Phase 2 Trial of KM-819 Recruiting Patients After Promising Safety Data

Increasing doses of KM-819 were found generally safe in healthy older adults

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Increasing doses of KM-819, a potential therapy being developed by Fascinate Therapeutics for Parkinson’s disease, showed a favorable safety profile in healthy older adults, according to data from the now-completed Part 1a of a Phase 2 trial.

The placebo-controlled trial (NCT05670782), which was launched last year, is designed to evaluate the disease-modifying potential of KM-819 in slowing or halting Parkinson’s progression.

Underway at the Parexel Early Phase Clinical Unit, in Glendale, California, the trial is now recruiting Parkinson’s patients, 40 and older, for Part 1b to help determine the optimal doses to be subsequently tested in additional patients in Part 2.

“We are pleased with the prospects of KM-819 as a disease-modifying treatment for Parkinson’s disease as we progress through Phase 2 trials. Part 1a showed favorable safety even at very high doses, and we are excited to now initiate Part 1b,” Fascinate stated in a company press release.

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KM-819 works to suppress FAF1 protein

The accumulation of toxic clumps of the alpha-synuclein protein is thought to contribute to the death of dopamine-producing, or dopaminergic, neurons that’s seen in people with Parkinson’s. Dopamine is a major brain messenger molecule that is essential for movement control.

Mutations in the GBA1 gene are known to promote the build-up of toxic alpha-synuclein aggregates and are therefore considered a genetic risk factor for Parkinson’s.

KM-819 is an oral molecule that suppresses FAF1, a protein that promotes regulated cell death and halts cells’ natural cleaning system — called autophagy. FAF1 is found at higher levels in Parkinson’s patients. Impaired autophagy fosters the accumulation of toxic waste, including alpha-synuclein.

We are pleased with the prospects of KM-819 as a disease-modifying treatment for Parkinson’s disease as we progress through Phase 2 trials

In preclinical studies, KM-819 showed neuroprotective properties for dopaminergic neurons in animal models of Parkinson’s, reducing the accumulation of alpha-synuclein in such cells. The therapy has also been shown to reduce abnormal behaviors in the animals.

“KM-819 shows great promise when it comes to the neuroprotection of dopaminergic cells, including GBA mutation, as well as in clearing alpha-synuclein,” the company stated.

The two-part Phase 2 trial is testing KM-819 in both healthy older adults and Parkinson’s patients at early and mid-stage disease, including those with GBA mutations.

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Part 1b will test three KM-819 doses in Parkinson’s patients

The study’s Part 1a, now completed, assessed the safety and pharmacokinetics of multiple escalating doses of KM-819 (400, 600, and 800 mg) against matching placebos in healthy participants. Pharmacokinetics refers to the therapy’s movement into, through, and out of the body. Certain doses had not been tested in previous Phase 1 trials (NCT03022799).

Part 1b will evaluate the pharmacokinetics and safety profile of three KM-819 doses (200, 400, and 600 mg) against a placebo, in people with Parkinson’s.

Results will help inform the selection of the best doses to be used in Part 2, in which additional patients will be randomly assigned to receive either the therapy or a placebo for two years.

This part of the trial will examine the therapy’s safety and efficacy — as assessed through changes in the Unified Parkinson’s Disease Rating Scale-Part 2: Activities of Daily Living.

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