Verge Genomics, a clinical-stage, tech-enabled biotechnology company pioneering the use of artificial intelligence and human data to transform drug discovery, announced that the first subject has been dosed in a Phase 1 clinical trial of VRG50635. VRG50635 is a small-molecule inhibitor of PIKfyve, a novel therapeutic target for amyotrophic lateral sclerosis (ALS) discovered by CONVERGE, Verge’s all-in-human, AI-powered platform.
Through the evaluation of more than 11.4 million data points from ALS patient tissue and genetics datasets, CONVERGE discovered loss of endolysosomal function as a new causative mechanism in ALS, and uncovered PIKfyve as a promising new therapeutic target. VRG50635 is a potent PIKfyve inhibitor that restores endolysosomal function in ALS patient neurons and has shown efficacy in multiple preclinical studies in ALS-relevant models of motor neuron degeneration. VRG50635 is the only PIKfyve inhibitor in clinical development that has been specifically optimized for treatment of central nervous system disorders like ALS, and has the potential for best-in-class characteristics.
This first-in-human study is a randomized, double-blind, placebo-controlled, single- and multiple-ascending-dose design to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of VRG50635 in healthy volunteer subjects (Phase 1a) and a multiple-dose study in patients with ALS (Phase 1b).
About PIKfyve
Verge discovered the relevance of PIKfyve in ALS using its computational platform, CONVERGE, which incorporates large multi-omic data sets from patients with disease. PIKfyve is a kinase that is believed to regulate endolysosomal function within a variety of cells, including neurons. The endolysosomal pathway is a critical cellular process involved in protein homeostasis. Verge and other top research groups have shown that in ALS, this pathway is dysregulated, leading to neuronal death and disease progression. After the discovery of PIKfyve as a therapeutic target for ALS, Verge developed PIKfyve inhibitors that have been effective in reversing disease-relevant pathology in multiple preclinical models of ALS.
About amyotrophic lateral sclerosis (ALS)
ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects neuronal cells in the brain and spinal cord. ALS often strikes people between the ages of 40 and 70, and it is estimated that 100,000 people worldwide may have the disease at any given time. ALS is fatal, there is currently no cure, and available therapies have only modest benefits. The majority of patients succumb to the disease within 2 to 5 years after diagnosis.