Verge Genomics (Verge) has announced that the first subject has been dosed in its phase 1 clinical trial evaluating VRG50635, a small molecule inhibitor of PIKfyve, as a treatment of amyotrophic lateral sclerosis (ALS), also known as motor neurone disease.
Characterised by a progressive degeneration of motor nerve cells in the brain and spinal cord, ALS leads to deteriorating muscle function, the inability to move and speak, respiratory paralysis and eventually death.
VRG50635 was discovered by the company’s all-in-human, AI-powered platform – CONVERGE – and is the only PIKfyve inhibitor in clinical development that has been specifically optimised for the treatment of central nervous system disorders like ALS.
The platform uncovered PIKfyve as a promising new therapeutic target through the evaluation of more than 11.4 million data points from ALS patient tissue and genetics datasets, unveiling loss of endolysosomal function as a new causative mechanism in ALS.
VRG50635 restores endolysosomal function in ALS patient neurones and has shown efficacy in multiple preclinical studies in ALS-relevant models of motor neurone degeneration.
“For years, researchers have heavily relied on animal or cell models to identify new targets, in a way that oversimplifies the enormous complexity of human biology, particularly for diseases like ALS,” said Robert Scannevin, chief scientific officer at Verge.
“The CONVERGE platform starts with, and integrates human data and human model systems throughout discovery and development. This provides unique insights into the biological underpinnings of ALS, and also predicts drug targets, like PIKfyve, that can broadly impact these complex, disease-relevant processes,” he added.
This first-in-human study is a randomised, 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 multiple-dose study in patients with ALS – phase 1b.
Alice Zhang, chief executive officer of Verge Genomics, said: “We are proud to be not just one of the few AI-driven biotech companies to have made it to the clinical stage, but also one of the first to bring forward a novel clinical compound against a novel target, that was entirely discovered and developed internally on our platform.
“…This is just the start of our plan to develop a robust clinical pipeline of new medicines demonstrating that a human-to-human rather than an animal-to-human approach has the potential to transform clinical success rates.”