Hilton San Francisco Airport Bayfront, Burlingame, CA
2014-11-05
DAY ONE - NOVEMBER 5-6, 2014
7:45 am Workshop Registration/Continental Breakfast
8:30 am WORKSHOP: Leveraging FDA Requirements to Optimize the Prospects for Commercialization of Innovative Pain Therapeutics (SEPARATE REGISTRATION REQUIRED)
Developers of innovative pain therapeutics face two crucial, and seemingly competing hurdles: achieving regulatory approval and optimizing commercial viability for their products. The first requires demonstration of efficacy and safety within a tightly controlled setting. The second requires demonstration of “real world benefits” over currently available options, given that regulatory approval is achieved. This workshop will address considerations in designing and analyzing data from clinical trials for novel pain therapeutics that can be leveraged to optimize the prospects for commercialization. Specifically the workshop will address: “real world” requirements that must be met to optimize access, coverage and reimbursement; identification, inclusion and analysis of clinical endpoints that will optimize commercialization without jeopardizing regulatory approval; and approaches that can be used to enhance commercialization opportunities during the execution or following the completion of registration trials. The format of the session will be interactive. Dr. Hankin will present an overview of the issues and provide cases studies for discussion. Participants will have the opportunity to share their concerns and experiences. Cheryl Hankin, Ph.D., President and Chief Scientific Officer, BioMedEcon, LLC 10:00 am Conference Registration 10:40 am Chairperson's Opening Remarks William K. Schmidt, Ph.D., President, NorthStar Consulting, LLC, VP Clinical & Regulatory, Centrexion Corp., VP Clinical & Regulatory, Cap Genesis, LLC, VP Clinical Development, EicOsis, LLC 10:45 am Lighting the Song With Sense and Color: A Humanistic Approach to Pain Research The 2011 Institute of Medicine report “Relieving Pain in America” provides a framework for addressing arguably this nations number one health, social and economic problem. Academic colleges and universities have important roles to play in helping address the burden that chronic pain places on the individual and the community. The presentation will highlight some of the efforts that the University of New England is taking in the areas of pain research and pain education. Highlights include the growth of a coordinated basic science research program that is studying the neurobiology of pain, efforts to build a clinical patient-centered outcomes research group, and the implementation of a truly interdisciplinary and inter professional approach for better preparing healthcare professionals in the prevention and treatment of chronic pain. The engagement of the arts and humanities, as well as patients and their families, in the education and research efforts will also be highlighted. The goal of the presentation is to facilitate discussion with the audience on the topic and think about collaborative ways to accomplish goals of the IOM report. Ed Bilsky, Ph.D., Professor of Pharmacology, COM, Vice President of Research and Scholarship, University of New England 11:15 am Techniques for Minimizing the Impact of Subject Dropouts on the Validity of Analgesic Clinical Trials - Increased Retention through Subject Education Followed by a Primer on Imputation Techniques When it comes to subject dropouts, an ounce of prevention is worth a pound of cure. Subject and study staff education can reduce dropout rates. The lecture will focus on educational paradigms designed to reduce dropouts and their efficacy. Regardless of technique, dropouts cannot be eliminated. When dropouts occur, they need to be statistically accounted for utilizing accepted imputation methods. In the recently released FDA draft analgesic guidance, a significant amount discussion was devoted to the appropriate statistical handling of missing data. Dr. Singla will provide a primer on accepted imputation techniques for acute and chronic analgesic studies. Neil Singla, MD, Founder & Chief Scientific Officer, Lotus Clinical Research 11:45 am Targeting Translation Control Mechanisms to Treat Pathological Pain Plasticity Translation control is a fundamental mechanism used by neurons to achieve long-term plasticity. Work from multiple labs in the past decade has revealed translation control of gene expression as a potential mechanism for large scale functional changes increasing sensitivity in injured nociceptors. Several key targets for pharmacological manipulation have emerged from this work. This presentation will focus on two of these: AMPK mediated control of mTOR and MAPK pathways and MNK signaling to eIF4E. Collectively these novel mechanistic studies reveal several new therapeutic opportunities for the treatment and possible reversal of pathological pain. Theodore Price, Ph.D., Associate Professor, School of Behavioral and Brain Sciences, University of Texas at Dallas 12:15 pm Luncheon 1:25 pm The Discovery and Development of ALD403, a Potent Anti-CGRP Antibody Effective in Headache Prevention Migraine is a highly disabling condition that affects almost 1 in 10 individuals in the United States with up to one-third experiencing greater than 5 headache days per month. Migraine represent a significant unmet need, since current preventive therapy is only marginally effective. ALD403 is a humanized, high affinity monoclonal antibody that targets the neuropeptide CGRP, which has been shown to play an important role in migraines. A summary of preclinical and in human clinical trial data will be shared with the audience. Leon F. Garcia-Martinez, Ph.D., Senior Director Target Biology, Alder Biopharmaceuticals 1:55 pm Opioids Built Around Novel, Proprietary Abuse-deterrent Technology Resistant to Common Methods of Abuse Prescription opioid abuse has reached epidemic levels in the United States, with 6.8 million current prescription drug abusers. Egalet’s Guardian technology combines physical and chemical properties to resist common methods of abuse including: crushing, injection or snorting; chewing; aqueous extraction for intravenous dosing and alcohol dose dumping. Using the Guardian technology, Egalet has two products in late-stage development. Egalet-001, is an abuse-deterrent, extended-release, oral morphine formulation which was designed to resist common methods of abuse, including the most common route for morphine via injection. Egalet has conducted Category 1 abuse-deterrent studies with EG-001 and results demonstrate that EG-001 resists all forms of common methods of manipulation and solubilization. Egalet has an ongoing bioequivalence study and the Company plans to submit an NDA in the fourth quarter of 2014. Egalet-002, an extended-release oxycodone, was designed to resist common methods of abuse, including crushing and snorting the most common route of abuse for oxycodone. In addition to its key abuse deterrent features, Egalet-002 was also designed to improve on the PK profile of OxyContin OP. Egalet has ongoing abuse-deterrence studied ongoing and plans to start the pivotal Phase 3 trial for Egalet-002 in the fourth quarter of 2014, with the intention of submitting an NDA to the FDA in the first half of 2016. Mr. Radie will discuss clinical results and the regulatory path for these two product candidates. Robert Radie, President & Chief Executive Officer, Egalet Corporation 2:25 pm Dissecting the Immune Response to Inflammatory Pain The molecular and cellular immune components involved in the pathogenesis of pain during inflammation are not yet well understood. Dr. Ghasemlou and colleagues have sought to characterize the cellular and molecular immune responses and their association with changes in pain behavior in two of the most commonly used models of inflammatory pain, that are widely used as preclinical surrogates of human disease. Their results highlight important distinctions between inflammatory models of pain, and the disparate contribution of immune cells to behavioral outcomes. Nader Ghasemlou, Ph.D., Research Fellow, Children's Hospital Boston & Harvard Medical School, F.M. Kirby Neurobiology Center 2:55 pm Refreshment Break / Scientific Poster Session Viewing 3:25 pm Abuse-deterrent Opioids – Addressing Drug Abuse and Patient Needs Extended-release (ER) opioids are an important part of the multi-modal approach to the treatment of moderate-to-severe chronic pain. While conferring clinical advantages to patients, abusers seek to tamper with these formulations in order to rapidly release the opioid to elicit a euphoric effect. This can lead to a potentially fatal overdose. Currently available abuse-deterrent formulations (ADF) are an improvement over non-ADF ER analgesics, but are still readily manipulated. There are novel opioids in development that may provide both clinical and abuse liability advantages, which will be presented in this lecture. Objectives of this talk include the following: Understand the concept of abuse liability Differentiate the different types of ADFs Identify currently available products Understand the FDA guidance on ADF development Identify ADF analgesics in development Discuss clinical advantages of ADF opioids Discuss abuse liability of ADF v. non-ADF opioids Ernest A. Kopecky, Ph.D., MBA, VP Clinical Development | Head, Neuroscience TA, COLLEGIUM Pharmaceutical 3:55 pm Presentation Title to be Announced Daniel Legault, JD, Chief Executive Officer and Director, Antibe Therapeutics 4:25 pm PANEL SESSION: An Open Dialogue and Q&A with the Day's Presenters Moderator: William K. Schmidt, Ph.D., President, NorthStar Consulting, LLC, VP Clinical & Regulatory, Centrexion Corp., VP Clinical & Regulatory, Cap Genesis, LLC, VP Clinical Development, EicOsis, LLC 5:10 pm Wine and Cheese Reception DAY TWO - NOVEMBER 6, 2014
7:45 am Continental Breakfast 8:15 am An Effort to Overcome the Crisis of the Current Drug Discovery in Pain Therapeutics Modern approaches to target-based drug discovery have grossly failed to deliver safe and efficacious medicine for CNS afflictions such as pain. This led to a new (or could be a roll-back) approach for drug discovery emphasizing network pharmacology or systems biology. According to these new perspectives, the efficacious and safe therapeutics should be multi-targeting drugs; however, there has been no practical methodology to identify such a multi-targeting drug. Vivozon’s unique core technology is built upon a tissue-based phenotypic screening that enables rapid and continuous discovery of agents that attenuate pain signaling through the modulation of a variety of known and unknown targets encompassing polypharmacology or "transient drugs.” As a result of the effort, Vivozon has identified a morphine comparable analgesic candidate (VVZ-149) that has antagonistic activity on GlyT2 & 5HT2a. We will introduce the practical approach for multi-targeting drug and preclinical/clinical data of VVZ-149. Doo H. Lee, Ph.D., Chief Executive Officer, Vivozon, Inc. 8:45 am Diagnosing and Treating Spine/Joint Related Pain: Harnessing The Body’s Own Defense Mechanism In this presentation, Dr. Scuderi will discuss his research in developing biologic therapies for traumatic musculoskeletal diseases based on protease inhibitors, a generation 2 platform. He will discuss application of these biologic therapeutics to degenerative diseases of the joints and spine and will outline the science behind Cytonics’ FACT assay, which detects a unique biomarker in the inflammatory cascade that can assist physicians pinpoint the source of pain. Gaetano Scuderi, MD, Founder, President, Cytonics Corporation 9:15 The Emerging Role of Genetics in Pain Management The selection, dosing, and evaluation of pain therapeutics presents a host of challenges. With most patients unable to control their pain with the approach to existing treatment decisions, practitioners generally resort to higher doses, potency, or class of medications, as well as surgeries and other interventional procedures. This has led to a rapid escalation of costs to treat chronic pain, a high rate of treatment failure, and an increase in prescription drug use and misuse. Genetic factors are involved in the outcomes of pain medications, and according to the National Institutes of Drug Abuse and the American Society of Addiction Medicine – genetics account for about 50% of substance abuse. The use of genetic testing is becoming more available to assist practitioners in pain management. Even though there is limited utility to the use of drug metabolizing enzyme (CYP-P450) genetic testing for opioids, there are various other tests available with data to support the clinical validity of genetic testing to improve the selection, dosing, and evaluation of pain therapeutics. Genetic testing can be used by clinicians to identify patients at greater risk for the misuse of narcotics, at greater risk for dependence to opioids, and to stratify their pain perceptions objectively to help interpret very subjective pain numerical rating scales. Brian Meshkin, Founder and President, Proove Biosciences 9:45 am Refreshment Break / Scientific Poster Session Viewing 10:15 am Sex, Pain and Drugs A growing recognition that many aspects of human disease are highly sexually dimorphic has lead to a growing interest in defining the implications of this research for treatment of pain. Receptors for sex hormones are found in pain and analgesic mechanisms at all levels of the neuraxis, and sex differences in pain conditions and response to analgesics are well established in humans. Sex hormones have recently been shown to have rapid action at G-protein coupled receptors as well as their well-established effects on gene regulation. Sex hormones also have profound effects on pain and analgesia that differ dramatically between females and males. One of the most dramatic clinical example of sexual dimorphism in response to analgesics is for the kappa-opioid analgesics, which produces delayed onset anti-analgesia in men but not women. Jon Levine, MD, Ph.D., Professor of Medicine, University of California, San Francisco 10:45 am Peripherally Acting Mu Opioid Receptor Antagonists For the Treatment of Opioid Induced Constipation: A Changing Development and Regulatory Landscape Managing chronic pain often leads to patients dealing with the substantial burden of constipation associated with opioid therapy. Unlike other opioid side effects, tolerance to constipation generally does not develop over time. Despite available options, a large proportion of patients do not receive adequate relief and the unmet need remains high. Peripherally acting mu opioid receptor antagonists directly target the cause of opioid-induced constipation (OIC), but the path for developing safe and effective drugs in this class is challenging and continues to evolve. Clinical and regulatory perspectives, including the potential impact of a recent FDA Advisory Committee meeting, will be discussed within the context of drug development for peripherally acting mu opioid receptor antagonists in the treatment of OIC. Lee M. Techner, DPM, Principal and Chief Clinical Consultant, Stage Gate Partners 11:15 am P2X3 Antagonism for Sensitization-driven Signs and Symptoms of Common Diseases: POC Results in Distressing Respiratory, Somatosensory and Visceral Conditions Afferent Pharmaceuticals has progressed the first clinical stage P2X3 antagonist, AF-219, to completion of four “proof of concept” studies in patients with painful and/or irritative symptoms in respiratory, somatosensory (painful OA of the knee) and visceral (interstitial cystitis/bladder pain syndrome) disorders. Outcomes from these studies have confirmed a number of preclinical findings and suggest broad potential of this innovative primary afferent target. For example, an unprecedented efficacy response to AF-219 in a two week study in patients with chronic cough, who have very limited effective therapeutic options, was observed and indicates that relief from the distress of chronic cough – and the first new antitussive for 50 years - could be on the horizon. Clinical experience reveals an excellent safety profile following up to 4 weeks of dosing at “definitive” dose levels, and augurs well for long term development of P2X3 antagonists for a range of common sensory indications with very high unmet needs. Anthony P. Ford, Ph.D., Chief Scientific Officer. Afferent Pharmaceuticals 11:45 pm Luncheon 12:55 pm Preventative Effects of a Formulation of Nasal Oxytocin for Chronic and High Frequency Episodic Migraine Headache Patients Through Block of CGRP Release Chronic and high frequency migraine patients suffer with 15 or more or 9-14 headache days/month respectively, and are highly debilitated by these conditions. Treatment choices for these conditions are currently inadequate. Dr. Yeomans and his team have previously shown that trigeminal neurons possess oxytocin receptors the expression of which is highly dependent on inflammatory state. They have also shown that nasal application of oxytocin attenuates responses of brainstem neurons to painful stimulation and produces profound analgesia in craniofacial behavioral assays. In this presentation, he will show that these physiologic and behavioral effects are likely mediated by inhibition of release of calcitonin gene related peptide - a pain neurotransmitter associated both with neurogenic inflammation of the dura as well as central sensitization of trigeminal nuclear neurons. He will also will describe the results of a multi-center phase II chronic dosing study in chronic and high frequency episodic migraine patients, where we have observed that nasal application of our formulation of nasal oxytocin produces robust and sustained decreases in the frequency of migraine attacks as well as of secondary migraines symptoms including nausea and vomiting, photophobia, and phonophobia. Finally, he will speculate as to a CGRP-dependent mechanism underlying these results. David Yeomans, Ph.D., Director of Pain Research, Faculty of Anesthesia, Stanford University School of Medicine, Founder & Chief Scientist, Trigemina, Inc. 1:25 pm Genetic and Pharmacologic Evidence Establishing a Role for the Nav1.7 Sodium Ion Channel Isoform in Itch and Pain In this presentation, Dr. Fremeau will present Amgen’s new mouse genetic data establishing that Nav1.7 is essential for histamine-independent itch as well as histamine-induced itch. He will then discuss the role of nociceptors in mediating itch and pain and discuss the relevance of itch to chronic pain. Evidence will be provided that histamine-induced itch is a translatable in vivo biomarker of Nav1.7 target engagement using highly potent and selective Nav1.7 small molecule inhibitors developed at Amgen. He will show that Amgen’s inhibitors produce potent and selective inhibition of TTX-sensitive currents in mouse dorsal root ganglion neurons. Additionally, he will establish confirmation of “on mechanism” activity of our Nav1.7 inhibitors in mouse histamine itch using this enantiomer pair. To address the potential relevance of itch to pain I will then show that the in vivo potency (EC50) of a lead molecule is comparabel at inhibiting mouse histamine-induced itch, mechanically-induced C-fiber firing in a skinned nerve prep, and established hyperalgesia in the UVB burn model. Robert Fremeau, Ph.D., Scientific Director, Department of Neuroscience, Amgen, Inc. 1:55 pm Panel Session: An Open Dialogue and Q&A with the Day's Presenters Moderator: William K. Schmidt, Ph.D., President, NorthStar Consulting, LLC, VP Clinical & Regulatory, Centrexion Corp., VP Clinical & Regulatory, Cap Genesis, LLC, VP Clinical Development, EicOsis, LLC 2:40 pm End of Conference
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