Phase 1 trial testing prosetin for ALS expands to EU countries

ProJenX study in healthy volunteers now moves to ALS patients for Part 1c

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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ProJenX has been given the green light to expand its ongoing Phase 1 clinical trial of prosetin for amyotrophic lateral sclerosis (ALS) across the Atlantic Ocean to testing sites in Europe.

The PRO-101 trial (NCT05279755), launched in 2022, is a three-part study evaluating prosetin’s safety, tolerability, and pharmacological properties. Its first two parts — 1a and 1b — involved healthy volunteers and indicated the treatment was generally safe and well tolerated.

Part 1c now is investigating the experimental therapy in people with ALS. The company was first cleared to launch that portion of the study in Canada, and this authorization allows enrollment to expand to patients in the European Union.

“This EU clinical trial authorization will allow us to expand the first study of prosetin for people living with ALS to European participants,” Erin Fleming, ProJenX’s co-founder and chief operating officer, said in a company press release.

“We are committed to initiating ALS patient enrollment as quickly as possible,” Fleming added.

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Cells Can Break Down Protein Clumps, But Don’t Know When to Do It

Phase 1 trial PRO-101 is 1st to test prosetin in humans

In ALS, the abnormal folding and clumping of certain proteins is thought to contribute to nerve cell damage and death. In particular, these protein clumps can cause stress in certain cellular compartments, including the endoplasmic reticulum, known as the ER.

This organelle normally works to produce, fold, and transport proteins. But it also can work to help abnormally folded proteins acquire their normal three-dimensional structure — or send them for recycling.

If the ER becomes overwhelmed by the presence of too many unfolded proteins, however, it can lead to cell death.

Prosetin is a first-in-class oral therapy that can reach the brain and reduce ER stress in nerve cells, thereby reducing neuronal damage. It works by blocking a protein called mitogen-activated protein kinase kinase kinase kinase, or MAP4K.

In preclinical studies, ProJenX’s co-founders at Columbia University discovered that blocking MAPK4 protected motor neurons, the cells that are damaged in ALS, in several patient-derived cell models. The team also was able to demonstrate that, by blocking MAPK4, prosetin could reduce inflammation and improve nerve cell survival in several animal models of ALS.

ALS is a devastating disease, and there is an immense unmet need for therapeutic options to slow or halt its rapid progression.

PRO-101 is the first-in-human trial of prosetin. In parts 1a and 1b, healthy volunteers received single or multiple ascending doses of prosetin or a placebo. Part 1c is now evaluating the treatment’s safety, tolerability, and pharmacological properties in people with ALS.

“MAP4K inhibition has been shown to protect motor neurons from [ER] stress and other well-established pathological mechanisms of ALS, and we are excited to partner with ProJenX on study PRO-101,” said Leonard H. van den Berg, MD, PhD, a professor of neurology at UMC Utrecht, chairman of the Treatment Research Initiative to Cure ALS (TRICALS), and a PRO-101 study investigator.

TRICALS is the largest European research initiative, encompassing 48 research centers in 16 countries, together with patient organizations and fundraisers, to find effective treatments, and ultimately, a cure for ALS.

According to van den Berg, this is “the first clinical trial to explore the potential benefits of MAP4K inhibition for ALS patients.”

Prosetin has been granted orphan drug designation by the U.S. Food and Drug Administration for the treatment of ALS. This designation provides several financial incentives, including tax waivers and seven years of marketing exclusivity if the drug ultimately is approved.

“ALS is a devastating disease, and there is an immense unmet need for therapeutic options to slow or halt its rapid progression,” van den Berg said.