2019 Summit Agenda

SEPTEMBER 23, 2019

7:45 am Registration/Continental Breakfast

8:25 am Chairperson's Opening Remarks
William Schmidt, Ph.D., President, NorthStar Consulting

8:30 am Translational Preclinical Pain Research: Hurdles and Comparative Opportunities
In this presentation, Dr. Lascelles will discuss the following:
  • The hurdles to successful pre-clinical translational pain research will be outlined
  • The opportunities for using pet dogs and cats to de-risk translational pain research will be described
  • The use of pet dogs and cats to inform discovery of novel, relevant targets will be discussed
Duncan Lascelles, Ph.D., Professor of Surgery and Pain Management, Translational Research in Pain, North Carolina State University College of Veterinary Medicine

9:00 am Opioid Sparing Outcomes: Updates from the November 2018 FDA Advisory Committee
In this presentation, Dr. Singla will cover the following:
  • An overview of the strengths and weaknesses of current opioid-sparing outcomes
  • Discussion of clinical trial design concerns in opioid-sparing studies
  • The potential utility of a new study endpoint: proportion of opioid-free patients
  • Significant findings from FDA’s November 2018 DAAAP Advisory Committee meeting on opioid-sparing outcomes
Neil Singla, MD, Chief Scientific Officer, Lotus Clinical Research

9:30 am Precision Medicine for Pain: New Biomarker Discovery (tentative title)
Alexander Niculescu, MD, Ph.D., Professor of Psychiatry & Medical Neuroscience, Indiana University School of Medicine

10:00 Refreshment Break/Exhibit & Poster Viewing

10:25 am Differentiating Novel CNS-active Analgesics on the Basis of Abuse Potential: Opportunities and Challenges
In light of the Opioid Crisis, efforts in the discovery and development of analgesics which work as well as classic opioids but with less potential for abuse have intensified. Many of these compounds are also CNS-active and thus remain subject to FDA guidances with regards to the assessment of their abuse potential. This panel will address 1) the challenges when utilizing current preclinical and clinical models to assess the relative abuse potential of novel compounds, 2) how to maximize the design of phase 2 and 3 trials to obtain pertinent data needed for an abuse potential assessment and 3) potential issues to be aware of when choosing “opioid-sparing” as a key efficacy and/or safety outcome.
Moderator: Judy Ashworth, MD, Chief Medical Officer, Pinney Associates
Panelists:
Reginald Fant, Ph.D.,, Director, Clinical Pharmacology and Abuse Potential Assessment, Pinney Associates
Ryan K. Lanier, Ph.D., Associate Director, Consulting, Analgesic Solutions
Kelly E. Dunn, Ph.D., Associate Professor, Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine

Sponsored by:
   


11:40 am Humanizing Pain: Implementing a Novel Translational Strategy to Advance Analgesic Drug Discovery and Development
Analgesic drug development has proven to be particularly challenging. A high number of chronic pain patients still lack safe and effective treatment options due to high development attrition rates. One major factor underscoring this problem is the difficulty translating preclinical data into successful clinical outcomes. This translational gap is likely multi-factorial and likely includes species differences, a limited understanding of the disease mechanism and the discordance between the genetic uniformity of animal models and the heterogeneity of the patient population. In recent years, several groups have tackled these challenges, with a special emphasis on strategies aimed at overcoming species differences by enabling the study of drug effects directly on human tissues and cells at the preclinical stage. This presentation will discuss these new translational approaches, using case studies to illustrate the current progress and challenges.
Andre Ghetti, Ph.D., Chief Executive Officer, AnaBios

12:10 pm Luncheon

1:10 pm The FDA Approach to the Opioid Crisis: Drug Development for Pain (tentative title)
Marta Sokolowska, Ph.D., Associate Director for Controlled Substances, Office of the Center Director, US FDA

1:40 Extended Question/Answer Session with the Morning Presenters

2:05 pm The NIH HEAL Initiative: Efforts Towards Accelerating the Discovery and Clinical Development of Non-Addictive Therapeutics for Pain
In April 2018, the NIH launched the HEAL (Helping to End Addiction Long-term) Initiative to stem the national opioid public health crisis. NINDS was tasked with the goal of enhancing pain management through identification of non-addictive pharmacologic and non-pharmacologic interventions. NINDS, along with multiple Institutes across the NIH, built a collaborative infrastructure of therapeutic development programs designed to enhance our understanding of the development and prevention of chronic pain. These programs span the discovery process from target validation through clinical trials. Programs included in the infrastructure support: (1) the discovery and validation of novel targets for safe and effective pain treatment, (2) a preclinical screening platform for pain (PSPP) focused on the identification and profiling of non-addictive/non-opioid therapeutics, (3) pharmacological and non-pharmacological therapeutic development, (4) biomarker discovery and development and (5) a robust clinical trials network, EPPIC-NET, to test new therapies for pain conditions in adults and children. Dr. Iyengar and Dr. Pelleymounter will discuss the program in depth and the opportunities to collaborate with NINDS on this initiative.
Smriti Iyengar, Ph.D., Program Director, Division of Translational Research, NINDS, NIH
Mary Ann Pelleymounter, Ph.D., Program Director, Division of Translational Research, NINDS, NIH

2:45 pm Refreshment Break/Exhibit & Poster Viewing

3:10 pm The Varied Roles of PIEZO2 in Touch and Pain
Piezo2 is a somatosensory mechanotransducer channel in mice and humans. The diversity of PIEZO2 facilitates sensory specialization. Piezo2 is not needed for acute pain sensation but it is required for mechanical hypersensitivity. In this presentation, Dr. Szczot will discuss the role of Piezo2 in pain and touch. In his research he has demonstrated that Piezo2 loss of function results in failure to develop mechanical allodynia. He has examined the importance of Piezo2 in the cellular representation of mechanosensation using in vivo imaging in mice. Piezo2-knockout neurons were completely insensitive to gentle dynamic touch but still responded robustly to noxious pinch. During inflammation and after injury, Piezo2 remained essential for detection of gentle mechanical stimuli. He has hypothesized that loss of PIEZO2 might eliminate tactile allodynia in humans.
Marcin Szczot, Ph.D., Postdoctoral Fellow, National Institutes of Health

3:40 pm CT-044, a Reactive Species Decomposition Accelerant (RSDAx) for the Treatment of Post-surgical Pain and Painful Diabetic Neuropathy
CT-044, is a non-metal based, orally bioavailable, small molecule Reactive Species Decomposition Accelerant which destroys peroxynitrite, thereby disrupting or preventing pathways that lead to neuronal sensitization and the development of pain. In vivo, CT-044 is efficacious in pre-clinical models of acute post-incisional hyperalgesia, both prophylactically and palliatively. CT-044 is also effective in traditional irritant-induced hyperalgesic models. CT-044 alleviates allodynia in rat models of diabetic neuropathy without central penetration thereby avoiding CNS side effects. CT-044 has entered clinical trials and is being developed as a non-opioid therapeutic to treat and prevent post-surgical pain and to treat painful diabetic neuropathy.
Scott L. Dax, MS, Ph.D., Chief Scientific Officer, CerSci Therapeutics

4:10 pm The Development of Proprietary High-strength Topical Capsaicin Formulations for the Treatment of Osteoarthritis Pain
In this presentation, Dr. Moore will focus on the evolution and development of proprietary topical capsaicin formulations for the treatment of OA pain. He will share the results of two separate Phase 2 studies with topical capsaicin for osteoarthritis.
William Moore, Ph.D., CEO & President, Vizuri Health Sciences

4:40 pm Extended Question/Answer Session with the Afternoon Presenters

5:05 pm Networking Reception


SEPTEMBER 24, 2019

7:45 am Continental Breakfast

8:15 am Discovery of Potent and Selective State-dependent Ca2+ Channel Modulators With Efficacy in Preclinical Models and Human Tissue: Novel Non-opioid Analgesics

The need for non-opioid analgesics devoid of side-effects and addiction liabilities is now widely recognized, and ion channels provide an alternative target class for pain modulation. Non-selective ion channel ligands or those with a mixed mechanism-of-action can be effective, but also suffer from a low therapeutic index. In this presentation Dr. Rogers outlines an 8 year project with a European pharma partner designed to identify novel, selective and state-dependent calcium channel modulators with improved efficacy and fewer side-effects, that specifically target active channels associated with nociceptive activity. Exemplar compounds exhibit nM potency for the inactivated state, >70 fold state-dependence and >30 fold selectivity over closely associated gene family members and cardiac ion channels. This promising in vitro profile translates into efficacy in nociceptive pain models and inhibition of Ca2+ channels in human tissue, delivering a lead compound and a back-up series with potential to treat a range of painful modalities in the clinic.
Marc Rogers, Ph.D., Chief Scientific Officer, Metrion Biosciences

8:45 am ASP0819, A Non-opioid Analgesic: Results of a Proof of Concept Trial in Fibromyalgia Patients
ASP0819 is a novel, first-in-class, orally active, well tolerated non-opioid analgesic being studied for the management of fibromyalgia. This small molecule ion channel opener has completed both Phase 1 healthy volunteer studies and a P2a proof-of-concept trial in fibromyalgia patients. Results of the POC trial, including both primary endpoint pain efficacy data along with several secondary endpoint patient-reported outcome (PRO) scales exploring other, non-pain symptoms of fibromyalgia will be presented.
Paul Blahunka, PharmD, Sr. Director, Global Development Project Leader (GDPL), Medical Specialties T.A., Astellas Pharma Global Development

9:15 am Best Practices in Clinical Pain Trials: Emerging ACTTION Guidance
In this presentation Dr. Katz will focus on:
  • Best practices in “confirmatory” clinical trials of treatments for pain that will be presented in the forthcoming guide to clinical trials from the ACTTION* group
  • Attention will be paid to areas that have not received adequate attention previously, including medication adherence, endpoint models, training, and central statistical monitoring
Nathaniel Katz, MD, MS, Founder and Chief Science Officer, Analgesic Solutions
*Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) is a public-private partnership with the United States Food and Drug Administration (FDA).

9:45 am Pain Measurement and Patient Reported Outcomes in a Military Setting (tentative title)
Chester Buckenmaier III, MD, Executive Director, Defense & Veterans Center for Integrated Pain Management, Uniformed Services University

10:15 am Refreshment Break/Exhibit & Poster Viewing

10:35 am Extended Question/Answer Session with Morning Presenters


11:00 am Precision Pain Therapeutics: What Can We Learn from Orphan Drug/Rare Disease Drug Development
In this presentation Mr. Sasinowski will discuss the challenges facing pain drug developers and how those engaged in the development of new drugs for pain can benefit from the lessons learned in the field of orphan drug and rare disease research. Mr. Sasinowski has assisted sponsors and patient organizations in developing new medicines and has helped secure FDA approval for hundreds of new drugs, including more than 65 new molecular entities, often for serious and/or rare diseases. He was awarded in 2013 with a NORD (National Organization for Rare Disorders) Lifetime Achievement Award and has also served on the organization’s Board of Directors.
Frank Sasinowski, MS, MPH, JD, Director, Hyman, Phelps & McNamara

11:30 am Panel Session: Does Your NCE Work? The Sooner You Know the Better! A Fast, Accurate and Cost Effective Paradigm to Assess that Critical "GO or NO GO" Decision
In this session, our panelists will discuss how to accurately determine the potential success of novel analgesic molecules as quickly and cost-effectively as possible. They will also outline why it is vital that sponsors think outside the box in this challenging development climate. They will also:
  • Analyze the strengths and weaknesses of the Dental Impaction Pain Model
  • Analyze the strengths and weakness of the Bunionectomy model
  • Discuss issues relating to the successful transitioning from hard to soft tissue models
  • Discuss specific strategies to shorten development time and costs
Todd Bertoch, MD, Chief Medical Officer, JBR Clinical Research
Stephen Cooper, DMD Ph.D., Key Opinion Leader, Advisory Board, JBR Clinical Research
Paul Desjardins, DMD, Ph.D., Key Opinion Leader, Advisory Board, JBR Clinical Research

Sponsored by:



12:35 pm Luncheon

1:25 pm Pain Management for the Future Battlefield
In the war of the future, the United States cannot expect to have the kind of air superiority we enjoy in today's conflicts, and thus, we cannot expect the capability to evacuate Service members wounded on the future battlefield with the same timelines that they're evacuated today. Instead of the typical hour, wounded Service members may not be able to be evacuated for hours or even days. The challenge of today's military medicine then, in preparation for the future, is to develop medical technologies which can stabilized and preserve the wounded Service member on the battlefield for hours or even days, until they can be safely evacuated. For pain management on the battlefield, the question becomes: Can we create an analgesic that can treat severe, post-traumatic pain that doesn't interfere with cognition or motor control? In the prolonged care scenario the fight goes on, and so pain treatments will be needed that treat pain effectively, but also allow the Service member to continue to shoot, move, and communicate.
Peter Murray, Ph.D., Pain Management Portfolio Manager, Clinical & Rehabilitative Medicine Research Program, US Army Medical Research & Development Command

1:55 pm Desmetramadol: Tramadol Improved
Tramadol is approved for moderate to moderately severe pain, and as a schedule IV analgesic is less prone to abuse than schedule II opioids and is considered safer. It is being used as a stop-gap solution in the Opioid Crisis. Tramadol is now the second most prescribed analgesic in the United States, with over 40 million annual prescriptions. Tramadol is a prodrug and its labeling describes multiple common metabolic liabilities that adversely affect its efficacy and safety, including black box warnings. In this presentation, Dr. Zebala will discuss the development of desmetramadol, the active metabolite of tramadol. He will share the results of recently published first-in-man trials that demonstrate desmetramadol has the analgesic profile of tramadol, but without its metabolic liabilities and related drug-drug interactions. The development of desmetramadol was funded by the National Institute on Drug Abuse (NIDA).
John A. Zebala M.D., Ph.D., CEO & President, Syntrix Pharmaceuticals

2:25 pm The Challenge of Addiction and Respiratory Depression in the Treatment of Pain: A Prototypical Endomorphin as a New Approach for Moderate-Severe Pain Relief
This talk will encompass a scientific review of the development of the endomorphin class of analgesics, endogenous peptides, that present the promise of potent and reliable pain relief without the burden on society of addiction and respiratory depression. CYT-1010 is the first endomorphin to enter clinical testing and, as such, will be compared to other opioids and other pain killers in development.
C. Dean Maglaris, Chief Executive Officer, Cytogel Pharma

2:55 pm Extended Question/Answer Session with Afternoon Presenters

3:20 pm End of Conference