A $3.9 million NIH HEAL Initiative grant is funding a multi-institutional team led by Sanford Burnham Prebys to develop a non-opioid pain treatment and advance it to a Phase 1 clinical trial.

The collaboration includes Duke University and the University of Minnesota with contributors like Steven H. Olson, Ru-Rong Ji, and Lauren M. Slosky, aiming to overcome opioid-related dependence and side effects.

The NIH HEAL Initiative supports accelerating solutions to the opioid crisis by improving pain management and reducing reliance on addictive medications.

Two 2025 publications underpin the approach: a Cell study showing SBI-810’s strong antinociceptive effects across pain models and a Nature study detailing the molecular blueprint of SBI-553 binding to NTR1.

Supporting Cell (2025) and Nature (2025) papers reveal SBI-810’s efficacy in rodent pain models and human sensory neurons, plus structural insights that guide design of improved analogs.

The research leverages these publications to inform rational design and biased GPCR signaling strategies for safer analgesics.

The project allocates two years to structure-based drug design and machine-learning–driven optimization, with preclinical testing in mice and rats and attention to sex as a biological variable.

Development proceeds in phases, starting with rodent optimization and safety validation, followed by IND filing and a Phase 1 trial, all while focusing on reducing cardiac safety liabilities.

The plan emphasizes maximizing analgesia while minimizing cardiac risks through AI-guided medicinal chemistry and evaluation in rodent models.

Sanford Burnham Prebys marks its 50th anniversary by highlighting its role in integrated drug discovery, data science, and collaboration to translate discoveries into clinical impact.

The institute stresses interdisciplinary work spanning chemistry, structural biology, pharmacology, and data science to accelerate therapies for pain and addiction.

The push for non-addictive analgesics comes amid large numbers of Americans experiencing postoperative and chronic pain, underscoring the need for new solutions.