# Mechanism and Efficacy of a Novel Opioid Adjuvant

> **NIH NIH R43** · AMALGENT THERAPEUTICS, INC. · 2024 · $220,668

## Abstract

PROJECT SUMMARY
Managing the complex risk-benefit profile of opioid therapeutics is a significant challenge for pain patients and
the physicians that treat them. Prescription opioid analgesics provide excellent pain relief but also put patients
in danger of severe adverse effects such as depression, dependence, abuse, and addiction. The opioid crisis
in the United States reflects these risks as over 2.4 million Americans suffer from opioid use disorder, and over
50,000 patients die yearly. Clinical guidelines address the problem of prescription opioid abuse and addiction
by urging physicians to minimize opioid doses. However, years of decreasing doses and a narrow therapeutic
window limit the ability to decrease doses further without losing pain relief effectiveness. Despite decades of
research, we still do not have a total opioid replacement. In the absence of an opioid replacement, there is a
critical unmet need for new technologies that minimize the risks associated with prescription opioids. Amalgent
Therapeutics, Inc. is addressing this need by developing a novel and proprietary opioid adjuvant. Adjuvants
provide an alternative strategy to addressing the problem of opioid use disorder. Our preliminary data show
that this adjuvant increases opioid pain-relieving efficacy by at least four-fold, allowing a substantial decrease
in effective opioid doses. In addition, our data show that the adjuvant mitigates the abuse potential of opioids,
prevents the development of opioid tolerance, and restores effectiveness in neuropathic pain. Amalgent plans
to bring this adjuvant technology to market in AMGT-0220, a fixed-dose combination therapeutic that combines
the adjuvant with a currently marketed opioid. Importantly, the adjuvant is currently approved and marketed for
use in non-pain indications. The combination of two approved drugs is regulated by the FDA under the 505(b)2
new drug approval pathway. This regulatory pathway allows decades of previously acquired safety and clinical
data to support IND submissions for AMGT-0220. The ability to leverage existing data substantially derisks the
AMGT-0220 development program and provides an accelerated path to the clinic. In this Phase 1 SBIR
proposal, we propose work to provide further mechanistic and dosing information for the adjuvant. In Aim 1, we
investigate the mechanism by which the adjuvant increases opioid pain-relieving efficacy and calculate the
minimal concentration needed to decrease opioid doses. In Aim 2, we directly the ability of the adjuvant to
decrease the dose of opioid needed for analgesia in an animal model of post-surgical pain. The work proposed
here will support a Phase 2 application for the nonclinical and clinical development of AMGT-0220.

## Key facts

- **NIH application ID:** 10786389
- **Project number:** 1R43DA059522-01
- **Recipient organization:** AMALGENT THERAPEUTICS, INC.
- **Principal Investigator:** MALCOLM A MEYN
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $220,668
- **Award type:** 1
- **Project period:** 2024-08-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10786389

## Citation

> US National Institutes of Health, RePORTER application 10786389, Mechanism and Efficacy of a Novel Opioid Adjuvant (1R43DA059522-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10786389. Licensed CC0.

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