Practices and Tips for Successful Technology Transfer Dr. Tamar Raz CEO, Hadasit Practices and Tips for Successful Technology Transfer an Academic Hospital Point of View

Hadasit Corporate Structure Hadassah 100% Established 1912 Established & Incorporated 1986 Hadassah hospitals are public hospitals owned by Hadassah organization which was established 100 years. Hadasit was established 26 years ago.

Hadassah Medical Organization (HMO) - Background Established in 1912 by “Hadassah” - the Women's Zionist Organization of America: For more than 100 years, Hadassah and its Hospitals have been leaders in medicine and nursing in Israel: 2 Hospitals (Mt. Scopus & Ein Kerem) 31 Operating theaters 9 Specialty ICUs 1,130 Beds 5,000 Employees 670 Physicians >1M Outpatients per year

Research in Hadassah Hadassah - Center of Excellence >2000 Scientific publications in the past 5 years >2000 Hadassah - Center of Excellence Oncology Immunology Neuroscience Cardiovascular Infectious Diseases Metabolic /Liver Cell Based Therapies Medical Patent Applications by Israeli Hospitals (1988-2015) …as reflected by the amazing number of grant awards obtained by Hadassah researchers compared to the other hospitals in Israel and publications in peer reviewed scientific articles. Source: The Israeli Medical Industry, a Patent Analytics Study, Dr. Sharon Bar-Ziv and Inbar Yasur 3

Hadasit – Solid Reality and Potential Upside Technology Transfer Company of Hadassah Medical Hospitals ~ 250 ACTIVE PATENT FAMILIES 39 % ALREADY LICENSED

Hadasit Selected Partners

Licensing Models - Best Practice Spin-off High involvement of Tech Transfer and inventor Funded by business angels and / or incubators High commitment of founders and Staff High risk and need for next rounds of funding Start-up Funded by venture capital and / or incubators Seasoned entrepreneurs Established company Funded by established company internal budgets Experienced R&D team High risk of NIH syndrome Next round of funding defined Higher risk of product shelving

DOXIL (J&J) for Cancer Treatment DOXIL - an anti cancer drug, used primarily to treat ovarian and breast cancer A lipid-based formulation that has a cancer-killing drug inside it. Prof. Yechezkel Barenholz Faculty of Medicine, HUJI Joint Development by Hebrew University and Hadassah Hospital License to a new start-up company Technology transferred to Alza cooperation Alza bough by Johnson & Johnson Prof. Alberto Gabizon Hadassah Medical Center Worldwide sales of DOXIL in 2015 were about US$810 M Royalties paid to Hebrew University & Hadassah Hospital until patent expirations (Estimated > $ 50M)

Travelan® - a Natural Product Specifically Designed to Prevent Travellers’ Diarrhea. Prof. Yaron Ilan Immuron’s Chief Medical Officer Immuron Ltd (ASX Code: IMC) is a publicly listed Australian company delivering Oral Immunotherapy for the treatment and prevention of disease using dairy-derived antibody products for humans.  Technology was licensed to Immuron by Hadasit in 2009 Travelan & Protectyn sales already producing royalties payments to Hadasit , and are expected to grow in the coming years Next generation product, based on Hadassah technology is IMM-124E , a natural product for the treatment of Fatty Liver and NASH. Currently in phase II clinical trials.

Granagard™ – a Natural Antioxidant for the Prevention and Treatment of Neurodegenerative Conditions. Granalix BioTechnologies focuses on developing science-based novel formulations of natural antioxidants. GranaGard™, a submicron self-emulsion formulation of pomegranate seed oil (PSO), is a supplement rich in Omega 5 - one of the strongest natural antioxidants. GranaGard™ was shown to prevent neurodegeneration diseases in mouse models, while showing high safety profile after long term administration First Patent Application April 2012 New Co Established and Technology Licensed March 2014 World Wide Sales Initiation March 2017 Prof. Ruth Gabizon Hadassah Medical Center

Novel Enteral Feeding Device The novel device eliminates the drawbacks plaguing existing devices and offers a secure, reliable, and discreet enteral feeding solution. Physicians morning meeting: Another case of accidental percutaneous endoscopic gastrostomy (PEG) dislodgement The problem was identified by Dr. Ishay Benuri, a young physician that came to Hadasit with suggested solution (drawing on a napkin) First Patent Application – June 2013 License to an Incubator Start Up Company (Sep 2014) 2017 Status: Over $1 million raised A clinical trial is ongoing at Hadassah

Identifying Innovation Passive process Active process Scouting Creating thinking groups Innovation training Partnerships

BioDesign Innovation An academic program which creates groups of Medical Students, Engineering Students, Business Students, and Law Students working together toward a single Biotech Product Original concept - Stanford University Needs Analysis Inception Design Prototype Provisional Patent Business Plan Hadassah Medical Organization Bioengineering Hebrew University Biodesign is a multi-disciplinary, team-based approach to medical innovation, created by the Hebrew University of Jerusalem and Hadassah Medical Center. The program takes outstanding medical fellows, bioengineering and business graduate students and tutors them in the science and practice of bringing a medical innovation to the market.   Biodesign  innovation  is  taught by  Hebrew  University  faculty, clinical experts, medical  device  entrepreneurs,  corporate  executives,  intellectual  property  attorneys,  and  venture  capitalists.  As  such,  it  provides  a  unique  opportunity to  gain  real  world  experience  in  an  academic environment growing a new generation of innovators

Evaluating Innovation Identifying unmet need Map existing solutions – also those under R&D Evidence in literature – is this important to others? Joint discussion BD & IP: IP: Is this new? BD: Is it important?

Business Models How can the technology make money? What is the product? How / where are the alternatives being sold? Disposable / reusable (Razor & blades / Capital) Current reimbursement status What is the potential? Market Size?

Potential Commercial Partners Who has an interest? Companies in the field Companies looking to enter the field Entrepreneurs What are they looking for? Market leader’s perspective Upcoming competition perspective Entrepreneur’s perspective What POC needs to be achieved? “Drawing on a napkin” Initial feasibility – quick and dirty Proof of concept – pre-clinical Full R&D – bring a product to the market Clinical studies $ Possibly independent $ $ $ $ $ $ $ $ $ Requires commercial entity $ $ $ $ $ $ $ $ $ $ $

Business Models Doctors have day (and sometimes night) jobs… Time, finance and R&D expertise will determine how far I can promote the technology independently before… Establishing a startup Partnering with an existing company

Establishing a Startup – Pros & Cons Focus on the technology Flexibility in R&D Adaptable approach to the market Maximal motivation to succeed “Exit” potential Cons Raising money Low chance to succeed Maximal distance to market Barriers for entering the market No financial security – survival mode “One shot at the target”

Partnering with an Existing Company – Pros & Cons Secured means for development Shorter time to market Low barriers for entering the market Existing know how and capabilities Cons Lower motivation Other agenda Less flexibility in R&D Less adaptiveness in approaching the market No “Exit”…

License Agreement License Agreement shall Include: Granting a royalty-bearing license to practice the licensed technology and/or the results of sponsored research Funding for ongoing research Preserving hospital personnel's right to publish Providing for fair compensation to the hospital if the product is successful in the marketplace Ensuring that the licensed technologies reach the marketplace in a timely manner for the benefit of the public by the inclusion of development milestones

License Considerations Upfront Payment License Fees Milestone Payments Sublicense Receipts Royalties from Sales Sales Milestones Equity Participation Exit Fees

Thank you. For further information please contact rtamar@hadassah.org.il