# Development of a monoclonal antibody to reverse overdose from fentanyl and its analogs: from manufacturing to clinical trials

> **NIH NIH UG3** · UNIVERSITY OF WASHINGTON · 2022 · $8,267,350

## Abstract

ABSTRACT. This project seeks funding to complete manufacturing and IND-supporting pharmacokinetic,
efficacy, and safety/toxicology preclinical studies for a Phase I clinical trial of a candidate humanized monoclonal
antibody (mAb) to treat and reverse toxicity associated with overdose involving fentanyl and its potent analogs.
The incidence of fatal drug overdoses has dramatically increased due to the proliferation and widespread
availability of fentanyl and its analogs, often found in street drug mixtures. Fatal drug overdoses totaled more
than 92,000 in 2020. Current medications are not always sufficient to prevent or reverse overdose from fentanyl
and its analogs. As a complementary strategy to current medications, our team has developed humanized mAbs
against fentanyl and its analogs. Lead mAbs are effective in preventing and reversing drug-induced respiratory
depression and bradycardia in rodents exposed to fentanyl and carfentanil. Anti-drug mAbs selectively sequester
the target drug from circulation. Due to their selectivity for the target(s), our mAbs do not interfere with
endogenous ligands, FDA-approved medications for treating opioid use disorders (OUD) and overdose, and
other critical medications. Anti-fentanyl mAbs can be co-administered with standard of care treatments for OUD
and/or overdose, and may offer longer-lasting clinical benefits over opioid receptor antagonists. Translation of
mAbs will benefit those with an OUD and other individuals at high-risk of fatal overdoses from accidental or
deliberate exposure to fentanyl and fentanyl analogs. This UG3/UH3 project proposes a milestone-driven
iterative developmental plan with predetermined go/no go criteria to advance a mAb against fentanyl and
its analogs to the clinic. AIM1 focuses on the GMP manufacturing of a lead candidate mAb in collaboration with
a partner CDMO. AIM2 focuses on IND-enabling potency and efficacy studies in key animal models. AIM3
focuses on the GLP toxicology and safety of the lead mAb. AIM4 focuses on Phase I clinical trials to first test
mAb safety, pharmacokinetics, and immunogenicity, and then mAb efficacy against fentanyl in healthy human
subjects. Completion of this project will provide clinical data to support mAb testing in future Phase II-III trials.

## Key facts

- **NIH application ID:** 10615519
- **Project number:** 1UG3DA057850-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** SANDRA D. COMER
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $8,267,350
- **Award type:** 1
- **Project period:** 2022-09-30 → 2025-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10615519

## Citation

> US National Institutes of Health, RePORTER application 10615519, Development of a monoclonal antibody to reverse overdose from fentanyl and its analogs: from manufacturing to clinical trials (1UG3DA057850-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10615519. Licensed CC0.

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