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Changing Landscape of Drug Discovery Barbara Slusher, PhD, MBA Director, Johns Hopkins BSi NeuroTranslational Drug Discovery Program Associate Professor, Neurology and Psychiatry February 2012 Changing Landscape of Drug Discovery AGENDA • What’s changed? – – – – Pharma Academia NIH Partnerships • Academic Drug Discovery Centers – Example • Distinct attributes of academic drug discovery US drug discovery ecosystem is changing OBSERVATION 1: The Pharmaceutical industry is Under Challenge • The industry is investing more than three times as much as a decade a ago to produce less than half as many new products • Phase II timelines have nearly doubled; Phase III timelines have increased by ~50% • Number of NMEs per $1B spent is a factor 50 worse than 30 years ago • $130 billion of patented sales to face generics by 2016 (57% of 2010 US sales) • >100K jobs lost in the last 2 yrs Bernstein research 2011; figure modified by Dr. S Paul Inverse Moore’s Law for Pharmaceuticals US drug discovery ecosystem is changing OBSERVATION 2: Academia and NIH are increasing efforts in drug translation In Academia: • In 1995 there were less than 10 academic drug discovery centers • In 2012, there are over 100 academic drug discovery centers At NIH: • National Center for Advancing Translational Sciences (NCATS) established in 2011 • $639 million budget • NIH 2013 budget is flat, NCATS increases by 11% Sources: • Frye, S., Crosby, M., Edwards, T., & Juliana, R. (2011). US Academic Drug Discovery. Nature Reviews Drug Discovery, 409-410. • Harris, G. (2011, January 22). Federal Research Center Will Help Develop Medicines. Retrieved from The New York Times: http://www.nytimes.com/2011/01/23/health/policy/23drug.html • Rare Diseases Clinical Research Network. (2012, January). National Center for Advancing Translational Sciences (NCATS) Established. Retrieved from Newsletter of the NIH Rare Diseases Clinical Research Network: http://rarediseasesnetwork.epi.usf.edu/spotlight/January2012/NCATS/ 100+ Academic Drug Discovery Centers and Programs in the US Baylor University Center for Drug Discovery Johns Hopkins University Johns Hopkins Brain Science Ins Brigham Young University Cancer Research Center Louisiana State University Neuroscience Center of Excellence Case Western Reserve University Case Comprehensive Cancer Center - Drug Discovery and Development Colorado State University Colorado Center for Drug Discovery Cornell University Memorial Sloane-Kettering Cancer Center - Experimental Therapeutics Duke University Drug Discovery Center Emory University Chemical Biology Discovery Center Florida Atlantic University-Boca Raton Harbor Branch - Marine Drug Discovery Georgia State University Center for Biotechnology & Drug Design Georgetown University Drug Discovery Program Georgia Institute of Technology Center for Drug Design, Development and Delivery Harvard University Center for Applied Cancer Science Harvard Neuro Discovery Center Institute of Chemistry and Cell Biology Institute in Systems Temple University Moulder Center for Drug Discovery Research University of Alabama at Birmingham Alabama Drug Discovery Alliance Massachusetts Institute of Technology Broad Institute of Harvard & MIT North Carolina Central University Biomanufacturing Research Institute and Technology Enterprise (BRITE) Northeastern University Center for Drug Discovery Northwestern University Center for Molecular Innovation and Drug Discovery Oregon State University Oregon Translational Research and Drug Development Institute (OTRADI) Pennsylvania State University Drug Discovery, Delivery and Development Core Purdue University Bindley Bioscience Center Purdue Center for Combinatorial Chemical Biology University of Arizona Southwest Comprehensive Center For Drug Discovery And Development University of California - San Diego Division of Pediatric Pharmacology & Drug Discovery University of California-San Francisco Small Molecule Discovery Center Department of Bioengineering & Therapeutic Sciences California Center for Antiviral Drug Discovery (UCLS/UCSF Collaboration) University of California-Santa Cruz Chemical Screening Center University of Cincinnati Drug Discovery Center University of Florida Center for Drug Discovery Rice University Chemical Genomics (GCC CG) University of Georgia Center for Drug Discovery The Rockefeller University High Throughput Screening Resource Center University of Illinois at Chicago Institute of Tuberculosis Research University of Kansas High Throughput Screening Laboratory Kansas Specialized Chemistry Center University of Michigan-Ann Arbor Center for Chemical Genomics Vahlteich Medicinal Chemistry Core University of Minnesota - Twin Cities Center for Drug Design Institute for Therapeutics, Discovery & Development Stanford University University of Texas at Austin MD Anderson Cancer Center for Targeted Therapy University of Mississippi National Center for Natural Products Research University of Toledo Center for Drug Design and Development University of New Mexico New Mexico Molecular Libraries Screening Center University of Utah Huntsman Cancer Institute’s Center for Investigational Therapeutics Program University of North Carolina at Chapel Hill Center for Integrative Chemical Biology and Drug Discovery University of North Carolina at Greensboro Center for Drug Discovery University of Washington-Seattle Campus Institute for Stem cell and Regenerative Medicine - Quellos High Throuput Screening Core University of Oregon Oregon Translational Research and Drug Development Institute University of Wisconsin-Madison UW National Cooperative Drug Discovery Groups Small Molecule Screening and Medicinal Chemistry Core Facility University of Pennsylvania Penn Center for Molecular Discovery Vanderbilt University Vanderbilt Program in Drug Discovery University of Pittsburgh Drug Discovery Institute University of Pittsburgh Molecular Libraries Screening Center Virginia Commonwealth University VCU Institute for Structural Biology and Drug Discovery (ISBDD) University of South Carolina MUSC Hollings Cancer Center Drug Discovery and the list goes on… Saint Louis University Center for World Health and Medicine USC Center for Molecular Pathways and Drug Discovery University of Tennessee, University of Tennessee Health Science Center Drug Discovery Research Area Texas Institute for Drug and Diagnostics Development University of South Florida Center for Drug Discovery and West Virginia University Blanchette Rockefeller Neuro Sciences Institute Yale University US drug discovery ecosystem is changing OBSERVATION 3: Academic-Industrial Partnerships on the Rise • Pharma sees academia’s strengths in biology /target identification • Academia realizes limitations in translating its technologies • Response: form collaborations to leverage each other’s strengths and overcome weaknesses • SHARED RISK approach Sources: * Scudellari, M. (2011). Clinical Drive Prompts Pharma and Academia to Partner Up. Retrieved from Nature Medicine: http://www.nature.com/nm/journal/v17/n1/full/nm0111-3.html * Ledford, H. (2011, June 22). Drug Buddies. Retrieved from Nature News: http://www.nature.com/news/2011/110622/full/474433a.html In the Headlines Jan 2010: Johnson & Johnson, Vanderbilt University partner to develop Schizphrenia Drugs ($10M over 3 years) January 2011: Sanofi-Aventis Enters into Two Research & Development Collaborations with UCSF (Covers multiple therapeutic areas; amount undisclosed) March 2010: University of Pennsylvania School of Medicine and AstraZeneca Working Together to Find New Therapies for Alzheimer’s Disease (2-year agreement, amount undisclosed) January 2011: Bayer HealthCare, UCSF Sign Pact for Research Projects (Covers multiple research projects; amount undisclosed) July 2010: J&J Teams With Koch Institute (5-year agreement; amount undisclosed) October 2010: Harvard, Sanofi-Aventis in Collaboration (Covers multiple therapeutic areas; amount undisclosed) November 2010: UCSF Partners With Pfizer to Improve Drug Discovery, Development ($85M over 5 years) January 2011: Johns Hopkins Brain Science Instit enters into an agreement with Ortho-McNeil-Janssen Pharmaceuticals (5-year agreement; amount undisclosed) February 2011: GSK Seeks to Fund Academic "Superstars" for New Drugs (Long-term relationship that will endure 10+ years) March 2011: Yale and Gilead Sciences Announce Cancer Research Collaboration ($100M over 3 years) Oct 2011: EISAI Enters into a Neurological Drug Discovery Research Collaboration with Johns Hopkins Brain Science (5-year agreement; amount undisclosed) • Lyman, S. (2011, May 10). Pharma-Academic Alliances: What the Numbers Don’t Tell You . Retrieved from Xconomy: http://www.xconomy.com/seattle/2011/05/10/pharma-academic-allianceswhat-the-numbers-dont-tell-you/ • Scudellari, M. (2011). Clinical Drive Prompts Pharma and Academia to Partner Up. Nature Medicine, 3. Drugs Coming from Academia is not new concept 252 NDA (1998-2007) 134 “Me-Too” 118 Novel 25% 44% 31% Novel = priority review; scientifically innovative; respond to unmet medical needs 47% novel 53% “me-too” 11% 18% 71% Sources: • Kneller, R. The importance of new companies for drug discovery: origins of a decade of new drugs. Nat Rev Drug Discov 9, 867-882 (2010). • Stevens, A.J. et al. The Role of Public-Sector Research in the Discovery of Drugs and Vaccines. New England Journal of Medicine 364, 535-541 (2011). • Slide courtesy of Tim Willson, GSK 1st Academic/Industry Research Partnership in 1920s In 1921, Dr. Frederick Banting and Charles Best of the University of Toronto discovered insulin as the treatment of diabetes Unable to mass produce insulin, the University of Toronto entered into a partnership with Eli Lilly to see if a manufacturing process could be developed. Recent examples of Drugs Discovered by Academia • • • • • • • • • • Lyrica (NorthWestern) neuropathic pain Vimpat (NIH, University of Houston) epilepsy Remicade (NYU) rheumatoid arthritis Vorinostat (Columbia, MSK) T cell lymphoma Ziagen (University of Minnesota) AIDS Restasis (University of Georgia) Dry eye Gardasil (Georgetown, U Rochester) human papillomavirus Epivir (Emory University) AIDS Alimta (Princeton University) Lung Cancer Renova (University of Pennsylvania) skin care/acne …and many more Source: • Stevens, A. J., D., P., Jensen, J. J., Wyller, K., Kilgore, P. C., Chatterjee, S., & Rohrbaugh, M. L. (2011). The Role of Public-Sector Research in the Discovery of Drugs and Vaccines. New England Journal of Medicine, 535-541. Science Translational Medicine, 2009 Changing Landscape of Drug Discovery AGENDA • What has Changed? – – – – Pharma Academia NIH Partnerships • Academic Drug Discovery Centers - example • Distinct attributes of academic drug discovery JHU Brain Science Institute (BSi) Started in 2007 from a philanthropic gift of >$100M from an anonymous donor Mission of BSi Solve fundamental questions about brain development and function and to use these insights to understand the mechanisms of brain disease Aide in the translation of these basic science discoveries into small molecule therapeutics Hopkins’ BSi NeuroTranslational Drug Discovery turning Hopkins’ brain discoveries into clinical therapeutics 20 drug discovery scientists from PHARMA industry Expertise in medicinal chemistry, animal pharmacology and toxicology, drug metabolism, pharmacokinetics, assay development Average of 15 years PHARMA experience in small molecule drug discovery Working collaboratively with >450 JHU brain scientists JHU Faculty Expertise Novel Drug Target Identification BSI NT Drug Discovery Center Expertise Drugability Evaluation HTS Hit to Lead Lead Optimization Candidate Selection JHU Faculty Expertise Clinical Trials First 2 Years at JHU 1. Built collaboration network 2. Initiated drug discovery projects 3. Started training and education courses 4. Established partnerships with industry to assist in drug discovery and commercialization Built Awareness of Druggable Targets at Hopkins Held individual meetings with >100 faculty interested in brain sciences School of Medicine, Public Health, Homewood, KKI Anesthesiology, Biology, Comparative Medicine, Neurology, Neurosurgery, Neuroscience, Ophthalmology, Psychiatry, Medicine, Mind Brain Institute, Pharmacology, Oncology, Immunology, Radiology Purpose Become aware of possible drug discovery projects on campus Assemble a database of faculty research to be used with PHARMA interested in collaborations with JHU Initiated Twenty Collaborations Synthesizing “tool compounds” Pin-1 inhibitor (P Worley); Wyeth BACE inhibitor (J Griffin); Rapamycin derivative (G Ming); Sutent analogs (D Zack); MrgX agonists and antagonist (X Dong); curcumin derivatives (T Dawson); lactosylceramide synthase inhibitor (S Chatterjee); mGlr1 PAM (R Huganir); GLS1 inhibitor (C Dang; G Riggins); Petidomimetic BACE inhibitors (P Wong); Biotinylated glutaminase inhibitor (C Dang); DMT inhibitor (Sumner); 4-Hydroxytamoxifen (Caterina) Conducting drug metabolism and pharmacokinetics studies Ethoxyquin (A Hoke) RR-DPT (A Sawa) Cyclo GRGDSP (T Nguyen) NAC / NACA (P Campochiaro) Aiding in assay development MCT1 / gliagenesis (J Rothstein) Mechanoreceptors (X Dong) Neurite outgrowth (A Hoke) Retinal ganglion cell survival (D Zack) Glutamate release (J Bressler) MrgX agonist/antagonist (X Dong) First 2 Years at JHU 1. Built collaboration network at JHU 2. Initiated drug discovery projects 3. Started training and education courses 4. Established partnerships with industry to assist in drug discovery and commercialization Established 4 Integrated Drug Discovery Projects D-Amino Acid Oxidase (DAAO) Inhibitors for Schizophrenia Collaboration with Akira Sawa (Psychiatry) and Michaela Gallagher (Psychology) Glutaminase Inhibitors for Cancer and Neurodegeneration Collaboration with Chi Dang (Medicine), Greg Riggins (Neurosurgery), Christine Zink (Comparative Medicine), Peter Calabresi (Neurology), Jeff Rothstein (Neurology), Walter Kauffman (KKI) MrgX1 Ligands for Pain / Pruritis Collaboration with Xinzhong Dong (Neuroscience) GCPII inhibitor for Peripheral Neuropathy and MS Collaboration with Mohamed Farah (Neurology), Adam Kaplin (Psychiatry) Initiated 3 Exploratory Drug Discovery Projects System xc- Inhibitors for Brain cancer Collaboration with Dr. Greg Riggins (Neurosurgery) MCT inhibitors/activators for Cancer/Neurodegeneration Collaboration with Jeff Rothstein (Neurology) Protein Kinase inhibition for Retinal Disorders Collaboration with Dr. Don Zack (Opthalmology) First 2 Years at JHU 1. Built collaboration network at JHU 2. Initiated drug discovery projects 3. Started training and education courses 4. Established partnerships with industry to assist in drug discovery and commercialization Contributing to JHU’s Educational Mission by Teaching/Training Drug Discovery Drug Discovery Course for graduate students Drug Discovery & Development Workshop for post doc fellows NeuroTranslational conference co-organized with Carey Business School Initiated Entrepreneurs' “Boot Camp” and “Vine-andVenture” seminar series on commercialization Drug Discovery Training program: post docs, undergrad, HS students First 2 Years at JHU 1. Built collaboration network at JHU 2. Initiated drug discovery projects 3. Sustained our funding 4. Started training and education courses 5. Established partnerships with industry to assist in drug discovery and commercialization Partnered Drug Discovery Program with PHARMA; Supported Pharma product development; Spun-Out New Company Press Release Eisai Enters Licensing Agreement on GCPII Inhibitors With Johns Hopkins Brain Science Institute By PR Newswire 03/12/10 - 09:30 AM EST Helsinn HealthCare sponsors JHU to evaluate MOA of its CIPN drug Press Release May 24, 2011 09:00 ET Cerecor, Inc Appoints Management Team and Board of Directors; Plans for a $20 Million Series Executed a Unique Pharma Collaborative High Throughput Screening Agreement JHU identifies new brain targets and develops screening assays Eisai screens their internal drug library collection and share “hits” with JHU JHU conducts medicinal chemistry/drug discovery and identify new clinical candidate compounds Eisai licenses the clinical candidates and provide JHU with milestone payments and royalties True “WIN-WIN” JHU: access to a large diverse library Eisai: access to novel targets PHARMA – ACADEMIA partnerships Changing Landscape of Drug Discovery AGENDA • What has Changed? – – – – Pharma Academia NIH Partnerships • Academic Drug Discovery Centers on the Rise – Example • Distinct attributes of academic drug discovery Academia vs Pharma: Survey Results Comparison Between Industry and Academia Medicinal Chemistry Assay Development and Screening 3.64% 7.273% 3.64% 16.36% 18.18% 40% 52.73% 23.64% 34.55% Organizational Commitment & Stability 10.91% 25.45% Aligned with Needs and Values of Society 1.82% 3.64% 23.64% 30.91% 23.64% Survey of 78 US academic drug discovery centers Nature Reviews Drug Discovery, June 2011, 409-10. 20% 40% 20% Innovation Disease Expertise 1.82% 5.45% 30.91% 21.82% 40% 3.64% 16.36% 38.18% 41.82% much better in industry somewhat better in industry about the same somewhat better in academia much better in academia Academia vs Pharma: personal perspective • Academic strengths in Drug Discovery – Depth of knowledge on specific diseases/targets unparalleled in Pharma – Enhanced clinical interactions – Access to new animal models – Can assume more risk less time line pressures Academia vs Pharma: personal perspective • Academic weaknesses in Drug Discovery – Individual vs. team oriented – Lack of expertise/interest – Rewards are based on publishing/grants, hypothesis-driven scholarly research, not product development – Funding/resources limited; reliance on grants – Pressure to publish will compromise patent strategy Summary Changing Landscape of Drug Discovery Academia/Industry partnerships will be key to leverage each other’s strengths and overcome weaknesses Partnership structures will benefit all involved — most importantly, patients.