Mikhail Sitkovsky Skolkovo im modernization of medicine


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  • 04/02/11
  • Mikhail Sitkovsky Skolkovo im modernization of medicine

    1. 1. Skolkovo in modernization of medicine and fostering the cutting edge biomedical enterprise in Russia <ul><li>The next 5 years… </li></ul>
    2. 2. The Cutting Edge Treatments and Technologies that stimulate and/or enable the world-class IP-generation In Russia. <ul><li>The thoughtfully arranged “repertoire” of networking Skolkovo companies… </li></ul><ul><li>But how to ensure that the Skolkovo-generated IP is NOT lost! </li></ul><ul><li>Because it is NOT validated in vivo! </li></ul><ul><li>Skolkovo Institute of Translational Medicine </li></ul><ul><li>= SITM: </li></ul><ul><li>But which Treatments and Technologies? </li></ul><ul><li>The Recruitment of Top Talent to Skolkovo </li></ul>
    3. 3. One of the desirable Skolkovo aims: to develop what “ everybody wants and nobody has ”. <ul><li>But Skolkovo also should develop what USA has, but Russia does not have </li></ul><ul><li>Or does not have IP to produce the needed treatment… </li></ul>
    4. 4. The “Cutting Edge” technologies
    5. 5. What is it that “ everybody wants and nobody has ”? <ul><li>For example, the effective immunotherapy of cancer . </li></ul><ul><li>Requires combined use and improvement of many medical technologies.. </li></ul><ul><li>Immunotherapy is the Biomedical “Decathlon” ! </li></ul><ul><li>Immunotherapy can serve as an unifying focus in selecting and offering priorities… </li></ul>
    6. 6. <ul><li>Attacking tumor with patient’s own anti-tumor CD8+ T-killer cells and Natural Killer Cells </li></ul><ul><li>To get rid of the residual tumor and metastases… </li></ul><ul><li>FDA USA: = 27 april 2010, “ Provenge ” Cancer Vaccine, Dendreon, </li></ul><ul><li>But the success rate is still low: ~ + 4 months? </li></ul><ul><li>Why?-Tumor protects itself from anti-tumor T-killer cells; </li></ul><ul><li>“ Hellstrom Paradox”… </li></ul>Immunotherapy of Cancer ( “Our last hope”… )
    7. 7. The “Hellstrom” Paradox”, Natur e, 1968; ? Anti-tumor T cells destroy tumor cells in vitro : The “Hellstrom-Schreiber” Paradox: -“ Equilibrium lesions ”(Nature, 2007) The Motivation: 1974, Moscow University In vivo tumor seems to be protected :
    8. 8. Adenosine puts anti-tumor T killer cells to sleep … The Solution Ohta and Sitkovsky, Nature 2001
    9. 9. <ul><li>Moscow University: 1974-1981 </li></ul><ul><li>Mass.Inst. of Technology: 1981-1984 </li></ul><ul><li>National Institute of Health, Lab.Immunology: : 1984-2004 </li></ul><ul><li>New England Inflammation and Tissue Protection Institute, NU: 2004-present : </li></ul><ul><li>Dana Farber Cancer Institute, Harvard Institutes of Medicine: 2005-present </li></ul><ul><li>“ Invisible “College” of Multiple Tough Reviewers: Nature , J.Exp.Med ., J. Biol. Chem ; PNAS ; J. Immunol ,..) </li></ul><ul><li>“ NewVac”: 2010-present </li></ul>Where the study was done…
    10. 10. <ul><li>Based on Solution of Hellstrom Paradox… </li></ul><ul><li>RedoxTherapies and ChemRar: </li></ul><ul><li>Founders of “NewVac” in Skolkovo. </li></ul><ul><li>The IP-Creating and the IP-attracting enterprise in Skolkovo </li></ul>Tumor Defense CounterMeasures
    11. 11. Tumor Defense Countermeasures
    12. 12. Tumor Rejection Survival
    13. 13. Tumor Rejection Anti-Tumor Hypoxia Drug Competitive A2AR Antagonist Tumor Hypoxia [O 2 ] Low Ecto-Enzymes [CD39] High [CD73] High ATP-->[Adenosine] High Elimination or Blockade of CD73
    14. 14. Preclinical evidence of tumor rejection and immunological memory to rejected tumor due to the action of the A2AR antagonist in different animal models of cancer
    15. 15. The Anti-Tumor Hypoxia Drug enables anti-tumor T killer cells to reject lung tumors 21% 40% 60%
    16. 16. <ul><li>If there is In Vivo Evidence  </li></ul><ul><li> No IP, No patents! </li></ul><ul><li>The decisive solution: </li></ul><ul><li>SITM </li></ul><ul><li>Skolkovo Institute of Translational Medicine </li></ul>The importance of animal models of diseases
    17. 17. <ul><li>=SITM develops cutting edge novel ideas </li></ul><ul><li>=SITM makes great ideas patentable by validating them in vivo </li></ul><ul><li>=SITM has Department of Animal Models of Human Diseases </li></ul><ul><li>=“Humanized” and KO mice </li></ul><ul><li>=SITM coordinates clinical trials of Skolkovo companies </li></ul><ul><li>Who can collaborate in launching SITM? </li></ul>SITM Skolkovo Institute of Translational Medicine
    18. 18. How Dana-Farber Cancer Institute at Harvard Organizes its 50:50 Balance of Clinical Care and Basic Research The Structure of Dana-Farber An Innovative Model for Cancer Research and Care <ul><li>Bone and Sarcoma </li></ul><ul><li>Cancer Genetics </li></ul><ul><li>Cutaneous and Mohs Surgery </li></ul><ul><li>Gastrointestinal </li></ul><ul><li>Women’s Cancers </li></ul><ul><li>Head and Neck </li></ul><ul><li>Genitourinary </li></ul><ul><li>Thoracic </li></ul><ul><li>Hematology </li></ul><ul><li>Neuro </li></ul><ul><li>Experimental therapeutics </li></ul><ul><li>Psychosocial </li></ul>DISEASE CENTERS <ul><li>Center for Cancer Vaccines </li></ul><ul><li>Center for Clinical Translational Research </li></ul><ul><li>Center for Experimental Pathology </li></ul><ul><li>Center for Cancer Genomics </li></ul><ul><li>Center for Cancer Systems Biology </li></ul><ul><li>Center for Applied Cancer Science </li></ul>INTEGRATIVE RESEARCH CENTERS <ul><li>Proteomics </li></ul><ul><li>Genomics </li></ul><ul><li>Chemistry </li></ul><ul><li>Computational Biology </li></ul><ul><li>Imaging </li></ul>TECHNOLOGIES
    19. 19. Some of the promising opportunities for Skolkovo Specific Examples…
    20. 20. <ul><li>For example, the NewVac in Skolkovo will have drug that may also improve the antibody-targeting therapies of breast cancer… </li></ul><ul><li>Monoclonal Antibody Herceptin. </li></ul><ul><li>But How to get it to Skolkovo? </li></ul>
    21. 21. <ul><li>DFCI, Harvard and U. Penn, Mark Greene. M.D. </li></ul><ul><li>The Skolkovo may have chance to develop the most superior treatment using the next Generation Herceptin; </li></ul>The answer #1: Recruiting the Discoverer of Herceptin
    22. 22. S22-Fc - a multi-specific binder to EGFR, Her3 and Her2/neu Binding to T6-17 (Her2) and NE91(EGFR) cells by S22-Fc MCF7 NE91 T6-17 S22-Fc S22 Fc
    23. 23. “ Creation of a trivalent antibody like molecule with picomolar activity against EGFr, HER2/neu and HER3” The molecule is already fully “human” …; Has potential to help all HER+ breast cancer patients as compared with 25% for original herceptin Ab… as compared with Zero with no “old” herceptin. Is not it something that “ everybody wants and nobody has ”?
    24. 24. Drugs that are not novel, but are much needed… and can be “novel again”… <ul><li>These drugs can be also very lucrative </li></ul><ul><li>Multi-$ Billion market </li></ul><ul><li>-The IP- is getting “old”… </li></ul><ul><li>But the international IP on them is still possible! </li></ul>
    25. 25. Not “Cutting Edge” on the first look… <ul><li>But these actually ARE cutting edge technologies… </li></ul>
    26. 26. Chronology of Key Biotech Product Approvals 1982 - 2007 Fabrazyme Amevive Xolair Bexxar Raptiva 2003 1987 1998 1997 1995 1996 1988 1989 1990 1991 1992 1993 1994 1999 2001 2000 CBER (N=48) CDER (N=14) Activase 1986 1985 Nutropin Glucagon Thyrogen Mylotarg Ovidrel Natrecor Protropin Cerezyme Ceredase Follistim Forteo Epogen /Procrit Neupogen Leukine Actimmune Proleukin Pulmozyme Betaseron ReoPro Intron A Abatacept Galsulfase Avonex Retavase Benefix Infergen Neumega Rituxan Zenapax Regranex Simulect Synagis Remicade Herceptin Enbrel NovoSeven Ontak Refacto Zevalin Elitek Humira Rebif Humulin R (1982) Achieved $1 Billion Annually in International Sales 2002 Campath Kineret Xigris Aranesp 2004 2005 2006 Avastin Erbitux Tysabri Lucentis Myozyme Elaprase Vectibix Humatrope Increlex Products Most Likely Off Patent by 2018 2007 2018
    27. 27. Why would you want to have a drug that is out of IP protection? <ul><li>Because it is proven to be safe… </li></ul><ul><li>Because it works! </li></ul><ul><li>It will bring you $$! </li></ul><ul><li>And it did not cost you $$$$ to develop! </li></ul><ul><li>Competition: China, India… </li></ul><ul><li>But safety still must be proven.. </li></ul>
    28. 28. Biosimilars in Skolkovo <ul><li>Our Chance? </li></ul><ul><li>New IP-based methods of inexpensive evaluation of Innovative and “Biosimilars”… </li></ul><ul><li>“ Evergreening ” of drugs on the market… </li></ul><ul><li>-New combinations </li></ul><ul><li>-New delivery </li></ul><ul><li>-New formulations </li></ul><ul><li>E.g. ChemRar and Sanofi-Aventis.. </li></ul>
    29. 29. “ The Potential Skolkovo Enterprise: <ul><li>New IP-based Technologies to evaluate “Biosimilar” biotech products ; </li></ul><ul><li>Less expensive validation of BioSimilars </li></ul><ul><li>Also minimize the $$$ risk with innovative drugs.. </li></ul><ul><li>“ Immunogenicity” … </li></ul><ul><li>-”scale-up”…. “omics” … </li></ul><ul><li>E. Reinherz, Harvard and Barry Karger, NU </li></ul>
    30. 30. GENERAL PRINCIPLE: Skolkovo must have strong requirement: The IP-generating technological platform <ul><li>The Example: </li></ul><ul><li>Monoclonal antibody/ Proteomics based and </li></ul><ul><li>The disease-specific diagnostic or outcome-predicting assays; </li></ul>
    31. 31. <ul><li>If there is NO need in immunotherapy! </li></ul><ul><li>Early diagnosis! </li></ul><ul><li>Need in superior biomarkers. </li></ul><ul><li>Proteomics and bioinformatics platforms </li></ul><ul><li>Not just for immunotherapy! </li></ul><ul><li>For any disease! </li></ul>What is even better than EFFECTIVE immunotherapy of cancer?
    32. 32. “ In Skolkovo ” mAB proteomics technology <ul><li>New IP to be created for every new disease </li></ul><ul><li>~10 000 mAB / experiments for proteome profiling </li></ul><ul><li>Disease specific mAB libraries detect the natural form of the proteome </li></ul><ul><li>Easy to translate </li></ul>
    33. 33. Generation of the BSI mAb library against native human plasma proteins using mAb proteomics (patent pending) Patent pending proteome normalization (10,000 mABs / experiment) No translation bottleneck Record speed form bench to market
    34. 34. “ In Skolkovo” created mAb/Proteomics diagnostics <ul><li>A test for early detection of lung cancer is in late development phase </li></ul><ul><ul><li>Expectation is improvement of survival from 16% to 50% </li></ul></ul><ul><li>Serum from patients with other diseases… </li></ul><ul><li>What e.g. about early bacterial infections? </li></ul><ul><li>What about prostate cancer? </li></ul><ul><li>What about heart disease? </li></ul>
    35. 35. <ul><li>Targeting NOVEL targets by NOVEL small molecules and NOVEL biotech products: </li></ul><ul><li>These are the most IP-rich technologies : </li></ul><ul><li>Must be based on “ Breakthroughs in understanding of molecular mechanisms of disease ”. </li></ul><ul><li>Now is the good time to identify some of these underfunded in USA/Europe breakthroughs. </li></ul><ul><li>Benefitting from failures of peer review at NIH.. </li></ul><ul><li>Skolkovo has all to attract the top world scientists! </li></ul>The Recruitment of Top Talent to Skolkovo
    36. 36. <ul><li>Yes : -Emotional to some…-Interesting to many.. </li></ul><ul><li>=Bad times in the West… - $$$ = is the “strongest chemo attractant!” </li></ul><ul><li>No: -1990s stories about “Russian Partners”… </li></ul><ul><li>-Yes : Skolkovo will dispel fears by excellent examples of Russian Partners! </li></ul><ul><li>Thus Skolkovo will play yet another great role for Russia by challenging the wrong image stereotype! </li></ul>Will The Top World Scientists Come to Russia with their Best to synergize with Russian scientists ?
    37. 37. What to Do? <ul><li>1. Identifying top scientists with cutting-edge discoveries that have significant translational potential </li></ul><ul><li>2. = SITM: </li></ul><ul><li>Skolkovo Institute of Translational Medicine </li></ul><ul><li>Novel Treatments and drugs IP-Creating companies in Skolkovo </li></ul>
    38. 38. Contacts USA numbers 617-669-88-16 - works in Moscow 617-800-52-65
    39. 39. Skolkovo is also uniquely qualified to catapult the medical care in Russia to the much higher levels <ul><li>One can think about the MedTechSOP-Transfer enterprise in Skolkovo; </li></ul><ul><li>The Medical Treatments, Standard Operating Procedures (SOP) and Technology transfer </li></ul><ul><li>Top clinician-scientists of Dana Farber Cancer Institute, Harvard Institutes of Medicine,Harvard Medical School.. </li></ul><ul><li>A lot of people to persuade, but there is some initial interest.. </li></ul>
    40. 40. Molecular Weight hGH ~ 3000 atoms Factor VIII ~ 55,000 atoms Need for Trials Biosimilars – Complexity leads to unknowns - If you don’t run trials – you won’t know the safety or efficacy Aspirin 21 atoms Complexity of biotech products IgG Antibody ~ 25,000 atoms 0 200,000 350,000 250,000 50,000 150,000 100,000 300,000 COOH OCOCH 3
    41. 41. Drug Discovery from Uncultur-able before Microorganisms ● 99% of all species of microorganisms on the planet do not grow in the lab ● Millions of new species, an enormous untapped resource for drug discovery ● A general method to grow uncultured microorganisms developed based on cultivation in situ in diffusion chamber and subsequent “domestication” for growth in the lab ● Growth factors for many uncultured species identified, an additional tool for growing them in the lab Patent: US 7,011,957 Kaeberlein et al., Science 296:1127-1129. Schumacher et al., 2009. Science 323:396-401. Dörr et al., PLoS Biol 8(2): e1000317. Lewis, K. 2007. Nature Rev. Microbiol. 5:48-56. D’Onofrio et al., 2010. Chem. & Biol. 17: 254–264.
    42. 42. IP-generating drug discovery in Russia <ul><li>“ Fishing expeditions”…. </li></ul><ul><li>But fishing expeditions DO catch fish! </li></ul><ul><li>Some times… </li></ul>
    43. 43. Generation of the BSI mAb library against native human plasma proteins using mAb proteomics (patent pending) Plasma Normalization Patent pending Shotgun Immunization Library characterization screening mAb Production mAb microarray Production QuantiPlasma™ PlasmaScan™ Microarray Libraries >600 mABs “ 10 000 mABs” Plasma Collection Nascent library generation HT Hybridoma Cloning mAb validation ELISA Characterization mAb/epitope/protein ID
    44. 44. An Open Forum on the Scientific and Regulatory Issues of Biosimilars and Follow-on Biologics Boston, MA USA Copley Marriott Hotel Address by: Senator Edward Kennedy Chairman of the Senate Health, Education, Labor and Pensions Committee Plenary by: Dr. Randall Lutter Acting Deputy Commissioner for Policy, US FDA Organizing Chair: Prof. Barry Karger Director, Barnett Institute, and James L. Waters Chair, Northeastern University Hosted by: A high level meeting of the international biotechnology and generics industries, together with government regulators and academic laboratories, for an open forum and collegial debate on the scientific and regulatory issues in the introduction of generic complex biological drugs. www.barnett.neu.edu/biogenerics/ For additional information or to receive updates, email Biogenerics2008@neu.edu BIOGENERICS March 2-4, 2008
    45. 45. BIOSYSTEMS INTERNATIONAL The antibody technology company