Mayo Clinic Ventures. Developing, Commercializing and Funding Mayo Clinic Discoveries. Dan Estes MFMER slide MFMER slide-1

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Mayo Clinic Ventures Developing, Commercializing and Funding Mayo Clinic Discoveries Dan Estes 2015 MFMER slide-1 2015 MFMER slide-1

Mayo Clinic Ventures (MCV) primary goals Facilitate the translation and commercialization of ideas developed at Mayo Clinic into products and services that: Enhance medical care and benefit patients Generate revenue to support Mayo Clinic s mission across all three shields Practice, Research, Education 2015 MFMER slide-2 2

1 MCV strategies Evaluate technologies and inventions for commercial potential and protect Mayo Clinic s intellectual property 4 Support proactive technology development using internal seed funding and project management 2 Develop and maintain relationships with industry contacts, potential investors and entrepreneurs 5 Spin out startup companies and support them through Mayo Clinic s venture fund 3 Facilitate and execute license agreements promoting technology commercialization and revenue generation 6 Support efforts in staff entrepreneurship at Mayo Clinic 2015 MFMER slide-3 3

MCV Portfolio of Technologies MCV receives invention disclosures from all Mayo Clinic sites and departments Medical devices Biologic and small molecule therapeutics Diagnostics Software / health care IT Health / wellness Research reagents 2015 MFMER slide-4 4

MCV Performance Highlights MCV receives more than two disclosed technologies per day from Mayo Clinic inventors (over 600/year) 56% of disclosed technologies licensed (15-year average) >1,900 issued patents 133 patent applications filed in 2015 Over 2,900 technologies licensed 100 license agreements in 2015 Over $461 million received in gross royalty income $47.6 million gross royalty revenue in 2015 Involvement in 132 start-up companies 8 start-ups in 2015 2015 MFMER slide-5 5

Number of License Agreements Generating Revenue (Top 24 Institutions 2014) Relative to its Peers, Mayo is Very Active in Partnering With Outside Groups to Advance Medical Technologies MAYO FOUNDATION Dana-Farber Cancer Institute The Jackson Laboratory St. Jude Children's Research Hospital Fred Hutchinson Cancer Research Center Memorial Sloan Kettering Cancer Center Children's Hospital Boston Cleveland Clinic Salk Institute for Biological Studies Wistar Institure Beth Israel Deaconess Medical Center Cold Spring Harbor Laboratory Whitehead Institute for Biomedical Research Children's Hospital Cincinnati National Jewish Health Cedars-Sinai Medical Center H Lee Moffitt Cancer Center Woods Hole Oceanographic Institute Hospital for Special Surgery Tufts Medical Center Boyce Thompson Institute for Plant Research Hackensack University Medical Center 76 70 68 55 52 51 36 23 13 10 10 2 0 101 96 174 174 159 146 136 130 332 0 50 100 150 200 250 300 350 6 2015 MFMER slide-6

Maximizing Commercial Viability and Financial Value VALUE Commercial interest and viability big hit opportunity Majority of disclosed ideas Development gap STAGE OF DEVELOPMENT 8 2015 MFMER slide-7

Mayo Clinic Ventures Seed Fund Programs 2015 MFMER slide-8 2015 MFMER slide-8

Maximizing Commercial Viability and Value Mayo Clinic has developed funding programs to address the development gap and move promising technologies from early stage concepts to clinical testing The premise is that by developing and de-risking technologies we positively impact patient care and increase the chances of commercial success and encouraging new company formation Programs Ventures Innovation Program (VIP) = early-stage proof of concept fund Discovery Translation Program (DTP) = mid-stage pre-clinical/validation fund Benefactor Innovation Fund (BIF) = late-stage clinical testing fund 8 2015 MFMER slide-9 9

Development of New Medical Therapies Discovery to Patient Care NIH Foundations Philanthropy $1-10Million? 1-10 Years? Mayo Clinic Ventures Innovation Program Discovery Translation Program Benefactor Innovation Fund $3-6Million 3-5 Years Venture Capital Industry Public Markets $50-300 Million 4-7 Years VIP DTP Benefactor Discovery Preclinical Fund Clinical Trials Clinical Practice/ Market I II III first-in-human & pivotal Mechanism of disease Physiology Proof of concept Reproducibility Efficacy (models) Toxicity Manufacturing Safety Efficacy Validation Therapeutic solutions Expanded indications 2015 MFMER slide-10 10

Ventures Innovation Program Seed funding and project management support to de-risk early stage ideas through proof-of-concept studies 2015 MFMER slide-11 11

Ventures Innovation Program Overview and Purpose Focused on early stage and concept technologies deemed to have the potential to improve healthcare and provide a financial return to Mayo Clinic Intended to fund development of a technology to enhance its commercialization/translational potential Can be applied to advancing non-mayo technologies when partnered with Mayo expertise and know-how Fund is established and maintained through a 4% allocation of Mayo Clinic Ventures net licensing income Fund balance is between $1-3M at any given time Awards can be up to $200,000; 10-year average is ~ $97,000/award 2015 MFMER slide-12 12

Ventures Innovation Program Metrics to Date: 2006- June 2016 Total VIP awards to date 173 Total award funding to date $16.4M Gross revenue received to date* $21.3M Program financial return $4.9M * Additional milestone, equity, and royalty revenue to be earned 2015 MFMER slide-13 13

President s Discovery Translation Program Overview and Purpose Catalyst to translate Mayo Clinic discoveries to clinical practice by advancing technology towards first-in-human studies Centered on development of Mayo Clinic technology that will lead to significant improvements in the safety, quality and efficiency of clinical practice Applications are competitive and peer reviewed Promotes milestone-based innovation Many of the awards have previously received VIP funding Leverages enterprise-wide strategic priorities Awards are $300,000; fund is maintained through an 8.5% allocation of Mayo Clinic Ventures net licensing income and philanthropy 2015 MFMER slide-14 15

Discovery Translation Program Metrics To Date 2005 June 2016 Total DTP awards to date 60 Total award funding to date $20.2M Gross revenue received to date* $51.5M Program financial return $31.3M * Additional milestone, equity, and royalty revenue to be earned 2015 MFMER slide-15 16

Benefactor Innovation Fund Overview and Purpose Envisioned to complete translational work by moving technologies through first-in-human studies and to commercialization Bridges the gap between discovery and clinical validation by establishing capital resources dedicated to advancing technologies through first-in-human studies Technologies selected will have high potential to become products and services that will broadly impact health care and provide a financial return to support Mayo Clinic s mission New fund that is currently raising capital 2015 MFMER slide-16 18

Mayo Clinic Ventures Partnering With Industry 2015 MFMER slide-17 2015 MFMER slide-17

Partnerships Industry partners seek synergistic technologies, access to new solutions, enhanced product performance / features / patient outcomes Developing relationships with industry partners is a necessary function of transforming the delivery of new, disruptive technologies to the marketplace Industry sponsored research Product validation Product development / design input Technology licensing New company formation 2015 MFMER slide-18

Partnerships 2015 MFMER slide-19

New company formation Seed funding to bridge to company formation Venture funding to participate in company capitalization Network of industry entrepreneurs, angel investors and venture funds Employee Entrepreneurship Program Encourages company creation by Mayo Clinic staff 2015 MFMER slide-20

Mayo Clinic Co-Investment Fund A Hybrid Venture Investment Program $100 million Mayo Clinic fund focused on venture capital and growth equity opportunities Partnership with Mayo Clinic Treasury Services Invests in companies that include Mayo Clinic technology or expertise License of Mayo-created technology or clinical know-how Substantive collaboration with Mayo Clinic Co-invests with leading healthcare venture capital or private equity firms Up to $2.5 million venture or $20 million growth capital total investment in a company 2015 MFMER slide-21

Fund Co-Investors 2015 MFMER slide-22

U.S. Venture Market - Overview With interest rates at essentially zero, venture capital continues to be able to raise funds Dollars invested / raised was flat between 2006-2013; on the increase since The U.S. venture capital industry continues to consolidate around a handful of global brands The top ten VC funds raised 62% of all dollars Funds monies were raised in 15 states, although 50 of 67 funds reside in CA, NY or MA What are they avoiding? Capital intensive businesses, low gross margin operations, me too companies. Focused on company fundamentals, discipline toward value, repeat entrepreneurs 2015 MFMER slide-23

U.S. Venture Market - Overview IPO activity remains woeful depressed 12 IPO s in Q2 (9 in the biotech space) 961 companies raised VC capital in the same quarter a frighteningly narrow funnel to IPO Majority of 2015 tech IPO s are trading below IPO price Significant increase in Angel dollars invested into technology companies 2011 = $8B 2013 = $8.5B 2014 = $14.5B 2015 = $18.9B Deal count is up nearly 2X over the same timeframe Private equity and corporate investment trends mirror the above 2015 MFMER slide-24

Venture Investing Healthcare Market Healthcare technology market continues to attract significant new investment A combination of regulatory reform and technology advances (mobility, computing power, analytics) are converging to drive innovation 1H 2016 saw between $3.6 $3.9B invested in digital health alone across over 400 companies (much in early stage) 2015 MFMER slide-25

Venture Investing Healthcare Market Major healthcare sectors attracting investment, 2016 YTD: Patient / Consumer experience ($1B) Wellness ($900M) Personalized Health ($525M) Big Data Analytics ($400M) Workflow ($325M) Clinical Decision Support ($235M) Seed and Series A rounds represent ~55% of YTD deal volume 2015 MFMER slide-26

Venture Investing - Summary Stage of investment reflects risk tolerance of investors Seed and early stage activity were down in Q2 (5% / 17% respectively) Investment in expanding companies was up 112% VC investors are doubling down on their perceived portfolio winners Less likely to take on new or perceived riskier ventures First time financings declined 8% Avoiding technologies / businesses that have been overfunded Seeking well positioned companies that can power through any economic environment The issues are complex and nuanced; the only absolute is there are no absolutes. 2015 MFMER slide-27

2015 MFMER slide-28 Questions?

Minnesota-based Companies with Mayo Intellectual Property Pharmacogenomics testing Vagal nerve blocking for obesity Peptide for resistant hypertension Device to treat GERD NEUROONE Next generation cortical EEG monitoring Decision support for the ICU Omnis Pharma Noninvasive imaging VSV for oncolytic tumor therapy Enhanced reading technology IPS cell services Stem cell media Software to improve blood transfusion use Mitral valve repair device Patient remote monitoring Magnetic resonance elastography Decision support software Joint company with U of M 2015 MFMER slide-29

Companies Incorporating Mayo Clinic Technology Biopharma Stem cell therapy for cardiovascular disease and injury http://www.c3bs.com/en Tissue engineered organs for transplant http://miromatrix.com/ Peptide therapeutics for cardiorenal disease (Nile merged with Capricor in 2013) http://capricor.com/ Regen Theranostics Discovering molecules that eliminate senescent, cells* Manufactures and provides ips cells Media for stem cell growth http://millcreekls.com/ Therapeutic peptides for cardiovascular disease* Peptide therapeutics for ocular pain Asterisks indicate Mayo venture fund investment 2015 MFMER slide-30

Companies Incorporating Mayo Clinic Technology Med-Tech MedTech Minimally invasive mitral repair device http://www.neochord.com/ Magnetic resonance elastography for measuring tissue elasticity/stiffness http://www.resoundant.com/ Molecular breast imaging http://www.gammamedic a.com/ Left atrial appendage closure device for stroke prevention in Afib patients Anorectal manometry device, extremity MRI coil, respiratory control system for imaging applications http://www.medspira.com/ Joint replacement implants. Acquired by Integra in 2011* http://www.integralife.com/inde x.aspx Vagal nerve blocking device to treat obesity* http://www.enteromedics.com/ Neurostimulation device for chronic pain* http://www.nevro.com/ Magnetic sphincter augmentation for GERD* http://www.toraxmedical.com/ CoreMetrics Web analytics and marketing software Asterisks indicate Mayo venture fund investment 2015 MFMER slide-31

Companies Incorporating Mayo Clinic Technology Healthcare IT Software system managing dosing of ESAs for dialysis patients http://www.physiciansoftwaresystems.com/ System for assessing hospital readmission risk* http://axialexchange.com/ Remote monitoring system for biometric data http://www.preventice.com/ IT system delivering evidence-based knowledge to providers and patients http://www.evidentiahealth.com/ System for exchanging medical image content and information* http://www.dicomgrid.com/ IT product determining costs for capacity planning and resource allocation* http://www.exactcost.com/ Asterisks indicate Mayo venture fund investment 2015 MFMER slide-32

Companies Incorporating Mayo Clinic Technology Diagnostic Personalized medicine for patients on psychotropic, ADHD or pain medications* http://assurexhealth.com/ Developing next generation sequencing panels for oncology http://oncospiregenomics.com/ Mayo Clinic collaboration with SVBio to implement whole genome diagnostics and interpretation* http://www.svbio.com/ Stool-based DNA test for early detection of colon cancer* http://www.exactsciences.com/ Asterisks indicate Mayo venture fund investment 2015 MFMER slide-33