There is an unmet need for disease-modifying ALS treatments that slow progression, extend survival, and improve quality of life. Verge Genomics’ CONVERGE^â artificial intelligence target discovery platform identified phosphatidylinositol 3-phosphate 5-kinase type III (PIKfyve)/FIG4 as an ALS drug target. VRG50635, aPIKfyve inhibitor, substantially reduces motor neuron death in vitro. Tolerability, emerging safety, and pharmacokinetics/pharmacodynamics support this first-in-ALS patient study.  

To investigate the changes in molecular and clinical disease biomarkers during the 8-week pretreatment run-in period of the VRG50635 amyotrophic lateral sclerosis (ALS) proof-of-concept study.

54 people with sporadic (N=37) or genetic (N=17), mostly limb-onset, ALS were enrolled in a 3-part within-subject, open-label dose escalation study (Part 1, 8-week pretreatment run-in; Part 2, 32-week within-patient dose escalation, up to 3 dose levels; Part 3, 40-week long-term extension period, highest tolerated dose). Here, we report novel biomarker sensitivity to disease progression during the 8-week run-in compared to traditional endpoints.

Results will be presented for clinical digital biomarkers being investigated for disease progression sensitivity during the 8-week pretreatment run-in using the 24/7 At-home Touchless Emerald sensor (turning in bed, gait speed, sleep efficiency, deep sleep percentage, breathing depression, breathing rate variability) and the Modality conversational assessment tool (word count, syllable count, speaking duration, canonical timing alignment). Little change has been observed for traditional endpoints in the pretreatment run-in over 8 weeks: slow vital capacity (SVC) (N=39; mean [SD], 3.7[1] and 3.5[1] liters), ALS Functional Rating Scale-Revised (ALS-FRS-R) (N=31; mean [SD], 37.5[3.3] and 35.9[5]), and plasma neurofilament light (NfL) (N=26; median [range], 72 [18-160] and 74 [20-192] pg/mL)].

During the 8-week pretreatment run-in period, SVC, ALS-FRS-R, and plasma NfL are mostly stable at the individual and group levels. Results will be presented for novel digital clinical biomarkers assessing whether they can measure disease progression over the 8-week run-in period.