Monday, October 6
8:00am Registration
PROSPECTS FOR REPURPOSING
9:00 Chairperson’s Opening Remarks
Thomas Barnes, Ph.D., Senior Vice President, Drug Repositioning Discovery, Ore Pharmaceuticals Inc.
9:10 Drug Repositioning: More Than One Way to Skin a Cat
Art Pappas, MBA, Managing Partner, Pappas Ventures
As the traditional approaches to developing new drugs, including in-house discovery and development efforts and in-licensing of externally-developed drugs, become increasingly more expensive and, in many cases, increasingly less productive, the growing need to fill shrinking pipelines has large pharma companies looking more and more at a third approach, namely the repositioning or repurposing of drugs for new indications that had been previously shelved for efficacy reasons in a different indication or set of indications. This talk will discuss several case histories of companies that have used various approaches to reposition drugs, including in vivo imaging, ex vivo bioanalytics, in vitro pharmacology and in silico biology. The implications of various patent strategies on the approach of repositioning drugs will also be addressed.
9:40 Repositioning With a Twist: Establishing New Composition of Matter IP and Indications for a Marketed Drug
Iain Dukes, MA, DPhil, President and Chief Executive Officer, Essentialis Inc.
We have been able to file novel composition of matter patent claims on an existing marketed compound (whose IP has long lapsed) and are in Phase II development for displidemia and type 1 diabetes, indications that are novel and not anticipated by its current indication and use.
10:10 Pfizer's Hunt for Repositioning Opportunities
David K. Rosen, DVM, Executive Director, Worldwide Business Development, Pfizer Inc.Pharmaceuticals companies, almost regardless of size, have “parked” R&D programs which are going unused. Using a variety of different business approaches, Pfizer is looking for ways to take these underutilized assets and evaluate them against new targets or new indications. We will examine some specific examples of business partnerships designed to create value from preclinical and clinical development programs that have failed their primary indication.
10:40 Coffee Break, Poster & Exhibit Viewing
11:15 Trends and Challenges in Drug Repositioning Deals and Collaborations
Richard B. Smith, Partner, Edwards Angell Palmer & Dodge LLP
Drug repositioning collaborations between big pharma and biotech/specialty pharma are becoming more popular as big pharma seeks access to biotech/specialty pharma’s drug discovery platforms, and biotech/specialty pharma seeks access to drug products having a higher probability of development success. This talk will look at the current trends in repositioning deals as well as some of the challenges unique to these types of collaborations and strategies to overcome them.
11:45 New Patents for Old Drugs? The Role of Label-Based Strategies
Ned Israelsen, JD, Managing Partner, Knobbe, Martens, Olson & Bear, LLP
This talk will cover strategies for obtaining patents that protect the FDA label for repurposed drugs. Label-based method patents are Orange Book listable, and potentially provide 20 years additional exclusivity for repurposed drugs. Even narrow patents, carefully tailored to cover the label’s indication, prescribing information, dosing, and even contraindications can potentially provide exclusivity. This talk will cover the pros and cons of label patents, the impact of recent court decisions on the standard of obviousness, and the type of coordination between regulatory and patent professionals that can bolster patent estates. The contributions of formulation, enantiomer, and polymorph patent strategies will also be addressed.
12:15pm Luncheon Workshop (Sponsorship Available) or Lunch on Your Own
HOW TO REPOSITION DRUGS
1:30 Chairperson’s Remarks
Christopher A. Lipinski, Ph.D., Scientific Advisor, Melior Discovery
Keynote Presentation |
 1:35 Repurposing of Enbrel for Alzheimer’s Disease
Edward Tobinick, M.D., Assistant Clinical Professor of Medicine, University of California, Los Angeles and Director, Institute for Neurological Research
Etanercept, a biologic anti-TNF fusion protein, received FDA-approval at the end of 1998 for the treatment of rheumatoid arthritis, and was subsequently FDA-approved for the treatment of psoriasis, ankylosing spondylitis, and additional forms of arthritis. In 2006, at a time when the amyloid hypothesis dominated the thinking of the Alzheimer community, a pilot study, using a novel form of administration of etanercept, suggested an entirely new field of use for this class of anti-TNF agents. The pilot study documented sustained clinical improvement through six months in 15 patients with probable Alzheimer’s disease ranging in severity from mild to severe, utilizing a novel form of perispinal administration of etanercept. In 2008, there are further reports of rapid improvement, beginning within minutes, in patients with severe dementia treated with perispinal etanercept. As the inventor of this repurposed use of etanercept, I will review how this paradigm shift occurred.
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2:15 From Repositioning Hypothesis Toward Reinitiation of Clinical Testing: The Case of GL1001
Stephen Donahue, M.D., Senior Vice President, Clinical Development, Ore Pharmaceuticals Inc.
GL1001, a selective inhibitor of ACE2, has completed testing in a clinical Phase I single-ascending dose study in the U.K. Good tolerability and safety were demonstrated through the highest dose tested. The original sponsor was pursuing an indication of obesity, but repositioning efforts pointed toward gastrointestinal (GI) indications. A genomic database derived from greater than 18000 human samples representing over 400 disease states was screened for increases in ACE2 expression. ACE2 over-expression was demonstrated in only a few GI disease states, including colitis and chronic gastritis. In vivo analysis demonstratedcompound specific anti-inflammatory effects in GI organs of NFkB-luciferase reporter mice in a lipopolysaccharide (LPS) induced inflammation model visualized by bioluminescent imaging. These findings were the basis for future investigations of GL1001 as a potential treatment for disorders with a predominant feature of inflammation of the GI tract. Animal models provided evidence that GL1001 reduces signs of injury and inflammation in experimental colitis, gastritis, and gastric ulcer.
2:45 Receptorome Screening: A Facile Approach to Target Discovery and Liability Assessment
Vincent Setola, Ph.D., Pharmacology, University of North Carolina, Chapel Hill
During the past decade, receptorome screening has advanced our understanding of drugs’ mechanisms of action. Recently, the approach has led to several significant discoveries with applications both to the pharmaceutical industry and academia. During this presentation, a few timely examples of the successes of receptorome mining will be highlighted. As will be discussed, receptoromics has proven a useful tool for understanding drug side effects, elucidating drug targets, and gaining insights into how currently approved drugs might be repositioned.
3:15 Repurposing and Repositioning in Drug Discovery
Anthony Macherone, Ph.D., Senior Director, Analytical & Bioanalytical Services, ASDI Biosciences
Compounds known to elicit biological activity reside in a relatively small and isolated region of chemical space. A priori it makes good scientific sense to begin the discovery phase in a region of space wherein activity, safety, and efficacy are presumed. Many in silico tools and filters have been developed since the publication of the Rule of Five by Lipinski, et al (1997). Our lab has examined several commercial compound collections with the idea of repositioning in mind and has used various in silico tools and filters to parse collections into biologically relevant space, pass physiochemical requirements, and avoid moieties with known liabilities prior to high-throughput screening. We have further participated in ADME and PK studies through a collaborative effort to examine the in vitro and in vivo efficacy of repurposed or repositioned drugs. There are a number of examples of successful repurposing especially in the area of tropical disease research. Herein we will examine some of the potentials and pitfalls to this approach as compared to de novo drug discovery paradigms.
3:45 Refreshment Break, Poster and Exhibit Viewing
4:30 Imatinib (Gleevec) for the Treatment of Autoimmune Diseases
William H. Robinson, M.D., Ph.D., Assistant Professor of Medicine, Immunology & Rheumatology, Stanford UniversityTyrosine kinases play a central role in the activation of cellular responses that mediate the pathogenesis of many autoimmune diseases. We demonstrated that imatinib potently treats a mouse model for rheumatoid arthritis, by abrogating signal transduction pathways mediating TNF-alpha production and fibroblast proliferation. We further investigated use of imatinib in an investigator-initiated open label study in systemic sclerosis, a sclerotic disease involving the skin and internal organs. Imatinib-mediated inhibition of a spectrum of signal transduction pathways and the downstream cellular responses may provide a powerful approach to treat a variety of autoimmune and inflammatory diseases.
5:00 “EffiPRO” – An Efficient, Comprehensive Platform for Efficacy Profiling of Compounds and Genetic Target Validation
David S. Grass, Ph.D, Vice President, Scientific Operations, In Vivo Discovery,
Caliper Discovery Alliances and Services, Caliper Life Sciences
To address the challenges facing the biopharmaceutical industry, Caliper Discovery Alliances and Services (CDAS, Xenogen Biosciences) was one of the first to develop and validate a broad, in vivo focused platform, which utilizes cost-efficient mice to comprehensively characterize drug development candidates and/or genetic targets, a program known as EffiPRO. In fact, this platform is now able to measure over 450 parameters associated with in vivo challenge and/or bioassays that are relevant for up to 15 therapeutic areas. For compounds, this platform identifies and confirms unanticipated “pre-positioning” indications for earlier stage compounds as well as “repositioning” opportunities for existing marketed therapeutics or clinical development compounds. For genetic targets, this platform has been used to characterize close to 200 targets efficiently, quickly and comprehensively, thus creating early positioning strategies for potential therapeutic agents.
5:15 Networking Reception
6:15pm Close of Day One