Phase 1 trial of investigational therapy ALX-001 doses first patient
Study assessing dopamine transporter protein changes as response marker
A Phase 1 trial of ALX-001, an investigational therapy for neurodegenerative conditions, has dosed the first patient with Parkinson’s disease.
The clinical trial (NCT06309147) is assessing the safety of Allyx Therapeutics‘ ALX-001 versus a placebo when given twice a day at either 50 mg or 100 mg for 28 days in adults, ages 21 to 80. The study is taking place at the Duke Clinical Research Institute in North Carolina and is supported with funding by The Michael J. Fox Foundation for Parkinson’s Research.
The study will also assess changes in the levels of the dopamine transporter protein as an early marker of response to treatment. Parkinson’s disease is caused by the progressive dysfunction and death of nerve cells responsible for making dopamine, a chemical messenger. The therapy’s pharmacokinetics, that is, its movement into, through, and out of the body, will be evaluated too.
Allyx is also developing ALX-001 for Alzheimer’s disease, with a parallel 28-day pilot study (NCT05804383) ongoing.
“Allyx Therapeutics is moving forward with strong momentum to develop ALX-001 as the first-ever disease-modifying small molecule for neurodegenerative diseases, with two concurrent safety studies in patients with Parkinson’s disease and with Alzheimer’s disease, adding important information to the body of knowledge for this novel therapeutic approach,” Tim Siegert, PhD, the company’s chief operating officer and co-founder, said in a company press release.
In Parkinson’s disease, the loss of dopamine-producing nerve cells is thought to boost glutamate signaling, another brain signaling molecule. Glutamate activity is mediated via its own receptors, including mGluR5, which has been associated with the loss of synapses caused by misfolded proteins at it happens in Parkinson’s. Synapses are the sites where neighboring nerve cells communicate.
What is ALX-001?
ALX-001, previously known as BMS-984923, is an oral small molecule that’s able to penetrate the brain to block mGluR5 and restore synapses. A disease-modifying therapy, it selectively targets mGluR5, leaving other glutamate pathways required for cognition untouched.
Allyx announced plans earlier this year to start a Phase 2 trial of ALX-001 in people with Parkinson’s.
“I’m excited to collaborate with the Allyx team as we advance understanding of how Parkinson’s disease affects the brain and what more we might be able to do to provide a real impact for patients,” said Laurie H. Sanders, PhD, professor of neurology at Duke. “Investigating the safety of this disease-modifying small molecule is a crucial first step, and one I’m proud to be a part of.”
Data from an open-label, Phase 1a trial (NCT04805983) with healthy volunteers showed ALX-001 was safe and was tolerated well at single doses from 10 to 200 mg. It also validated target engagement with mGluR5 receptors. The therapy continued to show safety and tolerability in a Phase 1b study (NCT05804383) with older adults with normal cognition. The doses of 50 mg and 100 mg were identified for use in further studies.
ALX-001’s clinical development has been supported by grants totaling more than $20 million from the Michael J. Fox Foundation, the National Institutes of Health, the Alzheimer’s Association, and others. Allyx obtained an exclusive worldwide license for ALX-001 from Bristol Myers Squibb and the Yale University.
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