# BMS-984923 Non-Clinical Development to Support Phase 2 Trials

> **NIH NIH R44** · ALLYX THERAPEUTICS INC. · 2023 · $1,339,527

## Abstract

SUMMARY/ABSTRACT
This project seeks to develop a novel disease-modifying compound for AD (AD) by targeting the underlying
mechanism of synapse loss. Synapse loss is tightly correlated with cognitive decline and is triggered initially by
amyloid-β peptide oligomer accumulation. Soluble amyloid-β oligomers bind to Prion Protein, thereby engaging
mGluR5 as a co-receptor, and activating PTK2B (Pyk2) and Fyn kinases to couple with Tau pathology and
synapse loss. Genetic knockout studies in rodents have shown that knockout of mGluR5 prevents disease onset,
and our target sits directly upstream of PTK2B, a GWAS hit in AD. These features provide strong evidence of
mGluR5 as a promising therapeutic target for developing novel Alzheimer’s treatments.
Allyx Therapeutics has obtained an exclusive license for use of BMS-984923 in neurodegenerative diseases
from Bristol Meyers Squibb and Yale University. Preliminary studies demonstrate robust efficacy of this small
molecule treatment in multiple preclinical mouse AD models. Drug treatment recovers synapse density, restores
hippocampal activity, and returns memory performance to normal levels. Pre-clinical development has
characterized a highly drug-like profile allowing for the recent approval of the BMS-984923 commercial IND for
the initiation of first time in human clinical studies. The overall goal is to develop disease-modifying oral drug
effective to slow, halt or partially reverse AD progression both in the MCI state and in mild dementia.

## Key facts

- **NIH application ID:** 10694083
- **Project number:** 5R44AG077984-02
- **Recipient organization:** ALLYX THERAPEUTICS INC.
- **Principal Investigator:** Timothy R Siegert
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,339,527
- **Award type:** 5
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10694083

## Citation

> US National Institutes of Health, RePORTER application 10694083, BMS-984923 Non-Clinical Development to Support Phase 2 Trials (5R44AG077984-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10694083. Licensed CC0.

---

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