Allyx Therapeutics Announces Expansion Into Parkinson’s Disease Clinical Research With Lead Compound Following IND Acceptance

Allyx Therapeutics recently announced the US FDA has accepted its Investigational New Drug Application (IND), enabling the company to proceed with clinical research in Parkinson’s disease. A 28-day safety study of ALX-001 in Parkinson’s disease patients will be initiated in Q1 2024.

“We are working with urgency to understand how the unique mechanism of action of ALX-001 at mGluR5, which preserves and protects synapses, can introduce meaningful clinical benefits for people living with Alzheimer’s disease and Parkinson’s disease,” said Allyx Therapeutics co-founder and CEO Stephen Bloch, MD. “Our aim is to deliver the first-ever disease-modifying small molecule for these and other neurodegenerative diseases.”

The ALX-001 program has received more than $20 million in grant funding from the National Institutes of Health, the U.S. Government’s highly competitive Small Business Innovation Research (SBIR) programs and The Michael J. Fox Foundation for Parkinson’s Research, among others. As studies in Parkinson’s disease begin, the company will continue to advance clinical development of ALX-001 in Alzheimer’s disease, which is funded through grants from the National Institutes of Health and other Alzheimer’s disease research nonprofit organizations.

“The generous grant from The Michael J. Fox Foundation for Parkinson’s Research contributes to research efforts around the potential of ALX-001, enabling our work to move into clinical research without delay,” added Tim Siegert, PhD, Chief Operating Officer and co-founder of Allyx Therapeutics. “We have the talent and the capital needed to rapidly advance our clinical development program and progress toward transforming the future for people living with serious and debilitating neurodegenerative diseases.”

“The Michael J. Fox Foundation is excited to leverage Allyx’s work in developing this approach for Alzheimer’s disease to assess its potential for those living with Parkinson’s disease,” said Brian Fiske, PhD, Chief Scientific Officer, The Michael J. Fox Foundation. “We look forward to seeing results from these clinical trials and the additional data they will provide.”

ALX-001 continues to demonstrate promise in ongoing studies that build on twelve years of research. A Phase 1b multiple ascending dose study (NCT05804383 Stage 1) in healthy volunteers was recently completed, following presentation of results from a single ascending dose study in October 2023 at the 16^th Clinical Trials on Alzheimer’s Disease (CTAD) meeting. The Phase 1a open-label single ascending dose study (NCT04805983) evaluated the safety, tolerability, pharmacokinetics, and brain receptor occupancy of increasing doses of orally-administered ALX-001. All doses were well-tolerated and there were no serious adverse events. Results from the recently-completed Phase 1b multiple ascending dose study will be presented in March at the AD/PD 2024 Conference in Lisbon.

ALX-001 (previously BMS-984923) is a silent allosteric modulator of mGluR5, and is a first-in-class compound that selectively blocks the pathogenic activation of the receptor while preserving the normal physiological glutamate signaling that is required for cognition. As such, ALX-001 has a wide therapeutic window that can saturate receptors while avoiding on-target toxicity observed with negative allosteric modulators. mGluR5 has been shown to be essential for mediating synaptic dysfunction and loss caused by multiple misfolded extracellular protein species, and as such, presents a novel approach for treating Alzheimer’s and Parkinson’s disease. Importantly, ALX-001 is an orally bioavailable and brain penetrant small molecule with demonstrated mGluR5 selective engagement. 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 Professor Stephen Strittmatter at Yale. Allyx Therapeutics obtained an exclusive worldwide license for use of ALX-001 from Bristol Myers Squibb and Yale University.

Allyx Therapeutics was founded in 2019 by a group of seasoned biopharma industry executives, venture capitalists, and scientific experts. The company aims to deliver a novel approach to preserve and protect synapses for people living with neurodegenerative diseases. Its lead compound, ALX-001, is a first-in-class oral therapy with a unique mechanism of action at mGluR5 in clinical development for Alzheimer’s disease and Parkinson’s disease. Learn more at allyxthera.com.