Allyx to advance synapse-protecting drug to Phase 2 trials in Alzheimer’s and Parkinson’s

Positive Phase 1 safety data leads to initiation of patient studies of ALX-001 in both Alzheimer’s and Parkinson’s disease patients.

Neurodegeneration-targeting biotech Allyx Therapeutics has revealed positive Phase 1b multiple ascending dose data that demonstrates the safety of its lead compound ALX-001. The New Haven, Connecticut-based company is now advancing ALX-001 into Phase 2 clinical development for both Alzheimer’s and Parkinson’s disease.

ALX-001, licensed from Bristol Myers Squibb and Yale University, is a synapse-targeted, disease-modifying oral therapy designed for Alzheimer’s and Parkinson’s diseases. The compound, a modulator of a glutamate receptor in the brain called mGluR5, selectively blocks pathogenic activation while preserving the normal physiological glutamate signaling critical for cognition. Allyx believes the approach presents a potential solution for the synaptic dysfunction and loss associated with neurodegenerative diseases.

The Phase 1b multiple ascending dose study evaluated the safety, tolerability, and pharmacokinetics of ALX-001 in 32 healthy adults aged 50-80. The results demonstrated the safety of ALX-001 across various doses (50mg to 150mg) in cognitively normal older adults, with two doses (50mg and 100mg) selected for further studies. Allyx reports that all doses were well-tolerated without serious adverse events.

“The data show that ALX-001 achieved high target engagement without any adverse events related to mGluR5, which supports our vision to mediate synaptic dysfunction and loss while avoiding the on-target toxicity observed with other treatment modalities,” said Dr Stephen Strittmatter, scientific founder of Allyx and professor of neuroscience at Yale.

The next phase of clinical development will be the initiation of two 28-day patient studies, which will be the first studies of ALX-001 in people living with Alzheimer’s and Parkinson’s disease.

“We believe that the results from the Phase 1b MAD study directly support larger scale Phase 2 clinical development to more fully understand the potential for ALX-001 to become the first-ever disease-modifying small molecule for neurodegenerative diseases,” said Dr Tim Siegert, COO of Allyx.

The ALX-001 program is backed by more than $20 million in grant funding from sources including the National Institutes of Health, Small Business Innovation Research programs, Alzheimer’s Association, and The Michael J. Fox Foundation for Parkinson’s Research, among others.

Allyx’s expansion into a clinical program in Parkinson’s disease, was marked by the recent acceptance of an Investigational New Drug Application by the FDA.

“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 Dr Stephen Bloch, CEO of Allyx. “Our aim is to deliver the first-ever disease-modifying small molecule for these and other neurodegenerative diseases.”