Allyx Therapeutics has secured a $3.3 million grant from the National Institutes of Health (NIH) to advance the clinical development of ALX-001, a first-in-class oral therapy targeting Alzheimer's and Parkinson's diseases. The funding, awarded under the Small Business Innovation Research Commercial Readiness Pilot program, will support a Phase I clinical pharmacokinetic drug-drug interaction study (NCT06632990) to evaluate the impact of multiple doses of ALX-001 on cytochrome P450 enzymes.
ALX-001: A Novel Approach to Neurodegenerative Disease
ALX-001 (previously BMS-984923) is a silent allosteric modulator of mGluR5. It selectively blocks the pathogenic activation of the receptor while preserving normal physiological glutamate signaling required for cognition. This mechanism offers a wide therapeutic window, potentially avoiding on-target toxicity seen with negative allosteric modulators. The molecule was originally identified by Bristol Myers Squibb, but the mechanism of action for neurodegenerative diseases and the identification of ALX-001 as disease-modifying for Alzheimer's disease was discovered by Allyx scientific founder Stephen Strittmatter at Yale School of Medicine. Allyx Therapeutics obtained an exclusive worldwide license for ALX-001 from Bristol Myers Squibb and Yale School of Medicine.
Clinical Development and Ongoing Studies
First doses of ALX-001 have already been administered to patients with Alzheimer's and Parkinson's diseases as part of two Phase Ib clinical studies (NCT05804383 and NCT06309147). According to Allyx Therapeutics, ALX-001 is ready to proceed to Phase 2 clinical development, irrespective of the ongoing studies' completion. The newly funded metabolism study will provide crucial insights into ALX-001's metabolic profile, particularly relevant for patient populations often managing complex polypharmacy and comorbidities beyond neurodegenerative conditions.
Significance of mGluR5 Modulation
mGluR5 plays a crucial role in mediating synaptic dysfunction and loss caused by misfolded extracellular protein species, making it a promising target for treating Alzheimer's and Parkinson's diseases. ALX-001's oral bioavailability, brain penetration, and selective mGluR5 engagement further support its potential as a disease-modifying agent.
Prior Funding and Future Directions
With this latest grant, the ALX-001 program has secured over $23 million in funding, including previous grants from the NIH, the Small Business Innovation Research (SBIR) program, the Alzheimer's Association, and The Michael J. Fox Foundation for Parkinson's Research. Allyx Therapeutics aims to leverage these resources to advance ALX-001 towards commercialization, offering a potential first-in-class disease-modifying oral therapy for Alzheimer's and Parkinson's diseases.
