Investigational Parkinson’s therapy ALX-001 advances to Phase 2 trial

Phase 1 study ID'd two doses for further studies

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by Andrea Lobo |

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Allyx Therapeutics will advance into Phase 2 clinical development of ALX-001, its investigational therapy for neurodegenerative conditions, in people with Parkinson’s disease.

The company announced the move alongside the presentation of positive data from a Phase 1b study (NCT05804383) at the International Conference on Alzheimer’s and Parkinson’s Diseases AD/PD 2024 last week in Lisbon, Portugal and virtually.

The results showed the treatment was safe and well tolerated in cognitively normal older adults, and no serious side effects were reported. Two doses, 50 mg and 100 mg, were identified for use in further studies.

Allyx is also advancing into Phase 2 development in people with Alzheimer’s disease.

“We believe that the results from the Phase 1b [multiple ascending dose] 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,” Tim Siegert, PhD, Allyx’s co-founder and CEO, said in a company press release.

The loss of dopamine-producing neurons in Parkinson’s is thought to increase the signaling of glutamate, a brain chemical messenger. Glutamate acts through several receptors, including the mGluR5, which has been associated with disease symptoms.

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What is ALX-001?

ALX-001 (previously BMS-984923), is an orally available, brain-penetrant small molecule that targets mGluR5 at the tiny junctions that let neurons (nerve cells) communicate with each other by transmitting electrical or chemical signals, called synapses.

The investigational molecule is a disease-modifying therapy that selectively inhibits disease-associated receptor activation while preserving the normal glutamate signaling needed for cognition.

The Phase 1b study completed testing ALX-001 in cognitively normal older adults, ages 50-80, at ascending doses that ranged from 50 mg to 150 mg twice daily, compared with a placebo.

The company has begun screening patients for two small 28-day pilot patient studies in Alzheimer’s and Parkinson’s. These will test ALX-001 at either 50 or 100 mg taken twice daily, versus a placebo.

“We are excited to begin the next phase of development with the initiation of two 28-day patient studies, the first studies of ALX-001 in people living with Alzheimer’s and Parkinson’s disease,” Siegert said.

The U.S. Food and Drug Administration (FDA) accepted Allyx’s application to test ALX-001 in Parkinson’s and Alzheimer’s patients based on topline data from a Phase 1a trial (NCT04805983), an open-label study with healthy volunteers at Yale University.

The trial demonstrated ALX-001 was safe and well tolerated at all doses tested, from 10 to 200 mg single doses, with no serious side effects reported. It also confirmed the oral bioavailability of the molecule and validated target engagement with mGluR5 receptors.

“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 Stephen Strittmatter, MD, PhD, Allyx’s scientific founder.

The ALX-001 program has received more than $20 million from the National Institutes of Health, Small Business Innovation Research programs, The Michael J. Fox Foundation for Parkinson’s Research, and the Alzheimer’s Association.