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Biochemical Pharmacology Discussion Group the New York Academy of Sciences

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Biochemical Pharmacology Discussion Group the New York Academy of Sciences BIOCHEMICAL PHARMACOLOGY DISCUSSION GROUP THE NEW YORK ACADEMY OF SCIENCES JULIA N. HEINRICH, PhD CHARLES A. LUNN, PhD STEVEN S. GROSS, PhD ILDIKO ANTAL, PhD Secretary, BPDG Program Coordinator, BPDG Co-Chair, BPDG Co-Chair, BPDG Bristol-Myers Squibb (908) 874-8018 Weill Cornell Medical College Bristol-Myers Squibb (609) 818-4157 [email protected] (212) 746-6257 (609) 252-6600 [email protected] [email protected] [email protected] EXECUTIVE COMMITTEE: 25 April 2014 Joshua Apgar, PhD Boehringer Ingelheim Colleagues: Mercedes Beyna, MS Pfizer Lakshmi Devi, PhD Mount Sinai Medical School On behalf of the Biochemical Pharmacological Discussion Group (BPDG) steering Ruth Duffy, PhD Otsuka America Pharmaceutical, Inc. committee, I am pleased to present to you the New York Academy of Science BPDG Ahmad Fawzi, PhD GPCR BioSciences Inc. proposals and ballot for the 2015 season. Please review the proposals, score the ballot with Carolyn Foster, PhD your selections and return to me. This process will be used to select the final program for John Hambor, PhD Boehringer Ingelheim next year. Feel free to distribute the ballot and program proposals to other members of your Huiping Jiang, PhD Boehringer Ingelheim institution. Kenneth Jones, PhD Forest Research Institute Kenneth LaMontagne, PhD Novartis Pharmaceuticals Score your 10 best programs from 1 to 10 with decreasing order of priority as follows: Scott M. MacDonnell, PhD Boehringer Ingelheim Robert Martone Covance Biomarker Center of Excellence 1st choice 1 Martha Matteo, PhD 2nd choice 2 Jose Perez, PhD Broad Institute 3rd choice 3 Barbara Petrack, PhD Drew University ······ ···· Pat Rose, PhD Esther Sabban, PhD 10th choice 10 New York Medical College Pallavi Sachdev, MPH, PhD Eisai, Inc. JoAnne Saye, PhD Please send the completed ballot to me as an e-mail attachment by EOB on Friday, 9 May ViroPharma Inc. June Sonnenberg-Reines, PhD 2014. The only way we are able to identify and present high interest/high quality programs Roland Staal, PhD Lundbeck Research USA is to obtain as much feedback from as many supporters as possible. If you need further Edward Tamer, PhD assistance, don’t hesitate to contact me. Thank you. W. Ross Tracey, PhD Novartis Institutes for BioMedical Research Lawrence Wennogle, PhD Charles A. Lunn Intra-Cellular Therapies Inc Program Coordinator, BPDG George Zavoico, PhD MLV [email protected] PROPOSAL #1 FULL DAY BPDG 2015 Symposium Proposal Title: “Growing Pains: The Future of Cytokines as Immunotherapies for Oncology, Infection and Inflammatory Disease” Outline: Cytokines are small, short-lived proteins produced by a broad range of cells that play an important role in health and disease, specifically in host responses to infection, immune responses, inflammation, trauma, sepsis, cancer, and reproduction. Preclinical studies have shown that many cytokines have considerable clinical potential as antiviral and anticancer agents or to suppress inflammatory and autoimmune conditions. However, in the clinic substantial systemic toxicity associated with low dosing regimens prevents escalation to therapeutically active regimens. One strategy to circumvent this toxicity problem is the development of immunocytokines: cytokines fused to a binding module such as a scFv-antibody fragment or a nanobody to target them to selected cells and/or sites of disease. Targeted delivery of immune-stimulatory or immune- regulatory cytokines represents a promising strategy for the treatment of cancer and chronic inflammatory diseases, respectively, by improving the therapeutic index with acceptable side effects. As of 2012 there were over 40 immunocytokines tested in animal models which assessed biodistribution properties and/or therapeutic performance; 9 of these have entered clinical development. Although the use of antibodies as the delivery vehicle has improved the therapeutic index of cytokines, additional efforts are still being explored. One such effort; “activity-by-targeting”, utilizes mutated cytokines that alter receptor binding properties combined with selective targeting to cells or tissues. Scientific Learning Objectives: At the conclusion of this symposium, participants will be able to: 1. Explore emerging strategies for how cytokines and immunocytokines can be applied in clinical practice. 2. Discuss limitations and toxicities with current marketed cytokine therapies. 3. Review aspects of cytokine and immunocytokine efficacy and safety in preclinical and clinical studies 4. Evaluate the application of targeted immunocytokine therapeutics for specific disease treatments Suggested speakers, affiliations and topics: Speaker (Institution): Michael B. Atkins (Georgetown Lombardi Comprehensive Cancer Center, Wash.DC) Title: Approved Cytokine Therapies: History of Proleukin/aldesleukin [interleukin 2 (IL2)] in the Treatment of Melanoma Speaker (Institution): Paul M. Sondel (University of Wisconsin) Title: Immunocytokine Therapies Through Enhanced ADCC Activity: Anti-GD2 + IL2 for Treatment of Neuroblastoma and Melanoma Speaker (Institution): Julien Laurent (Merck KGaA, Germany) Title: Increasing Therapeutic Indices through Tissue Targeting: EMD 521873 (Selectikine; IL-2 Fusion Protein) in the Treatment Cancer Speaker (Institution): John G. McHutchison M.D. (Duke Clinical Research Institute) or Michael W. Fried MD (University of North Carolina) Title: Approved Cytokine Therapies: PEG-Interferon in the Treatment of Hepatitis C Infection Speaker (Institution): Gilles Uze (University Montpellier II, France) Title: Increasing Therapeutic Indices of Immunocytokines: High Efficiency Targeting of Interferon (IFN)2 Activity Speaker (Institution): Dario Neri (Philogen, Zürich, Switzerland) Title: Dekavil (F8-IL10): An Immunoregulatory “Armed Antibody” for the Treatment of Rheumatoid Arthritis Proposal Submitted By: Name: Kerry Ralph, Boehringer Ingelheim Pharmaceuticals Inc. E-mail: kerry-leigh.ralph@boehringer- ingelheim.com Name: Scott Brodeur, Boehringer Ingelheim Pharmaceuticals Inc. E-mail: scott.brodeur@boehringer- ingelheim.com BPDG Delegate(s) Submitting Proposal: Scott MacDonnell PROPOSAL #2 FULL DAY BPDG 2015 Symposium Proposal Title: Insight into GDF-11 and related proteins and their potential role in cardiomyocyte hypertrophy and fibrosis during diastolic heart failure Outline: Heart disease is one of the leading causes of mortality worldwide. The adult mammalian heart has very limited regenerative capacity. Indeed, the replacement of the damaged tissues after myocardial infarction with fibroblast and extracellular matrix generates a robust scar that does not conduct electricity or actively contract. Therefore, one of the greatest challenges is the redirection of the heart’s innate fibrosis repair program to generate new contractile muscle cells. Recently, a novel approach to reverse age-dependent cardiac hypertrophy has emerged with the observation that specific systemic factors are declining in an aging animal model. One factor identified, GDF-11 (or BMP-11), has been proposed to be a central negative regulator of age related diastolic heart failure. GDF-11 belongs to the BMP subfamily of TGF-β ligands, and is highly similar to myostatin (another BMP molecule involved in muscle growth). While the identification of a specific regulator is appealing from a therapeutic perspective, cardiac hypertrophy appears to be the result of a delicate balance between growth and inhibitory signals, including myostatin and GDF-11. The level of each of these signals either tips the balance to growth or potentially to regression. Future work needs to focus on understanding how distinct factors from the systemic environment control cellular outcome across tissues during aging. More specifically, it will be interesting to see whether and how circulating factors impact other aged phenotypes such as reduced skeletal mass, increased adiposity and reduced insulin sensitivity. Scientific Learning Objectives: At the conclusion of this symposium, participants will be able to: 1. Gain a working knowledge of recent advances in the TGF-β/BMP receptors type I/II and signaling pathways (Smad and non Smad) 2. Understand the common features and differences between GDF-11 and GDF-8 (myostatin) (receptor sensitivity, expression and signaling pathway) 3. Understand the role of BMPs in heart hypertrophy, skeletal mass, increased adiposity and reduced insulin sensitivity 4. Understand the potential challenges and benefits of targeting TGF-β/BMP pathways Suggested speakers, affiliations and topics: Speaker (Institution): Dr. Anthony Atala (Wake Forest Inst. for Regenerative Medicine, Winston-Salem, NC) Title: Cell therapy approach for Regenerative Medicine Speaker (Institution): David Glass (Novartis Institute for Biomedical Research, Cambridge, Boston, MA) Title: Targeting Activin type II receptor Speaker (Institution): Se-Jin Lee (JHU, Baltimore, MD) Title: Regulation of GDF-11 and myostatin by specific inhibitors Speaker (Institution): Thomas Thompson (University of Cincinnati, OH) Title: Interaction between Myostatin: follistatin and receptors Speaker (Institution): Anthony Rosenzweig (Beth Israel Deaconess Medical Cntr & Harvard Medical School) Title: Effect of MSTN deletion in aging mice Speaker (Institution): Kenneth Boheler (National Institute of Aging, Baltimore, MD) Title: Molecular mechanism of cardiomyocyte aging Speaker (Institution): Alan Schneyer (University of Massachusetts-Amherst, Springfield, MA) Title: Role of TGF-B superfamily in beta cells and glucose tolerance
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