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4th International Metabolic Diseases Drug Discovery World Summit

 
  February 04, 2005  
     
 
Strategic Research Institute, Embassy Suites Hotel
April 11-12, 2005


Monday, April 11, 2005 (Day 1)

7:00 - 8:00
Registration, Networking & Exhibits



8:00 - 8:15
Chairs’ Opening Remarks

Michael Jirousek, Ph.D.
Director, Head of Diabetes/Obesity Therapeutic Area
PFIZER GLOBAL R&D - LA JOLLA LABORATORIES

Brett Monia, Ph.D.
Vice President, Antisense Discovery
ISIS PHARMACEUTICALS

Wick Johnson, Ph.D.
Director, Licensing & Development
PFIZER INC.



8:15 - 9:00
Novel Targets for Drug Discovery Through RNAi

Development of the next generation of drugs for metabolic diseases will require the discovery of novel protein targets with relatively specific expression and function in such tissues as liver, muscle, fat, islets of Langerhans and the hypothalamus. Through genomics approaches over the last several years proteins with high expression in these tissues have been revealed. Now novel technologies afforded by the discovery of RNAi has provided the means for rapid functional analysis of these proteins in a high throughput mode. Our laboratory has developed a high throughput, 96 well siRNA-based gene silencing system that determines function of proteins in adipocytes or other cells on such processes as insulin sensitivity, GLUT4 regulation, fatty acid synthesis and oxidation, AMP kinase and adiponectin secretion. This screen has revealed novel proteins that are negative regulators of insulin sensitivity and thus potential drug targets. In vivo validation of such potential targets is achieved by lentivirus-based shRNA vectors that promote tissue-specific knockdown of genes in adult mice or in mouse embryos, producing tissue specific gene knockdown mice. These RNAi-based technologies to discover and validate novel drug targets promise to speed the development of powerful future therapies for metabolic diseases.

Michael Czech, Ph.D.
Professor and Chair, Program in Molecular Medicine
UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL



9:00 - 9:45
Rimonabant® (CB1 Antagonist): Clinical Development in Obesity-Related Metabolic Disorders

Pierre Rosenzweig, M.D.
VP, Internal Medicine Clinical Development
SANOFI AVENTIS



9:45 - 10:05
Diet Influences the Development of the Metabolic Syndrome in Humans and Laboratory Animals

Changes in diet composition (the quantity and type of fat and carbohydrate; and low or high salt and cholesterol) can repeatedly accelerate or delay the onset of this cluster of diseases. Purified ingredient diets allow controlled, reportable and repeatable modifications of these components. Hence, a diet-driven phenotype provides scientists with a powerful and relevant research tool for studying therapeutic and preventative treatments.

Dr. Edward A. Ulman PhD
President
RESEARCH DIETS, INC.



10:05 - 10:35
Networking, Refreshments & Exhibits



10:35 - 11:05
Unraveling New Pathways Involved in the Development of Insulin Resistance using RNAi Mediated Gene Silencing

Alterations in the early steps of insulin signaling such as IRS-1 phosphorylation and degradation have been recognized as important components of many insulin-resistant states. To elucidate the signaling pathways involved in the development of insulin resistance, a human RNAi library was used to identify kinases that 1) prevent IRS-1 loss after chronic insulin treatment and 2) enhance insulin-induced phosphorylation of AKT/PKB in human hepatoma cells. From approximately 500 kinases screened, 26 hits were identified and confirmed. Among those, new kinases that were not known to be involved in insulin resistance or diabetes were identified. Thus, multiple kinase-dependent pathways are involved in the development of insulin resistance in hepatocytes.

Cristina Rondinone, Ph.D.
Group Leader, Metabolic Diseases
ABBOTT LABORATORIES



11:05 - 11:35
Role of Gut Hormones in the Treatment of Diabetes and Obesity

Through the emergence of diabetes and obesity as modern day epidemics, the gastrointestinal tract has become the site of increasing interest for its role in assimilating fuel at the time of feeding and the secretion of key hormones involved in fuel homeostasis and body weight control. From the pancreas, the long-standing acknowledgement that insulin is the key anabolic hormone is now complemented by the understanding of companion islet hormones, glucagon and amylin. Glucagon exhibits anti-insulin-like action and likely plays a role in dysregulated glucose homeostasis in diabetes, and amylin, a partner hormone to insulin, plays a role in glucose influx at the time of feeding and body weight control. From the gut, the secretion of two key hormones, GIP and GLP-1, which collectively are responsible for the so-called incretin effect: the signal that augments the beta-cell response to ingested calories. The latter, GLP-1, is also thought to play a role in beta-cell health and body weight control. Through this collective understanding, we have gained new insights into the pathophysiology of the overweight patient with diabetes and are developing potential new therapeutics through the replacement of deficient hormones or by harnessing the incretin effect.

Alain Baron, M.D.
Senior Vice President of Clinical Research
AMYLIN PHARMACEUTICALS



11:35 - 12:05
Intervention of Hepatic Glucose Production to Ameliorate Diabetic Syndrome

Excessive hepatic glucose production contributes significantly to hyperglycemia in type 2 diabetes. Glucagon and glucocorticoids are hormones enhancing hepatic glucose production. We have applied antisense oligonucleotides technology to selectively inhibit the expression of glucagon or glucocorticoid receptor in liver of ob/ob or db/db mouse. This antisense oligonucleotides treatment significantly reduced blood glucose levels at fed and fasted condition, improved glucose handling during glucose challenge, as well as increased insulin sensitivity. No hypoglycemia occurred in diabetic or lean mice during treatment. The plasma corticosterone and ACTH levels in glucocorticoid receptor antisense treated mice were not significantly different from that in controls.

Yin Liang, M.D., Ph.D.
Principal Scientist, Endocrine Therapeutics & Metabolic Disorders
JOHNSON & JOHNSON PHARMACEUTICAL R&D



12:05 - 12:25
The Benefits of Collaborating with a Contract Research Organization Focused in Metabolic Syndrome

Troy Gobbett
Contract Services Manager
PreClinOmics, Inc.



12:25 - 1:40
Luncheon Sponsored By: PreClinomicsTM

ABOUT YOUR LUNCHEON GOLD SPONSOR:

PreClinOmicsTM (PCO), a Contract Research and Service Company, is focused to provide pre-clinical, in-vivo, laboratory services for the Pharmaceutical and Biotech industry. PCO specializes in designing and executing compound efficacy studies in rodent models of disease disorders such as Metabolic Syndrome, Obesity, Diabetes, Renal Failure, Hypertension and Cancer. Our laboratory is capable of analyzing broad range of clinical chemistry endpoints as well as the harvesting and preservation of tissues. PCO, via a partnership agreement, is also able to coordinate PK protocols in primates.



Luncheon Sponsored By: PreClinomicsTM Sponsored By...

1:40 - 2:10
Clinical Evaluation of Antisense-based Therapies for the Treatment of Type 2 Diabetes and Hyperlipidemia

Lise Kjems, Ph.D.
Executive Director, Clinical Development
ISIS PHARMACEUTICALS



2:10 - 2:40
Glucokinase Activators for Treatment of T2D: Potential for Dual Effect on Insulin Secretion and Suppression of Hepatic Glucose Production

Glucokinase (GK) plays a key role in whole-body glucose homeostasis by catalyzing the phosphorylation of glucose in cells that express this enzyme, such as pancreatic Beta cells and hepatocytes. Genetic insufficiency of GK results in MODY-2 in humans providing a rationale for the development of small molecule activators of GK. GK activators (GKAs) represent a novel class of antidiabetic agents that augment both hepatic glucose metabolism and glucose stimulated insulin release from isolated rodent islets, consistent with the expression and function of GK in both cell types. In rodent models of type 2 diabetes, GKAs lower basal blood glucose levels, improve glucose tolerance and increase hepatic glucose uptake. GKAs are being developed as an oral treatment for type 2 diabetes.

Rebecca Taub, Ph.D.
Vice President, Metabolic Diseases Research
HOFFMAN-LA ROCHE



2:40 - 3:10
Antagonizing Glucagon Receptor for Glycemia Control and Beyond

Glucagon, a peptide hormone secreted by pancreatic alpha cells of the islets of Langerhans, is a key regulator of glucose homeostasis. Glucagon signaling provides a major counter regulatory mechanism for insulin by stimulating hepatic glucose output. Elevated glucagon levels or altered insulin to glucagon ratios are associated with the development of type 2 diabetes. Glucagon receptor is a member of seven transmembrane G-protein coupled receptor superfamily. Peptide and non-peptidyl glucagon receptor antagonists have been long sought as potential therapeutic agents for diabetes. Characterization of glucagon receptor knockout mouse model has also implicated that antagonizing the receptor will have beneficial effects on diabetes and metabolic syndrome.

Bei B. Zhang, Ph.D.
Senior Director, Metabolic Disorders-Diabetes
MERCK RESEARCH LABORATORIES



3:10 - 3:40
Networking, Refreshments & Exhibits



3:40 - 4:10
The Underlying Role of Adipose Tissue in the Inflammation of the Metabolic Syndrome

The prevalence of obesity is rapidly increasing. Obesity associated alterations in adipose tissue are important protagonists in the development of diabetes and cardivovascular disease. With obesity, macrophages reside in adipose tissue and a heightened inflammatory protein profile enuses. Expression levels of adiponectin fall while cytokines such as TNF-alpha, interleukin -6, MCP-1 increase. Increased rates of fatty acid release from adipocytes, in combination with cytokines, act on multiple tissues to perpetuate the metabolic syndrome. This talk will discuss the causes of adipose tissue inflammation and its role in obesity associated diseases.

Andrew S. Greenberg, M.D.
Director, Obesity and Metabolism Laboratory Jean Mayer USDA HNRCA
TUFTS UNIVERSITY



4:10 - 4:40
Nutrient Sensing Pathways, Metabolism and Lifespan

The highly conserved, nutrient-sensing insulin and Tor pathways modulate metabolism, growth, reproduction and lifespan in response to nutrient availability. How signals from these pathways regulate such complex aspects of the adult phenotype at the transciptional level is not understood. A high-resolution study of trancriptional dynamics in response to nutrients reveals complex and rapid regulation of genes involved in energy sensing, utilization and storage. The involvement of key transcription factors in coordinating these responses suggests conserved pathways whose dysregulation may underlie human metabolic diseases.

Robert S. Garofalo, Ph.D.
Principal Research Investigator, Metabolic Diseases
PFIZER GLOBAL R&D - GROTON LABORATORIES



4:40 - 5:30
Licensing, Collaborations & Business Development Overview

This will be an interactive session of what is important in developing business relationships between companies. A summary of what is expected from first contact to negotiations and project management will be briefly presented from the perspective of the company represented by each panelist. Big pharma and biotech expectations often differ and understanding “do’s” and “don’ts” can be a big advantage in opening a dialogue. Following the brief presentations of the panelists, the audience will be invited to query the panel on issues relating to partnering and to share their experiences and expectations in business development.

MODERATOR:

Wick Johnson, Ph.D.
Director, Licensing & Development
PFIZER INC.

PANELISTS:

Michael Step
Vice President, Corporate Development
AMYLIN PHARMACEUTICALS

Jennifer Griffiths, Ph.D.
Director, Search and Evaluation - Global Business Development
NOVARTIS PHARMACEUTICALS

Don A. Madren, R.Ph., MBA
Associate Director, Strategic Alliances
PFIZER GLOBAL RESEARCH & DEVELOPMENT

To Be Announced
Business Development
SANKYO PHARMACEUTICALS USA (INVITED)



5:30 - 5:50
Reception Sponsor



5:50 - 7:15
Networking Reception



Tuesday, April 12, 2005 (Day 2)

7:45 - 8:45
Breakfast, Networking & Exhibits



8:45 - 9:30
Adipocyte-Derived Factors: Viable Drug Targets?

A number of adipocyte-derived factors have been implicated as modulators of insulin sensitivity, inflammation and atherosclerosis. Specifically, resistin has been shown to cause decrease sensitivity in hepatocytes. In contrast, the adipocyte-derived secretory factor adiponectin has a potent insulin-sensitizing activity on hepatocytes. Pharmacological interventions that lead to changes in the circulating levels of these proteins as well as therapeutic approaches directed at lowering the potent pro-inflammatory properties of adipocytes have significant potential to have a beneficial impact on insulin sensitivity.

Philipp E. Scherer, Ph.D.
Associate Professor, Department of Cell Biology & Medicine
Division of Endocrinology Diabetes Research & Training Center
ALBERT EINSTEIN COLLEGE OF MEDICINE



9:30 - 10:00
Role of Glucocorticoids in the Obese Phenotype

Andrew G. Swick, Ph.D.
Director of Cardiovascular and Metabolic Diseases
PFIZER GLOBAL R&D - GROTON LABORATORIES



10:00 - 10:30
Networking, Refreshments & Exhibits


TRACK A: DIABETES

TRACK B: OBESITY



10:30 - 10:40
TRACK A: Chairperson’s Recap of General Sessions

Brett Monia, Ph.D.
Vice President, Antisense Discovery
ISIS PHARMACEUTICALS



10:30 - 10:40
TRACK B: Chairperson’s Recap of General Sessions

Michael Jirousek, Ph.D.
Director, Head of Diabetes/Obesity Therapeutic Area
PFIZER GLOBAL R&D - LA JOLLA LABORATORIES



10:40 - 11:10
TRACK A: Small Molecule Compounds to Elevate Secreted Adiponectin Levels Through a PPARƒ×-Independent Pathway

PPARƒ× agonists increase adiponectin concentrations in humans. However, these compounds can cause serious side effects. Using an adiponectin ELISA assay and a human preadipocyte cell line, we screened for small molecules that can augment the levels of secreted adiponectin. We found a compound that is as potent as the PPARƒ× agonists in their ability to up-regulate adiponectin expression but that acts through a different mechanism. The in vitro and in vivo characterization of this compound will be presented.

Mirta Grifman, Ph.D.
Group Leader, Metabolic Diseases
IMMUSOL, INC.



10:40 - 11:10
TRACK B: Emerging Treatments and New Targets in Obesity

The identification of new targets for obesity therapeutics represents a key priority for the pharmaceutical industry. This has been driven by the large and growing numbers of obese individuals around the world, the high incidence of serious co-morbidities, and a market predicted to reach $3.7 billion by 2008. Obesity occurs when calorific intake exceeds energy expenditure. In this presentation, Dr. Yancopoulos will review recent treatments and targets upcoming in the obesity field.

George D. Yancopoulos, M.D, Ph.D.
Chief Scientific Officer
REGENERON PHARMACEUTICALS



11:10 - 11:40
TRACK A: Antisense Strategies Targeting Type 2 Diabetes and Metabolic Syndrome

As a rapid and highly efficient platform, antisense technology has been used for target validation and drug discovery in several therapeutic areas, including type 2 diabetes and related metabolic disorders. Using Isis’s 2nd generation of antisense oligonucleotide, we targeted a number of metabolic genes in different animal models of metabolic disorders, and made direct head-to-head comparisons on different gene targets. The studies have resulted in identification of several genes that could potentially be novel therapeutic targets for treatment of different aspects of metabolic syndrome. Data from different animal models on the specificity, potency and efficacy of the antisense oligonucleotide against these novel targets will be presented.

Xing-Xian Yu, Ph.D.
Assistant Director, Antisense Drug Discovery
ISIS PHARMACEUTICALS



11:10 - 11:40
TRACK B: Regulation of Food Intake and Body Weight by Novel Small Molecule Melanocortin-4 Receptor Agonists

A number of genetic, pharmacological and physiological studies have suggested that the central melanocortin system is involved in the regulation of energy homeostasis and provides a target for the development of pharmacological agents to treat obesity. Using MIDAS™ (Metal Ion-induced Distinctive Array of Structures) technology, we have developed novel small molecule agonists with selectivity for the MC4 subtype of melanocortin receptors. In rodent models of obesity, administration of the novel agonist resulted in a decrease in food intake associated with a significant reduction in body weight as well as improvement in metabolic parameters (e.g. levels of blood glucose). Administration of the agonist did not result in adverse effects, such as sickness, taste aversion or disruption of normal behavior. Furthermore, the agonist did not increase erectile activity as commonly seen with administration of non-selective melanocortin agonists. These data lend further support to the use of MC4 receptor agonists as a potential treatment for obesity in humans.

Kevin D. Burris, Ph.D.
Executive Director, In-vitro Biological Research
PALATIN TECHNOLOGIES



11:40 - 12:10
TRACK A: Discovery of Orally Efficacious, Potent, Selective DPP-IV Inhibitors for the Treatment of Type 2 Diabetes

Pharmacological elevation of GLP1 levels and the associated improvement in glycemic and insulin responses in type 2 diabetes can be achieved through inhibition of GLP1 degradation using DPP-IV inhibitors. We present here the discovery of novel, potent, selective and orally efficacious DPP-IV inhibitors. These inhibitors are orally active in rodents, dogs and monkeys, have excellent solubility and stability, show durable inhibition of DPP-IV over a 24 hour period and have promising ADME and toxicological profiles. We will describe their glucose lowering effects, PK/PD relationships across these different species.

Peter McNamara, Ph.D.
Associate Director, Metabolic Diseases
PHENOMIX CORPORATION



11:40 - 12:10
TRACK B: NOX-B11: A Potent Ghrelin Inhibitor

We have generated biostable RNA-based compounds (Spiegelmers), that specifically bind n-octanoyl-ghrelin, the endogenous ligand of the GHS receptor. Ghrelin is a potent stimulant of growth hormone-release, food intake and adiposity. We demonstrate that our lead compound NOX-B11 inhibits ghrelin-mediated GHS-receptor activation in cell culture with an IC50 of 5 nM. Intravenous administration of PEGylated NOX-B11 efficiently suppresses ghrelin-induced growth hormone release as food intake in rat models. These results demonstrate for the first time that the neutralization of circulating bioactive ghrelin leads to inhibition of ghrelin's actions in the central nervous system.

Sven Klussmann, Ph.D.
Chief Scientific Officer
NOXXON PHARMA AG



12:10 - 1:15
Luncheon



1:15 - 1:45
TRACK A: Novel Orally Active Dipeptidyl Peptidase IV Inhibitors Exhibiting Potent Activity in Animal Models of Diabetes

The proof of concept for DPP-IV inhibitors as a novel treatment for diabetes has been well established. DPP-IV inhibition leads to an increase GLP-1 and insulin levels only in the presence of a glucose load. We present here an overview of our DPP-IV program, wherein we have been successful in identifying diverse, potent, selective DPP-IV inhibitors with different durations of action. GRC-8200, a long-acting competitive and reversible inhibitor, showed an IC50 of 1.61 nM in human recombinant DPP-IV enzyme assay, specificities greater than 10,000 fold over DPP-II, PPCE and other proteases tested. It shows duration of action of at least 8 hours in an OGTT experiment with 47% reduction in glucose excursion (AUC 0-120) at 3 mg/kg p.o. GRC-8200 exhibited an excellent PK profile and PK/PD correlation. GRC-8116, a short-acting competitive and reversible inhibitor, showed an IC50 of 6.27 nM in human recombinant DPP-IV enzyme assay. GRC-8116 had specificities greater than 600 fold over DPP-II, PPCE and other proteases tested. GRC-8116, at 3 mg/kg p.o. produced ~50% reduction in glucose excursion (AUC 0-120). GRC-8116 also exhibited a favorable pharmacokinetic profile in rats and dogs. The detailed pharmacological, pharmacokinetic and toxicological profile of these potent DPP-IV inhibitor molecules under active development will be discussed.

Shridhar Narayanan, Ph.D.
General Manager-Biological Research
GLENMARK RESEARCH CENTRE



1:15 - 1:45
TRACK B: APD356 - A Potent and Novel Selective 5HT2C Agonist With Potential for the Treatment of Human Obesity

APD356, a selective 5HT2C agonist under development for treatment of obesity, dose-dependently produces weight loss in diet-induced obese rats. In Humans we have demonstrated in a pharmacology study (double blind placebo cross over design) that APD356 could reduce acute food intake at a dose of 10 mg. The compound had an excellent pharmacokinetic profile with minimal subject variability and an 11 hour half life suitable for once daily dosing. In addition, APD356 was well tolerated in a phase 1b human clinical safety trial at doses up to 20 mg after 14 days of repeated dosing. We conclude that in preclinical studies APD356 significantly reduces body weight and body fat. Furthermore, our early clinical evaluation demonstrates that APD356 is well tolerated up to 20 mg and can acutely reduce food intake in humans.

Dominic P. Behan Ph.D.
Chief Scientific Officer & Senior Vice President
ARENA PHARMACEUTICALS, INC.



1:45 - 2:15
TRACK A: Design, Synthesis & Evaluation of Novel Phosphonates as Potent and Selective FBPase Inhibitors with Oral Efficacy in Rodent Models of Type 2 Diabetes

Hepatic glucose output is often upregulated in type 2 diabetes (T2DM) and is a significant contributor to both postprandial and fasting hyperglycemia. Increased gluconeogenesis (GNG) accounts for this increased hepatic glucose output, suggesting that inhibitors of the GNG pathway might be potential drug candidates for T2DM. Fructose-1,6-bisphosphatase (FBPase) is a key rate-limiting enzyme of GNG and is a well known target for T2DM. Previous efforts targeting FBPase, however, were unable to find potent, specific and cell-permeating inhibitors. Herein we present the discovery of a series of low molecular weight heterocyclic phosphonates that mimic AMP and are potent inhibitors of FBPase. The initial series of compounds was identified using structure-based drug design. Key pharmacophores were identified by SAR analysis of several series of heterocyclic FBPase inhibitors (FBPaseIs) and were used to discover a series of inhibitors with low nanomolar inhibitory potency, high FBPase specificity and potent oral glucose lowering activity in rodent models of type 2 diabetes. Recently, a compound discovered from this program successfully completed a second Phase IIA clinical trial. The design, synthesis, SAR and in vivo efficacy of FBPaseIs will be presented for the first time.

Max Dang, Ph.D.
Associate Director, Medicinal Chemistry
METABASIS THERAPEUTICS, INC.



1:45 - 2:15
TRACK B: Obesity Drug Development Facilitated by RAGE

Drug development risk can be substantially mitigated by undertaking parallel discovery programs that utilize multiple validated disease targets. Unfortunately, such an approach is often not feasible due to restrictions on the use of many drug targets. The RAGE (Random Activation of Gene Expression) technology provides a means by which validated targets can be accessed for use in drug discovery. Here we demonstrate the application of RAGE to create cell lines that express distinct hypothalamic GPCRs implicated in the control of appetite. These cell lines were utilized in high-throughput screening and subsequent compound optimization activities. Lead compounds will be discussed that show favorable ADMET properties, good CNS penetration, and activity in rodent and canine food intake models.

Kurt Brunden, Ph.D.
Senior Vice President, Biopharmaceuticals
ATHERSYS, INC.



2:15 - 2:45
TRACK A: Is a Gold Standard for the Pharmacodynamic Evaluation of New Hypoglycemic Compounds Available?

The toolbox of diabetes therapy is filled with quite a number of effective drugs. The pharmcodynamic (PD) characterization of these compounds e.g. insulins, insulin analogues or oral agents, is until today based on a variety of scientific tests. Amongst others the PD profiling of hypoglycemic compounds is done by means of Frequent Sampling Intravenous Glucose Tolerance Tests, manual euglycemic hyperinsulinemic glucose clamps, automated euglycemic hyperinsulinemic glucose clamps.

Marcus Hompesch
President/CEO
PROFIL INSTITUTE FOR CLINICAL RESEARCH



2:15 - 2:45
TRACK B: Rodent Models for Obesity, Metabolic Syndrome and Type 2 Diabetes

Obesity, metabolic syndrome and type 2 diabetes are increasing dramatically in a many societies. The major risk factors for these conditions are genetics, food availability, and sedentary lifestyle. A variety of animal models, have been and are being developed based on these risk factors. The combination of genetic factors for obesity and diabetes, have resulted in rodent models that have been used for a number of years such as the ob/ob and db/db mice and the fa/fa and cp/cp rats. These leptin and leptin receptor mutations result in obesity and lethargy. These traits in combination with background strains that have diabetic potential can result in diabetic animal models. Obesity in rodent models can also be produced by diet. DIO mice and rats have been characterized and demonstrate significant weight gains. These weight gains can result in metabolic syndrome and even diabetes depending on the genetics of the strain, diet and age. When properly characterized these models can answer questions related to the reasons for the above metabolic conditions and can be used in testing compounds which chemically target these diseases. The value of these models in preclinical research studies will be discussed.

Richard G. Peterson, Ph.D.
Vice President, Research & Development
PreClinOmics, Inc.



2:45 - 3:15
TRACK A: Translating Preclinical Data Into Human Efficacy: A Case for Biosimulation

The current inability to consistently predict human efficacy based on preclinical data contributes significantly to the high failure rate of drugs in clinical trials. Using biosimulation, insulin-induced reductions in liver glycogen therapy would be expected to increase hypoglycemic risk in type 2 diabetics. To test this prediction, streptozotocin-treated rats were implanted with subcutaneous insulin capsules. Despite reductions in plasma glucose, liver glycogen remained unchanged. We hypothesize that elevated hepatic portal insulin, as indicated by C-peptide, maintained glycogen. In contrast, subcutaneous insulin therapy in human type 2 diabetics causes C-peptide to decrease (60%). Computer simulations better represent the response of human patients to insulin therapy than our rat model, making it a novel method to understand the therapeutic implications of species differences.

Jeff Trimmer, Ph.D.
Senior Scientist
ENTELOS



2:45 - 3:15
TRACK B: Development of Chaparone Co-induction Activators for the Treatment of Type II Diabetes and Complications

Oxidative stress plays a significant role in the development and complications of obesity and diabetes. CytRx Corporation has recently acquired from Biorex several novel orally active compounds which act to protect cells from oxidative damage through a mechanism which involves the co-induction of molecular chaparones. This talk will focus on the preclinical and clinical development of Arimoclomol, a novel charparone co-inducer entering phase II clinical trials for diabetes and diabetic complications. Results from animal studies and human phase I data will be presented.

Mark A. Tepper, Ph.D.
President
CYTRX LABORATORIES



3:15 - 3:20
Conference Concludes

 
 
Organized by: Strategic Research Institute
Invited Speakers: Novel Targets for Drug Discovery Through RNAi

Michael Czech, Ph.D.
Professor and Chair, Program in Molecular Medicine
UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL

Rimonabant® (CB1 Antagonist): Clinical Development in Obesity-Related Metabolic Disorders

Pierre Rosenzweig, M.D.
VP, Internal Medicine Clinical Development
SANOFI AVENTIS

Adipocyte-Derived Factors: Viable Drug Targets?

Philipp E. Scherer, Ph.D.
Associate Professor, Department of Cell Biology & Medicine
ALBERT EINSTEIN COLLEGE OF MEDICINE

 
Deadline for Abstracts: .
 
Registration:


4th International
Metabolic Diseases Drug Discovery World Summit

April 11 - 12, 2005

Select Pricing Option

$1,195.00 1. Earlybird rate for Delegates
(offer ends March 4, 2005 : will be $1395 thereafter)
$695.00 2. Academic/Gov’t/ Hospital Rate


E-mail: sgrodsky@srinstitute.com
 
   
 
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