Wednesday, October 5
7:30-8:15am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee
PHASE 0 AND EARLY DEVELOPMENT
8:15-8:20 Chairperson’s Opening Remarks
Terri Roberson, Senior Director, Global External Research and Development, Lilly Research Laboratories
8:20-8:50 Phase 0 Studies for Drug Development
Sean Zhang, M.D., Medical Director, Discovery Medicine and Clinical Pharmacology, Bristol-Myers Squibb
Phase 0 studies are generally referred to human microdosing studies in accordance with the US FDA Guidance on Exploratory Investigational New Drug (IND) Studies. However, the term of Phase 0 studies has been sometimes extended beyond the concept of microdosing to include no-drug administration methodology and sub-therapeutic exploratory studies. Examples of human microdosing studies for drug R&D include PET imaging, biomarker or endpoint validation and absolute bioavailability studies. Sub-therapeutic exploratory study is increasingly being used for early candidate screening on human PK and PD. In this presentation, the basic concepts, regulatory guidance and IND enabling toxicology studies for Phase 0 studies will be reviewed. Case studies utilizing human Phase 0 studies for drug R&D will be elucidated. Finally, the challenges and limitations of Phase 0 studies will be discussed.
8:50-9:20 Short Stories of Early Development Decisions Using Fit-for-Purpose Biomarkers
Chan Beals, M.D., Ph.D., Executive Director, Head, Experimental Medicine, Merck & Co.
One proposed solution to high cost and low success in early development is to utilize biomarkers to confirm a pharmacodynamic effect in humans before further development. This talk will provide a high level overview of clinical biomarker qualification, and describe specific applications to effect early clinical decisions at Merck. While biomarkers may utilize many technologies for numerous uses, they will not realize their value without seemless integration into the discovery and development interface, focus on the pipeline, and excellent negotiation skills.
9:20-9:50 Innovative PoC Strategies: The VC Perspective and Approach
Peter Neubeck, M.D., Ph.D., M.B.A., Principal, TVM Capital GmbH
Life Science Venture Capital is in a state of dramatic transition:
Biotech venture model is broken and it is very difficult fundraising environment
But there is hope:
Key success factors going forward revolve around getting to PoC in a smart and fast way:
9:50-10:25 Networking Coffee Break with Exhibit and Poster Viewing
10:25-10:55 Envisioning the Future of Early Phase Clinical Trials
Timothy Yap, Ph.D., Senior Clinical Research Fellow, Royal Marsden Hospital and The Institute of Cancer Research, UK
The development of novel molecularly targeted cancer therapeutics remains slow and expensive with many late-stage failures. There is an urgent need to accelerate this process by improving early clinical anticancer drug evaluation through modern and rational trial designs that incorporate predictive, pharmacokinetic, pharmacodynamic, pharmacogenomic and intermediate end-point biomarkers. In this talk, I will discuss current approaches and propose strategies that will potentially maximize benefit to patients and expedite the regulatory approvals of new anticancer drugs.
10:55-11:55 Roundtable Discussion Results
Results of the roundtable exercise to define Proof-of-Concept will be presented and discussed (results available post-conference to registered attendees).
11:55-12:10pm Selected Poster Presentation
12:25-1:40 Lunch On Your Own
1:40-2:10pm Strategies to Reduce Compound Attrition in Early Development
Lloyd Dethloff, Ph.D., Vice President, Drug Safety R & D, Worldwide Research and Development, Pfizer, Inc.
Attrition of drug candidates in the early stages of research and development continues to vex small and large pharmaceutical companies alike. Given that critical elements of successful drug development programs are established at the time of target and molecule selection, it is imperative to maximize the likelihood for success through cost-effective, data-driven means in the early stages. Rational, staged investment approaches, including deeper knowledge of targets and pathways, probabilistic assessments of toxicity associated with physicochemical properties, knowledge-based design of more cost-effective in vivo screening approaches prior to escalation of resource commitments, and strategic use of alternative IND approaches will be reviewed.
2:10-2:40pm Accelerating Proof-of-Concept for Novel/Novel Drug Combinations in Oncology
Samuel C. Blackman, M.D., Ph.D., Director, Early Development Unit/Oncology, GlaxoSmithKline
Successes and failures in monotherapy application of targeted therapeutics in oncology and expansion of pipelines have lead to a marked increase in novel/novel drug combination Phase I trials. The number of potential novel/novel combinations and the complexity of the development path for combinations has prompted the development of various strategies to address the “Combination Problem.” This talk will define the scope of this problem, strategies for prioritization, and methods for accelerating proof-of-concept using novel clinical trial designs.
2:40-3:10pm Cancer Immunotherapy: Challenges in Clinical Development
Robert Sims, M.D., Senior Medical Director, Dendreon Corporation
Sipuleucel T is an autologous cellular immunotherapy for asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer. The IMPACT study demonstrated an improvement in overall survival (OS) for subjects treated with sipuleucel T compared with control (HR=0.78 [95% CI: 0.61, 0.98]; P=0.03), indicating a 22% reduction in the risk of death. No significant differences in time to objective disease progression were observed between groups. Immune responses to the immunizing antigen were observed, with correlations between these measures and OS. Challenges encountered in the development of sipuleucel-T will be discussed, along with the use of immunologic biomarkers and considerations for future development.
3:10-3:40pm Learning From Failure: The COX-2 Saga
Tilo Grosser, M.D., Research Assistant Professor, Pharmacology, Institute for Translational Medicine and Therapeutics, University of Pennsylvania
Nonsteroidal antinflammatory drugs (NSAIDs) inhibit prostaglandin formation by cyclooxygenases (COX) -1 and -2. NSAIDs selective for inhibition of COX-2 are less likely than traditional drugs to cause serious gastrointestinal adverse effects, but predispose to adverse cardiovascular events, such as heart failure, myocardial infarction and stroke. Evidence from human pharmacology and genetics, genetically manipulated rodents and other animal models and randomized trials indicates that this is consequent to suppression of COX-2 dependent cardioprotective prostaglandins, particularly, prostacyclin. Lessons drawn from how this saga unfolded are relevant to how we integrate diversified forms of information, approach PoC efficacy and safety research and might pursue a more personalized approach efficacy and risk.
3:45pm End of Conference
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