DAY ONE - SEPTEMBER 23, 2015
7:30 am Registration/Continental Breakfast
8:15 am Chairperson's Opening Remarks
William K. Schmidt, Ph.D., President, NorthStar Consulting, LLC, VP Clinical & Regulatory,Centrexion Corp., Chief Medical Officer, Signature Therapeutics, VP Clinical Development, EicOsis, LLC
8:20 am Current Approaches to Discovery of Novel Pain Therapeutics
With the much discussed lack of success in delivery of novel, efficacious analgesics to market, the field of pain therapeutics has been going through a transformative phase. From how to gain greater confidence in the target to how to model and assess pain in preclinical systems and even how to improve the accuracy of method and data reporting in publications it seems that all areas have received attention. This presentation will provide examples that support the notion that the field is moving in a direction that will deliver the success that the investment demands.
Nick Andrews, Ph.D., Instructor and Manager, Pain Core and Neurodevelopmental Behavioral Core, Boston Children’s Hospital, Harvard Medical School
8:50 am Integrated Pain Quantification Index: A New Measure to Characterize Chronic Multi-Site Pain
Current pain assessments such as VAS or NRS are too simplistic, and do not capture adequate information about the patient’s pain. Pain drawings overcome some of the limitations of VAS and NRS scores, provide detailed information about spatial distribution, and are quantified using a multitude of pain descriptors such as percent area in pain, number of painful areas etc. These multiple measures provide distinct information about pain, and all of these need to be reported for complete pain characterization, thus making them cumbersome to use. This talk will focus on a novel method that combines several measures chronic pain into a single value thereby overcoming limitations of both the scales, and still providing a better characterization of pain experience. Clinical data using this method in a large patient of chronic pain patients is also presented.
Jai Shetake, Ph.D., Senior Clinical Scientist, Boston Scientific
9:20 am Soft Tissue Acute Pain Surgical Models: New Perspectives
Soft tissue surgical models have the lowest assay sensitivity out of the four basic acute pain models (dental surgery, bunionectomy, joint replacement and soft tissue). In this talk, Dr. Singla will discuss the reasons why and some potential solutions for drug developers looking to register drugs in Phase III. The FDA currently requires that most Phase III programs demonstrate efficacy of the IP in both a soft tissue and a bony surgical model. The bony model is typically served by bunionectomy leaving sponsors with the question of what to do for the soft tissue component. This talk will provide options and new perspectives on how this gap can be addressed.
Neil Singla, MD, Chief Scientific Officer, Lotus Clinical Research
9:50 am Refreshment Break
Sponsored by:
10:15 am Pain, Osteoarthritis & Translational Veterinary Medicine
In this presentation, Dr. Kamerling will discuss the following:
- Medical management of OA and pain in people and pets
- What is being done now? What does the future hold?
- What can be learned across species (i.e. translational medicine) with regard to models and spontaneous diseases?
- Focus on pharmaceutical/biopharmaceutical approaches
Steven Kamerling, RPh., Ph.D., Research Fellow and Therapeutic Area Head for Pain, Inflammation and Oncology, Global Therapeutics Research, Veterinary Medicine Research and Development, Zoetis (formerly Pfizer Animal Health)
10:45 am Pain in Europe: A Market Apart From the US
Allen Downs, Senior Corporate & Business Development Lead, Corporate and Business Development, Mundipharma International Ltd.
11:15 am Update on Tanezumab - Monoclonal Antibody Inhibitor of Nerve Growth Factor
Mark S. Juhn, D.O., Senior Director, Field Medical Director - Pain, North American Medical Affairs, Pfizer Inc.
11:45 am Traveling the Road of Abuse-Deterrent Opioid Formulation Clinical Development- Update on the Regulatory Landscape
The approach to the clinical development of abuse-deterrent opioids has been an area of rapid change in the last several years. In April, the U.S. Food and Drug Administration released the finalized guidance on evaluation and labeling of abuse-deterrent opioids with some changes compared to earlier versions. This talk will focus on clinical development of abuse-deterrent opioid formulations in the context of the new finalized guidance.
Wendy Niebler, DO, MBA, Senior VP of Clinical Development and Medical Affairs, Egalet
12:15 pm Luncheon
Sponsored by:
1:15 pm Investigator Initiated trials: Should the Pharmaceutical Industry Support Them?
This presentation will focus on the potential advantages and disadvantages of investigator initiated trials that may help the industry explore post market opportunities. These pilot studies may be of help to expand the label or change the language without undue financial burden. They may also be of help for designing future large, multi-center trials including choosing the right outcomes and logistical challenges.
Srinivas Nalamachu, MD, President and Medical Director, International Clinical Research Institute
1:45 pm Human Abuse Liability Trials: A Pictorial Evaluation of End Points
Human Abuse Liability (HAL) for any drug is assessed through a large number of endpoints for Pharmacodynamic and Pharmacokinetic assessments. From voluminous data collected, a large number of summary tables and subject listings are produced for evaluation and conclusions on human abuse liability. The graphical presentation of same summary results makes it very easy for understanding and interpretation. Additionally, the same graphs could also be used for any publication or in a public presentation. Types of analyses for HAL studies, including ADF trials, that could be considered for reporting of Pharmacodynamic and Pharmacokinetic results would include time-course summary statistics by treatments; endpoints by treatments and between treatments comparison; dose-response; percentage of responders by endpoint and treatments and PK-PD Relationship in time-course data and/or endpoints.
Bijan Chakraborty, Principal Biostatistician, Algorithme Pharma, Vince and Associates
2:15 pm The Search for New Pain Therapeutics with Low Inherent Abuse Potential—A Case for Prodrugs
In this presentation, Dr. Guenther will discuss the following:
- Case studies of new opioid agonists currently being developed
- Examples of different approaches for finding new pain drugs with improved side effect and abuse profile
- Introduction of prodrugs and their potential application in pain therapy
- Overview of two prodrugs currently being developed by KemPharm, Inc.
Sven Guenther, Ph.D., Executive Vice President of Research and Development, KemPharm
2:45 pm Investigating Peripheral and Central Headache Mechanisms Using Preclinical Rodent Models
Migraine is the 3rd most prevalent disease on the planet and the 8th most disabling (according to the 2012 Global Burden of Disease Study). Currently available therapeutics are suboptimal for most patients which contributes to the high burden of this disorder. The mechanisms contributing to migraine are poorly understood, slowing the progress of novel therapeutic development. Work in the Dussor laboratory is focused on furthering the understanding of the pathophysiology of the pain phase of migraine (the headache) using rodent behavioral and in vitro models. Dr. Dussor will discuss some of the findings from his studies using stimulation of the dura mater with interleukin-6. He will present data demonstrating that this cytokine can both sensitize dural afferents and lead to plasticity in central pathways in the brainstem, both of which may prime the meningeal nociceptive system to future stimuli.
Greg Dussor, Ph.D., Associate Professor, The University of Texas at Dallas, School of Behavioral and Brain Sciences
3:15 pm Refreshment Break
Sponsored by:
3:40 pm Beyond Translational Models: Use of Natural Disease to Advance Animal and Human Development Programs
Translational medicine moves from mouse to man. Along the way animals are used to assess safety and to evaluate efficacy through induced pain models. These are important to establish a preclinical understanding of the potential for pharmaceutical development candidates. However, they often do not predict the outcome in naturally occurring disease once a compound reaches man. In a number of painful conditions there are corollaries of natural disease that occur in both man and animals. Where these exist, dual development programs allow data gathered exploring safety and efficacy in animals with natural disease to directly contribute to study design for human studies. The result is further risk reduction for human development and the potential for an animal health product.
Peter Hanson, DVM, Ph.D., DACVS, Executive VP, Pharma Development and Chief Veterinary Officer, Centrexion
4:10 pm Topical Anti-Inflammatory Therapy in the Treatment of Acute Migraine: Potential Role of Trigeminal Nerves
This presentation will present clinical evidence that acute migraine can be treated topically by the application NSIDs. Recent clinical study with TopofenTM a proprietary gel formulation containing 5% ketoprofen was effective in alleviating migraine pain and associated symptoms. The potential involvement of neuroinflammation of the trigeminal neuronal system as the trigger and propagation of migraine will be discussed.
Crist Frangakis, Ph.D., CEO and President, Achelios Therapeutics
4:40 pm An Open Dialogue and Q&A with the Day's Presenters
5:15 Evening Reception
DAY TWO - SEPTEMBER 24, 2015
7:45 am Continental Breakfast
8:15 am Migraine and Cluster Headache: New Understanding and New Approaches to Therapy
Advances in the understanding of migraine and cluster headache are revealing new therapeutic targets for these extraordinarily common disorders. This talk will provide an overview of current concepts of migraine and cluster headache pathophysiology, the successes and shortcomings of current management approaches, and new opportunities for therapy that are currently in development.
Andrew Charles, MD, Professor, Director, Headache Research and Treatment Program, Department of Neurology, UCLA School of Medicine
8:45 am NaV1.7 Peptide Inhibitors: Opportunities to Advance Ion Channel Biology and Develop Novel Pain Therapeutics
In this presentation, Dr. Moyer will present Nav1.7 peptide inhibitors and how they represent an opportunity to both advance Nav1.7 ion channel biology and develop new pain therapeutics. He will discuss Nav1.7 a high-value pain target with human genetic validation and the impact of ion channel inhibitory peptides on furthering basic understanding of ion channel biology, structure, and function. Data will be shown describing the process used to identify novel Nav1.7 inhibitory peptides from the venom of poisonous species. The potency and selectivity of peptides against a panel of Nav channels will be reviewed followed by peptide chemistry efforts to optimize Nav1.7 potency as well as selectivity over Nav1.4 using high-throughput electrophysiology methods. The biophysical mechanism of action of peptide block will be described along with the mapping of a functional peptide interaction site using Nav channel chimeras. The effect of tool peptides, derived from structure-activity campaigns, on endogenous Nav currents in dorsal root ganglion neurons and C-fiber action potential firing in an ex vivo skin nerve prep will be shown. Finally, evidence for Nav1.7 peptide target engagement in vivo via a histamine scratch model will be presented.
Bryan Moyer, Ph.D., Principal Scientist, Neuroscience Department, Amgen
9:15 am From Pain Mechanisms to Medicines: There’s Many a Slip ‘Twixt Cup and Lip'
In this presentation, Dr. Dworkin will discuss the following:
- False positive and false negative results of analgesic clinical trials and their explanations
- Recent efforts to optimize the design of analgesic clinical trials and thereby reduce false positive and false negative clinical trial outcomes
Robert H. Dworkin, Ph.D., Professor of Anesthesiology, Neurology, and Psychiatry, Professor of Neurology in the Center for Human Experimental Therapeutics, Director, Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), a public-private partnership with the FDA, University of Rochester School of Medicine and Dentistry
9:45 am Refreshment Break
Sponsored by:
10:10 am Panel Session: Methodological Challenges of Pain Clinical Trials
In this session, our panelists will be discussing the following subjects:
- Accelerating the development of better analgesic drugs
- Acute vs. chronic pain regulatory pathways
- Reliable chronic pain models
- Reliable acute pain models
- Regulatory pathways for abuse-deterrent drugs
Panelists:
Robert H. Dworkin, Ph.D., Professor of Anesthesiology, Neurology, and Psychiatry, Professor of Neurology in the Center for Human Experimental Therapeutics, Director, Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), a public-private partnership with the FDA, University of Rochester School of Medicine and Dentistry
Srinivas Nalamachu, MD, President and Medical Director, International Clinical Research Institute
Neil Singla, MD, Chief Scientific Officer, Lotus Clinical Research
Ira Gottlieb, DPM, Medical Director, Chesapeake Research Group
10:55 am Transcriptomics of Pain and Peripheral Neuropathies
Michael Iadarola, Ph.D., Senior Research Scientist, Department of Perioperative Medicine, Clinical Center, National Institutes of Health
11:25 am Propofol Hemisuccinate for the Acute Treatment of Migraine
Numerous reports indicate that intravenous propofol at subanesthetic doses is effective in the acute treatment of severe refractory migraine in adults and children. Propofol hemisuccinate (PHS) is a novel, proprietary propofol prodrug that is being developed for pulmonary administration. Proof-of-concept studies in animals indicate that PHS has CNS activity when administered via the lung. A key advantages of pulmonary delivery is rapid onset of action compared to other routes of administration, including the intranasal route. PHS has been manufactured GMP and a proprietary formulation has been developed. IND-enabling studies are in progress in anticipation of first-in-man.
Michael Rogawski, MD, Ph.D., Professor of Neurology, University of California, Davis
11:55 am Luncheon
Sponsored by:
12:55 pm TRV130: A Novel G Protein Biased Ligand Provides Rapid, Significant Pain Relief in Patients after Bunionectomy Surgery
This talk will cover the results from Trevena's adaptive phase 2 trial of TRV130, focusing on the points of differentiation of TRV130 vs morphine. Future plans, including a summary of the on-going study enrolling patients after abdominoplasty surgery, will also be highlighted.
David G. Soergel, MD, Senior VP, Clinical and Chief Medical Officer, Trevena
1:25 pm Update on the Development of Fulranumab: A Human Monoclonal Anti-NGF
Nerve Growth Factor (NGF) is a key regulator of nociceptive pain and has shown strong efficacy in clinical trials to date. NGF antagonists act by sequestering NGF and preventing its binding to either of its two receptors, the tropomyosin-related kinase A (TrkA) and p75. Clinical trials, which were put on hold by the FDA, due to safety concerns, are set to continue. In this presentation, Dr. Upmalis will discuss the following:
- Review of clinical data to date
- Update on regulatory status and review of regulatory issues
- Clinical Plans for Fulranumab
David Upmalis, MD, Senior Director, Compound Development Team Leader, fulranumab, Janssen Research and Development
1:55 pm TEV 48125, A Monoclonal antibody, (anti-CGRP) for Migraine
In this presentation, Dr. Aycardi will be discussing the clinical development program and recent clinical trial data for Teva Pharmaceuticals’ anti-CGRP therapy for Migraine, TEV 48125. CGRP ligand mAbs provide a peripheral sink for CGRP released from activated perivascular trigeminal sensory nerve fibers. Disrupting CGRP signaling has shown to be efficacious in the acute treatment of migraine. TEV -48125 (formerly LBR-101 / RN-307) is a fully humanized monoclonal antibody that potently and selectively binds to CGRP. TEV-48125 showed to be efficacious in phase 2, for the prophylactic treatment of chronic and episodic migraine, with significant improvement over placebo.
Ernesto Aycardi, MD, Sr Director Clinical Development, Migraine & Headaches, Teva Pharmaceuticals
2:25 pm An Open Dialogue and Q&A with the Day's Presenters
3:00 pm End of Conference
