John McCulloch PhD Venture Group Advisor MaRS Discovery District

 Post-doc at UCL Medical School, London, UK  Licensed monoclonal antibodies to US company  Negotiation, license and transfer process  Impressions ◦ Ease of funding vs. grant system ◦ Calculation of value and royalty rates ◦ Seeing our work make a difference in the outside world  UK academic culture re. commercialization

 Drug Royalty Corporation in 1994 (DRI Capital)  $1.0 billion under management  Life sciences investor – acquires royalties on drugs, diagnostics, etc.  Security = due diligence  Reviewed hundreds of opportunities, many arising from academic labs in the US and UK  Joined MaRS in 2007

 MaRS is an international convergence centre based in Toronto  Our mission is to create successful global businesses built from Canada’s science and technology  We provide advisory services, entrepreneurship programs, conference space and office/lab facilities  Wide range of tenants at MaRS: startups to Merck  Recently launched MaRS Innovation ◦ Will commercialize innovations from 16 Toronto institutions ◦ Will select most promising inventions and provide funding for patent prosecution and pre-investment development (POP and “de-risking”)

 Government ◦ Medical Research Council ◦ $1.0 billion R&D ◦ 130 patent families ◦ $152 million license revenue in  Private ◦ Wellcome Trust ($23 billion endowment)  Charities ◦ Cancer Research UK ◦ Arthritis Rheumatism Campaign ◦ National Heart Research Fund ◦ Diabetes UK

 National Research Development Corporation (1948) ◦ Mission: to commercialize publicly funded research  Fused with National Enterprise Board in 1981 to create the British Technology Group (BTG) ◦ BTG became custodian of many NRDC assets ◦ 1992 – management buyout ◦ 1995 – LSE flotation = BTG plc  Major BTG assets = MRI, BeneFIX, Campath  Initially “de-risked” technologies and licensed out  Evolved to product development focus

 Founded in 1913  Numerous landmark discoveries: ◦ Influenza virus ◦ Penicillin ◦ DNA ◦ Link between smoking & lung cancer ◦ Monoclonal antibodies ◦ C. elegans genome  35 MRC institutes across UK

 Founded in 1947 (Cambridge, UK)  13 Nobel laureates  Basic molecular biology research led to a wealth of antibody technologies: ◦ Monoclonal antibodies (Milstein & Kohler, 1975)  NRDC did not file patents! ◦ Chimeric antibodies (Neuberger & Rabbits 1984) ◦ Humanized antibodies (Winter 1986) ◦ Human antibodies (Winter 1990s) ◦ Human antibody genome mice (Neuberger 1990s) ◦ Single domain antibodies (Winter & Tomlinson 2000)

 Humira (Abbott)  RA, Crohn’s, psoriasis  US$1.54 billion sales  Tysabri (Biogen Idec)  MS  Actemra (Roche/Chugai)  RA  Campath (Genzyme/Bayer)  lymphoma, RA  Vectibix (Amgen)  Colorectal cancer

 Celltech  acquired by UCB ($2.25 billion)  Cambridge Antibody Technology  acquired by AstraZeneca ($1.25 billion)  Domantis  acquired by GlaxoSmithKline ($411 million)  Licenses to 37 other companies  MRC-LMB has played a critical role in the development of powerful, selective drugs for autoimmune disease and cancer

 ◦ Humanized antibodies = $150 million ◦ Human antibodies = $227 million  MRC-sourced antibody products are still growing ◦ Humira is a blockbuster drug ◦ >$1.5 billion sales/year  MRC uses the revenues from antibody technology to support basic research and expand research infrastructure

 The UK has been extremely successful in life sciences commercialization based on top tier research  If you can’t patent an initial technology, keep innovating! ◦ LMB created five next generation technologies after mABs  Get the technology out in the field as widely as possible via non-exclusive licenses  Reinvest the proceeds in basic research ◦ Main driver of innovation in MRC-LMB case  Importance of angels

John McCulloch PhD