# Process Development, Manufacturing, and Preclinical Evaluation of a Monoclonal Antibody for Fentanyl Overdose

> **NIH NIH U01** · CESSATION THERAPEUTICS, LLC · 2020 · $6,107,502

## Abstract

Abstract.
Opioid use disorder (OUD) is a significant public health problem in the United States. Particularly troubling is the
rapid evolution of an opioid epidemic within the past decade, characterized by a surge in unintentional overdose
deaths involving synthetic opioids, such as fentanyl. A large contributor to this surge is the increased frequency
of heroin and other illicit opioid being contaminated or “cut” with fentanyl and its analogs. The current standard
of care for opioid overdose is treatment with opioid antagonist naloxone, which is considerably less effective
when combating fentanyl due to fentanyl’s high potency and the short half-life of naloxone. As a novel approach,
therapeutic monoclonal antibodies (mAbs) against fentanyl have been designed to reverse the pharmacokinetic
distribution of the drug out of the central nervous system, averting overdose and attenuating opioid-induced
respiratory depression. The Janda group at TSRI recently disclosed the generation and use of murine mAbs that
were able to reverse fentanyl-induced behavior and prevent overdose lethality in mice. Recently, we have
generated human mAbs with high-affinity for fentanyl and broad cross-reactivity to its analogs with negligible
binding to structurally-unrelated medications such as buprenorphine and naloxone. Our lead mAb can reverse
the antinociceptive effects of fentanyl in rodents and rhesus macaques and has shown a duration of action in
non-human primates of over 2 weeks. Furthermore, the mAb can rescue mice from carfentanil-induced
respiratory depression with similar efficacy to naloxone, but with a much more durable effect. Following our
reengineering efforts to enhance stability for manufacturing, we have contracted with Selexis SA to produce a
stable cell line. Under the aims of our grant, KBI Biopharma, a partner of Selexis SA, will undertake tasks in
process development and GMP manufacturing to establish a manufacturing process, quality assurance protocol
and stability profile for our antibody. Subsequent production of cGMP material will enable GLP toxicology studies
in rats and dogs and eventually a Phase I/IIa clinical trial. This material will also be used in final opioid-induced
respiratory depression studies in mice and non-human primates to confirm therapeutic efficacy of final drug
product. In sum, these activities will enable us to file for an investigational new drug application for our mAb
candidate with the FDA.

## Key facts

- **NIH application ID:** 10155301
- **Project number:** 1U01DA051071-01A1
- **Recipient organization:** CESSATION THERAPEUTICS, LLC
- **Principal Investigator:** Paul T Bremer
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $6,107,502
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155301

## Citation

> US National Institutes of Health, RePORTER application 10155301, Process Development, Manufacturing, and Preclinical Evaluation of a Monoclonal Antibody for Fentanyl Overdose (1U01DA051071-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10155301. Licensed CC0.

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