ProJenX, a biotechnology company focused on developing therapies for amyotrophic lateral sclerosis (ALS) and other brain diseases, has announced a partnership with Unlearn to augment its Phase 1 clinical trial PRO-101 using advanced generative artificial intelligence (AI) technology. The collaboration aims to enhance the evaluation of prosetin, ProJenX's investigational MAP4 kinase (MAP4K) inhibitor, in patients with ALS.
Unlearn will implement its ALS-Digital Twin Generator (ALS-DTG) to create digital twins of participants in the PRO-101 trial. These digital twins will serve as placebo counterparts, enabling researchers to compare the clinical outcomes of patients treated with prosetin against their AI-generated counterparts. The primary outcomes to be evaluated include changes in ALSFRS-R scores, Slow Vital Capacity, and plasma neurofilament light levels over a 52-week open-label extension.
How Digital Twins Will Be Used
Unlearn's ALS-DTG is a machine-learning model trained on patient-level data to forecast individual clinical trial participants' health outcomes. Baseline data collected at the start of the trial will be used by the ALS-DTG to forecast longitudinal clinical placebo outcomes, biomarkers, and labs, irrespective of the participant's treatment assignment. This approach aims to address key challenges in clinical development by providing a more robust and efficient way to assess treatment effects.
According to Stan Abel, president and CEO at ProJenX, this collaboration will allow for valuable insights that can expedite clinical trials and more efficiently evaluate prosetin in individuals living with ALS. By comparing participants dosed with prosetin to their digitally generated placebo versions, the collaboration seeks to enhance the interpretation of prosetin's effects on ALS patients, supporting a more efficient and data-driven clinical development program.
About the PRO-101 Trial
PRO-101 is a hybrid phase 1 clinical trial designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of prosetin in healthy volunteers and patients with ALS. Parts 1a and 1b, which have been completed, consisted of a randomized, double-blind, placebo-controlled, dose-escalating study to evaluate the safety, tolerability, and pharmacokinetics of single ascending and multiple doses of prosetin in healthy volunteers. Parts 1c and 1d will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of prosetin in ALS patients. Patients who complete part C, which runs for up to 56 days, will be invited to enter part D, an open-label extension phase where all participants will receive prosetin for 52 weeks.
Prosetin's Mechanism of Action
Prosetin is a brain-penetrant molecule designed to inhibit MAP4K in the brain. In preclinical studies, MAP4K inhibitors have shown potential in reducing inflammation and promoting motor neuron survival under endoplasmic reticulum stress conditions, which are implicated in the pathogenesis of ALS. The goal is to ease ALS symptoms by protecting neurons under stress conditions in the brain.
ALS and Unmet Needs
ALS is a progressive neurodegenerative disease affecting motor neurons, leading to muscle weakness, paralysis, and eventually death. There is a significant unmet need for effective treatments that can slow or halt the progression of the disease. The collaboration between ProJenX and Unlearn represents an innovative approach to accelerate the development of potential new therapies for ALS.
