2020 Conference Agenda

All Times Central Time Zone (Chicago)

SEPTEMBER 21, 2020

8:50 am Chairperson's Opening Remarks
William Schmidt, Ph.D.
, President, NorthStar Consulting

9:00 am The Preclinical Screening Platform for Pain (PSPP): Facilitating the Identification of Non-Opioid, Non-Addictive Therapeutics

The NIH recently launched the Helping to End Addiction Long-term (HEAL) Initiative, a trans-agency effort to provide scientific solutions to the opioid crisis. One aim of the HEAL Initiative is to reduce the reliance on opioids by advancing research to improve pain management. With HEAL support, NINDS has developed the Preclinical Screening Platform for Pain (PSPP) to facilitate the identification of non-addictive treatments, including small molecules, biologics, devices, and natural products, for acute and chronic pain conditions. PSPP is directly aligned with the HEAL Initiative goal of “accelerating the discovery and preclinical development of non-addictive pain treatments.” The overall goal of the PSPP is to provide researchers from academia and industry, in the US and internationally, an efficient, rigorous, one-stop resource to accelerate identification and efficacy profiling of non-opioid therapeutics for the treatment of pain. Profiling in the PSPP will be a key step in transitioning HEAL preclinical programs into clinical programs for the development of pain therapeutics. In this presentation Dr. Iyengar will outline and illustrate how the PSPP is advancing pain research.
Smriti Iyengar, Ph.D., Program Director, Preclinical Screening Platform for Pain (PSPP) Program, Division of Translational Research, NINDS, National Institutes of Health

9:30 am Harnessing Real-World Data to Evaluate the Effectiveness of Abuse-Deterrent Opioid Formulations
This presentation will define RWD and RWE, discuss the sources and platforms from which the data is collected. Examples of existing RWD confirming effectiveness of abuse-deterrent opioid formulation in deterring abuse, misuse, and diversion will be presented.
Richard Malamut, MD, Chief Medical Officer, Collegium Pharmaceuticals

10:00 am Morning Networking Break

10:20 am Targeting Differences: Strategies to Demonstrate the Benefits of Novel CNS-active Analgesics
The need for safer and more effective analgesics remains high while, in parallel, pipelines have been thinning out due to the opioid crisis, market access challenges, current lack of regulatory guidance for analgesics, amongst other reasons. With this as a backdrop, this panel session will present ideas how developers of novel CNS-active analgesics can:
1) utilize innovative non-clinical assessments to identify novel analgesics with reduced risks for abuse and dependence
2) design phase I trials to adequately support a sound risk-benefit assessment
3) build Target Product Profiles geared to meet both regulatory and market access expectations
Moderator:
Jack E. Henningfield, Ph.D., Vice President, Research, Health Policy and Abuse Liability, Pinney Associates
Panelists:
David Heal, Ph.D., Executive Director, DevelRx
Reginald Fant, Ph.D., Director, Clinical Pharmacology and Abuse Potential Assessment, Pinney Associates
Judy Ashworth, MD, Vice President, Rx Strategic Services and Chief Medical Officer, Pinney Associates

11:20 am Real-World Experience with Perioperative Use of DSUVIA
Pamela Palmer, MD, Ph.D., Chief Medical Officer, AcelRx

11:50 am Recent Advances in the Design of Studies of Pain Therapeutics: Improving Assay Sensitivity
In this presentation, Dr. Farrar will provide insights that will allow attendees to:
• Recognize key features of study design that affect study efficiency
• Identify methods to control some of the study design features to improve efficiency
• Consider issues that may have affected previous studies and how to interpret study results in this context
John Farrar, MD, Ph.D., Associate Professor of Epidemiology in Biostatistics & Epidemiology, University of Pennsylvania

12:20 pm Lunch/Networking Break

1:05 pm The NIH HEAL Initiative and Advancing the Clinical Development of New Pain Therapies
In this address, Dr. Koroshetz will provide an overview of the efforts being made by the HEAL Initiative to advance new pain therapies through the clinical pipeline. He will also discuss the Early Phase Pain Investigation Clinical Network (EPPIC-Net) as well as the testing platform and the mechanisms to fund therapy development.
Walter Koroshetz, MD, Director, NINDS, National Institutes of Health

1:25 pm Are There Brain Imaging and Psychophysical Measures of Pain That Can Serve as Biomarkers for Personalized Pain Management
The one-size-fits-all approach to treat pain works poorly because each person experiences and copes with pain differently.  Brain imaging has provided evidence that that individual pain sensitivities may be linked to variability in brain circuitry. This talk will provide an overview of the dynamic pain connectome (DPC) concept of brain networks that operate at specific spaces and times to govern an individual’s pain sensitivity, capacity to modulate pain, and ability to perform tasks while in pain (Kucyi and Davis, 2015). Data will then be provided pointing to the utility of brain imaging pain sensitivities that may serve as biomarkers for personalized pain management.
Karen Davis, Ph.D., FCAHS, Professor, Department of Surgery & Institute of Medical Science/President, University of Toronto/Canadian Pain Society

1:55 pm All-optical Electrophysiology Screening Platform to Identify Nav Channel Modulators as Pain Therapeutics
To develop novel pain therapeutics, we have created an all-optical electrophysiology (Optopatch) platforms based on engineered excitable HEK cells (spiking HEK cells) with heterologous expression of Nav channels targets implicated in pain transmission, including Nav1.7, Nav1.8 and Nav1.9. To achieve a throughput of 10,000 compounds/day, we developed a next generation kinetic plate reader (SWARM) capable of recording 24 wells simultaneously. To further qualify candidate compounds identified from our Nav1.7 HTS effort, we have developed proprietary secondary assays for hit prioritization, which combined the Optopatch platform with an in vitro model of chronic pain, in which dorsal root ganglion (DRG) sensory neurons are exposed to a mixture of inflammatory mediators. This assay leverages our custom Firefly microscope to make highly-parallelized measurements of DRG excitability, where ~100 neurons can be measured in parallel with single-cell precision and ms-temporal resolution.
Hongkang Zhang, Ph.D., Senior Scientist, Q-State Biosciences

2:25 pm End of Day's Presentations

SEPTEMBER 22, 2020

8:50 am Chairperson's Opening Remarks
William Schmidt, Ph.D.
, President, NorthStar Consulting

9:00 am The NIH HEAL Initiative’s Early Phase Pain Investigation Clinical Trial Network: EPPIC-NET

The NIH HEAL Initiative was launched in 2018 to address the U.S. opioid crisis. This presentation will inform about pain research programs within HEAL and focus on the NINDS program, EPPIC-Net. EPPIC-Net offers pain researchers with novel or repurposed pain therapeutics ready for Phase II testing, an expert, robust network to develop and conduct pain clinical trials, with ownership and intellectual property rights to the therapeutic retained by the applicant. We will discuss the EPPIC-Net structure, facilities and function, as well as the application, review, and selection processes.
Barbara Illowsky Karp, MD, Program Director, NINDS, National Institutes of Health

9:30 am Unlocking NaV1.7’s Pain Potential
Efforts to develop NaV1.7 inhibitors for pain therapeutics have consistently failed. Post-translational modifications of NaVs and/or auxiliary subunits and protein-protein interactions have been reported as NaV-trafficking mechanisms. Dr. Khanna recently reported that modification of the axonal collapsin response mediator protein 2 (CRMP2) by a small ubiquitin-like modifier (SUMO) controls both trafficking and currents of NaV1.7 (Dustrude et al., J. Biol. Chem. 288: 24316-31 (2013)). Capitalizing on this unique pathway for NaV1.7 regulation, Regulonix Holding Inc. identified compounds by computationally docking 50,000 small molecules to a pocket encompassing the residue SUMOylated (K374) in CRMP2. These compounds were designed to inhibit the E2-conjugating enzyme Ubc9-CRMP2 interaction, which, in turn, would block CRMP2 from being SUMOylated by Ubc9. Superb anti-allodynic activities without loss of motoric performance or sympathetic side effects were observed for several compounds. Dr. Khanna and his team are advancing an innovative approach by focusing on a unique mechanism of action of the compounds that involves an indirect targeting to control surface expression and activity of the NaV1.7 channel.
Rajesh Khanna, Ph.D., Professor of Pharmacology, Anesthesiology and Neuroscience, University of Arizona

10:00 am Morning Networking Break

10:20 am Lipid Signals Controlling the Transition from Acute to Chronic Pain
Recent data identify a critical time window following an acute painful episode, in which specific lipid signals regulate the consolidation of a chronic pain state. Pharmacological or genetic enhancement of such signals interrupts pain chronification, and represents a novel modality of pain management.
Daniele Piomelli, Ph.D., MD, Distinguished Prof. of Anatomy & Neurobiology, Pharma. Sciences & Biological Chemistry, Louise Turner Arnold Chair in the Neurosciences, University of California, Irvine

10:50 am Intraarticular Injection of Synthetic Capsaicin for the Management of Osteoarthritis Pain
Osteoarthritis pain remains one of the most important health care problems in the world, affecting the quality of life of millions of people. Treatment options continue to be limited. Total joint replacement may be ultimately required but even this operation does not provide adequate pain control for many and substantial numbers of patients are not candidates for this major surgery. This presentation will provide an update on the clinical development of the novel use of intraarticular capsaicin for managing the pain associated with osteoarthritis of the knee. This presentation will review the procedures used to administer capsaicin and present the latest updates on efficacy and safety.
James Campbell, MD, President, Chief Scientific Officer, Centrexion Therapeutics

11:20 am To Measure Neuropathic Pain at its Origin: A Hybrid Translatable Pain Biomarker Signature of Peripheral Neuropathic Pain
Painful peripheral neuropathy, whether idiopathic, or associated with chemotherapy and other drugs, diabetes, metabolic syndrome or hereditary disease afflicts 6-10% of the US population. There is a lack of effective treatments, leading to opioid prescriptions in most patients, with the resulting morbidity. The development of medications that reduce spontaneous peripheral nociceptor transmission is hindered by a lack of a practical response biomarker specific for the different pain fiber types. This presentation will review currently available methods and present a novel peripheral ongoing (spontaneous) neuropathic pain mechanistic biomarker signature based on specific and selective assessment of C and Aδ nociceptors sensitivity by diode laser stimulation (DLss). DLss is a first fully translatable biomarker that allows the separation of patients with painful neuropathy from those with painless neuropathy.
Mikhail "Mike" Nemenov, President, Chief Scientific Officer, LasMed

11:50 am A Phase 2 Double-Blind Clinical Trial (VZU00025) to Examine the Tolerability, Safety and Effects of CGS-200-5 (5% Capsaicin Topical Liquid) on Osteoarthritis Knee Pain (OAKP)
VZU00025 was a study of high concentration capsaicin in CGS-200 vehicle for the treatment of OAKP. CGS-200 vehicle is a novel, patented aqueous formulation platform that allows for good tolerability for high-strength topical capsaicin and does not require pre-application of a local topical analgesic. In this presentation Mr. Warneke will review new, previously unpresented results of post-hoc analyses of VAS scores from VZU00025 as well as safety and tolerability, and WOMAC Total scores during the 12 weeks following the initial once-daily for four consecutive days treatment period.
Tim Warneke, MS, Vice President Clinical Operations, Propella Therapeutics

12:20 pm Lunch/Networking Break

1:05 pm A Multicenter, Open-Label, Phase 1b Study to Assess the Safety and Define the Maximally Tolerated Dose of Epidural Resiniferatoxin Injection for the Treatment of Intractable Pain Associated with Cancer
Despite advances in the treatment of many forms of cancer including innovative new medications, radiation and cellular therapy, satisfactory management of pain related to cancer remains elusive. Resiniferatoxin (RTX) is a highly potent TRPV1 calcium channel agonist. RTX exposure results in prolonged calcium influx and ablation of TRPV1-positive nerve endings. In preclinical osteoarthritis models, RTX treatment produced prolonged analgesia through selective neurolysis of TRPV1-expressing pain sensory fibers and leaves non-TRPV1 sensory and motor neuron function intact. We report the first complete safety and efficacy results from a phase 1B dose-escalation trial of RTX administered in the epidural space as a one-time injection in subjects with moderate to severe pain due to cancer.
Srdjan Nedeljkovic, MD, Associate Professor of Anaesthesia, Harvard Medical School/Brigham & Women's Hospital

1:35 pm Development of Biomarkers for Pain: A Fit for Purpose Approach
One of the reasons for the low probability of clinical success in pain drug candidates is the lack of biomarkers that can facilitate dose selection and clinical trial design in all phases of clinical testing. Predictive biomarkers and prognostic/diagnostic biomarkers can have a very positive impact on Phase II clinical study design, in that they allow a more informed approach to group assignment and inclusion criteria. It has been shown that patient selection biomarkers can improve clinical success by as much as 17.5% from Phase I to FDA approval. NINDS supports the identification and validation of biomarkers for pain with funding opportunities that allow flexible entry into biomarker discovery or biomarker validation, depending upon the development stage of the application. These funding opportunities encourage a rigorous, milestone-driven approach to the efficient delivery of biomarkers for pain that are aligned with FDA standards. The goal of these funding opportunities is to deliver pain biomarkers that will facilitate clinical trial design and decision-making in clinical practice. In this presentation, Dr. Pelleymounter will discuss the science of pain biomarkers and the work that NINDS is doing to advance their application in pain drug development.
Mary Ann Pelleymounter, Ph.D., Program Director, NINDS, Division of Translational Research, National Institutes of Health

2:05 pm Improving the Accuracy and Reliability of Study Results by Integrating Training, Electronic "Smart Questionnaires," and Central Statistical Monitoring
ICH requires that sponsors use measures to “ensure the reliability of study results,” which aligns with sponsors’ interest in avoiding failed studies. Various methods have been used to improve reliability of study results, including training, electronic diaries, and central statistical monitoring; however, these methods have been scattershot and not directly linked to reliability of trial results. In this presentation Dr. Katz will review an evidence-based approach for integrating these modalities to improve the accuracy and reliability of ultimate study results.
Nathaniel Katz, MD, Chief Science Officer, Analgesic Solutions

2:35 pm End of Conference