Optimizing Non-Addictive Therapies to Treat Pain


The Research Need

More than 25 million Americans suffer from chronic pain, a highly debilitating medical condition that is complex and lacks effective treatments. Recent decades have seen an overreliance on opioids for chronic pain despite their poor ability to improve function. This overreliance has contributed to a significant and alarming epidemic of opioid use disorder. Therefore, the development of new therapies as viable alternatives to opioids is urgently needed.

About the Program

This program supports the development and preclinical optimization of safe, effective, and non-addictive small-molecule and biologic therapeutics to treat pain. This research includes optimization and early development of promising small molecules and biologic agents, studies that enable investigational new drug (IND) applications, and culminating in Phase I clinical trials. The goal of the program is to accelerate the development of promising small-molecule and biologic leads toward clinical trials.

Researchers plan to develop novel pain relievers with improved specificity, fewer side effects, and low risks of misuse or dependency. This research will use in vitro assays and animal studies to advance multiple drug candidates. In the long term, the research will advance low-risk treatment options for chronic pain toward clinical development.

Program Details

To date, through the Helping to End Addiction Long-termSM Initiative, or NIH HEAL InitiativeSM, NIH has awarded five grants to research institutions and small businesses to support the development of non-addictive small molecules and biologic agents to treat chronic pain. 

These research institutions and small businesses will undertake preclinical research and development that will provide new viable alternatives to opioids for treating pain. All of the program’s funded grants use biphasic cooperative agreements. The projects will be milestone driven and involve discovery and developmental research. Only the most promising projects will advance to the second phase of the program directed toward filing IND applications for clinical exploration and commercialization.

Research Examples

Through their awards, the research organizations will develop and optimize non-addictive small molecules and biologic agents for the treatment of chronic pain.

The awardees will conduct research to:

  • Develop a novel antibody-drug conjugate for the targeted treatment of nerve pain
  • Optimize a targeted central nervous system-penetrant small molecule to treat nerve pain
  • Develop selective inhibitors of sodium channels to treat chronic pain
  • Optimize a new MNK inhibitor to treat nerve pain

  • 4e Therapeutics Inc. – Texas
  • Johns Hopkins University – University of Maryland
  • Knopp Biosciences, LLC – Pennsylvania
  • University of California at Davis – California
  • Vanderbilt University – Tennessee
  • Weill Medical College of Cornell University – New York

Funded Projects

Development and Optimization of MNK Inhibitors for the Treatment of Neuropathic Pain
Mar 19, 2020
Development of MRGPRX1 positive allosteric modulators as non-addictive therapies for neuropathic pain
Mar 19, 2020
Novel HCN1-selective small molecule inhibitors for the treatment of neuropathic pain
Mar 19, 2020
Novel mGlu5 negative allosteric modulators as first-in-class non-addictive analgesic therapeutics
Mar 19, 2020
Selective Kv7.2/3 activators for the treatment of neuropathic pain
Mar 19, 2020

Open Funding Opportunities

HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional)
Sep 16, 2020

Closed Funding Opportunities

HEAL Initiative: Optimization of Non-addictive Therapies [Small Molecules and Biologics] to Treat Pain - (U44 Clinical Trial Not Allowed)
Sep 25, 2019
Optimization of Non-addictive Therapies [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Not Allowed)
Sep 25, 2019