Cocrystal Pharma, Inc. Novel antiviral drug products and technologies 1 1
Forward-Looking Statement This presentation contains forward-looking statements. These forward- looking statements are subject to risks and uncertainties, including the factors described under the Risk Factors section of our most recent annual or quarterly report that we have filed with the Securities and Exchange Commission and made available on our website at: www.cocrystalpharma.com. When evaluating Cocrystal’s business and prospects, careful consideration should be given to these risks and uncertainties. These statements speak only as of the date of this . document, and Cocrystal undertakes no obligation to update or revise these statements. This presentation and the information contained herein do not constitute an offer or solicitation of an offer for sale of any securities. 2 2
Cocrystal’s Mission To develop and commercialize novel small-molecule antiviral drugs using proprietary breakthrough technologies 3 3
Investment Thesis Viral diseases as a group represent one of the world’s largest and greatest unmet medical needs Cocrystal has proprietary technologies that enable the creation of first- and best-in-class antiviral products Pharma and big biotech have great interest in this market and in our technology, creating attractive partnering and M&A opportunities 4 4
Cocrystal Founders Gary Wilcox, Ph.D., Chairman, CEO & Founder Icos Corporation, Executive Vice President, 13 years Ingene Inc., Chairman, President & CEO, 7 years, Professor, Department of Microbiology, UCLA, 10 years Sam Lee, Ph.D., President & Founder Icos Corporation, Group Leader, 8 years Postdoctoral Studies, Stanford School of Medicine Roger Kornberg, Ph.D., Chief Scientist & Founder Nobel Laureate in Chemistry 2006 Professor, Department of Structural Biology, Stanford School of Medicine 5
Board of Directors Gary Wilcox, Ph.D. , Co-Chairman Dr. Gary Wilcox served on the Board of Directors of Icos Corpora)on (ICOS-NASDAQ) from 1993 to 2007 and was Executive Vice President, Operations. Previously, he served as Vice Chairman, Executive Vice President, and Director of Xoma Corpora)on (XOMA-NASDAQ). Prior to his work at Xoma, he co-founded Ingene (IGEI-NASDAQ) where he was Chairman, CEO, and President prior to the merger of Ingene into Xoma. Dr. Wilcox served as a professor in the Department of Microbiology at UCLA for 10 years. Raymond F. Schinazi, Ph.D. , Co-Chairman Dr. Raymond Schinazi is the Founder and Director of RFS Pharma, LLC, a position he has held since 2004. He has been at Emory University since 1978 and currently serves as the Frances Winship Walters Professor of Pediatrics and Director of the Laboratory of Biochemical Pharmacology at Emory University. Since 1983, he has been affiliated with the Atlanta Department of Veterans Affairs and currently serves as Senior Research Career Scientist. He is also the Director of the Scientific Working Group on Viral Eradication for the NIH-sponsored Emory University Center for AIDS Research (CFAR). In addition, Dr. Schinazi currently serves as a Governing Trustee for the Foundation for AIDS Research (amfAR) and serves as a non-executive Director of Gliknik Inc. and also reViral Ltd. Philip Frost, M.D. Dr. Phillip Frost is the Chairman and CEO of Opko Health, Inc. (OPK-AMEX). Dr. Frost is the Chairman of the Board of Teva Pharmaceuticals (TEVA-NASDAQ). In January 2006 Teva acquired IVAX Corpora)on. Dr. Frost had served as Chairman and CEO of IVAX Corpora)on since 1987. He serves on the Board of Regents of the Smithsonian Institution, is a member of the Board of Trustees of the University of Miami, is a Trustee of each of the Scripps Research Institutes, and is a director of numerous other organizations. 6
Board of Directors Jane Hsiao, Ph.D. Dr. Jane Hsiao is Vice Chairman and Chief Technical Officer of Opko Health, Inc. She served as the Vice Chairman-Technical Affairs of IVAX from 1995 to January 2006, when Teva acquired IVAX. Dr. Hsiao served as IVAX’s chief technical officer from 1996, and as chairman, CEO, and president of IVAX Animal Health, IVAX’s veterinary products subsidiary, from 1998. She is a director of Opko Health, Inc (OPK-AMEX). David Block, Ph.D. Dr. Block has served since 2007 as President and Chief Executive Officer of Gliknik Inc., a biopharmaceutical company which he founded to create new therapies for people living with cancer and immune disorders. From 1990 through its successful sale in 2002, Dr. Block held a number of commercial positions at DuPont Merck and DuPont Pharmaceuticals, ultimately as EVP of International Operations. He was subsequently COO of Celera Genomics and CEO of venture-funded Ruxton Pharmaceuticals prior to founding Gliknik. Dr. Block has been an active HIV physician at Johns Hopkins since 1992. Jeffrey Meckler Mr. Meckler, 48, is the Managing Director of The Andra Group, a life sciences consulting firm, a position he has held since 2009. Since 2012, he has served on the Board of Directors for QLT, Inc., an ultra-orphan ophthalmic biotechnology company and since 2014, he has also served on the Board of Directors of Retrophin, Inc., also an orphan biopharmaceutical company focused on the treatment of catastrophic diseases. Previously, from 2011 to 2012, Mr. Meckler acted as a Director and Interim CEO of Cypress Bioscience Inc. after its acquisition by Royalty Pharma. He also served as a Director of ClearFarma USA from 2010 to 2012, Kyalin Bioscience from 2011 to 2012 and Alveolus Inc. from 2007 to 2009. From 1990 to 2007, Mr. Meckler held a series of positions at Pfizer Inc. in Manufacturing Systems, Market Research, Business Development, Strategic Planning and Corporate Finance. Steve Rubin, J.D. Steven D. Rubin, J.D., is Executive Vice President-Administration and a director of OPKO Health, Inc. Previously, he was Senior Vice President and General Counsel of IVAX. Prior to IVAX, Mr. Rubin was Senior Vice President and General Counsel of Telergy Inc. Mr. Rubin holds a B.A. from Tulane University and a J.D. degree from University of Florida. 7
Viral Diseases - An Unmet Medical Need 8
Viral Replication Enzymes are Proven Targets for Small Molecule Drugs Replication enzymes are essential for viral multiplication - they are the Achilles heel of all viruses. Replication enzymes are highly conserved - they are nearly identical in all viruses and therefore targets for pan-viral (broad spectrum antiviral) drugs. 9
HCV Is Major Worldwide Problem Seven major HCV genotypes: 1a, 1b, 2a, 3a, 4a, 5a, and 6a 10
HCV Nucleoside Therapies Target the Viral RNA Polymerase Gilead’s Sofosbuvir is first in class Gilead’s Sofosbuvir + Ledipasvir (NS5a inhibitor) was recently approved to treat genotype 1 hepatitis C Sofosbuvir has high barrier to resistance and broad spectrum activity in recent clinical trials Many clinical trials of nucleoside therapeutics (>15) have been discontinued due to toxicity 11
The Cocrystal Pharma Approach Non-nucleoside inhibitors of the viral RNA polymerase Inhibitors designed on the basis of the RNA polymerase mechanism rather than the conventional hit-or-miss approach, resulting in a high barrier to resistance and in pan-viral activity Inhibitors selected from proprietary drug candidate libraries, based on RNA polymerase structure and advanced synthetic chemistry 12
Cocrystal’s Leads Show Superior Activity Against HCV Drug Resistant Variants Cocrystal’s leads show a high barrier to drug resistance HCV-796 1800 IC 50 fold change 1600 Drug resistance variants 1400 S365T (NNI-4) Cocrystal’s Cocrystal’s 1200 NNI-5 Leads NNI-4 Leads N316Y (NNI-4) 1000 800 L419M (NNI-2) 600 S282T (Nuc) 400 200 0 1 2 3 4 5 31228 31244 959 985 HCV-796 13
HCV Helicase Lead Development Status Properties of HCV NS3 helicase lead molecule: Novel pan-genotypic helicase unwinding inhibitor Excellent combination therapy candidate with HCV polymerase (NNI &Nuc) or protease inhibitors Good antiviral activity No cytotoxicity No ATPase inhibition Lead optimization in progress 14
Helicase - All Genotype Crystals Developed CDI’s proprietary HCV genotype crystals (1a - 6a) GT6a GT5a GT4a GT3a GT2a GT1a GT1b FL GT1b 15
Influenza is Major Worldwide Health Problem Seasonal worldwide health problem with pandemic potential: 3-5 million cases of severe illness, up to 500,000 deaths worldwide each year (source: World Health Organization) Pandemic influenza: Up to 62 million deaths worldwide (source: Lancet, 2006; 368:2211) $10 billion market forecast in 2015 16
Key Properties of Influenza Drug Broad spectrum activity • Inhibit the endonuclease activity of the viral polymerase that is present in all influenza serotypes High barrier to resistance • Target the extremely conserved regions of the endonuclease protein Well-tolerated • There is no similar endonuclease activity in humans 17
Why Dengue Virus? (A) Areas of dengue transmission (B) Dengue infection, 1955-2007 2.5 billion people at risk Four major serotypes: DEN-1, DEN-2, DEN-3, DEN-4 18
Why Norovirus? Most common cause of food-born outbreaks in US 19-20 million illness each year (1 in 14 Americans become ill each year) 56,000 - 71,000 hospitalization 570-800 deaths per year in US Economic costs-$5.8B 3-5 million deaths per year worldwide More than 200,000 deaths of children <5 years old in developing countries 19
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