# Nezavist a Novel Molecule for Treatment of Alcohol Use Disorder

> **NIH NIH R44** · LOHOCLA RESEARCH CORPORATION · 2024 · $1,710,386

## Abstract

According to the 2019 National Survey on Drug Use and Health, 14.1 million adults ages 18 and older had
Alcohol Use Disorder, and approximately 825,000 people indicated heavy alcohol use. However, only about
8% of individuals who had AUD in 2018 received treatment. In part, the lack of treatment results from the
paucity of effective therapeutics available to treat AUD, and research is ongoing to develop new therapeutic
approaches. Lohocla Research Corporation has been developing such a therapeutic, called Nezavist, which
was shown in nonclinical models to reduce alcohol relapse in dependent individuals. The goal of Lohocla is to
produce a treatment for individuals, including those with AUD, who wish to reduce their alcohol consumption.
Nezavist acts as a positive allosteric modulator of GABA-A receptors, acting at a novel site on the receptor
distinct from other modulators such as benzodiazepines. The other novel characteristic of Nezavist is its site of
action within the intestine, where Nezavist modulates the activity of the enteric nervous system and produces
its effect on alcohol consumption through a gut-brain communication pathway. By this means, Nezavist can
influence brain activity without itself entering the brain. This application is for a Phase IIB renewal of SBIR
U44AA024905, which will support the completion and submission of an IND application to the FDA and the
performance of Phase1 safety and tolerability clinical trials of Nezavist. During the course of the current SBIR
grant, Lohocla developed a method to scale up the synthesis of Nezavist, using flow chemistry to circumvent
hazardous steps, and obtained kilogram quantities of cGMP Nezavist. A spray-dried dispersion formulation has
been produced that enhances bioavailability. In vitro ADME studies were performed, including determining
pathways of metabolism, and investigating metabolic processes in tissues from several species, which
assisted in the choice of species for in vivo toxicology and pharmacokinetics. In vitro interactions with
transporters and CYP450 enzymes were also completed. The spray-dried dispersion formulation was used to
assess pharmacokinetics and toxicology in several species, and the results of the toxicology studies provide
the data needed to determine the dosing levels for the first-in-human studies. A pre-IND meeting was
accomplished with a favorable outcome. Overall, Lohocla has completed most of the IND-enabling studies
needed to progress to clinical trials, including the development of methods for administering the drug to
humans. The proposed Phase IIB renewal includes completion of the mass balance study recommended by
the FDA to be included in the IND application, and synthesis of cGMP formulation that can be used in the
clinical trials. Once the IND is approved, Phase 1a and Phase 1b clinical trials are proposed. Concurrent with
the clinical trials, a long-term nonclinical toxicology study in rat will be performed that will be needed to provide
a ...

## Key facts

- **NIH application ID:** 11077971
- **Project number:** 4R44AA024905-07
- **Recipient organization:** LOHOCLA RESEARCH CORPORATION
- **Principal Investigator:** Boris Tabakoff
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,710,386
- **Award type:** 4N
- **Project period:** 2015-09-25 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11077971

## Citation

> US National Institutes of Health, RePORTER application 11077971, Nezavist a Novel Molecule for Treatment of Alcohol Use Disorder (4R44AA024905-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11077971. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*