2023 Conference Agenda

Registration/Continental Breakfast

Chairperson's Opening Remarks
William Schmidt, Ph.D., President, Northstar Consulting

NIH HEAL Initiative PRECISION Human Pain Network: From Genes to Cellular Function to Therapeutic Target Discovery for Human Pain
The NIH HEAL Initiative PRECISION Human Pain Network was established to: 1) discover and characterize human pain genes and cells, in order to better understand of the molecular/cellular targets and mechanisms that specifically underlie human pain conditions, and 2) identify cellular bases underlying human susceptibility to different pain conditions, and validate human pain therapeutic targets. The network to mandated to generate comprehensive datasets of molecular signatures, cell types, and cellular function phenotypes that underlie human pain transduction, transmission and processing, using primary human tissues and cells. A coordinated multi-center effort is in place to optimize and harmonize protocols, assays, and data collection to allow integrated analysis across centers, in collaboration with a data coordination and integration center, and with the HEAL Data Ecosystem for comprehensive database/knowledgebase development and wide dissemination and public sharing. The presentation will summarize the progress and findings from this network.
DP Mohapatra, Ph.D., Program Director for Pain, National Institute of Neurological Disorders and Stroke, National Institutes of Health

Unraveling the Nociceptor-immune Interactome of Inflammatory Pain
Pain can occur due to a surgical injury, autoimmunity, and infections. In all these cases, immune cells trigger the sensitization of nociceptor sensory neurons, which is the underlying cause of pain or tenderness. The neuroimmune axis, therefore, has become an attractive therapeutic target for pain in recent years. But the diversity of immune cells and the vast array of ligands they produce present a significant challenge in systematically mapping the neuroimmune landscape of a painful tissue to develop novel immunotherapeutics. We have constructed a comprehensive knowledgebase of receptor-ligand pairs between immune cells and sensory neurons that can be applied to any tissue or injury to enable the identification of novel immune pathways that contribute to pain.
Aakanksha Jain, Ph.D., Senior Postdoctoral Fellow, Harvard University

ZF-TF Mediated Epigenetic Repression of SCN9A Gene as a Therapeutic Approach for Painful Peripheral Neuropathies
The voltage-gated sodium channel Nav1.7, encoded by SCN9A gene, is involved in a spectrum of inherited human pain disorders, highlighting the central role of Nav1.7 in pain transmission to the brain. However, development of selective and efficacious Nav1.7 inhibitors has been challenging due to similarities in protein sequence and structure among the Nav channels. We hypothesized that lowering Nav1.7 via selective repression of the SCN9A gene using engineered zinc finger repressors (ZF-Rs) would reduce the expression of Nav1.7, and therefore reduce neuropathic pain. To evaluate the feasibility of this approach, ZF-Rs specifically targeting the mouse Scn9a were designed and assessed in vivo in a neuropathic pain spared never injury (SNI) mouse model. AAV-mediated ZF-Rs delivery resulted in up to 70% bulk repression of Scn9a in mouse dorsal root ganglion (DRG) tissue. Scn9a repression was associated with significant reduction in pain 1-month post-treatment as measured by increased mechanical and cold allodynia threshold in the SNI model of neuropathic pain. ZF-Rs were well tolerated at all doses tested with no adverse findings and no general toxicity related to treatment. These results support the continued progression to IND-enabling nonhuman primate study.
Mohammad Samie, Ph.D., Associate Director - Neurological Disorders, Sangamo Therapeutics

Automated Preclinical Behavioral Characterization of Pain in Mice
David Roberson, Ph.D., Co-founder & CEO, Blackbox Bio

Morning Networking & Refreshment Break

Panel Session: The Patient Perspective on Novel Pain Drug Development
Who are the patients living with pain, how do they view the risk/benefit equation, and what role should they play in new drug development? Two prominent patient advocates, one living with chronic migraine and autoimmune disease, and the other living with chronic back pain, delve into the vast need for pain therapeutics. They argue for closer collaboration of new drug developers with the patient advocacy community during every phase of drug development - a collaboration that should begin with fundamental neurobiological research, through pre-clinical, early, mid and late phase clinical trials, NDA, launch, real world experience, and even post-development payer coverage.
Cindy Steinberg, National Director of Policy & Advocacy, US Pain Foundation
Shoshana Lipson, Executive Director, Hope in Pain

Capsaicin 8% Patch as a Disease-modifying Treatment for Neuropathic Pain: Novel Concept and Clinical Evidence in Diabetic and Other Neuropathies
Current oral treatments for neuropathic pain in diabetic peripheral neuropathy do not affect its progression or pathology, i.e., disease modification. However, in our recent clinical trial, we reported that Capsaicin 8% patch (Qutenza) treatment could provide pain relief and improve nerve fibre density and function via nerve fibre regeneration in painful and non-painful diabetic peripheral neuropathy. We previously reported similar findings in painful chemotherapy-induced peripheral neuropathy, and Non-freezing cold injury (Trench Foot) i.e., pain relief and partial reversal of both these neuropathies. Hence, we have proposed the concept of Capsaicin 8% patch as a Disease-Modifying Anti-Neuropathy Drug "DMAND", analogous to Disease-Modifying Anti-Rheumatic Drugs “DMARDs”. Clinical trial and tissue evidence for this novel concept, with the underlying molecular mechanisms, will be provided.
Praveen Anand, MD, Professor of Clinical Neurology, Imperial College London

Efficacy and Safety of LX9211 in Patients with Peripheral Neuropathic Pain: Results from two Phase 2 Double-blind, Randomized, Placebo-controlled Trials (RELIEF-DPN 1 & RELIEF-PHN 1)
LX9211 is a potent, orally administered inhibitor of adaptor-associated protein kinase 1 (AAK1), a novel, non-opioid target for neuropathic pain. Here we present the efficacy and safety results from two phase 2 clinical trials in patients with painful diabetic peripheral neuropathy and postherpetic neuralgia.
Suma Gopinathan, Ph.D., Executive Director, Clinical Development, Lexicon Pharmaceuticals

Luncheon

Panel Session: What has Happened to Novel Analgesic Development Programs Following 5 Years of HEAL Funding (2018-2023)
Chair: William Schmidt, Ph.D., President, Northstar Consulting
Walter Koroshetz, MD, Director, National Institute of Neurological Disorders & Stroke, National Institutes of Health
Sharon Hertz, MD, Retired, Director, FDA Division of Analgesia, Anesthesia, Addiction Medicine, and Pain Medicine/Partner, US FDA/Hertz & Fields Consulting
Jeff Gudin, MD, Faculty, Department of Anesthesiology & Pain Management, University of Miami, Miller School of Medicine
Neil Singla, MD, Chief Scientific Officer, Lotus Clinical Research
Rebecca Baker, Ph.D., Director, HEAL Initiative, National Institute of Neurological Disorders & Stroke, National Institutes of Health
Josh Blacher, MBA, Chief Financial Officer, South Rampart Pharma

What To Expect When You Are Expecting? Frightening Unknowns About Clinical Trial Design That Can Make or Break Your New Analgesic Program
John Lennon sang, “nobody told me there’d be days like these.” For sponsors conducting clinical trials for new analgesics, there are some hidden pitfalls and roadblocks that are almost never recognized or addressed during program development. A clear understanding of what lies ahead is critically important for correct decision making, and will save time, money, and frustration in the end.
Todd Bertoch, MD, Chief Executive Officer, Cenexel JBR

Afternoon Networking and Refreshment Break

Arylepoxamides: A New Class of Safer Analgesic
The Arylepoxamide Receptor (AEAr) is a newly discovered receptor in the pain pathway which has very promising pharmacology. SBS-1000 is an AEAr selective ligand which demonstrates potent analgesia in thermal, inflammatory, and neuropathic pain but does not demonstrate respiratory depression, abuse potential, or physical dependence / withdrawal. SBS-1000 is currently in a phase 1 clinical trial. The presentation will provide an overview of the underlying biology of the receptor, the pharmacology of SBS-1000, and an overview the phase 1 clinical trial.
Jeff Reich, MD, Co-founder & CEO, Sparian Biosciences

Cocktail Reception

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