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Wednesday, June 6
12:30 pm Registration
1:20 Chairperson’s Opening Remarks
» 1:25 KEYNOTE PRESENTATION
From Mechanisms to Medicines: What ACTTION Can be Taken to Accelerate Analgesic Drug Development?
Robert H. Dworkin, Ph.D., Professor of Anesthesiology, Neurology, Oncology, and Psychiatry; Professor, Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry; Director, Analgesic Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), a public-private partnership with the FDA
A substantial percentage of patients with pain either are refractory to existing analgesic treatments or obtain only partial relief of their pain. To address the limitations of existing analgesics, the FDA has established a public-private partnership. The primary objective of this partnership is to accelerate the identification of treatments with improved efficacy and safety. One important focus of the partnership’s activities involves optimizing clinical trial methods to increase assay sensitivity and study efficiency.
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2:10 A Novel Genetic Based Approach for Demonstrating Target Engagement of Nav1.7 Inhibitors
Y. Paul Goldberg, M.B., Ch.B., Ph.D., FRCPC, Vice-President, Clinical Development, Xenon Pharmaceuticals, Inc.
Demonstrating proof-of-mechanism (POM) in a fast and economical manner is crucial for the timely and successful development of new Nav1.7 inhibitors. We have used a rare genetic condition, inherited erythromelalgia (IEM), to develop a novel model for rapid assessment of target engagement for these inhibitors. IEM is an autosomal dominant disorder of spontaneous or easily evoked pain in the hands and feet, caused by SCN9A missense mutations resulting in gain-of-function in Nav1.7. Therefore, therapeutics that inhibit Nav1.7 are expected to relieve the pain associated with IEM. Pain in IEM patients can be readily evoked under experimental conditions by providing a heat stimulus. Here we describe the features of this model in a context of an exploratory clinical trial conducted with a novel, potent Nav1.7 small molecule inhibitor (XEN402). A randomized, double-blind, two-period crossover study was conducted in four mutation-proven IEM patients. XEN402 or matching placebo was given orally in each treatment period (2 days), separated by a 2-day washout. Patient reported outcomes of pain intensity and/or relief were recorded and the time taken to induce pain was measured. XEN402 significantly suppressed the IEM pain induction compared to placebo (42% less pain, p = 0•014), demonstrating POM in this patient population. Important insights were gained from this study in the optimization of this model. The results of this study showed that the IEM pain can be reliably induced, standardization of experimental conditions and pain induction methods are important, heat can be used as a safe and reliable method of pain induction, the time required for pain induction can be used as a useful endpoint, and repeated pain and induction measurements are required for data interpretation. This pilot study showed that XEN402 blocks Nav1.7 mediated pain associated with IEM, thereby demonstrating the utility of using rare genetic disorders with mutant target channels as a novel approach to evaluate sodium channel inhibitors to demonstrate rapid target engagement.
2:40 Pharmacology and First Clinical Experience of the Dual Enkephalinase Inhibitor PL37
Bernard P. Roques, Ph.D., Vice President & Scientific Director, Pharmaleads
Michel Wurm, M.D., Director, Drug and Business Development, Pharmaleads
3:10 Sponsored Presentations (Opportunities Available)
3:40 Refreshment Break in the Exhibit Hall with Poster Viewing
4:10 Talk Title to be Announced
Anthony W. Bannon, Ph.D., Associate Director II, Neuroscience Drug Discovery, Global Pharmaceutical Research & Development, Abbott
4:40 Interactive Discussion Groups
Concurrent problem-solving discussions on specific topics, to provide a forum for exchanging ideas, voicing opinions and meeting potential collaborators. Discussions will be led by a moderator/s, limited to 15 participants per table, and open to all attendees and exhibitors.
5:40 End of Day
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