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WEDNESDAY, NOVEMBER 4

7:30 am Continental Breakfast Breakout Discussions

DRUG DEVELOPMENT CHALLENGES

8:35 Chairperson’s Remarks

8:40 Development of the First FDA-approved Dopamine Agonist for the Treatment of Type 2 Diabetes

Anthony H. Cincotta, Ph.D., President and Chief Scientific Officer, VeroScience

Cycloset is a unique, quick release formulation of bromocriptine, a sympatholytic dopamine D2 receptor agonist. Using this agent to treat type 2 diabetes evolved from basic science investigations of animals in the wild that exhibit marked annual cycles of metabolism, including insulin sensitivity. We found that cycloset can be added to a variety of non-dopamine agonists, peripheral acting anti-diabetes agents to provide added glycemic control benefit. Moreover, Cycloset was not associated with adverse cardiovascular event rates relative to placebo. This talk covers the R&D program of Cycloset from concept to FDA approval.

9:10 Is my Lead Diabetes Candidate “Developable” – Focusing on Biopharmaceutical and Formulation Issues from the Start

Akash Jain, Ph.D., Principal Scientist, Chemical & Pharmaceutical Profiling, Novartis Institutes for Biomedical Research

This presentation focuses on developability assessment of new drug candidates for diabetes and related CV and metabolic diseases. Time and material saving approaches for rapid selection of optimal physical form and formulation strategy for first-in-human studies will be highlighted. Application of a formulation risk assessment tool to early lead candidates for identifying solubility and exposure related development risks will be discussed. Early selection of suitable clinical and toxicology formulation principles for new diabetes candidates with sub-optimal physicochemical properties will be demonstrated using few case studies.

9:40 Update on Next Generation Incretin-Based Therapies

Michael Trautmann, M.D., Medical Fellow, Global Exenatide Team, Eli Lilly and Company

Studies with the incretin hormone GLP-1 have elucidated the therapeutic potential for augmenting GLP-1 receptor activity and improving glucose control in patients with Type 2 Diabetes. DDP-IV inhibitors increase GLP-1 levels roughly twofold by inhibiting the breakdown of endogenous GLP-1 while peptide therapeutics binding to the GLP-1 receptor directly mimic even higher levels of GLP-1. The different modes of action of GLP-1 including glucose-dependent insulin stimulation and suppression of glucagon result in significant HbA1c reductions without weight gain. In addition GLP-1 receptor agonists delay gastric emptying and decrease appetite resulting in significant weight loss.

10:10 Networking Coffee Break in the Exhibit Hall

11:40 PANEL SESSION: Clinical Landscape for New Diabetes Drug Candidates

Moderator: Steven Nissen, M.D., M.A.C.C., Chairman, Department of Cardiovascular Medicine, Cleveland Clinic Foundation

• What will the standard diabetes regimen of the future look like? Which combinations are likely to have best safety profile, efficacy and ease of use?
• Glucose lowering -- should that be the main goal of therapies? What are other possible end points?
• CV toxicity -- where to draw the line?
• Incretin based therapies and their CV profile -- are there better options?

Panelists:

Michael Trautmann, M.D., Medical Fellow, Global Exenatide Team, Eli Lilly and Company

Jorge Plutzky, M.D., Assistant Professor of Medicine, Harvard Medical School; Director, Vascular Disease Prevention Program, Brigham and Women’s Hospital

12:25 pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

CLINICAL CANDIDATES

1:55 Chairperson’s Remarks

2:00 DB959: A Novel, Dual PPAR delta/gamma Agonist for the Treatment of Type 2 Diabetes

Mary Kay Delmedico, Ph.D., Project Leader, Dara Biosciences

An important class of drugs for the treatment of T2D includes drugs which target peroxisome proliferator-activated receptors, known as PPARs. DB959 is a non-TZD dual agonist of PPAR-delta and -gamma subtypes, and is the first compound in development with this subtype profile. In March 2009, the United States Food and Drug Administration cleared the Investigational New Drug Application to begin Phase 1 trials for DB959. We will present an overview of the favorable nonclinical pharmacology, toxicology, and safety studies and provide an update on clinical plans.

2:30 ARRY-403: A Glucokinase Activator with Excellent Efficacy in Multiple Models of Type 2 Diabetes

Thomas D. Aicher, Ph.D., Principal Research Investigator, Medicinal Chemistry, Array BioPharma, Inc.

ARRY-403 is a small molecule, glucokinase activator (GKA) that entered clinical trials in April, 2009. Supporting preclinical data, including its selectivity and excellent oral bioavailability in multiple animal species will be presented. In several, well-established in vivo models of Type 2 diabetes, ARRY-403 was highly efficacious in controlling both fasting and non-fasting blood glucose and demonstrated less potential for hypoglycemia than known competitor GKAs. In combination with standard-of-care drugs, ARRY-403 provided additional benefit of controlling glucose with no adverse consequence on serum lipid homeostasi

3:00 Networking Ice Cream Refreshment Break in Exhibit Hall (Last Chance for Viewing)

3:40 Targeting Sodium-Glucose Co-transporter 2: Knockout and Pharmacology program of LX4211

Melanie K. Shadoan, Ph.D., Senior Scientist, Metabolism and Cardiology, Lexicon Pharmaceuticals, Inc.

LX4211, an oral small molecule inhibitor of SGLT2 intended to treat type 2 diabetes, is currently in early-stage clinical trials. SGLT2 was identified from our analysis of nearly 5,000 druggable mammalian genes, using mouse gene knockout (KO) technologies. SGLT2 KO mice excreted large amounts of urinary glucose and were among the most glucose tolerant of our KO lines. In preclinical studies, LX4211-treated diabetic mice showed increased urinary glucose excretion, lower HbA1c levels and improved glucose tolerance. Normal rats and dogs receiving LX4211 also showed high urinary glucose and reduced body weight gain despite higher caloric intake.

4:10 A Diabetes Clinical Candidate Against a New Target: Soluble Epoxide Hydrolase

D. Euan MacIntyre, Ph.D., Senior Vice President, Drug Discovery, Arete Therapeutics

4:40 Clinical Results on a 2nd Generation FBPase Inhibitor (MB07803) for the Treatment of Type 2 Diabetes

Barry Gumbiner, M.D., Vice President, Clinical Development & Chief Medical Officer, Metabasis

MB07803 is a novel investigational drug that inhibits fructose 1,6 bisphosphatase, a key enzyme regulating hepatic glucose production.  Recent clinical trial data will be presented demonstrating that in patients with well-established and poorly-controlled type 2 diabetes, treatment with MB07803 monotherapy results in rapid and pronounced fasting and postprandial glucose-lowering.  Additional data describing the drug’s tolerability and safety profile will be presented, including data suggesting that MB07803 may exhibit reduced effects on lactate metabolism and acid-base balance compared to the first generation compound.

5:10 Close of Conference

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