Wednesday, October 8, 2008
THE CHANGING FACE OF DRUG DEVELOPMENT
7:15 am Registration and Morning Coffee
8:20 Chairperson’s Opening Remarks
Herman Scholtz, Ph.D., Corporate VP, Worldwide Head Early Drug Development, PAREXEL International Corporation
8:30 “Learn and Confirm” - Implementing Early Proof-of-Concept at Wyeth
Charles Gombar, Ph.D., Vice President, R+D Strategy and Business Improvement, Wyeth Pharmaceuticals
At Wyeth, the old divide between discovery and development is being re-engineered. “Learn” teams now take projects through to Proof-of-Concept (traditionally Phase II) where they pass them on to “Confirm” teams. The real objective is to make sure we really understand the molecule and its mechanism of action, pharmacology, Pharmacokinetics, etc . . . We will examine how Wyeth is implementing this new “Learn and Confirm” early drug development process. Topics addressed include:
- Beyond the Phase Trial Model - The need for a more effective early drug development process
- Designing a more engaged, creative approach to early development
- Implementation issues in re-engineering the drug development process
9:05 Implementing New Approaches for Increasing Productivity of Drug Development
Dongzhou (Jeffery) Liu, Ph.D., M.Sc., M.B.A., Assistant Director, New Products Research & Development, GlaxoSmithKline
The challenge of an increasingly tough business environment in the industry requires doing more of the right studies the first time to generate less failure as drug candidates move into the more pricey later stages of the development process. Some advanced tools are increasingly being used for POC and confirmation of a drug candidate’s ability to reach the therapeutic window, enabling an effective development process. This presentation will introduce and apply some of these tools and techniques including IVMS, IVIVC, and others to improve drug development productivity as well as early decision making processes.
9:40 Pharmaceutics During the Developability Phase: Is It Just About Speed?
Jan Van Gelder, Ph.D., Head, Preformulation, Eli Lilly and Company
Early phase timelines are shorter than they have ever been. In addition, the continuously increasing portfolio demands, without directly proportional resource increases, further complicates the early phase development process. These expectations cannot be met without applying a phase-appropriate, risk-based approach to clinical drug product design. This simplified design process does not directly align with the continuously increasing complexity of new drug candidates, especially from a developability perspective (e.g. solubility-limited absorption). Given these considerations, a sole focus on speed does not allow a Pharmaceutical Research & Development organization to deliver the desired clinical outcomes at this stage of development. At Lilly, we have developed and successfully implemented a rational drug product design process that enables rapid POC testing of small molecules, without jeopardizing desired clinical outcomes. This process requires expertise to be maximally utilized and integrated across various areas of pharmaceutical sciences. This presentation will walk the audience through the rational design process, from the discovery of a new drug candidate to POC testing. The areas of the process that will be emphasized are: Developability Assessment; Preclinical Formulations Solid-Form Selection, Clinical Drug Product Design and Modeling for in-vivo Performance.
10:15 Networking Coffee Break - Poster and Exhibit Viewing
10:45 In-vitro and In-vivo Validation
Paul L. Domanico, Ph.D., Founder and Managing Partner, INNOVALYST, LLC
A significant reason for high attrition is poor correlation between preclinical assays and human trials, for example, if you are developing advanced chip-based screens that rely on primary cells from lung, liver, or lung tissue. This presentation examines such questions as: What are the validation criteria to demonstrate that for the life of the assay the extracted cells or tissue behave like “non-extracted organ”? We also examine how the scientist must account for different scientific goals. We examine the implications of the fact that the validation depends on the purpose of the assay, such as testing efficacy, toxicity, metabolism and examine validation approaches for different purposes.
11:20 New Drug Development Models in Early Phase Clinical Research
David Wessels, Ph.D., Senior Director and Unit Head, PAREXEL Clinical Pharmacology Research Unit, PAREXEL International
This session will focus on adaptive new drug development models alongside the unique advantages of the adaptive approach in early phase clinical development. Combination protocols will be highlighted as a primary example of these models, which offer significant benefits in early phase programs. In addition to accelerating the overall program timeline and combining various elements into a single protocol, this model can reduce regulatory submissions, create greater cost efficiencies and provide drug developers the information they need to make more effective and informed go/no-go decisions as early as possible in the drug development process. This session will also highlight how combination protocols can employ the strategic use of pharmacokinetics to serve as an integral part of the drug development plan and design.
12:00 pm Networking Luncheon Sponsored by 
Following the Critical Path: Development of Novel Approaches for Sensitive and Specific Detection of Drug-Induced Toxicity
Ralph L. McDade, Ph.D., Strategic Development Officer, Rules-Based Medicine, Inc.
- RBM has developed two novel approaches to assess compound toxicity using Multi-Analyte Profiles (MAPs) developed specifically for this purpose.
- A nephrotoxicity MAP was developed and validated in conjunction with the FDA’s Critical Path Initiative-Predictive Safety Testing Consortium. This success story demonstrates that public-private collaboration can address these issues that confront the pharmaceutical industry.
- TruCulture™, the first fully closed, reproducible whole blood culture system completely replaces the problematic Peripheral Blood Mononuclear Cell (PBMC) cultures and allows one to assess immune-toxicity of compounds.
AFTERNOON SESSION
MATCHING THE RIGHT APPROACHES AND TECHNOLOGIES TO THE JOB
1:15 Chairperson’s Introduction
David S. Grass, Ph.D., Divisional Vice President, Scientific Operations, in-vivo Discovery, Caliper Life Sciences
1:25 Biomarkers in Early Stage Drug Development: Challenges and Opportunities - The Changing Face of Early Drug Development at AstraZeneca
Victor Sandor, M.D., Global Product Head, Executive Director, Oncology, Clinical Development, AstraZeneca Pharmaceuticals
The talk will focus on the practical use of biomarkers in drug development. It will focus on specific examples of how various biomarkers that cover the spectrum of biological changes that make cells malignant (growth factor signalling, angiogenesis, metastasis and genetic plasticity) were used in real development programs at AstraZeneca to make decisions to either move a drug forward or to stop development. In addition, issues related to how these markers were developed and validated will be reviewed.
2:00 Portfolio Optimization through Diverse Development Styles
Neil Bodick, M.D., Ph.D., Chief Operating Officer, Flexion Therapeutics
The conduct of small clinical experiments (experiments that are specifically designed to address key area of uncertainty) has been shown to dramatically increase productivity in early phase development. However, in the context of large pharmaceutical firms, this style of work may not be compatible with strategies that invoke large-scale parallel processing (early in the development cycle) in an effort to minimize time to market. In addition, it is often difficult to coordinate these two different styles (minimal experiments to absorb risk vs. parallel processing to reduce time to market) within a single organization – an unfortunate circumstance given that portfolio optimization requires both. This discussion will center on risk sharing between organizations – risk sharing that promotes portfolio optimization through simultaneous deployment of diverse styles of drug development.
2:35 Biopharmaceutical Drug Development at the National Cancer Institute
John Gilly, Ph.D., Deputy Director, Biopharmaceutical Development Program, SAIC-Frederick/NCI-Frederick
The resources and approaches used by the NCI to support drug development are not widely known. Novel therapeutic concepts that reach the clinic for Proof-of-Concept human study have been translated into industry for further development. This presentation will describe the Rapid Access to Intervention Development (RAID) program at the NCI. This program provides biomolecule development resources to investigators with candidates that demonstrate strong scientific innovation and exceptional novelty for the potential treatment of cancer. Since this program is oriented to Proof-of-Concept development of very novel concepts, there are unique challenges for development processes, program management and feasibility analysis to assure each step of development can provide value to the project.
3:10 Networking Refreshment Break - Poster and Exhibit Viewing
3:40 Multi-Modality Imaging in Early Drug Development
Barry Bedell, M.D., Ph.D., Chief Operating Officer & Chief Science Officer, Biospective, Inc.; Director, Small Animal Imaging Lab, Montreal Neurological Institute, McGill University
The session will present the use of state-of-the-art imaging technologies in the evaluation of CNS and oncology drugs. The use of multi-modality imaging (MRI, PET, digital histopathology/immunohistochemistry) in pre-clinical studies of CNS diseases and oncology offers insight into the structural, functional, and molecular consequences of novel therapeutic agents. The seamless integration of quantitative imaging data from animal models during the pre-clinical phase of drug development allows for the generation of a set of well-validated imaging biomarkers which can be readily translated to clinical studies. The use of the proper imaging biomarkers allows for early, cost-effective, go-/no-go decisions and acceleration of promising drugs to clinical evaluation. This session will focus on multi-modality pre-clinical imaging studies, validation of imaging studies against gold-standard biomarkers, and translation of imaging biomarkers to early-phase clinical trials.
4:15 GMX1778 Case Study: Using Metabolomics to Determine the Mechanism of Action of an Anti-Cancer Compound
Mark Watson, Ph.D., Associate Director of Biology, Gemin X Pharmaceuticals Canada, Inc.
This talk will describe how a collaboration between Gemin X Pharmaceuticals and Metabolon led to the identification of the mechanism of action of the anti-cancer agent GMX1778. The determination of the molecular target of GMX1778 has revealed unsuspected opportunities for the clinical development of the prodrug GMX1777 including the identification of pharmacodynamic markers and the rational design of adjunct therapies. Gemin X approached Metabolon to apply their global unbiased metabolomics profiling approach to identify the metabolic pathways perturbed by the action of GMX1778. This analysis identified the nicotinamide adenine dinucleotide (NAD+) pathway as the target for the action of the anticancer agent GMX1778. Detailed biochemical and cell biological analyses carried out by Gemin X further characterized GMX1778 as a potent inhibitor of nicotinamide phosphoribosyltransferase (NAMPRT), the rate-limiting enzyme in the biosynthesis of NAD+. This positions GMX1777 in a new class of anti-cancer agents that interfere with NAD+ biosynthesis.
4:50 Using Exploratory INDs and PET Imaging Agents to Accelerate Proof-of-Concept in Alzheimer’s Disease
Michael Pontecorvo, Ph.D., Vice President, Clinical Development, Avid Radiopharmaceuticals
Avid has used the new Exploratory IND guidance to investigate nine different PET and SPECT amyloid imaging agents and a VMAT2 imaging agent and has selected compounds in two of these areas to go forward into Phase II. This presentation will discuss Avid’s experience with Exploratory INDs. Additionally, Avid’s novel imaging agents and their role complementing therapeutic drug studies in early stage drug development will be discussed. We also examine Avid’s experience collaborating with Pharma in these areas.
5:30 End of Accelerating Proof-of-Concept Conference