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Dana-Farber Cancer Institute Capabilities and Collaboration Opportunities Japan Delegation Visit October 22, 2014 O. Prem Das, PhD Chief Research Business Development Officer http://pinker.wjh.harvard.edu/photos/boston_I/pages/Weeks%20bridge.htm The Belfer Institute For Applied Cancer Science is a Bridge Between Academia & Industry © 2012 – Belfer Institute for Applied Cancer Science DFCI’s Distinguishing Feature: The “Balanced Portfolio” • A 50:50 mix of outstanding patient care and cutting-edge research • Part of our core mission The Balanced Portfolio drives the way we think about cancer research DFCI: Balanced Portfolio A 50:50 mix of outstanding patient care and cutting-edge research Key differentiating factor: next highest institution has a 4:1 ratio $500M Expenses $500M Expenses Clinical Margin Philanthropy Clinical Margin Clinical Revenue Clinical Activity Research Revenue Research Activity Academic Structure • All Dana-Farber faculty are also faculty in departments at one of the Harvard schools (mostly HMS, some HSPH) • IP and Research belongs to where the laboratory is located • Dana-Farber has 7 internal departments – Medical Oncology – Pediatric Oncology – Radiation Oncology – Psychosocial Oncology and Palliative Care – Cancer Biology – Cancer Immunology and AIDS – Biostatistics and Computational Biology Clinical Care & Research • Pediatric oncology care delivered through Jimmy Fund Clinic & divisions in Boston Childrens Hospital – Organized in programs & disease centers • Medical oncology care delivered through 12 Disease Centers – Anatomically based Disease Centers – Early Drug Development Center • Disease Centers are sites of clinical trial activity • Clinical trials managed through Dana-Farber/Harvard Cancer Center (DF/HCC) – Consortium of 5 hospitals (DFCI, BIDMC, BWH, BCH, MGH) and 2 Harvard schools (HMS, HSPH) – Single IRB oversees trials at all 5 hospitals – DF/HCC runs over 700 active trials enrolling over 3500 patients Research Model • Faculty laboratory & group leaders are “independent contractors” – DFCI provides support for unfettered discovery research – Recruitment focused on “best athlete • Amended model needed – Pace of translation of research findings to clinical impact too slow – DFCI recognized need to introduce concepts of project management into academic translational research • DFCI Strategic Planning – Goal: implement project management principles to translate discoveries into clinical benefit while preserving the culture of independent discovery – Faculty identified 10-12 areas ripe for translation – Created “Integrative Research Centers” around each The “new” Research Infrastructure at DFCI INTEGRATIVE RESEARCH CENTERS DISEASE CENTERS • Bone and Sarcoma • Cancer Genetics • Cutaneous and Mohs Surgery • Gastrointestinal • Women’s Cancers • Head and Neck • Genitourinary • Thoracic • Hematology • Neuro • Experimental therapeutics • Psychosocial SELECTED TECHNOLOGIES • NextGen DNA sequencing • PDX Models • Pathology • Proteomics • Chemistry • Computational Biology • Imaging (animal and human) • Belfer Institute for Applied Cancer Science • Cancer Vaccine Center (CVC) • Blais Proteomics Center • Cell Manipulation Core Facility (CMCF) • Center for Biomedical Imaging in Oncology (CBIO) • Lurie Family Imaging Center (LFIC) • Center for Cancer Computational Biology (CCCB) • Center for Cancer Genome Discovery (CCGD) • Center for Cancer Systems Biology (CCSB) • Center for Clinical and Translational Research • Center for Functional Cancer Epigenetics (CFCE) • Center for Molecular Oncologic Pathology (CMOP) • Joint Center for Cancer Precision Medicine • Medicinal Chemistry Core • Early Drug Development Center (EDDC) INVESTIGATORS • Basic • Translational • Clinical Integrative Research Centers • Founded on business rules & accountability – Faculty leader of each Center charged with developing a business plan – Business plan included explicit milestones & deliverables over 5 years • Deliverables built around specific project endpoints rather than academic metrics – Financial plan required to bring Center to self-sufficiency within 5 years • Incentivizing “independent contractor” faculty to lead Centers – Seed funding to start Center activities • Not released until business plan approved by President – Research scientist hiring track • Non-tenure track faculty with project management experience • Rigorous promotion ladder & opportunities for responsibility & advancement • Over 100 research scientist faculty members • Oversight – VP for Strategic Planning & CSO for day-to-day – Internal Oversight Committees & External Advisory Boards The Lurie Family Imaging Center: State of the Art Experimental Therapeutics Facility The Lurie Family Imaging Center MRI Harbor Campus Opened August 2009 14,000 sq ft 3,300 cages Optical Full treatment options: •Expert technical support •Radiotherapy Full spectrum of endpoints: •Anatomic and molecular imaging •Conventional metrics •Access to mouse histopathology Ultrasound PET/ SPECT/CT Radiochemistry Full spectrum of mouse cancer models: •GEMM •Primary xenografts •Cell line xenografts Image-guided irradiator Expert design and data analysis: •Physicists •Cancer Biologists •Biostatistician •Clinicians •Data/Image Analysts Belfer Institute’s Scientific Scope • Target discovery – • Target validation – – – – • Tumor maintenance in vivo Delineate therapeutic significance of new target Responder ID: the context Define clinical path Target biology to enable drug discovery & development – – – – • Both genomic evidence and biological (in vivo) activities Mechanisms: response, resistance, combination Target engagement and predictive biomarkers Delineate mechanisms of resistance Develop clinical strategies to address resistance Developing strategies for existing therapies – Identify & develop best combination therapies – Expand indications Target Validation Deep Target Biology Clinical Path Hypothesis Address clinical path hypotheses upfront Patient Derived Xenograft (PDX) disease models • PDX mouse models recapitulate the genetic complexity of human cancers • Established by implanting mice with patient cancer cells/tissues from biopsy samples • Solid and liquid tumor PDX models to help develop new therapies, combinations, and biomarkers • Luciferized PDX models created for real-time tumor monitoring • Tumor volume can be correlated with serum biomarker expression or circulating free human DNA (cfDNA) • Valuable for drug efficacy and drug combination studies PROFILE: Institution-wide Genomic Profiling of Tumors • DFCI sees 16,000 new patients per year • Management and integration of 2 categories of data – Clinical data: Data generated during the course of clinical care of patients – Specimen data: molecular or other data derived from specimens • PROFILE: Institution-wide Genomic Profiling of Tumors – offers specimen genotyping & clinical data linkage for all patients – 75% patient consent rate • Process for working with companies PROFILE’s Impact • Clinical Impact – – – • Research Impact – Genotype/Phenotype Studies in Humans – – – • Clinically actionable results returned when participants consent to return of results Allows physicians to identify patients whose tumors have mutations for which approved drugs are available Allows physicians to identify patients who may qualify for clinical trials requiring specific mutations for eligibility Can ask questions about the association of specific mutations with clinical behavior Eg, is a specific set of mutations associated with Herceptin failure in Stage II breast cancer patients? Eg, does the presence of a specific mutation predict for a specific clinical behavior? Research Impact – Clinical Research – Investigators can retrieve all patients with a specific mutation & contact those who have consented to re-contact for enrollment on a trial of an agent directed against that mutation Office of Research and Technology Ventures (ORTV) Four areas of activity: • Patent inventions to incentivize industry licensing • License patents to companies big and small • Generate industry-sponsored research and collaborations • Serve research community: MTAs, CDAs etc. Our mission: Get DFCI technologies into the clinic What has changed in Oncology Drug Development? Drug Candidates from Research FDA-approved Cancer Drug <10% Overall Success VALUE RISK Target Discovery Target Validation Academia Small Molecule Antibody/ Biological Animal PoC Optimize lead Pre-IND Tox PK/PD Industry, but Academia? Venture capital investment in biotech lower No funding to reduce early stage risk 15 Phase I, II Trials Phase III Trials FDA Approval Industry Cancer driven by mutations, not tissue type Clinical development model unclear Activity Growth 80 70 Inventions 60 Patent Filings 50 40 30 Growth would be significant even if new disclosures were flat 20 10 0 2008 2008 2009 2009 2010 2010 2011 2011 2012 2012 2013 2013 2014 2014 H1 H2 H1 H2 H1 H2 H1 H2 H1 H2 H1 H2 H1 H2 16 $30 TOTAL SRA FUNDING $25 TOTAL LICENSING INCOME $20 $15 $10 $5 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 $- 2001 Millions Income Trends and Goals Small Molecules in the Clinic: Productivity License Date Development Stage 10/7/2008 Phase I in 2012 2/11/2010 Phase I in 2013 2/19/2010 Phase I in 2013 2/11/2010 Phase I in 2014 12/19/2011 Phase I in 2012 7/22/2011 Phase I in 2013 12/9/2011 Preclinical (nonchemistry) 4/9/2013 Preclinical 4/9/2013 Preclinical Start-up Success Most DFCI start-ups are successful in exits and raising money 2007 2008 2009 Eutropics (NIH-funded) Immunology Company (nearing transaction) Shape (acquired by Tetralogic) Metamark NKT ($35M raised; Therapeutics New Mgt) (Third Party) DNAR Oncomethylome/ MDxHealth (IPO in Brussels Stock Exchange) Aileron >$110M raised Alive, funded GateKeeper (rights acquired by Clovis) 2010 Acetylon (Raised $52M; $100M Celgene option to buy) Ligon Discovery (Third Party) Alive but no Investment 2011 2012 2013 Tensha (Series A) Ember (Third Rock Funded) Syros ($30M Series A) OncoPep (Funded Series A) Costim (Acquired by Novartis) SixOne Solutions (Third Party) Margaux (funded by Angel Investor) Genometry (Third Party) Crowd-sourced Not Alive Successful exit Success: PD-1 and PD-L1 PD-1 and PD-L1 inhibition: example of bench to business to bedside – – – – Dr. Gordon Freeman’s work Large patent portfolio Licensed non-exclusively to several companies 5 most promising drugs in clinic; Merck drug approved 9/4/14 Collaboration models Virtual startup model Clinical + preclinical work on compounds Develop compounds with Centers and labs Traditional licensing and sponsored research Sponsored research with groups of investigators Identify and validate targets ORTV Mission: Bring Drugs to the Clinic to benefit Patients Multiple avenues to collaborate with industry: Collaborating with DFCI O. Prem Das, PhD Inna Nusinzon, PhD Chief Research Business Development Officer Technology Transfer Specialist Office of Research and Technology Ventures Office of Research & Technology Ventures Dana-Farber Cancer Institute, BP309 Dana-Farber Cancer Institute, BP 304D 450 Brookline Ave, Boston, MA 02215 450 Brookline Ave, Boston, MA 02215 Phone: (617) 632-5893 Phone: (617) 582 7223 Fax: (617) 632-4012 Fax: (617) 632-4012 [email protected] [email protected] http://www.dana-farber.org/Research/Technology-Transfer.aspx