# A Fentanyl Vaccine to Prevent Overdose

> **NIH NIH R43** · HEPIONE THERAPEUTICS INC. · 2020 · $261,742

## Abstract

ABSTRACT
 Hepione Therapeutics, Inc. is a biotech startup with access to a novel, proprietary platform to
generate antibodies and vaccines to small molecules and peptides for a wide range of research,
diagnostic, and therapeutic needs. The focus of this SBIR is to use this platform to raise antibodies to
fentanyl in mice, and to extend from mice to rats our animal model proof-of-concept for a fentanyl
vaccine. Our long-term goal is to make an FDA-approved vaccine that conveys long-term immunity to
fentanyl overdose. The mortality of fentanyl overdose is not merely restricted to the use of fentanyl, a
synthetic opioid 100 times more potent than morphine, or even the use of opioids generally, but rather
is a crisis that has profoundly impacted the overdose rates of almost every addictive substance used
today. The National Institute on Drug Abuse (NIDA) reports that over 70,000 Americans died of drug
overdoses in 2017, a two-fold increase since 2007. Of these, 67% of these deaths involved the use of
fentanyl. In the cases where overdoses were attributed to other elicit substances, co-involvement of
fentanyl significantly contributed to increased mortality in the last decade. Heroin mortalities saw a 622-
fold increase in deaths that involved fentanyl between 2007 and 2017, compared to the 3.1-fold increase
in heroin-related overdoses without fentanyl involvement. Psychostimulant overdoses involving fentanyl
saw a 73-fold increase, cocaine a 33.1-fold increase, Rx opioids a 9.1-fold increase, and even
benzodiazepines and antidepressants saw an 11.2-fold and 4.8-fold increase in fentanyl involved
deaths in the last decade, respectively.
 Medical interventions to prevent fentanyl overdose are desperately needed to combat this rise in
fatalities. Just 2-3 mg of fentanyl can be lethal, causing sedation, vomiting, and respiratory depression.
Overdose is more common for patients who relapse early in recovery, where abstinence upregulates
endogenous opioid receptors and lowers tolerance. Fentanyl overdose is treated with mixed results by
opioid blockers such as naloxone (NARCAN®). Patient revival requires multiple doses, often not
delivered in enough time. Fentanyl also causes rigidity in the chest wall muscles, rendering CPR chest
compressions ineffectual. For these reasons, prophylactic approaches, such as vaccines or
immunotherapies, would be highly desirable interventions.
 We have developed a viable immunotherapy platform to block fentanyl overdose. This platform can
be used without adjuvants and at low antigen doses to robustly and reliably generate specific antibodies
to small molecule compounds. Our preliminary data establish that this vaccine is wholly protective
against fentanyl intoxication in mice. To proceed to clinical trials, we aim to show efficacy in additional
animal models, specifically the rat in this application (Aim 1). We also aim to analyze the immune
response elicited by the vaccine at the repertoire level, which will allow us to ca...

## Key facts

- **NIH application ID:** 10142643
- **Project number:** 1R43DA052960-01
- **Recipient organization:** HEPIONE THERAPEUTICS INC.
- **Principal Investigator:** Joseph P Verdi
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $261,742
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142643

## Citation

> US National Institutes of Health, RePORTER application 10142643, A Fentanyl Vaccine to Prevent Overdose (1R43DA052960-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10142643. Licensed CC0.

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