Skin in the Game: An Analysis of Venture Capital Investment in Dermatology from 2002 to 2021

Abstract

View Large Image Figure ViewerDownload Hi-res image Download (PPT) Across >$9 billion invested in dermatology companies from 2002-2021, annual deal counts, total investment value, and the range of deal sizes have increased, while average investment size and post-investment company valuations decreased; funding was largely directed to pharmaceuticals/biotechnology, though historical maximum funding amounts for clinics/outpatient services, health information technology, and medical devices were achieved in 2021. Venture capital (VC) financing plays a central role in bringing novel technologies, therapeutics, and processes into clinical practice (Cwalina et al., 2022Cwalina T.B. Jella T.K. Acuña A.J. Samuel L.T. Kamath A.F. Venture capital investment in orthopaedics: has the landscape changed over the past two decades (2000–2019)?.Surg Innov. 2022; 29: 103-110Google Scholar; Rathi et al., 2019Rathi V.K. Murr A.H. Feng A.L. Tauscher J.L. Naunheim M.R. Kozin E.D. et al.Analysis of venture capital investment in therapeutic otolaryngologic devices, 2008–2017.JAMA Otolaryngol Head Neck Surg. 2019; 145: 387-389Google Scholar). The role of VC in medicine has been expanding; a notable example is the digital health segment, where the growth rate of the total invested amount was over five times higher than that of all other fields from 2010 to 2017 and over 25 times higher than the growth rate of overall healthcare spending during the same period (Gondi and Song, 2019Gondi S. Song Z. The burgeoning role of venture capital in health care. Health Affairs.https://www.healthaffairs.org/do/10.1377/forefront.20181218.956406/Date: January 2, 2019Date accessed: July 30, 2022Google Scholar). In the field of dermatology, traditional private equity buyouts of physician practice groups have increasingly received attention (Tan et al., 2019Tan S. Seiger K. Renehan P. Mostaghimi A. Trends in private equity acquisition of dermatology practices in the United States.JAMA Dermatol. 2019; 155: 1013-1021Google Scholar). VC investing, by contrast, is conventionally associated with acquiring a stake in a private business at an earlier stage often long before a company has any commercial products or revenues, with the intent of selecting and helping to grow businesses with the highest expected promise for an outsized return on invested capital (Lehoux et al., 2016Lehoux P. Miller F.A. Daudelin G. How does venture capital operate in medical innovation?.BMJ Innov. 2016; 2: 111-117Google Scholar). Innovation in dermatology is broad, ranging from precision biopharmaceuticals to mobile and even behavioral health (Bezalel and Otley, 2019Bezalel S.A. Otley C.C. Invention in dermatology: a review.J Drugs Dermatol. 2019; 18: 904-908Google Scholar). Effective development and clinical translation from early-stage ventures would be expected to require significant capital (Cwalina et al., 2022Cwalina T.B. Jella T.K. Acuña A.J. Samuel L.T. Kamath A.F. Venture capital investment in orthopaedics: has the landscape changed over the past two decades (2000–2019)?.Surg Innov. 2022; 29: 103-110Google Scholar). A recent analysis indicated that both VC deals and total funding have grown since 2011 in the broader skin-related sphere, which in one published analysis included skin-related consumer products that make up an outsized percentage of such funding (Venkatesh and Nambudiri, 2022Venkatesh K. Nambudiri V. Characterization of venture capital investments in dermatology: a cross-sectional analysis, 2011 to 2021.J Am Acad Dermatol. 2022; ([e-pub ahead of print])https://doi.org/10.1016/j.jaad.2022.06.1177Date accessed: July 10, 2022Google Scholar). However, given the implications of VC-driven commercialization for patient care and healthcare markets (Cwalina et al., 2022Cwalina T.B. Jella T.K. Acuña A.J. Samuel L.T. Kamath A.F. Venture capital investment in orthopaedics: has the landscape changed over the past two decades (2000–2019)?.Surg Innov. 2022; 29: 103-110Google Scholar), it is important for stakeholders, including researchers, providers, and payers, to understand the evolving impacts of VC in areas of dermatology that involve the diagnosis and management of diseases. In this study, using a private capital markets information database, we characterize significant trends in dermatology VC financing activity worldwide over a 20-year period from 2002 to 2021. In total, there were 873 VC deals involving dermatology-focused companies from 2002 to 2021, totaling $9.1 billion of investment (Figure 1a). Inflation over this same period totaled 50.6%. Of these deals, 641 (73.4%) were in pharma/biotech, 49 (5.6%) were in clinic/outpatient services, 65 (7.5%) were in health information technology (IT), and 118 (13.5%) were in medical devices. Annual deal count (mean = 43.7, range = 12‒72) increased at an average rate of 11.5% or 2.89 deals per year, with the greatest annual increases of 46.7% (seven deals) and 46.2% (12 deals) seen in 2006 and 2010, respectively (Figure 1a). Deal count has remained on a primarily upward trajectory, although 2014, 2017, and 2020 exhibited the largest drops in the most recent decade of 11 (17.7%), 11 (15.7%), and 4 deals (5.7%), respectively (Figure 1a). The change in deal count in 2021 represented the smallest recorded positive growth at one deal (1.5%) and a total of 67 deals, not recovering to the levels seen in 2018‒2019, before the COVID-19 pandemic (average of 71 deals) (Figure 1a). Total annual invested capital (mean = $452.8 million, range = $124.3–$995.6 million) has been on an upward trend of $23.4 million (14.5%) annual growth, although this displays cyclicality, with the 2002‒2011 annual average being $296.4 million and that of 2012‒2021 being $609.2 million (Figure 1a). Although there was less volatility in the 2000s, in the most recent decade, 2018 and 2019 were marked by increases in total annual investment of $306.1 million (69.5%) and $248.8 million (33.3%), respectively, whereas 2020―the year in which the global COVID-19 pandemic began in earnest―showed the greatest decrease, $413.4 million (41.5%); recovery in the following year was only $102.3 million (17.6%) (Figure 1a). The average overall deal size (mean = $10.4 million, range = $10,000–$299.2 million) was highly cyclical for each segment. The average annual change in deal size decreased by $1.2 million in the first decade and increased by $140,000 in the second decade, resulting in an average annual decline of $520,000 over the entire period (Figure 2a). The average deal size was $12.1 million for pharma/biotech, $4.7 million for clinic/outpatient services, $5.5 million for health IT, and $6.0 million for medical devices. Pharma/biotech and medical devices had associated VC activity since 2002, whereas health IT contributions began in 2010, and clinic/outpatient investments emerged in 2011 (Figure 2a). The total investment amount in all segments also showed cyclicality. From 2002 to 2011, the average total annual investment in dermatology-related pharma/biotech was $267.3 million and was $508.5 million from 2012 to 2021, although a decrease of $360.2 million (41.8%) in total pharma/biotech funding was seen in 2020 (Figure 2b). Funding in this category was at its lowest in 2003 ($124.0 million) but peaked in 2019 ($861.8 million) (Figure 2b). Average annual total funding for clinic/outpatient services, health IT, and medical devices was $5.6 million, $6.9 million, and $27.1 million, respectively, in the first decade and $22.3 million, $34.2 million, and $44.1 million, respectively, in the subsequent period (Figure 2b). All sectors experienced drops of at least 22% in 2020 but rebounded to historical maxima in 2021 at $48.0 million, $103.3 million, and $110.5 million, respectively, and since their corresponding VC activity inception years, they have grown by $42.4 million (758%), $96.01 million (132%), and $79.0 million (251%), respectively (Figure 2b). Overall minimum deal size decreased from $750,000 to $30,000 during 2002‒2011 and further to $10,000 in 2021, whereas the maximum deal size was relatively stable during the first decade at an average of $49.4 million, although it reached its height at $299.2 million in 2019 (Figure 1b). Of the 873 total deals, 360 had disclosed premoney and postmoney valuations. During the first decade, premoney and postmoney valuations averaged $48.6 million and $65.9 million, respectively, and $43.0 million and $54.50 million in the second period, respectively (Figure 1c). The difference between average premoney and postmoney valuations during 2012‒2021 was $5.3 million less than that during 2002‒2011 (Figure 1c). Of all dermatology companies in which a VC investment was made, 188 (57%) were headquartered in the Americas, 93 (28.2%) were headquartered in Europe, 43 (13%) were headquartered in Asia, and 6 (1.8%) were headquartered in Oceania. VC investment can be a useful representation of the direction of innovation within a specific field (Ackerly et al., 2009Ackerly D.C. Valverde A.M. Diener L.W. Dossary K.L. Schulman K.A. Fueling innovation in medical devices (and beyond): venture capital in health care.Health Aff (Millwood). 2009; 28: w68-w75Google Scholar), and monitoring trends can help stakeholders to better understand the broader environment of VC-driven impacts. Venture funding has been characterized as three times more effective than traditional research and development spending in developing intellectual property (Ackerly et al., 2009Ackerly D.C. Valverde A.M. Diener L.W. Dossary K.L. Schulman K.A. Fueling innovation in medical devices (and beyond): venture capital in health care.Health Aff (Millwood). 2009; 28: w68-w75Google Scholar). Although inherently a form of private equity, VC differs from traditional private equity by its focus on early stages companies, often development stage and before commercial, where there is a high risk from a large startup failure rate (53%) and extended illiquidity (Ackerly et al., 2009Ackerly D.C. Valverde A.M. Diener L.W. Dossary K.L. Schulman K.A. Fueling innovation in medical devices (and beyond): venture capital in health care.Health Aff (Millwood). 2009; 28: w68-w75Google Scholar), making significant commercialization and business growth necessary for investors to receive a favorable return on investment. As a result of the broad-scale appeal and dissemination required for the business growth needed to qualify a successful investment, VC has been previously described as a positive force for advancement in medical fields (Shah and Berry, 2020Shah R.N. Berry O.O. The rise of venture capital investing in mental health.JAMA Psychiatry. 2020; 78: 351-352Google Scholar). Recent analyses have shown VC activity to be increasing across many different medical specialties. From 2000 to 2019, orthopedics VC deal numbers have grown at a rate of 9.53%, and total investment value has grown by nearly 5% (Cwalina et al., 2022Cwalina T.B. Jella T.K. Acuña A.J. Samuel L.T. Kamath A.F. Venture capital investment in orthopaedics: has the landscape changed over the past two decades (2000–2019)?.Surg Innov. 2022; 29: 103-110Google Scholar). In plastic surgery, from 2011 to 2018, total annual VC funding rose by over 600% to over $350 million at the end of the period (Khetpal et al., 2022Khetpal S. Pourtaheri N. Lopez J. Alperovich M. Venture capital investments in plastic surgery: an 8-year analysis.Plast Reconstr Surg. 2022; 149: 179e-180eGoogle Scholar). Ophthalmologic VC funding increased by over 90% overall from 2011 to 2020, reaching $680 million in 2020 (Gupta et al., 2022Gupta S. Uppal N. Chang E.K. Fetter T. Hunter D.G. Trends in venture capital investments in ophthalmology companies (2011–2021).Ophthalmology. 2022; 129: 353-354Google Scholar). Our analysis reveals that investment growth in many other specialties is outpaced by that in dermatology, where the overall deal count has increased by over 11% annually, funding amount has increased by nearly 15% annually, and the respective annual invested capital has attained larger total amounts than those of the ending years of all specialty-specific analyses mentioned earlier. Within dermatology, the vast majority of VC deals since 2002 were in pharma/biotech and medical devices, although clinic/outpatient services and health IT began receiving attention around the end of the first decade, indicating that although the primary emphasis is on therapeutic development, more implementations of technology and novel care delivery/evolved patient experiences may characterize the future of dermatologic practice. The largest deals with implications in care delivery involve vertically integrated dermatology telehealth services with direct prescription delivery, on-demand digitized pathology services, and technologically driven customized treatment planning coupled with rapid-service dermatology office locations, among others in related domains. Our analysis shows that deal count almost consistently increased during every year in the evaluated period, although to a larger degree from 2002 to 2011, before recently stabilizing around the high-60s annually during 2017‒2021. The increased number of investments in clinically relevant ventures by VC firms suggests both the expansion of dermatologic innovation in areas of relevance to patient care and increasing confidence in the specialty at large. This may also underscore an expected greater demand for dermatologic services in the near future, consistent with skin disease’s role as a top five leading cause of nonfatal disease and the associated threat to QOL and mental health (Seth et al., 2017Seth D. Cheldize K. Brown D. Freeman E.F. Global burden of skin disease: inequities and innovations.Curr Dermatol Rep. 2017; 6: 204-210Google Scholar). Although there were notable decreases in deal making in 2014 and 2017, subsequent years consistently marked complete recovery, showing the general resilience of dermatology VC investment over the longer term. Importantly, deal count decreased in 2020 as well; although lower in magnitude and proportion, it did not recover in 2021 to previous levels, likely attributable in part to continued public health and economic impacts of the COVID-19 pandemic and shifts in investment priorities. In parallel with the increase in deal count, overall total annual investment has increased as well since 2002, with slumps in the mid-2010s and 2020, consistent with the shift in VC’s focus to invest over 40% more in pandemic-related areas (Bellucci et al., 2022Bellucci A. Borisov A. Gucciardi G. Zazzaro A. The reallocation effects of COVID-19: evidence from venture capital investments around the world.J Bank Financ. 2022; : 106443Google Scholar). In the context of growing annual funding and deal counts, it is important to note that minimum deal size has decreased by over 98% since 2002 and that average deal size has increased in all segments except pharma/biotech. The observed increase in average deal size for three of four segments is in agreement with broader VC trends, where there is a growing preference for larger later-stage investments (Colecchi and Tancredi, 2016Colecchi C. Tancredi D. Broadview ventures: investing in the future of cardiovascular technology.JACC Basic Transl Sci. 2016; 1: 87-93Google Scholar). Conversely, in pharma/biotech, the trend of smaller average deal size is more suggestive of an increasing focus on early-stage investments and greater portfolio diversification for investors (more deals at fewer dollars per deal). Although in contrast to other segments, this finding may reflect an increase in open innovation, where multinational pharmaceutical corporations are engaging in more investments into and acquisitions of smaller pharmaceutical ventures to mitigate the risks of failure and to more efficiently fill their own pipelines (Schuhmacher et al., 2016Schuhmacher A. Gassmann O. Hinder M. Changing R&D models in research-based pharmaceutical companies.J Transl Med. 2016; 14: 105Google Scholar). An openness to acquiring external innovation by big pharma and big biotech can render smaller, broader investments in boutique pharma/biotech a potentially appealing approach for VC firms. In addition, given pharma/biotech’s overwhelming proportion of total deals and funding, the lower premoney and postmoney valuations during 2012‒2021 lend further support to increasingly smaller and earlier-stage deals in this segment in more recent years. Despite the deal size, total annual investments in pharma/biotech, although cyclical, have generally trended upward since 2002, far outpacing any other segment in magnitude of funding increase, suggesting that the dermatology market may be able to expect the continued emergence of improved novel therapeutics in future years. Consistent with generalized deal count decreases, large declines in pharma/biotech funding were seen in 2020 and 2021 (ending at over 30% lower than the 2019 historic maximum), although at a decreasing rate and still greater than the funding amount at any point in the previous decade, lending possible preliminary support to a potential rebound in the coming years. By contrast, all of the clinics/outpatient services, health IT, and medical devices segments showed all-time highs in total funding in 2021. This may be consistent with documented post‒COVID-19 trends in dermatology toward hybrid and technology-supported care delivery models (Kassamali et al., 2021Kassamali B. Tan A. Franciosi E. Rashighi M. LaChance A. Teledermatology before, during, and after Covid-19: a vital tool to improve access and equity in specialty care.J Cell Immunol. 2021; 3: 61-67Google Scholar) as well as a general digitalization within the specialty (Mehta-Ambalal and Nisarta, 2021Mehta-Ambalal S.R. Nisarta M. Dermatology 2.0- how the Internet is changing us, our patients and our practice.Indian Dermatol Online J. 2021; 12: 593-596Google Scholar). Of the investee companies analyzed, most clinics/outpatient services and health IT companies were involved in the provision of hybrid and on-demand care, whereas medical device companies were largely involved in more rapid/accurate clinical diagnostics and in-practice aesthetic procedures. Finally, the overwhelming presence of VC-backed clinically relevant dermatologic companies in the western world may reflect an unmet need among lower-income demographics elsewhere and potentially highlight an area where strategic policymaking is needed to stimulate greater innovation and funding to support global health equity. VC financing of dermatologic innovation has increased since the early 2000s. Although nearly three quarters of VC activity and an even higher proportion of total funding are concentrated in the pharmaceuticals and biotechnology sector, there has been a growing interest in clinics and outpatient services, health information technology, and medical devices in recent years and particularly in 2021 after the initial period of the COVID-19 pandemic. In addition to the development of new therapeutics, the noted acceleration in other segments suggests a shift toward more patient-centric care delivery models in technologically integrated, personalized formats. The direct impacts of privately commercialized innovation in the clinical dermatology environment have not been well-characterized in the literature, so the impacts on specific stakeholders are not completely understood. Given the significant volume of capital injected into dermatology companies, future studies are needed to investigate the effects of VC activity and funding trends on areas, including patient outcomes, the value of care, and patient‒provider dynamics. Our study has a number of limitations: the funding amounts reported may be underestimated owing to the exclusion of transactions with an undisclosed investment size. This uncharacterized funding activity may impart additional variability to various aspects; although given the large sample size of 873 deals, it is likely that the observed trends are sufficiently robust. There is also the possibility of deals that are absent from the Pitchbook (Pitchbook, 2022PitchbookThe insights you need to pull ahead.http://www.pitchbook.comDate: 2022Date accessed: July 8, 2022Google Scholar) platform; however, it is broadly trusted in the private capital markets industry and has been utilized in a number of previous academic analyses, many of which have been referenced in this study. Owing to its legally protected nature, the original dataset cannot be made openly available. Further information about data terms of use and access is available at https://pitchbook.com/terms-of-use. The authors state no conflict of interest. SJO serves on the boards of Almirall Srl and R2 Technologies and as a senior advisor to Pharus Advisors. Conceptualization: AA, SJO; Data Curation: AA, SJO; Formal Analysis: AA, SJO; Writing – Original Draft Preparation: AA, SJO; Writing – Review and Editing: AA, SJO Investment and company information for venture capital (VC)-backed enterprises was sourced from Pitchbook Data (Pitchbook, Seattle, WA), a database covering private capital markets. We conducted a cross-sectional analysis of VC investments from January 1, 2002 through December 31, 2021 using keywords related to dermatologic care as well as 14 skin disease‒related terms (acne, alopecia, basal cell carcinoma, bullous, dermatitis, eczema, hives, mycosis, nail fungus, psoriasis, squamous cell carcinoma, tinea, urticaria, and vitiligo), which expanded the search to capture a broad group of relevant companies and transactions. Each of 555 captured companies in which a VC investment was made was individually screened for clinical relevance to dermatology; in particular, only companies developing a dermatologically related pipeline drug/biotechnology, creating dermatologic medical-grade devices, providing health information technology (IT) services with at least some patient and dermatologist interfacing element, and provisioning care within the clinical dermatology outpatient setting were included. Companies targeting medical care broadly, including generalized health IT, nonspecific devices, and heterogeneous clinical specialties, were excluded from this analysis. We also excluded companies exclusively involved with consumer nondurables or consumer-only technologies, largely comprising personal care products. Pharmaceuticals and biotechnology companies were included as long as there was at least one explicit dermatologic indication under development. Although it is an active area of venture investment, our search did not include companies focused on treatments for melanoma or other advanced cancers that would not generally be managed by a dermatologist. A total of 330 relevant companies were identified. Deals for these companies included those of any stage round of VC funding. Data were analyzed to determine trends in investment amount, deal flow, and segments of high interest, along with the activities and characteristics of VC-backed firms operating in the dermatology space. Four primary segments, pharma/biotech, clinics/outpatient services, health IT, and medical devices, were identified and analyzed. On the basis of company industry codes/keywords and description per the company website, if available, each company was assigned to the corresponding segment. Pharma/biotech included the following industry codes/keywords: biotechnology, drug delivery, drug discovery, pharmaceuticals, laboratory services (healthcare), other pharmaceuticals and biotechnology, and discovery tools (healthcare). Clinics/outpatient services included the eponymous industry code/keyword and other services, and health IT consisted of application software, communication software, decision/risk analysis, media and information services (business-to-business), medical records systems, other healthcare technology systems, other healthcare/commercial services, telemedicine, and practice management. Medical devices comprised diagnostic equipment, monitoring equipment, other devices and supplies, surgical devices, laser equipment, and therapeutic devices. Consistent with previous analyses in other specialties, deals with undisclosed financing amounts were excluded (Rathi et al., 2019Rathi V.K. Murr A.H. Feng A.L. Tauscher J.L. Naunheim M.R. Kozin E.D. et al.Analysis of venture capital investment in therapeutic otolaryngologic devices, 2008–2017.JAMA Otolaryngol Head Neck Surg. 2019; 145: 387-389Google Scholar).