ProJenX has dosed the first subject in the first-in-human Phase 1 PRO-101 clinical trial of its investigational new drug, prosetin, in healthy subjects and amyotrophic lateral sclerosis (ALS) patients.

An oral, brain-penetrant, mitogen-activated protein kinase kinase kinase kinase (MAP4K) inhibitor, prosetin acts on endoplasmic reticulum (ER) stress. 

ER stress is a common characteristic of ALS’ sporadic and familial forms.

In a patient-specific, cell-based discovery platform developed by Columbia University scientists, MAP4Ks were detected as the crucial ER stress-mediated motor neuron loss regulators.

The three-part, hybrid trial will analyse the safety, tolerability, pharmacokinetics and pharmacodynamics of the drug in healthy subjects and individuals with ALS.

Parts 1a and 1b will be double-blind, randomised, placebo-controlled, dose-escalating studies for assessing the safety, tolerability and pharmacokinetics of single ascending and multiple doses of prosetin in healthy subjects. 

On evaluating data from these parts, Part 1c of the trial will assess the drug’s safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with ALS.

The PRO-101 trial was designed following talks with the Food and Drug Administration (FDA), various clinicians and community advisors for ALS.

It seeks to validate the safety and biomarker data required for selecting the dose and designing late-stage trials. 

ProJenX co-founder and Operations senior director Erin Fleming said: “We are excited to advance prosetin, a potential first-in-class treatment for ALS and related neurodegenerative diseases, into the clinic. 

“PRO-101 will provide essential safety, pharmacokinetic, and biomarker data about prosetin to inform our decisions on future clinical testing, including potential registrational studies.” Project ALS, a nonprofit organisation funded the preclinical development of prosetin. 

Clinical Trials Arena previously looked into how to build a clinical trial in ALS for approval.