• PRO-101, the Phase 1b study of prosetin in ALS participants, is fully enrolled
• Prosetin is safe and well-tolerated over long-term dosing at target active exposures in ALS participants, and demonstrates exposure-related, statistically significant target engagement
• Data will be presented at the European Network to Cure ALS (ENCALS) 2026 meeting

NEW YORK, June 16, 2026 /PRNewswire/ — ProJenX, a clinical stage biotechnology company developing novel, targeted, brain-penetrant therapies for the treatment of amyotrophic lateral sclerosis (ALS) and other debilitating brain diseases, today announced a clinical update from PRO-101, a Phase 1b clinical study evaluating prosetin—a potent, selective, CNS-penetrant MAP4K inhibitor—in participants with ALS. PRO-101 was designed to evaluate the safety, tolerability, pharmacokinetics (PK), and target engagement of prosetin. Interim data from the multiple ascending dose (MAD) portion of PRO-101, which includes 41 ALS participants across five dose levels, support continued development of prosetin as a potential ALS treatment based on its favorable, consistent safety and tolerability, predictable PK activity, and exposure-related peripheral target engagement.

“I am encouraged by these interim findings from PRO-101,” said Jinsy Andrews, MD, MSc, Director of the NYU Langone ALS Center and ALS Clinical Trials at NYU Langone and Co-Chair of the Network of Excellence for ALS (NEALS) consortium. “Compelling preclinical data supported evaluation of prosetin as a potential disease-modifying treatment for sporadic ALS—but in this first-ever clinical study of a brain-penetrant MAP4K inhibitor, our goal was to answer critical questions about whether prosetin could be safely administered at active dose levels in people living with ALS. Today’s data answers that question, supporting continued evaluation of prosetin for ALS.”

While the MAD portion of PRO-101 is complete, ProJenX continues to evaluate long-term effects of prosetin through the 2-year open-label extension (OLE) portion of PRO-101, available to all study participants who completed the MAD. In addition to evaluating long-term safety, tolerability, and PK, the OLE evaluates exploratory biomarker and functional assessments. These include neurofilament light chain (NfL), a panel of neuroinflammatory biomarkers, and the revised ALS Functional Rating Scale (ALSFRS-R).

Erin Fleming, Co-Founder and Chief Operating Officer of ProJenX, said, “While PRO-101 was designed primarily to evaluate whether a safe and active dose of prosetin could be achieved in people living with ALS, longitudinal data from the OLE will guide critical decisions around upcoming study design, allowing us to select scientifically-driven eligibility criteria and study endpoints for a rigorous Phase 2 study of prosetin in ALS.”

Interim results from the PRO-101 study include:

• Prosetin is generally safe and well-tolerated across all dose levels studied in PRO-101 (0.16 – 1.05 mg/kg/day). No clinically significant abnormalities or trends were observed on study safety assessments. Critically, no prosetin-related serious adverse events have been reported to date, including in long-term evaluation across the OLE portion of the study.
• Plasma concentrations of prosetin at the two highest dose levels (0.70 and 1.05 mg/kg/day) achieved the target therapeutic exposure dose range established by preclinical PK/PD models.
• Prosetin treatment is correlated with a statistically significant, exposure-related decrease in phosphorylated MAP2K4 (pMAP2K4) in peripheral blood mononuclear cells (PBMCs) collected from PRO-101 participants.
  • Evaluation of pMAP2K4 is a novel target engagement assay for MAP4K inhibition. pMAP2K4 is increased both in ALS stem cell-derived motor neurons—where it is attenuated by MAP4K inhibition—and in ALS patient PBMCs when compared to healthy control PBMCs.

ENCALS PRESENTATION DETAILS

Interim data from PRO-101 will be presented at the ENCALS meeting, June 24 – 26, Madrid, Spain:

Wednesday, June 24, 10:30am CEST: Study update from PRO-101 at the TRICALS satellite meeting, Insights from recent and upcoming trial results

Wednesday, June 24, 5:20pm CEST: Poster #409, PRO-101, A Hybrid Phase 1 Study Evaluating The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Prosetin In Participants With ALS

ABOUT PROSETIN

Prosetin is a potent, selective, CNS-penetrant, orally available MAP4K inhibitor under evaluation for the potential treatment of ALS. While MAP4K was initially identified as a critical regulator of proteotoxic stress-mediated motor neuron loss in a human stem cell-based discovery platform developed by ProJenX scientific founders at Columbia University, more recent internal and independent data have demonstrated that MAP4K inhibition confers broad neuroprotective effects in diverse preclinical ALS models, including significant rescue of TDP-43 pathology in vitro. Prosetin is an investigational new drug and has not been approved by the FDA.

ABOUT PROJENX

ProJenX is a clinical-stage biotechnology company developing novel, brain-penetrant, targeted therapies to address debilitating brain diseases, with an initial focus on ALS. ProJenX was created out of a long-term research collaboration between Project ALS and researchers at Columbia University to rapidly develop and commercialize its lead therapy candidate, prosetin, for people living with ALS. At the heart of ProJenX’s approach is an innovative, patient-specific, cell-based drug discovery platform that can be leveraged for research and drug development for ALS and other neurodegenerative diseases. For more information, visit projenx.com.

Media Contact: 
media@projenx.com
9174236476

View original content to download multimedia:https://www.prnewswire.com/news-releases/projenx-announces-a-development-update-for-prosetin-a-first-in-class-cns-penetrant-map4k-inhibitor-302801015.html

SOURCE ProJenX