WEDNESDAY OCTOBER 3, 2012
7:45 Registration and Continental Breakfast
8:30 Chairperson's Opening Remarks
William K. Schmidt, Ph.D., President, NorthStar Consulting, LLC, VP Clinical & Regulatory, Arcion Therapeutics, VP Clinical Development, CrystalGenomics (CG Pharmaceuticals)
8:45 Pain, Addiction, Abuse and Psychiatric Co-morbidities
Dr. Medve will discuss managing critical interplays and putting the patient at the center of the treatment team.
The session will cover:
- Addiction - what is it?
- Animal models - can they predict human addiction?
- Psychiatric illness vs pain vs addiction - how do these interplays work?
- Opioids and the future of pain care
- How best to manage patients in a complicated care system
Dr. Medve will also discuss Nektar's recently Fast Tracked NCE opioid NKTR-181, which is designed to have a slow rate of entry into the brain to reduce the attractiveness of the molecule as a target of abuse and to reduce its CNS-mediated side effects.
Robert Medve, MD, Senior Vice President & Chief Medical Officer, Nektar Therapeutics
9:15 Allosteric Inhibitors of the NGF/TrkA Pathway: a Novel, Small Molecule Approach to Inhibiting Peripherally Mediated Pain
Nerve Growth Factor (NGF) plays a significant role in the generation and maintenance of the nociceptive pain associated with a variety of human diseases. Array Biopharma has used a structural biology driven approach to develop potent, highly selective small molecules that inhibit TrkA kinase activity through allosteric modulation. The efficacy of TrkA inhibitors in rodent models of peripheral pain will be detailed. Additionally, potential mechanistic differentiation from the anti-NGF strategy will be discussed as will in vivo efficacy and long term safety associated with their small molecule inhibitors.
Steve Miller, Ph.D., Senior Director, Translational Medicine, Array BioPharma
9:45 New Models of Pain in Freely Moving Rodents
The pain field has been frustrated by the limitations of the current evoked nociception models that are used for screening or target discovery. Regeneron has been working on several non-evoked models of visceral pain and deep tissue pain that are providing some interesting mechanistic insights. Dr. LaCroix-Fralish's in vivo pharmacology team is seeking to develop therapeutics for the treatment of pain and neurological disability. In this presentation, he will discuss his team's efforts to develop new models for visceral and deep tissue pain.
Michael LaCroix-Fralish, Ph.D., Staff Scientist, Pain Therapeutics Group, Regeneron Pharmaceuticals
10:15 Poster Viewing & Refreshment Break
10:45 Evaluating Abuse Resistance of Delivery Systems
Countless resources have been expended and will continue to be expended to develop effective abuse resistant delivery systems. Compounds with the highest abuse potential, particularly opioids, have seen the greatest number of new delivery systems with abuse resistance features. The FDA’s draft industry guidance published in January 2010 under the title, “Assessment of Abuse Potential of Drugs,” contains the following statement:
“Currently, the concept of abuse deterrence is viewed as the introduction of some limits or impediments to abuse, as opposed to the outright elimination of abuse. For all dosages of such products, extractability and solubility studies should be designed to determine whether any of the drugs present in the combination might be differentially solubilized and extracted, and thus separated from the API.”
In this presentation, Mr. Bianchi will discuss in vitro studies designed to evaluate the extractability or tamperability of some of the abuse resistant delivery systems currently in use.
Robert Bianchi, VP & Chief of Scientific and Technical Affairs, Prescription Drug Research Center
11:15 Gene Therapy to Control Intractable Pain in Cancer Patients: A New Paradigm?
A very high proportion (up to 85%) of terminal cancer patients suffer from severe pain; current therapies, principally opioids, are of limited use. Benitec Biopharma Ltd. is developing a gene therapy strategy to control pain in such patients using intrathecal delivery of lentiviral particles expressing shRNA constructs designed to inactivate the Protein Kinase C gamma gene (PKCg) in neurones of the spinal cord. Others have demonstrated the strategy works in neuropathic pain models in rats. Benitec has developed constructs that strongly inactivate PKCg in vitro; these particular shRNAs target sequences within PKCg that are absolutely conserved between rat and humans as well as pre-clinical test species (dogs and macaques), simplifying pre-clinical testing. These new constructs are being validated in rat pain models and protocols for pre-clinical testing are being developed. Benitec believes a gene therapy approach for pain control in terminal cancer patients is warranted, the approach is relatively low risk and offers the prospect of a single treatment providing long term pain relief.
Dr. Michael Graham, Chief Scientist, Benitec Biopharma
11:45 Pain in Children: Challenges in Conducting Pediatric and Neonatal Pain Studies and Treating Pain in Children
This presentation will cover the following:
- Developmental physiology and pharmacology, including enzyme maturation and drug metabolism
- Pain measures: assessments from neonates through adolescents
- Challenges in clinical study design, including: recruitment, use of placebo, blood volume restrictions and formulations
- Current concepts in the treatment of pain in children
Ernest A. Kopecky Ph.D, MBA, VP Clinical Development, Head, Neuroscience TA, COLLEGIUM Pharmaceutical, Research Fellow, Division of Clinical Pharmacology/Toxicology, Hospital for Sick Children
12:15 Luncheon
1:30 Transition from Acute to Chronic Pain States
Tony L. Yaksh, Ph.D., Professor & Vice Chair for Research, Department of Anesthesiology and Professor of Pharmacology, University of California, San Diego
2:00 Minimizing Experimental Error in Analgesic Research by Reducing Placebo Response and Variability
The properly educated patient can be your greatest ally in producing a positive analgesic clinical trial. A significant portion of an analgesic investigation's variability is produced secondary to cognitive gaps that the patient may have when interpreting the various protocol mandated scales and questions. All pharmaceutical companies spend a large amount of time perfecting their protocol and selecting/educating quality sites so that the efficacy of their drug can be statistically demonstrated. However, an equal amount of effort is rarely placed on patient education. This piece of the puzzle is the responsibility of the site and as such, we have developed educational materials to reduce placebo response and garner data that is as "true" as possible. This talk will discuss placebo response training and other ways to mitigate variability in analgesic clinical trials.
Neil Singla, MD, Founder & Chief Scientific Officer, Lotus Clinical Research, LLC
2:30 Analgesic Potential of TRPA1 Antagonists
TRPA1 serves as a broad sensor for the detection of both endogenous and exogenous reactive chemicals. This presentation will review the rationale for targeting TRPA1 for the treatment of pain, including peri-operative, inflammatory, visceral and neuropathic conditions. In addition, recent progress on the clinical development of TRPA1 antagonists will be summarized, including data from Cubist and Hydra Bioscience's clinical development programs.
Magdalene Moran, Ph.D., Vice President, Biology, Hydra Biosciences
3:00 Poster Viewing & Refreshment Break
3:30 Overview of Analgesic Efficacy and Safety of Tanezumab, a Monoclonal Antibody Targeting Nerve Growth Factor for Treatment of Chronic Pain
Nerve growth factor (NGF) has been increasingly implicated as a facilitator of pain in human diseases and related animal disease models. Monoclonal antibodies targeting NGF have shown compelling efficacy in relieving pain in a number of painful conditions. This presentation will review the current analgesic efficacy and safety profile of tanezumab, a monoclonal antibody in late-stage development for chronic pain.
Mark T. Brown, MD, Executive Director, Clinical Program Leader for Osteoarthritis and Cancer Pain Studies, Pfizer Inc.
4:00 Conotoxins: Molecular Tools to Dissect Pain Pathways
Conotoxins are disulfide-rich peptides isolated from the venom of the predatory cone snail. Millions of years of natural selection fine-tuned this complex mixture of venom peptides to be highly potent and selective to various ion channels, transporters and GPCRs. In particular their subtype selectivity make them preferred tools for the study of receptors (e.g. ionchannels) involved in neuropathic pain. With ready access to sequencers we are now able to mine the transcriptome of the venom ducts, providing us with more sequence information than we can produce, certainly putting the pressure back on developing better synthetic methodologies. In this presentation, Dr. Muttenthaler will describe the discovery, synthesis and application of this class of compounds with a focus on the latest advancement in creating a diverse toolbox for neuroscientists.
Markus Muttenthaler, Ph.D., Departments of Chemistry and Cell Biology, The Scripps Research Institute
4:30 Making Investment Choices in Pain Management
In this presentation, Dr. Meltzer will walk the audience through some top line discussions of how Purdue Pharma is looking at the current and future marketplace of pain management and how that influences investment choices.
Brian Meltzer, MD, Executive Director, R&D Innovation, Purdue Pharma
5:00 Emerging Data on the Impact of Clinical Trial Design and Conduct on Outcomes of Chronic Pain Studies
The epidemic of failed clinical trials of analgesics known to be efficacious has prompted first a soul searching, then a search for evidence, on how specific aspects of clinical trial design and conduct can influence outcomes. Dr. Katz will present emerging data on:
- The relationship between the patients’ ability to report pain accurately and study outcome
- The impact of a specific program to reduce placebo effects on patient expectation of treatment benefit (which is the main driver of the placebo response)
- The impact of the number of clinical research sites on the study outcome
- A bedside method for subtyping patients based on putative pain mechanism
- A new approach to differentiating analgesics based on an integrated risk-benefit composite measure
The presentation will conclude with recommendations on what research sponsors can do to take advantage of these findings to reduce risk of failure of analgesic studies.
Nathaniel P. Katz, MD, MS, President & CEO, Analgesic Solutions
5:30 Cocktail Reception - Sponsored by:
THURSDAY OCTOBER 4, 2012
7:45 Continental Breakfast
8:30 Chairperson's Opening Remarks
William K. Schmidt, Ph.D., President, NorthStar Consulting, LLC, VP Clinical & Regulatory, Arcion Therapeutics, VP Clinical Development, CrystalGenomics (CG Pharmaceuticals)
8:35 Addressing Acute and Persistent Pain at its Origins: Transcription Factor Decoys For Pain Prevention and Treatment
Adynxx Inc. is developing a transformative technology platform addressing pain at its molecular roots - preventing the development of pain following surgery or trauma and resolving established chronic pain syndromes. The Adynxx platform utilizes a proprietary form of oligonucleotide technology - small pieces of DNA that bind to transcription factors and inhibit their activity. Adynxx's lead compound, AYX1, is designed to prevent acute post-surgical pain and the transition to persistent or chronic pain with a single intrathecal administration at the time of surgery. AYX1 acts by inhibiting the spinal cord activity of transcription factor EGR1, a powerful molecular switch whose function is critical in the establishment and maintenance of post-surgical or trauma-related pain. In this presentation, Dr. Manning will discuss the concept of transcription factor decoys, the preclinical data from several rodent models of post-surgical pain, mechanical hyperalgesia and functional recovery. AYX1 entered clinical trials in Q2 2012 and data from Phase 1 safety and general development plans will be discussed.
Donald C. Manning, MD, Ph.D., Chief Medical Officer, Adynxx Inc.
9:05 Overview of Fulranumab, an Anti-NGF Antibody for Treatment of Chronic Pain
A variety of anti-NGF compounds are currently in development. Fulranumab is a fully human anti-NGF antibody that shows promise in relief of a variety of pain models. This presentation will review the clinical efficacy and safety profile that has been developed to date.
David Upmalis, MD, Senior Director and Compound Development Team Leader, fulranumab, Janssen Research Foundation
9:35 Selective A3 Adenosine Receptor Agonists for Chronic Neuropathic Pain
The clinical management of chronic neuropathic pain is limited by marginal effectiveness and unacceptable side effects of current analgesics such as opiates, gabapentanoid or drugs that modulate the noradrenergic/serotonergic pathway: novel analgesics are therefore needed. Dr. Salvemini's findings identify therapeutic use of selective A3 adenosine receptor (A3AR) agonists in chronic neuropathic pain of distinct etiologies including chemotherapy-induced neuropathic pain caused by paclitaxel, oxaliplatin and bortezomib. In addition, A3AR agonists increase the potency and efficacy of morphine, gabapentin and amitriptyline. Her team's findings provide the pharmacological rationale for therapeutic development of A3AR agonists, as novel analgesics for the management of chronic neuropathic pain.
Daniela Salvemini, Ph.D., Professor, Saint Louis University School of Medicine
10:05 Poster Viewing & Refreshment Break
10:35 Mechanisms and Novel Treatment of Neuropathic Pain
Allan Basbaum, Ph.D., Professor and Chair, Department of Anatomy, University of California, San Francisco
11:05 Panel Session: Treating Pain in the Clinic - the Physician's Perspective on Unmet Need and the Challenges Facing Pain Drug Developers
Chair: William K. Schmidt, Ph.D., President, NorthStar Consulting, LLC, VP Clinical & Regulatory, Arcion Therapeutics, VP Clinical Development, CrystalGenomics (CG Pharmaceuticals)
Sean Mackey, MD, Ph.D., Chief, Division of Pain Management, Stanford University School of Medicine, Associate Professor of Anesthesiology, Director, Stanford Systems Neuroscience & Pain Lab
Lynn Webster, MD, Medical Director, CRI Lifetree, President-Elect, The American Academy of Pain Medicine
Michael S. Leong, MD, Clinic Chief, Stanford Pain Medicine Center, Clinical Associate Professor, Anesthesia, Stanford University
12:05 Luncheon
1:15 Neuroimaging Based Pain Detection: Findings and Applications
Dr. Mackey will cover recent advances in neuroimaging as an objective tool for the detection of pain. He will discuss recent data for both detection of acute and chronic pain, and potential applications.
Sean Mackey, MD, Ph.D., Chief, Division of Pain Management, Stanford University School of Medicine, Associate Professor of Anesthesiology, Director, Stanford Systems Neuroscience & Pain Lab
1:45 Panel Session: NGF Antagonists Back on Track: Clinical Development Challenges and Opportunities Moving Forward
Chair: William K. Schmidt, Ph.D., President, NorthStar Consulting, LLC, VP Clinical & Regulatory, Arcion Therapeutics, VP Clinical Development, CrystalGenomics (CG Pharmaceuticals)
Mark T. Brown, MD, Executive Director, Clinical Program Leader for Osteoarthritis and Cancer Pain Studies, Pfizer Inc.
David Upmalis, MD, Senior Director and Compound Development Team Leader, fulranumab, Janssen Research Foundation
Steve Miller, Ph.D., Senior Director, Translational Medicine, Array Biopharma
2:45 End of Conference