# TMP-301, A Negative Allosteric Modulator of type 5 metabotropic glutamate receptors (mGluR5), for Treatment of Cocaine Use Disorder

> **NIH NIH U01** · TEMPERO BIO, INC. · 2022 · $2,060,520

## Abstract

Project Summary / Abstract
 CUD is associated with dysregulated glutamate neurotransmission. Preclinical studies indicate that the
modulation of glutamate signaling through the antagonism of the mGlu5 receptor can attenuate cocaine
mediated drug-induced behaviors such as drug-seeking, self-administration, and reinstatement (relapse) of
cocaine-seeking behavior (34-36), supporting an important role for the mGlu5 receptor in the modulation of
addictive behavior induced by cocaine and that antagonists of the mGlu5 receptor could be useful for the
treatment of CUD.
 TMP-301, a mGluR5 negative allosteric modulator (NAM) that is the subject of this application, has been
demonstrated to be safe and well-tolerated in a FIH study in healthy volunteers. TMP-301 showed preclinical
efficacy and significantly reduced cocaine self-administration and relapse as well as voluntary alcohol drinking
and positive reinforcement function in an animal efficacy model.
 CUD with AUD is the more prevalent form of the disorder (14-16). Thus, TMP-301 may not only be efficacious
in a population of CUD patients but also in a broader clinical population of CUD with AUD patients. In addition to
the nonclinical supporting rationale, recent data from a Phase 2 clinical study of the mGluR5 NAM mavoglurant
in patients with CUD demonstrated a significant reduction in the proportion of cocaine use days and alcohol use
days in patients receiving mavoglurant relative to patients receiving placebo (NCT03242928, (27)). These
findings suggest that the pharmacological negative allosteric modulation of mGluR5 is a feasible therapeutic
approach to modulate cocaine-seeking behavior and prevent relapse. Despite positive results, mavoglurant is
not currently advanced for addiction. TMP-301 has the potential to be administered once daily. This represents
an important advantage for TMP-301 over mavoglurant, which must be administered twice daily. Medication
adherence among addiction patients is often challenging; therefore, a once-daily regimen could significantly
improve medication adherence.
 We propose advancing TMP-301 from FIH through additional Phase I testing, including a Multiple Ascending
Dose study with a new formulation and a Phase Ib Interaction study of TMP-301 and cocaine in cocaine-
experienced volunteers. We propose performing the necessary toxicology studies to allow for longer duration
studies in Phase II and Phase III. Thus, the clinical and preclinical studies proposed will allow TMP-301 to move
to Phase II studies.

## Key facts

- **NIH application ID:** 10544285
- **Project number:** 1U01DA057118-01
- **Recipient organization:** TEMPERO BIO, INC.
- **Principal Investigator:** Charles Daniel Meyers
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,060,520
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10544285

## Citation

> US National Institutes of Health, RePORTER application 10544285, TMP-301, A Negative Allosteric Modulator of type 5 metabotropic glutamate receptors (mGluR5), for Treatment of Cocaine Use Disorder (1U01DA057118-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10544285. Licensed CC0.

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