The Agenda for the 2019 Summit Has Not Yet Been Announced
Presentations From our 2018 Summit Included:
From clinical studies, anti-NGF treatment has been reported to lead to profound analgesia. However, safety concerns, including rapid progression of osteoarthritis (OA) and transient parathesia have been reported. LEVI-04 is a novel biologic with unique pharmacology that safely modulates the neurotrophin pathway (NGF, NT-3, BDNF and NT-4) leading to analgesia and interestingly from pre-clinical models, evidence of disease modifying properties in OA. LEVI-04 is currently in clinical trials for treatment of chronic pain. This talk will cover the role of NGF in bone repair and maintenance, pre-clinical mechanisms of anti-NGF leading to rapid progression of OA, neurotoxicity of anti-NGF, mode of action, pre-clinical efficacy and safety of LEVI-04 and the clinical development path for LEVI-04.
Simon Westbrook, Ph.D., CEO and Founder, Levicept
IT has had a profound effect on nearly every aspect of modern culture, most would agree with mixed results, but largely beneficial. What has been the impact of IT in pain diagnosis and management and what should we expect in the future. This talk will look at the current state and potential for improvement in the diagnosis and management of pain, using headache medicine as an example.
Robert Cowan, MD, FAAN, Clinical Professor, Neurology & Neurological Sciences Clinical Professor, Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine
Currently, the diversity of cannabinoid ligands is very broad and continues to expand rapidly. Whether cannabinoid ligands exert their biological activities via a cannabinoid receptor-dependent or an off-target-mediated mechanism remains unclear. In our efforts to understand and to improve the treatment of pain, we sought to design and synthesize a chemical library of cannabinoid ligands. In our initial lead compound set, we identified T-type Ca2+ channel antagonists that analgesic effects in different in vivo pain models. In this presentation, Dr. Diaz will report details of the design, in vitro characterization, and in vivo testing of this new series of compounds.
Philippe Diaz, Ph.D., Associate Professor, University of Montana, Co-founder and Chief Scientific Officer, DermaXon
In this presentation, Dr. Bekker will describe the pharmacologic and physiologic effects of cannabis, assess the use of cannabis for treatment of various pain conditions and analyze the legal aspects of recommending cannabis and the controversy between state and federal laws as applied to cannabis regulation.
Alex Bekker, MD, Ph.D., Chair, Department of Anesthesiology, Professor, Department of Physiology and Pharmacology, Rutgers New Jersey Medical School
AfaSci, Inc., a San Francisco biotech has discovered an IND-candidate with backups for the treatment of neuropathic pain and cancer pain. The candidate is a non-opioid new chemical entity. It produces use-dependent inhibition of human Cav3.2 channel and displays favorable pharmacokinetics leading to strong analgesic effects in neuropathic pain and cancer pain models in rodents with promising safety margins. The drug candidate is now ready for IND-enabling studies and if successful clinical trials. In this presentation, Dr. Xie will present details regarding the compound's mechanism of action as well as preclinical trial data.
Xinmin Simon Xie, MD, Ph.D., Founder and Chief Executive Officer, AlfaSci Research Labs
The microglia, acting as key elements of the immune system of the brain, have long been identified as critical in their role in maintaining CNS health. The last two decades have also advanced our understanding that they may also participate in various pathological processes in the CNS, including neuropathic pain. Learning objectives for this talk:
• Review of microglial activity in health and disease
• Discuss evidence of microglial activity in neuropathic pain
• Identify potential therapeutic targets based on our understanding of microglial activity
Joseph F. Foss, MD, Founder, Neurotherapia
This presentation will focus on efforts to improve clinical trial research methods as a means of accelerating the identification of analgesic medications with improved efficacy and safety. The major impetus for efforts to improve clinical trial methods has come from the observation that multiple recent clinical trials have failed to show efficacy of medications known to be efficacious. In ongoing research, methodologic factors and patient characteristics of analgesic clinical trials are being systematically examined so that possible sources of adverse effects on trial outcomes can be identified and then modified in future trials. On the basis of such research, recommendations will be presented for improving analgesic clinical trial assay sensitivity.
Robert H. Dworkin, Ph.D., Prof. of Anesthesiology & Perioperative Medicine, Dir., Analgesic, Anesthetic, & Addiction Clinical Trial Translations, Innovations, Opportunities, & Networks (ACTTION), University of Rochester School of Medicine & Dentistry
In this presentation, Dr. Royal will address the following
• Review of TRPV1 agonist mechanism of action and rational for potential efficacy
• History of products in development (e.g., Adlea) and approved topical approaches (e.g., Qutenza)
• Desired target product profile and why it matters
• Introduction of Concentric’s approach
• Concentric’s candidate: preclinical and clinical data
Mike Royal, MD, JD, MBA, Chief Medical Officer, Concentric Analgesics
In this presentation, Dr. Katz will discuss the following:
♦ What are the clinical features of visceral pain?
♦ What is the epidemiology of visceral pain?
♦ What has been the experience in clinical trials of visceral pain?
♦ What are current best practices and future directions in optimizing clinical trial design and conduct in visceral pain?
Nathaniel Katz, MD, MS, CEO, Analgesic Solutions, Adjunct Associate Professor of Anesthesia, Tufts University School of Medicine
While the experience of pain, as does consciousness, reflects supraspinal processing, this processing is driven by the encoding of sensory information at the spinal level. Work on the biology of nociceptive processing has shown that the input output function of the spinal cord relevant to the pain state may be modified in a surprisingly specific fashion by the local targeting of spinal systems though neuraxial drug delivery. Following demonstration of the effects of spinal opiates, the complexity of dorsal horn pharmacology has evolved to reveal drugable targets present at the level of the first and second order neuron that can robustly regulate pain processing. Development of chronic delivery systems and the evolving development of intrathecal toxins and transfection methodologies suggest the utility of regulated effects upon pain processing in managing persistent pain states.
Tony Yaksh, Ph.D., Professor, Departments of Anesthesiology and Pharmacology, University of California, San Diego
Dr. Oshinsky will discuss the research priorities and goals of the NIH Helping to End Addiction Long-term (HEAL) Initiative. He will emphasize the opportunities for basic science, translational research, and clinical trials supported by the HEAL initiative and other funding mechanisms at the NIH.
Michael L. Oshinsky, Ph.D., Program Director, Pain and Migraine, NINDS/NIH
Dr. Singla will discuss key elements of clinical trial design and conduct for long-acting local anesthetics. Topics include: optimum formulations, early-phase stopping rules, dose escalation paradigms, safety review committee concerns, proof of concept models, Phase 3 pivotal models and other key issues for these programs.
Neil Singla, MD, Chief Scientific Officer, Lotus Clinical Research
Intranasal ketamine is preferentially used by the U.S. Military in deployed locations to treat acute trauma pain. Ketamine is extensively metabolized to several active and inactive metabolites. Amorsa’s proprietary compounds are based on the selective deuteration of ketamine’s primary active metabolite. These compounds demonstrate improved oral bioavailability, a prolonged duration of action and the potential for reduced CNS side effects. Patented extended release formulations designed to limit ketamine’s CNS side effects and reduce the abuse potential have also been developed. The presentation will cover Amorsa’s pre-clinical development of these novel compounds and patented formulations.
Michael G. Palfreyman, Ph.D., DSc., Chief Scientific Officer, Amorsa Therapeutics
The voltage-gated sodium channel NaV1.7 is a genetically-validated target for analgesic drug development; humans lacking functional NaV1.7 are unable to experience most types of pain. Efforts to discover selective inhibitors of NaV1.7 have been complicated by the high homology between NaV isoforms, and results from early clinical trials have been disappointing. This presentation will disclose preclinical results generated with a novel class of NaV1.7 inhibitors patterned on natural products that bind to the extracellular vestibule of the sodium channel. Certain compounds exhibit >200-fold selectivity over other human NaV isoforms and reduce noxious thermal sensitivity in animal models. The implications of these results on outstanding questions in NaV1.7 drug development will be discussed.
John Mulcahy, Ph.D., Vice President and Chief Scientific Officer, SiteOne Therapeutics
Gene therapy is generally thought of as a way to fix a broken genetic code. For example, Sarepta recently had a gene therapy treatment approved for Duchenne muscular dystrophy, a rare but deadly and irreversible disease in which the gene coding for the dystrophin protein is dysfunctional. Gene therapy approaches can also be applied to conditions where the code is fine, but there is a pathological overexpression of the protein coded. For example, in many chronic pain conditions, we know that there is overexpression of certain genes, including certain encoding sodium channels in the peripheral nerves providing pain input to the CNS. A gene therapy approach in this case would be to decrease expression of the target gene. This presentation will focus on the use of recombinant herpesviral vectors as a means of knocking down expression of pain-associated genes or introducing novel genes into nociceptors. Herpesviruses are optimal for this as they allow for large genetic payload and are neurotropic – naturally targeting the same cells that we want to modify.
David Yeomans, Ph.D., Director of Pain Research, Professor of Anesthesia, Stanford University School of Medicine
Dr. Nedeljkovic will present the results of an exploratory study of patients who received VVZ-149 after undergoing laparoscopic colorectal surgery. Results showed a 34.2% reduction in opioid consumption (24 hr) and remarkably fewer PCA demands in the VVZ-149 group compared to placebo. These and other results suggest that VVZ-149 may have a particular role in reducing the affective component of pain as one of the mechanisms by which it exerts its analgesic efficacy and opioid sparing effects. Dr. Nedeljkovic will also present data from a study of VVZ-149 conducted on patients undergoing laparoscopic or robotic-assisted gastrectomy. This Phase 2 study assessed the preliminary efficacy of VVZ-149 for postoperative pain and opioid sparing as well as its safety profile with intraoperative administration.
Srdjan Nedeljkovic, MD, Associate Professor, Anesthesia and Pain Management, Harvard Medical School, Brigham and Women's Hospital