche the capital into a deal around important milestones, you should. By metering in the money, an investor can monitor not only the derisking of the science, but equally important we can observe how the team executes and delivers what they claim. We've been burnt repeatedly in the past on the big raises that weren't tranched. These can't be anorexic high frequency tranches of funding, but appropriately designed 9-18 month tranching is optimal.

????? Later-stage 'opportunistic' or spec pharma deals are often much riskier than meets the eye. I've riffed on this theme before more generally (here), but we know this first hand because we've previously been seduced by their siren song. We've not done well with low-risk repositioned late stage assets like Ivrea, ARCA, Shogoo, Newron, Xytis and Nitec from the 2003-2005 period. Our big takeaway lesson was to avoid these type of plays, and you won't find them in any new deals since early 2007.