# 26- & 39-Week Toxicity Studies of ANS-6637 in Rats and Monkeys (respectively) to Enable 6+ Months Dosing in Alcohol (and other Substance) Use Disorder Phase 3 Studies

> **NIH NIH U01** · AMYGDALA NEUROSCIENCES, INC. · 2020 · $450,000

## Abstract

PROJECT SUMMARY
The Surgeon General has stated “substance misuse remains a national public health crisis”1. In 2015, 15 million
adults had Alcohol Use Disorder (AUD) in the United States (US)2. However, less than 7% with AUD received
treatment3. In the US, 88,000 people die from alcohol related causes4 and the economic burden of AUD is over
$250 billion per year5. To solve help the national public health crisis of AUD and more broadly of substance
use disorder (SUD), more tools including new pharmacotherapy treatments for SUD are needed.
Amygdala is developing the novel treatment, ANS-6637, for AUD and SUD. The proposed Specific Aims will
generate chronic toxicity data required to establish appropriate treatment duration for ANS-6637 as a treatment
for SUD.
ANS-6637 is an orally bioavailable prodrug of the selective Aldehyde dehydrogenase 2 (ALDH2) inhibitor GS-
548351. In-Vitro and In-Vivo studies have demonstrated that ALDH2 inhibition suppresses the surge in dopamine
release common to all addiction27. Pharmacology studies have demonstrated that ALDH2 inhibition reduces
craving and drug-seeking behavior in multiple rodent models including reinstatement models of alcohol relapse.
ANS-6637 has been studied in Phase 1 clinical studies in 135 human subjects. ANS-6637 had been evaluated
in 28-day & 13-week rat & monkey toxicity studies which support clinical dosing of up to 3-months duration.
Substance Use Disorders including AUD are chronic relapsing diseases. Therefore, treatments for SUD and
AUD should be developed to be used for extended (i.e., more than 3-months) duration. For AUD clinical
development, Food and Drug Administration (FDA) guidance calls for Phase 3 trials of 6-months duration29.
Prior to human clinical studies of 6-months or more duration, or for marketed exposure of >1 month, FDA and
the International Council for Harmonisation (ICH) Guidance require that sponsors conduct 6-months rodent and
9-month non-rodent repeat dose toxicity studies30,31. The Specific Aims of this grant application (chronic toxicity
testing of 6-month duration in rodents and 9-month duration in non-human primates) will generate data required
to assess if clinical studies of 6-months or longer duration with doses up to 600 mg QD can be conducted.

## Key facts

- **NIH application ID:** 10020884
- **Project number:** 5U01AA028003-02
- **Recipient organization:** AMYGDALA NEUROSCIENCES, INC.
- **Principal Investigator:** Ivan Diamond
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $450,000
- **Award type:** 5
- **Project period:** 2019-09-20 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020884

## Citation

> US National Institutes of Health, RePORTER application 10020884, 26- & 39-Week Toxicity Studies of ANS-6637 in Rats and Monkeys (respectively) to Enable 6+ Months Dosing in Alcohol (and other Substance) Use Disorder Phase 3 Studies (5U01AA028003-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10020884. Licensed CC0.

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