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TRANSLATIONAL TOOLBOX

Broadview VenturesInvesting in the Future of Cardiovascular Technology

Christopher Colecchi, BA, MPH, David Tancredi, MD, PHD

SUMMARY

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Translational investigators and companies face a challenging economic environment when seeking funds to move

pre-clinical stage research into human testing and beyond. Specifically, funding for cardiovascular research and product

development is difficult to secure, whether from the NIH, venture capitalists, or industry. But new funding models for

advancing patient-oriented science to the commercial sector are emerging. Boston-based Broadview Ventures, created by

the LeducqFamilyTrust, promotes thedevelopment of technology for thediagnosis and treatment of cardiovascular disease

and stroke through direct equity-based investments. It targets early stage companies seeking to fund proof-of-concept for

technologies that hold promise as future breakthroughs for patient care.With 27 such investments over the last seven years,

Broadviewhas considerable experience in the seed/early-stage space, and its investmentmodel is demonstrating early signs

of success. Broadview actively seeks collaborations with world-class translational investigators, inventors, and their com-

panies, andwelcomes scientific inquiries, discussion and proposals for funding. (J AmColl Cardiol Basic Trans Sci 2016;1:87–

93) © 2016 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open

access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

F or translational investigators in cardiovasculardisease and stroke, securing funds to movepre-clinical stage research into human testing

and beyond remains a challenge. This “translationalfunding gap” is widening, and although many claimto fund early stage work, the data and experience ofentrepreneurs in academia and elsewhere provedifferently (Figure 1) (1). Despite recent increases infunding for translational research, the National Insti-tutes of Health primarily supports basic discoveryresearch, and has experienced significant budgetpressure over the past years. Indeed, cardiovascularand stroke research continue to be relatively under-funded with respect to their impact on globalhealth—as compared with cancer, for example (2,3)—and foundations and charitable organizations suchas the American Heart Association can only make upsome of this difference (Figure 2). In industry overthe last decade, spending on research and

m Broadview Ventures, Boston, Massachusetts. Mr. Colecchi is the mana

sident of Broadview Ventures; and is the executive director of the Leduc

nuscript received January 14, 2016; revised manuscript received January

development has remained unchanged, whereas thecost to bring new drugs and devices to market isincreasing, making access to industry funding by in-dependent clinical investigators more difficult. Andthe percentage of venture capital funding directed to-ward start-up/seed investments is diminishing—withventure capital preferring to fund later-stage, lower-risk product development activities (Figure 3) (4).

The good news in this challenging picture is thatnew funding models for advancing patient-orientedscience to the commercial sector are emerging. Fam-ily offices, foundations, incubators, angel groups, andothers are stepping into new territory and directingfunds toward the translational gap to help developnew therapies for patients (Figure 4) (5).

Boston-based Broadview Ventures is one such or-ganization. Created by the Leducq Family Trust,Broadview Ventures was designed to promote thedevelopment of technology for the diagnosis and

ging director of Broadview Ventures. Dr. Tancredi is

q Foundation.

21, 2016, accepted January 27, 2016.

FIGURE 1 Translational Funding Gap

DoD ¼ Department of Defense; FY ¼ fiscal year; NIH ¼ National Institutes of Health; VC ¼ venture capital.

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treatment of cardiovascular disease and strokethrough direct equity-based investments (cash in ex-change for equity position). It targets early-stagecompanies seeking to fund proof of concept for tech-nologies that hold promise as future breakthroughs forpatient care. With 27 such investments over the last 7years, Broadview has considerable experience in theseed/early-stage space, and its investment model isdemonstrating early signs of success.

FIGURE 2 Public and Private Funding for Cardiovascular Disease Tra

FY ¼ fiscal year; IPO ¼ initial public offering; M&A ¼ mergers and acqu

HISTORY: LEDUCQ FOUNDATION AND

BROADVIEW VENTURES

The mission and structure of Broadview Venturescan be traced to the Leducq Foundation and its sup-porting trust, created in 1996 by French entrepreneurand industrialist Jean Leducq, together with his wifeSylviane. Motivated by a multigenerational familyhistory of cardiovascular illness, and inspired to work

ils That of Cancer

isitions; R&D ¼ research and development.

FIGURE 3 VC Dollars Exist, But Are Predominantly Focused on De-Risked, Late-Stage Programs

VC ¼ venture capital.

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at the international level through years of living andworking abroad, the Leducqs used the proceeds of thesale of the family’s multinational linen and uniformservices businesses to establish a foundation for car-diovascular research with a mission to improve hu-man health through international efforts to combatcardiovascular and neurovascular disease. The foun-dation’s signature program, the Transatlantic Net-works of Excellence in Cardiovascular andNeurovascular Disease, supports international net-works of experts in cardiovascular disease and strokethat work collaboratively to advance scientific

FIGURE 4 Start-Ups Are Turning to New Sources of Funding to Fill

CRO ¼ contract research organization; VC ¼ venture capital.

knowledge, bring new technology to patient care, andhelp to train early career investigators. Since makingits first award in 1999, the foundation has committedover $350 million to cardiovascular and neuro-vascular research, supporting 47 research networks at130 institutions in 19 countries.

From the outset, the Leducq organization wasinterested in promoting the technology that wasdeveloped through the research it supported. Theboard of the Leducq Family Trust soon determinedthat the best way to accomplish this objective was tocreate an independent organization dedicated solely

the Gap

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to promoting and investing in technology. In 2008, itdecided to create Broadview Ventures, specificallyaddressing the translational gap by providing seedand early-stage funding for companies on the path todeveloping commercial products for patients withcardiovascular and neurovascular disease. Broadviewshares a mission in cardiovascular and neurovasculardisease with the Leducq Foundation, but proceedsthrough a direct investment model, whereas thefoundation works through a more traditional grantprogram.

Broadview is purposefully structured as a for-profit venture capital firm so that it can interacton equal ground with like-minded venture capital-ists and corporate partners that have financial re-turn on investment as a primary goal. That said,Broadview is mission-, not profit-driven, and de-fines success through social impact and improvingpatient care. Its mission orientation allows Broad-view to invest in important areas that others maysee as less interesting due to market size or riskissues (e.g., pediatrics). The sole shareholder ofBroadview is the Leducq Family Trust, which canmanage both the risk and long-term capital com-mitments associated with early-stage investing.Broadview is structured as an evergreen fund andall generated profits are used for additional earlystage investments or to support activities of theLeducq Foundation.

FIGURE 5 Broadview Investments by Indication

AF ¼ atrial fibrillation; CAD ¼ coronary artery disease; HF ¼ heart failure

arterial hypertension.

BROADVIEW ACTIVITY

In sourcing investments, Broadview defines cardio-vascular disease broadly. In addition to investing inthe core therapeutic areas within cardiovascular dis-ease such as myocardial infarction, heart failure,arrhythmias, and valvular disease, Broadview is alsointerested in underlying pathways such as inflam-mation and atherogenesis; predisposing factors suchas hypertension; and comorbidities such as car-diorenal and cardiopulmonary conditions. Type 2diabetes, obesity, and dyslipidemia, as cardiovascularrisk factors, are also considered to fall within thescope of the mission. Stroke is the primary indicationwithin Broadview’s neurovascular focus.

The investments made thus far by Broadviewinclude microRNA, stem cell, and gene therapies;nonsurgical and minimally invasive delivery tech-niques for valves and devices; and mechanical andpharmacological treatments for atrial fibrillation,hypertension, stroke, diabetes, and obesity (Figure 5).Broadview invests in all technology platforms relatedto its mission—diagnostics, therapeutics, and devices(Figure 6). Five of its investments have been made tosupport technology developed by grantees of theLeducq Foundation.

Broadview receives approximately 300 proposalsannually and invests $1 million in 4 to 5 of theseopportunities each year. Broadview seeks high-

; HTN ¼ hypertension; MI ¼ myocardial infarction; PAH ¼ pulmonary

FIGURE 6 Broadview Investments by Technology

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impact science that has the potential to change thepractice of cardiology. To be considered for invest-ment, the technology must have adequate intellec-tual property protection and a clear ability toinfluence patient therapy and/or standard of care.The proposed use of funds must be well defined withquantifiable and achievable milestones. And theremust be a clear understanding of future fundingrequirements to bring the technology through clinicaldevelopment to market.

Broadview is fortunate to be guided by a world-classstrategic advisory board composed of thought leadersfrom academia, finance, and industry (Figure 7). It alsohas access to a network of cardiovascular and neuro-vascular medicine experts developed over the yearsvia the Leducq Foundation. Broadview utilizes theserelationships for deal sourcing, diligence, investmentcounsel, clinical development advice, and portfoliocompany guidance. Without a doubt, these thoughtleaders have played a critical role in the developmentand advancement of the Broadview Ventures invest-ment model.

The Boston-based Broadview investment team, ledby Christopher Colecchi, consists of physicians, sci-entists, and business professionals who oversee dealsourcing, diligence, and the investment process. Afterinvestment, the Broadview team plays an active rolevia board participation, offering long-term supportthroughout the life of its portfolio companies.

CASE STUDY

Although improving patient care is its main goal,Broadview also hopes to share its learning andexperiences with other family offices and venture

FIGURE 7 2016 Broadview Strategic Advisory Board

Eugene Braunwald – Dis nguished Hersey Professor of MTIMI Study Group at the Brigham and Women’s Hospital.

Kim Fox – Consultant Cardiologist and Director of CardiologClinical Cardiology, Imperial College.

Thomas Hughes – President and CEO of Zafgen, Inc. and Dmember of several SABs, including Nimbus Discovery, LLC.

Jerry Karabelas – Partner at Care Capital and chairman of tBioVenture fund and former CEO of Novar s Pharma.

Mar n Landaluce – President, Board of Directors of the Le

Joseph Loscalzo – Hersey Professor of the Theory and PracChairman of the Department of Medicine and Physician-in-ChDirector of the Brigham Biomedical Research Ins tute.

Eric Rose – Academic physician and entrepreneur, former SColumbia, and Chairman of the Dept. of Surgery at ColumbiaLife Sciences at MacAndrews & Forbes, and CEO of Siga Tech

David Tancredi – Execu ve Director, Leducq Founda�on,a

philanthropic investors. Although still evolving as afund, Broadview has seen some early signs ofsuccess, most notably the recent acquisition byEdwards Lifesciences of CardiAQ Valve Technologies,a company funded by Broadview that is focused ondeveloping a percutaneous mitral valve technology.

The CardiAQ story demonstrates the many steps,layers of funding and expertise, and persistencenecessary for successful early stage investing. In2008, Broadview was connected with a surgeonand business executive both working in their sparehours to develop a percutaneous mitral valve im-plantation device. Later that year, after a significantlevel of diligence and review by its strategic advisoryboard, Broadview made a $750,000 seed invest-ment in CardiAQ to develop a device prototypeand conduct early animal testing. This investmentattracted additional corporate and board leadership

edicine at Harvard Medical School, and Chairman of the

y at the Royal Brompton Hospital, and Professor of

irector on the Board of miRagen Therapeu cs, Inc. and

he board of several companies. Founder of Novar s

ducq Founda�on

ce of Medicine at Harvard Medical School, andief at the Brigham and Women's Hospital, and Vice

urgeon-in-Chief at the New York Presbyterian Hospital/University, currently the Execu ve Vice President fornologies, Inc.

nd President, Broadview Ventures

FIGURE 8 CardiAQ Valve Technologies: From Idea to First-In-Man

CEO ¼ chief executive officer; CVT ¼ CardiAQ Valve Technologies.

FIGURE 9 Broadvi

Broadview V125 High Str9th FloorBoston, MA(617) 457-59

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from within the valve industry and led to a $5MSeries A financing round in 2011 in which Broad-view also participated. The company establishedstate-of-the-art facilities in Irvine, California, andsuccessfully completed the first-ever transcathetermitral valve replacement in a porcine model. In 2012,the company conducted successful first-in-humanimplantation of the valve in Europe. This milestoneattracted a large Series B financing round withparticipation by several large, well-known, venturecapital investors (OrbiMed, InVus, Versant, andAdvent). With this funding, a second-generation de-vice was developed and successfully implanted inseveral more patients. In August of 2015, EdwardsLifesciences acquired CardiAQ Valve Technologies for$400 million (Figure 8).

Although the financial return on investment waspositive for all involved, most important to Broad-view is that the technology, through Edwards’ market

ew Ventures Contact Information

entures, Inc.eet,

0211044

Christopher ColecchiManaging Directorccolecchi@broadviewventures.org

Nichole SchifferManager of Opera onsnschiffer@broadviewventures.org

www.broadviewventures.org

leadership and extensive resources, will now move tolarge-scale clinical trials for regulatory approval—andhopefully become a commercial product that willimprove the lives of patients with mitral valve dis-ease. In addition, the investment story demonstratesthat mission-related, philanthropic-based funds canbe deployed at an early stage to help science cross thetranslational gap to move through the clinical devel-opment pathway.

For every dollar invested by Broadview, itsportfolio companies have raised seven additionaldollars in co-investments, follow-on funding, andgrants. This additional funding has enabled smaller“surrogate markers of success” that demonstrate day-to-day progress at Broadview’s portfolio companies—such as movement from pre-clinical work to first-inhuman trials, achievement of regulatory approvalfor products, and a successful European productlaunch. In addition, many of Broadview portfoliocompanies have developed relationships with stra-tegic investors and industry partners to supportmovement toward commercial product approval.

THE FUTURE

The leadership, vision, and resources of the LeducqFamily Trust have been critical to the ability ofBroadview to look past the near term for high-risk–high-reward, longer-term solutions to today’s press-ing problems in cardiovascular and neurovasculardisease. With early-stage investing in the life sciencescomes acceptance that the road for the fund and itsportfolio companies will be challenging. There will

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be many failures to get to far fewer successes.Importantly, however, this work remains consistentwith the vision and values of the founders, whosebequest will ensure that the foundation and Broad-view remain true to their mission in cardiovascularand neurovascular science and will have the re-sources to continue the good work that started withthe Leducq Foundation 20 years ago.

Broadview actively seeks collaborations withworld-class translational investigators, inventors, and

their companies, and welcomes scientific inquiries,discussion and proposals for funding (Figure 9). In-vestigators seeking funding should send an executivesummary of their proposal to Broadview at the e-mailaddress provided (Figure 9).

REPRINT REQUESTS AND CORRESPONDENCE: Mr.Christopher Colecchi, Broadview Ventures, Inc., 125High Street, 9th Floor, Boston, Massachusetts 02110.E-mail: ccolecchi@broadviewventures.org.

RE F E RENCE S

1. Milken Institute. Fixes in Financing: Financial In-novations for Translational Research. Milken Insti-tute FasterCures. April 2012. Available at: http://www.fastercures.org/assets/Uploads/FixesInFinancingWeb.pdf. Accessed January 5, 2016.

2. NIH Research Portfolio Online Reporting Tools(REPORT). Research Project Success Rates by NIHInstitutes for 2014. Available at: https://report.nih.gov/success_rates/Success_ByIC.cfm. Accessed January5, 2016.

3. Booth B. Disease-Specific Allocations: The PastDecade of Venture, IPOs, and Deal-Making. Life SciVCwebsite. Available at: http://lifescivc.com/2015/06/disease-specific-allocations-the-past-decade-of-venture-ipos-and-deal-making/. AccessedJanuary 5, 2016.

4. PricewaterhouseCoopers, National VentureCapital Association. MoneyTree Report: Q3 2015.October 2015. Available at: https://www.pwcmoneytree.com/HistoricTrends/CustomQueryHistoricTrend. Accessed February 2016.

5. Greeley M. The Venture Funding Gap IsWidening;What Does It Mean? January 27, 2015. Xconomywebsite. Available at: http://www.xconomy.com/boston/2015/01/27/the-venture-funding-gap-is-widening-but-what-does-that-mean/. AccessedJanuary 5, 2016.

KEY WORDS cardiovascular, philanthropy,venture capital