Final part of Phase 1 trial to test prosetin in ALS patients

ProJenX is 'laser-focused on initiating ALS patient enrollment in Canada'

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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Health Canada has cleared ProJenX to open the third part of its ongoing Phase 1 clinical trial and begin testing the experimental therapy prosetin in people with amyotrophic lateral sclerosis (ALS).

The first two parts of the PRO-101 trial (NCT05279755) involved healthy participants and showed that the therapy has a good safety and tolerability profile. This final portion now will continue to evaluate prosetin’s safety, tolerability, and pharmacological properties in ALS patients.

“Following Health Canada’s [clinical trial application] authorization, we will be able for the first time to evaluate prosetin in people living with ALS,” Erin Fleming, ProJenX’s co-founder and chief operating officer, said in a press release.

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“We are encouraged by the safety and tolerability profile that has emerged from completed healthy volunteer studies of prosetin, and we are laser-focused on initiating ALS patient enrollment in Canada as quickly as possible,” Fleming added.

In ALS, certain proteins are folded abnormally and more prone to form clumps, which is known to contribute to nerve cell damage and death. One way these clumps affect cells is by causing stress in certain cellular organelles, including the endoplasmic reticulum (ER).

This cellular compartment normally works to produce, fold, and transport proteins, but when it becomes overwhelmed with too much unfolded proteins, it can trigger cell death.

“Despite scientific advances, ALS remains a fatal, devastating neurodegenerative disease that demands more meaningful treatment options,” said Angela Genge, MD, associate professor at the Neurology and Neurosurgery Department at McGill University. Genge also is director of the ALS Centre of Excellence for Research and Patient Care at the Montreal Neurological Institute (The Neuro).

How prosetin works

ProJenX’s lead candidate, prosetin, is a first-in-class oral therapy designed to revert ER stress and reduce damage to motor neurons — the nerve cells that are affected in ALS. It works by blocking a protein called mitogen-activated protein kinase kinase kinase kinase (MAP4K).

Based on the discovery that blocking MAP4K protected motor neurons in several patient-derived cell models, ProJenX’s co-founders at Columbia University optimized prosetin to reach the brain and potently inhibit MAP4K in nerve cells. Their studies showed that prosetin reduced inflammation and improved nerve cell survival in an animal model of ALS.

ProJenX was created in 2022 out of a research collaboration between Project ALS and Columbia University in New York City to rapidly develop and commercialize prosetin for people living with ALS. Following its launch, the first-in-human PRO-101 trial began evaluating the candidate therapy in healthy volunteers and ALS patients.

The trial is divided in three parts. In parts 1a and 1b, a number of healthy volunteers received single or multiple ascending doses of prosetin or a placebo. Now, Part 1c will evaluate the treatment in people with ALS.

“ProJenX has generated compelling preclinical data showing that prosetin may protect motor neurons against well-established pathological [disease-causing] mechanisms in ALS,” said Genge, who also is an investigator in the PRO-101 trial.

Prosetin was granted orphan drug designation for ALS by the U.S. Food and Drug Administration in 2020. The status grants several incentives to companies developing medications for rare disorders, including financial benefits and seven years of market exclusivity if the therapy is ultimately approved.