# Clinical development of an mGlu2 positive allosteric modulator to treat nicotine addiction

> **NIH NIH U01** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 2020 · $3,703,043

## Abstract

PROJECT SUMMARY
This application entitled “Clinical development of an mGlu2 positive allosteric modulator to treat nicotine
addiction” is in response to PAR-18-219 “Grand Opportunity in Medications Development for Substance-Use
Disorders (U01 Clinical Trial Optional)”. This application represents the continuation of our current work under
the U01 DA041731 funded from 9/1/2017 through 5/31/2020 entitled “Preclinical Studies for the Development of
Selective mGlu2 Positive Allosteric Modulators to Treat Substance Abuse Disorders”. Cigarette smoking,
attributable primarily to the addictive properties of nicotine, is one of the largest preventable causes of disease
and death in the US. Metabotropic glutamate receptor subtype 2 (mGlu2) receptor positive allosteric modulators
(PAMs) represent an innovative strategy to treat nicotine addiction. Medications that activate mGlu2 receptors
can be effective via a dual mechanism by a) reversing the acute effects of nicotine, thus decreasing drug
reinforcement, and b) restoring glutamatergic function to normal levels, thus preventing relapse to drug use. Our
lead drug candidate, SBI-0069330, is a potent and selective mGlu2 PAM with excellent drug-like properties
including oral bioavailability, brain penetration, and metabolic stability. Importantly, SBI-0069330 reduces
nicotine self-administration and cue-induced nicotine reinstatement in rats without affecting natural food reward.
In addition, SBI-0069330 has been shown to be well-tolerated and safe in 14-day toxicology studies in rats and
dogs. We are on track to complete the data package to support SBI-0069330 as a clinical candidate under the
current U01 DA041731 grant by May 31, 2020. The overall objective of this grant application is to advance SBI-
0069330 into the clinic and determine its safety, tolerability and pharmacokinetic (PK) profile in healthy human
subjects. The specific aims of this proposal are: (1) Complete the investigational new drug (IND) application for
SBI-0069330, submit for Food and Drug Administration (FDA) review, and obtain allowance for human testing;
(2) Manufacture drug product with a formulation suitable for human dosing in Phase 1 clinical studies; (3)
Complete Phase 1 clinical studies in healthy volunteers and determine the safety, tolerability, and PK profile of
SBI-0069330 in humans and (4) Complete CMC development and toxicology testing to support a future 12-week
Phase 2A clinical efficacy trial. We have assembled a multidisciplinary team of investigators who have the depth
and breadth of knowledge and experience to achieve these milestones. This team has been collaborating
fruitfully and effectively with the team of Jane Acri and David White at NIDA under the current U01 DA041731
grant. The infrastructure required to undertake the proposed work is fully established and operational. We have
also manufactured sufficient active pharmaceutical ingredient (API) of SBI-0069330 that can be readily
formulated into drug product ...

## Key facts

- **NIH application ID:** 9983504
- **Project number:** 1U01DA051077-01
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **Principal Investigator:** ROBERT M ANTHENELLI
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $3,703,043
- **Award type:** 1
- **Project period:** 2020-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983504

## Citation

> US National Institutes of Health, RePORTER application 9983504, Clinical development of an mGlu2 positive allosteric modulator to treat nicotine addiction (1U01DA051077-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9983504. Licensed CC0.

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