Abstract Details

Title Clinical Progress Update From PRO-101, a Hybrid Phase One Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Prosetin in Participants With ALS

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P10 - Poster Session 10 (8:00 AM-9:00 AM)

Poster/Presentation
Number 9-007

Objective

Study PRO-101 is a hybrid Phase 1 study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of prosetin in participants with ALS.

Background

ProJenX is developing prosetin, a novel, orally available, CNS-penetrant, highly potent, MAP4K inhibitor, for ALS. In preclinical models of ALS, prosetin strongly protects motor neurons against proteotoxic stress and other well-established drivers of disease pathology. PRO-101 is the first-in-human study of prosetin in healthy volunteers and participants with ALS.

Parts A and B of PRO-101 evaluated the safety, tolerability, and PK of single and multiple ascending doses of prosetin in 48 healthy volunteers. No serious adverse events or abnormalities in any safety assessments were identified, and plasma levels of prosetin increased in a predictable manner.

Design/Methods PRO-101, Part C is a double-blind, placebo-controlled, dose escalation study in which approximately 32 people with ALS receive prosetin, or matching placebo, at a 6:2 ratio over 14 days. All participants who complete Part C can choose to continue into Part D of the study, a 2-year open-label extension with additional data collection. In addition to safety and PK, exploratory endpoints measuring target engagement and impact on ALS disease progression are being evaluated.

Results

Baseline characteristics from PRO-101 represent a heterogeneous ALS population, consistent with the study’s broad eligibility criteria. Interim data supports a favorable safety and tolerability profile of prosetin, and consistent plasma PK behavior. Analyses of exploratory endpoints, including target engagement, neurofilament light chain, neuroinflammatory cytokines, ALSFRS-R, SVC, and ALSAQ-5, are ongoing.

Conclusions A growing body of evidence links MAP4K inhibition to neuronal survival in ALS, making it an attractive target for therapeutic intervention. Available data from PRO-101 demonstrates a favorable safety profile for prosetin in ALS participants and supports further evaluation of this potential first-in-class MAP4K inhibitor in people living with ALS.

Authors/Disclosures
Erin Fleming PRESENTER	Ms. Fleming has received personal compensation for serving as an employee of ProJenX. Ms. Fleming has received personal compensation for serving as an employee of Project ALS. Ms. Fleming has or had stock in ProJenX.
Kristiana Salmon, Other (QurAlis Corporation)	Miss Salmon has received personal compensation for serving as an employee of QurAlis Corporation. Miss Salmon has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for ProJenX. Miss Salmon has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant with ALS Canada.
April Ruby	April Ruby has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for ProJenX, Inc.
Hilde Williams	Hilde Williams has received personal compensation for serving as an employee of Vima Therapeutics, Inc.. The institution of Hilde Williams has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for ProJenX Inc.. Hilde Williams has stock in PharmaStory Corp.. Hilde Williams has received intellectual property interests from a discovery or technology relating to health care.
Ingela Danielsson-Sanden, MD, PhD (Ingela Danielsson-Sanden)	Dr. Danielsson-Sanden has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ProJenX.

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