2023 Conference Agenda

Continental Breakfast

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

Cebranopadol, a First-in-class Dual Agonist NOP/MOP Analgesic
The nociceptin/orphanin FQ peptide (NOP)receptor was discovered in the 1990s as a promising therapeutic target with potential applications in the treatment of pain, addiction and other CNS disorders. In addition to providing analgesia, NOP agonism was shown to decrease negative effects associated with MOP agonism in animals, including motivation to self-administer, respiratory depression and physical dependence. Cebranopadol is a first-in-class dual NOP and μ-opioid peptide (MOP) receptor agonist with both receptors contributing to its analgesic properties and NOP ameliorating the negative effects typically associated with its MOP receptor agonism, including abuse potential, physical dependence, and respiratory depression. Cebranopadol’s unique safety features have been demonstrated preclinically and clinically including a recently completed oral human abuse potential study that showed the drug is significantly less liked by recreational opioid users than tramadol and oxycodone and a ventilatory response to hypercapnia (VRH) trial that showed the drug has a respiratory depression ceiling. Its novel mechanism of action as well as preclinical and clinical data highlight cebranopadol’s potential to address a significant unmet need as an important new option for the treatment of pain and safer alternative to traditional opioids.
James Hackworth, Ph.D., President, Tris Pharma

Machine-Learning Enabled High Throughput Rodent Behavioral Screening to Develop First-in-Class Analgesics
Cacti is utilizing AI/ML analysis of voluntary rodent behavior to develop novel therapeutics for neuropathic and nociplastic pain. To do this we've identified a set of behavioral features that reflect the internal "state of mind" of mice and rats, including sensitive, real-time readouts of their pain, fear, and fear of pain. We're employing these new approaches to develop first-in-class "nociplastigens" - compounds that induce neuronal plasticity selectively in peripheral and central pain circuits.
Kaitlin Roberson, Co-founder & CEO, Cacti Therapeutics

Utilizing Human DRG Neurons As A Translational Tool For The Development Of Novel Pain Therapeutics
The translation from preclinical animal pain models to human outcomes is far from reliable and represents a major hurdle for successful drug discovery. One underlying cause is the cross-species differences in pharmacological and toxicological responses. To address this challenge, AnaBios has pioneered a novel preclinical discovery strategy that relies on the utilization of primary pain-sensing Dorsal Root Ganglion sensory neurons and tissues recovered from consenting organ donors. By combining novel technologies and reagents that minimize donor organ ischemia-reperfusion damage with innovative cell- and tissue- interrogation methods such as patch clamp analysis, calcium imaging, and RNA scope it is now possible to evaluate drug effects on physiological activity in human ex-vivo preparations at the preclinical stage. Finally, the effects measured in the human ex-vivo preparations, provide a quantitative assessment of drug potency and can help aid in determining the therapeutic window and furthermore can be used to guide dosing during the first-in-human clinical studies.
Ian Orozco, Ph.D., Senior Scientist, Anabios

Panel Session: Overview of the Current Regulatory Landscape and Challenges in the Development of New Safer and Effective Analgesic Drugs
There is a high unmet medical need to develop new effective analgesics that offer safety advantages over currently available pain relievers such as opioids, which carry a high risk of abuse, overdose, and addiction. Recent efforts to develop new drugs with novel mechanisms of action have so far proven futile, whether due to insufficient evidence of effectiveness or the emergence of significant safety concerns. Efforts by industry to develop new analgesics have diminished in recent years for many reasons related to the numerous challenges associated with developing medications within this class. Recent changes in the regulatory landscape and public health initiatives intended to steer drug development efforts may provide some support and guidance to companies but may also introduce confusion or stifle development. This panel session will provide:

(1) An update on recent regulatory actions and public health efforts to promote the development of new, safer analgesics, such as the publication of new FDA draft guidances on analgesic drug development and public health initiatives such as the National Institutes of Health Helping to End Addiction Long-term® Initiative (NIH HEAL).

(2) An overview of the perspectives and challenges that companies now face when developing novel analgesics that range from obstacles to obtaining adequate financing, to demonstrating effectiveness via positive clinical trials, to navigating regulatory hurdles including, but not limited to, adequately assessing abuse potential and allowing for appropriate label differentiation from existing drugs.
CHAIR: Judy Ashworth, MD, Senior Vice President, Pinney Associates
Panelists:
Ryan Lanier, Director, Clinical Development & Abuse Liability, Pinney Associates
Marc Lesnick, Ph.D., Chief Development Officer, Tris Pharma
Jeff Reich, MD, Co-founder & CEO, Sparian Biosciences

Morning Refreshment & Networking Break

Transcriptomic Signature, Bioactivity and Safety of a Non-hepatoxic Novel Non-opioid Analgesic: From Discovery to the Clinic
The potential for misuse and addiction associated with opioids, nephrotoxicity, and gastrointestinal damage from chronic NSAIDs use, as well as acute liver injury from paracetamol overdose, are unresolved challenges. To address them, we developed a non-opioid and non-hepatotoxic small molecule, SRP-001. Compared to paracetamol, SRP-001 is not hepatotoxic as it does not produce NAPQI and maintains hepatic tight junction integrity at high doses. SRP-001 has comparable analgesia in pain models, including the CFA inflammatory von Frey. Both induce analgesia via AM404 formation in the midbrain PAG nociception area, with SRP-001 generating higher amounts of AM404 than ApAP. Single-cell transcriptomics of PAG uncovered that SRP-001 and ApAP also share modulation of pain-related gene expression and cell signaling pathways, including the endocannabinoid, mechanical nociception, and fatty acid amide hydrolase (FAAH) pathways. Interim Phase 1 trial results demonstrate SRP-001’s safety, tolerability, and favorable PK.
Hernan Bazan, MD, DFSVS, FACS, CEO & Co-founder, South Rampart Pharma

Luncheon

Interim Analyses in Acute Pain Trials: Maximizing Your Chances of Success and Accelerating Drug Development
Adaptive designs and interim analyses have gained acceptance in late-phase clinical trials and offer an approach to mitigating risk in a drug development program. However, these benefits do not come without some associated challenges, costs, and penalties. This session will cover the interim analysis options available to implement; risks and benefits to each; and practical considerations around timing, site management and data flow.
Becky Baggett, BS, RAC, Associate Vice President, Project Delivery, Rho
Ben Vaughn, MS, RAC, Chief Strategist, Biostatistics & Protocol Design, Rho

The Discovery and Development of Non-addictive Analgesics Utilizing Mebias’ Novel Drug Discovery Platform
Mebias Discovery has used its novel GPCR drug discovery platform to progress multiple programs for pain treatment. Our Mu-Opioid Receptor program (MEB-1170) is in Phase 1 human clinal trials and holds the analgesic potency of morphine without the traditional opioid on-target adverse effects including respiratory depression and abuse liability. Our preclinical program targeting the Sphingosine-1-Phosphate Receptor to treat neuroinflammation/neuropathic pain is in advance lead optimization.
Shariff Bayoumy, Co-founder & Managing Partner, Mebias Discovery

Cannabinoids as Chronic Pain Therapeutics: Does Pharmacology Make a Difference?
Cannabinoids have become a topic of resurging interest as targets for the treatment of pain. Indeed, there is considerable preclinical evidence of efficacy in preclinical studies, especially for neuropathic pain. Evidence of efficacy is not as robust for clinical studies, which unlike the preclinical studies, feature plant-based cannabinoids with mixed pharmacology rather than selective cannabinoid receptor modulators. The reason for the discrepancy between preclinical and clinical efficacy of cannabinoids is likely complex, ranging from the fidelity of translation between preclinical and clinical studies to the difference in availability of selective cannabinoid receptor modulators in the two types of studies. A wide range of cannabinoids are available for preclinical studies, whereas that is not the case for clinical trials due to the psychiatric effects of specific CB1 receptor modulators. As a result, most clinical studies feature plant-based cannabinoid mixtures rather than selective CB1 receptor modulators. This session is focused on defining the current landscape of potential cannabinoid approaches for the treatment of pain within the context of the cannabinoid pharmacology of each approach. Speakers will discuss a variety of approaches directed toward clinical trials that feature both mixed cannabinoid formulations and selective CB1 receptor agonists. The session will conclude with a panel discussion focused on the feasibility and promise of cannabinoids as therapeutics for chronic pain.

End of Conference