Tuesday, October 7

8:00am Breakfast Workshop
Recent 505(b)(2) Experiences with FDA
Kenneth Phelps, President & Chief Executive Officer, Camargo Pharmaceutical Service
The 1999 505(b)(2) Guidance is becoming less helpful in determining what is needed for a successful 505(b)(2) application. The FDA’s interpretation of the regulations is evolving. Moreover, each review division has its own interpretation. We will discuss what Camargo has learned over the last 5 years in ten’s of pre-IND meetings.

8:45 Break

CASE HISTORIES

8:55 Chairperson’s Remarks

Keynote Presentation

9:00 The Indications Discovery Unit at Pfizer: First Year Check Up
Donald E. Frail, Ph.D., Head, Indications Discovery Unit, Pfizer Global Research and Development
At this conference last year, a new dedicated effort for drug repositioning at Pfizer was described. This dedicated effort, the Indications Discovery Unit, is a preclinical unit within Research focused on the identification and validation of new indications for compounds in the Pfizer development pipeline. The effort has now been operating for a year and is delivering value to the organization. This presentation will illustrate through numerous examples the opportunities, the challenges, and the lessons learned. Topics that will be highlighted include efficacy, pharmacokinetics, legal/regulatory, data management, and risk sharing partnerships.

9:45 The MLR-1023 Story: Reverse Drug Discovery
Andrew G. Reaume, Ph.D., MBA, CoFounder & President & CEO, Melior Discovery
Melior Discovery has developed an optimized, high-throughput pharmacology platform that is able to rapidly and systematically identify novel indications for small molecule drug candidates. Melior’s theraTRACESM system typically utilizes compounds that have been shown to be previously safe and well tolerated in mid/late stage human clinical trials. The platform has also found significant utility in profiling pre-clinical stage drug candidates prior to the crucial “go/no go” development decisions. Melior’s lead candidate, MLR-1023, has been successfully repositioned from a former development candidate in the treatment of gastric ulcers to a novel therapeutic for Type II diabetes. MLR-1023 is entering clinical development for this new indication.

10:15 Coffee Break, Poster and Exhibit Viewing

10:45 Viagra Attenuates Doxorubicin-Induced Cardiomyopathy in Mice
Rakesh C. Kukreja, Ph.D., Professor of Medicine, Biochemistry, Physiology and Emergency Medicine, Eric Lipman Chair of Cardiology, Virginia Commonwealth University
Doxorubicin is an effective chemotherapeutic agent commonly used in the treatment of many blood and solid tumor malignancies. Despite doxorubicin’s clinical efficacy for treatment of cancer, its use is associated with a delayed and progressive cardiomyopathy. We have shown that Viagra induces powerful protective effect against injuries resulting from ischemia/reperfusion and myocardial-infarction-induced heart failure. Further animal studies also demonstrated that administration of Viagra confers protection against doxorubicin-induced cardiomyopathy as indicated by attenuated myocyte apoptosis, preserved myofibrillar integrity and alleviated left ventricular dysfunction. This research holds promise for the potential use of Viagra and other erectile dysfunction drugs in patients receiving doxorubicin as part of their chemotherapeutic regimen with the goal of reducing the incidence of doxorubicin-induced cardiomyopathy.

11:15 Case Study of the Rational Design and Testing of VT-122, a Promising Phase 2 Product Candidate for Cancer Cachexia
Newell F. Bascomb, Chief Operating Officer, Vicus Therapeutics
The development of VT-122 for cancer cachexia provides a case study of the rational design and testing of a promising Phase 2 product candidate comprised of a novel combination of two generic drugs. Cachexia is a debilitating, progressive muscle wasting condition manifested by unintentional weight loss, muscle weakness, anemia, fatigue, and death. There is currently no FDA-approved therapy for treating cancer cachexia. We used a three step process to design and test the VT-122 candidate: Developed a cancer cachexia disease model that predicted blocking systemic inflammation would reverse the wasting process.
Chose the optimal pair of synergistic chemistries, dosage levels, release profiles and titration regimen to maximize the therapeutic effect and minimize the known safety risks. Evaluated VT-122 in a series of Investigator-led pilot trials and then under a US FDA IND in a multicenter, randomized open-label, controlled Phase 2 trial.

11:45 There’s Still Low Hanging Fruit: Three Repositioned Drugs in Clinical Testing for Brain Injury Patients
Neal Farber, Ph.D., Chief Executive Officer, NeuroHealing Pharmaceuticals, Inc.
NeuroHealing Pharmaceuticals is a clinical stage company developing innovative treatments for brain injury and neurodegenerative diseases. Three repositioned drugs are being developed for new indications - each with early evidence of clinical efficacy, extensive human safety data and based on novel formulation and/or drug delivery strategies. NH001 is a dopaminergic agent reformulated to be administered via a continuous sc pump and designed to accelerate the recovery and improve the cognitive and functional outcome of patients from a coma following a traumatic brain injury. NH004 is an anticholinergic drug reformulated in a proprietary intra-oral, slow dissolving thin strip designed for patient convenience to control sialorrhea (drooling). NH02D is a stereoisomer of a marketed, novel mechanism drug reformulated for sublingual delivery.

12:15pm Luncheon Workshop (Sponsorship Available) or Lunch on Your Own

1:30 Chairperson’s Remarks
Stephen Donahue, M.D.

1:35 From Asthma to Atherosclerosis – A Repositioning Case Study
Tilmann Brotz, Ph.D., Senior Director, Preclinical Development, VIA Pharmaceuticals
VIA Pharmaceuticals is a small, focused biotech company repositioning existing Pharma and Biotech drug assets. VIA’s Phase II compound, VIA-2291, will be presented as a case study on how a Phase III Asthma drug was repositioned for Atherosclerosis based on genomic profiling of novel targets for cardiovascular disease. VIA leverages the flexibility of a small company, the innovative use of biomarkers and imaging-driven clinical trials to add value to these assets. Strategies to generate additional intellectualproperty derived from advantageous drug properties and novel treatment concepts within the repositioning framework will also be discussed

2:05 The Chemokine Receptor CXCR4 as a Therapeutic Target: The Discovery and Development of Plerixafor (AMD3100)
Simon P. Fricker, Ph.D., Distinguished Scientific Fellow, Genzyme Corporation
The history of the research and development of plerixafor, a selective antagonist of the chemokine receptor CXCR4, will be described. CXCR4 is widely expressed on a variety of hematopoietic cells including T and B lymphocytes, monocytes, and hematopoietic stem cells (HSC), where it plays an important role in trafficking and homing. It is one of the co-receptors used by HIV for viral entry and infection of host cells. CXCR4 is also found on endothelial, epithelial cells, and many cancer cells. Plerixafor was initially identified as a potent inhibitor of HIV infection, and its mechanism of action was subsequently defined as inhibition of CXCR4. Subsequent clinical trials in HIV-infected patients validated CXCR4 as a target for HIV. Plerixafor also exhibited activity in animal models of inflammatory disease. However it is plerixafor’s ability to mobilize HSC from the bone marrow into the circulation that has led to its development as a mobilizer of HSC for autologous transplantation in patients with lymphoma and multiple myeloma. Plerixafor has successfully completed two randomized phase III clinical trials in these patient populations, exceeding the primary endpoint by two-fold.

2:35 Refreshment Break, Poster and Exhibit Viewing

3:00 Repositioning Milnacipran for Fibromyalgia
Srinivas G. Rao, M.D., Ph.D., Chief Scientific Officer, Cypress Biosciences
After identifying Fibromyalgia (FM) as an attractive target for drug development, Cypress in-licensed milnacipran, a unique dual-reuptake inhibitor approved for a non-pain condition in over 50 countries. Cypress began its clinical program to develop milnacipran for FM in 2001. Following a successful Phase III program, we submitted a New Drug Application (NDA) for milnacipran to the FDA where it is currently under review.

3:30 Foundation Driven Drug Discovery & Development for Huntington’s Disease
John Wityak, Ph.D., Director, Medicinal Chemistry, CHDI Foundation, Inc.
Individuals who are at risk or suffer from rare diseases are growing increasingly impatient with the paucity of activity and productivity within the private sector aimed at identifying treatments for these orphan indications. One such malady, Huntington’s disease (HD), is a fatal, autosomal-dominant, neurodegenerative disorder for which there are currently no therapies. Driven by their quest for a cure, many disease foundations are now catalyzing the evolution of roles across the industrial, government, and not-for-profit sectors to collaboratively enable translational drug discovery efforts. CHDI Foundation, Inc. is a time-motivated, foundation-funded, not-for-profit biotechnology company that is exclusively focused on the discovery and development of drugs for HD. While our efforts include the development of new chemical entities, evaluating existing drug molecules for targets of interest may represent a more rapid, complementary, and opportunistic way of delivering clinical candidates.

4:00pm Close of Conference