Are Biotechnology Startups Different?

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Are Biotechnology Startups Different? Hervé Lebret Ecole Polytechnique Fédérale de Lausanne Vice-Presidency for Innovation, CH-1015 Lausanne, Switzerland Email: herve.lebret@epfl.ch Phone: +41 21 693 70 54 Orcid : https://orcid.org/0000-0002-2420-1216 Abstract In the domain of technology startups, biotechnology has often been considered as specific. Their unique technology content, the type of founders and managers they have, the amount of venture capital they raise, the time it takes them to reach an exit as well as the technology clusters they belong to are seen as such unique features. Based on extensive research from new databases, the author claims that the biotechnology startups are not as different as it might have been claimed: the amount of venture capital raised, the time to exit, their geography are indeed similar and even their equity structure to founders and managers have similarities. The differences still exist, for example the experience of the founders, the revenue and profit level at exit. Keywords: startup, innovation, venture capital, technology, biotechnology, entrepreneurship JEL classification numbers: L26, L65, M13, O32, Q55. Introduction Startups have been a major phenomenon of technology innovation in the last 60 years and can be dated to the beginnings of Silicon Valley in 1957. Among them, biotechnology startups have been a more recent and as important phenomenon. Their beginnings can be traced to Cetus Corporation and Genentech, both founded in the 70s, also in Silicon Valley. Today, biotechnology has become an industry in itself with some unique features. It is generally considered that the scientific content of biotechnology firms is higher than their counterparts and given the lengthy clinical trials associated with their growth, their development is slower, more costly and even riskier. The literature on biotechnology startups is rich both from an academic as well as business-oriented standpoint. A few general books can be quoted (Shimasaki 2014, Binder 2008, Hughes 2011) and academic work is numerous even if again a few articles are worth being mentioned (Audretsch 2001; Bradford 2003; Brännback et al. 2009; Zahn and Patel 2005; Zucker et al. 1998). A recent publication by Tzabbar & Margolis (2017) exemplifies some unique features of the roles of founders. Through research launched since 2010, the author has built two databases of information related to technology start-ups. The first one analyzes more than 5 600 Stanford-affiliated corporations and entrepreneurs (Lebret, 2017a) with a focus on fields, fundraising of the companies and background of the founders; the second one deals with more than 400 companies which had filed to go public (Lebret 2017b), with more focus on the equity structure of the companies. Both data sets include a large enough number of biotechnology startups which make it possible to revisit the specific features (if any) of these among high-tech startups. The features of the startups It seems to be common knowledge that biotechnology 1 startups would be different because of the nature of their lengthy and costly process from invention to commercialization. This would induce a longer than usual time to exit for startups as well as more fund raising from (private) investors such as venture capitalists. Some of our results are shown in Table 1 for the Stanford-related companies. The relatively surprising results are: biotechnology companies do not raise more venture capital (even if a higher percentage of firms access their 1 Biotechnology (or biotech) uses living organisms to develop drugs whereas medical technologies (or medtech) deal with the development of medical instruments through electronics, mechanics and even information technologies (IT).

capital), they do not take more time to exit (time to exit means the number of years from foundation to either an acquisition M&A, an initial public offering - IPO or a liquidation); a much higher ratio of these goes public and fewer are acquired. Field # #VCbacked VC VC ($M) Time to exit # M&As M&A M&A ($M) # IPOs IPO Value at IPO ($M) 12m. after IPO Biotechnology 258 171 66 44 6.6 66 26 77 82 32 203 176 Medtech 211 146 69 37 7.8 76 36 144 48 23 237 185 IT Hardware 879 485 55 49 7.9 378 43 219 154 18 635 443 IT Software 803 380 47 34 6.6 336 42 137 78 10 577 661 Internet 745 395 53 42 4.0 269 36 159 66 9 1 977 2 477 Other tech. 192 27 14 110 11.0 39 20 124 12 6 297 521 Total 2 3 088 1 604 52 43 6.5 1 164 38 167 440 14 687 711 Table 1: Features of startups by field: venture-capital (VC), years to exit, merger and acquisition (M&A) and initial public offering (IPO). Source: Stanford- affiliated corporations (Lebret 2017a). The explanations may be not very complex to guess as for example one unique feature of biotechnology companies is to go public on stock exchanges much earlier than others as Table 2 illustrates in terms of commercial development of the company (revenues, profits, employment). The difference in the type of exits (IPO vs. M&A) and value created at exits can be again correlated to the longer time span to profitability. Field # Sales ($M) Income ($M) FTEs Biotech. 122 10-17 76 Medtech 22 21-12 173 HW/Comp./Tel 68 92-7 432 Semiconductor 36 63-5 386 Software 62 110 1 582 Internet 106 336 3 1344 Energy/Env. 17 58-48 500 Other 6 169-15 391 Total 439 124-8 563 Table 2: Additional features of startups by field:sales, incomes and employees at time of IPO (filing) Source: Lebret 2017b. Table 3 gives the list of the most active venture capitalists in the Stanford-related high-tech companies. Whereas biotech has been considered as a field with its own specialized investor funds, the reality is that the most active funds in biotech are in fact general funds (the ones in italics in the table). VC Deals VC investing in Biotech Deals VC investing in Biotech Deals Kleiner Perkins Caufield & Byers 141 Kleiner Perkins Caufield & Byers 29 Brentwood Venture 5 Sequoia Capital 125 New Entreprise Associates 16 Advent Venture Partners 5 New Entreprise Associates 114 Alta Partners 14 Arch Venture Partners 5 Mayfield Fund 93 Venrock Associates 13 Bay City Capital 5 Draper Fisher Jurvetson 79 Abingworth Management 11 Flagship Ventures 5 Accel Partners 65 Mayfield Fund 11 HBM Bioventures 5 Institutional Venture Partners 65 Sequoia Capital 11 Novartis Venture Funds 5 Mohr Davidow Ventures 56 InterWest Partners 9 Prospect Venture 5 U.S. Venture Partners 56 Asset Management Company 8 CDIB Bioscience 4 Menlo Ventures 54 Institutional Venture Partners 8 Charter Life Sciences 4 Sutter Hill Ventures 53 Morgentahler Ventures 8 Montreux Equity 4 Venrock Associates 50 MPM Capital 8 Skyline Ventures 4 InterWest Partners 48 Domain Partners 7 GSK 3 Greylock Partners 48 Sofinova Partners 7 Longitude Capital 3 Benchmark Capital 47 Versant Ventures 7 OrbiMed Advisors 3 Morgenthaler Ventures 39 Aberdare Ventures 6 Pfizer 3 Norwest Venture Partners 37 Oak Investment Partners 6 Polaris 3 Bessemer Venture Partners 36 Oxford Bioscience Partners 6 Rho Management 3 Oak Investment Partners 35 SR One 3 Alta Partners 33 U.S. Venture Partners 3 Table 3: Most active venture capital funds overall and in biotechnology. Source: Lebret 2017a. There are however specialized funds in biotech such as Abingworth Management, Asset Management Company, MPM Capital, Domain Partners, Sofinova Partners, Versant Ventures, Aberdare Ventures or Oxford Bioscience Partners among the most active ones (but this is not different from other fields such as IT which also has its dedicated funds such as Andresseen Horowitz, the Founders Fund or Benchmark Capital). Kleiner Perkins 2 The 5'800 corporations affiliated to Stanford University include companies in the fields of finance, law, consulting, and are not considered as high-tech start-ups.

Caufield & Byers is the most active fund and interestingly enough was a fund which invested in both Cetus and Genentech, the first biotechnology startups ever The features of the founders and management teams The two databases provide also interesting information about the founders, managers and equity structure of the startups. Table 4 shows the relatively higher percentage of professors, PhDs and lower percentage of MBAs among biotechnology founders whereas Table 5 illustrates the higher age of founders, their smaller equity ownership at IPO as well as the higher ownership of investors and new shareholders at IPO. Field professors PhDs MBAs Licenses from Stanford Biotechnology 70 27 62 24 45 17 83 32 Medtech 44 21 21 10 38 18 42 20 IT Hardware 83 9 304 35 115 13 50 6 IT Software 48 6 174 22 191 24 28 3 Internet 19 3 76 10 276 37 5 1 Other tech 6 3 32 17 49 26 6 3 Total 270 9 669 22 714 23 214 7 Table 4: Involvement of Stanford professors, PhDs and MBAs. Source: Lebret 2017a. Field Founders' Ownership Non founding CEOs Age Founders Employees Investors IPO # Biotech. 45 7 15 57 22 52 43 Medtech 42 8 18 52 22 8 36 HW/Comp./Tel 37 13 28 45 16 26 38 Semiconductor 38 12 26 44 18 15 42 Internet 33 17 22 48 14 33 31 Software 33 17 27 41 17 16 26 Energy/Env. 37 8 20 55 18 7 41 Other 39 10 21 52 20 3 50 Total 38 13 22 49 18 160 36 Table 5: Features about founders, non-founding CEOS and other shareholders. Source: Lebret 2017b. One can link the higher status of founders (professors, PhDs) in biotechnology with their age, when founding companies and this seems to be also an illustration of the higher scientific content of the startups or longer experience of the founders, which can exist after many years of research only. As a non-surprising and correlated note, the non-founding CEOs are relatively more frequent. Professors seldom leave their academic position and do not have full-time, not even executive positions in the startups, but have often advisory roles. Region Biotech Medtech Software Internet HW/Comp./Tel Semicon. Energy/Env. Other Total Silicon Valley 15 4 13 26 20 7 6 2 93 Boston Area 22 2 5 5 3 3 1 41 Southern California 17 5 1 2 1 26 West Coast 3 2 3 2 1 1 12 East Coast 20 3 5 1 2 31 Midwest 2 2 3 1 2 1 11 Switzerland 7 2 1 1 11 United Kingdom 2 3 5 France 4 3 1 3 5 2 1 19 Other EU 1 3 3 2 9 China 1 1 8 10 Israel 1 1 1 3 Rest of the World 1 2 2 5 Total 93 16 36 62 36 12 17 4 276 Table 6: Geographic information about 276 firms which had filed for an IPO since 2007. Source: Lebret 2017b. The two main technology clusters are well-known to be Silicon Valley and the Boston area. Indeed Boston is argued to be the biotech cluster. The numbers in Table 6 slightly mitigate that point of view as California as a whole has more start-ups than Boston but it remains a fact that Boston has a higher proportion of biotech startups than Silicon Valley, but not more than Southern California though. Features about licensing Licensing of technologies for high-tech companies is an important topic. Many not to say most high-tech startups are dependent at foundation upon intellectual property (IP) such as patent applications. The last column of

Table 4 shows that biotechnology companies are even more dependent than others upon IP licensing from Stanford University. The database of companies having filed to go public shows similar results. Out of the 430 filings, 38 companies had indicated licensing technologies from a university, out of which 24 were biotechnology companies (63 of the total even if this last figure may not be statistically relevant). The license terms are generally a combination of equity in the startup and royalties on sales. It is interesting to notice that the average equity stake of universities in biotech startups is 10 at creation and 5 after series A (of an average size of $6M), numbers which are typical of academic licenses to startups in any technology field (Lebret 2017b). The main difference in academic licenses with biotechnology startups has not to do with the equity component but with the royalty one. Royalties typically range from 2 to 4 of revenues based on licensed IP in biotech and this even replaces the equity component in some cases. Royalties are (known to be) much less accepted in other fields. This might have to be related to the revenue amount at time of exits which are much lower in biotech than in other fields so that managers and investors in biotech might be less sensitive to that last feature. As a conclusion Even if the author tried to provide mainly facts and figures from two specific databases, it is interesting to try and interpret this data. The higher scientific content of biotech startups seems to be confirmed by the nature and status of their founders. Their lengthy development is not confirmed during their phases as private firms but only through their situation at IPO: biotech firms go public with less commercial validation, and therefore before the end of their clinical trials. The IPO is just another step in their funding process and not a final validation of their commercial prospects. Biotech are embedded in the same technology clusters as the other high-tech startups and they are often funded by the same venture capitalists. In any case, startups have developed historically in parallel with venture capital, and this industry has indeed shaped the high-tech corporations through their own model. With a ten-year life span VC funds must experience exits of their portfolio company during the fund life. They have also shaped the management and equity structure of these companies to maximize their likeliness of success. These facts may be illustrations of why biotech startups are not very different from other technology startups, despite their different initial content. References Audretsch, D. (2001) The Role of Small Firms in U.S. Biotechnology Clusters. Small Business Economics 17: 3 15. Binder G. (2008) Science Lessons, What the Business of Biotech Taught Me About Management. Boston, MA. Harvard Business Review Press. Bradford, T. (2003) Evolving symbiosis--venture capital and biotechnology.nature Biotechnology, 21 (9) 983-4. Brännback M., Carsrud A., Renko M., Östermark R., Aaltonenand J. & Kiviluoto N. (2009) Growth and Profitability in Small Privately Held Biotech Firms: Preliminary Findings. New Biotechnology, 25 (5) 369-376. Edwards M., Murray, F. & Yu R. (2003) Value creation and sharing among universities, biotechnology and pharma. Nature biotechnology, 21 (6) 618-24. Hughes, S. S. (2011) Genentech, the Beginnings of Biotech. Chicago, Il. The University of Chicago Press. Lebret, H. (2017a) Startups and Stanford University https://arxiv.org/abs/1711.00644 Lebret, H. (2017b) Equity in Startups https://arxiv.org/abs/1711.00661 Shimasaki, C. (2014) Biotechnology Entrepreneurship: Starting, Managing, and Leading Biotech Companies. Academic Press.

Tzabbar, D. & Margolis J. (2017) Beyond the Startup Stage: The Team s Human Capital, New Venture s Stage of Life, Founder CEO Duality, and Breakthrough Innovation. Organization Science 28(5):857-872. Zhan J. & Patel N. (2005) The Dynamics of California s Biotechnology Industry. San Francisco, CA. Public Policy Institute of California. Zucker L., Darby M. & Brewer M. (1998) Intellectual Human Capital and the Birth of U.S. Biotechnology Enterprises. The American Economic Review, 88, (1) 290-306.