Vanqua Bio's investigational drug VQ-101, an orally administered, brain-penetrant allosteric activator of glucocerebrosidase (GCase), has shown positive interim results in a Phase 1a trial. The treatment demonstrated target engagement in healthy volunteers across single and multiple ascending doses, prompting the company to proceed with a Phase 1b trial in Parkinson's disease (PD) patients, with data anticipated in 2025.
Phase 1a Results
The Phase 1a trial revealed that VQ-101 activated lysosomal GCase by over 75% in single-dose cohorts and maintained sustained activation after multiple doses. This exceeded the study's initial target engagement goal of 50% activation, which was based on human genetics and preclinical studies. These earlier studies, using patient-derived dopaminergic neurons, showed that 50% activation of GCase significantly blocked the accumulation of insoluble alpha-synuclein, a known pathological hallmark of Parkinson's disease.
Jim Sullivan, PhD, cofounder and CEO of Vanqua Bio, stated, "We are excited to announce that VQ-101 demonstrated robust activation of lysosomal GCase and high levels of CSF exposure at doses that were safe and well tolerated in healthy volunteers... These results, paired with data from our preclinical patient-derived neuronal models, support the potential for VQ-101 to stop the accumulation of alpha synuclein in Parkinson’s patients and slow or stop disease progression."
Phase 1b Trial Design
The Phase 1b portion of the study, conducted at the Centre for Human Drug Research in the Netherlands, will involve a 28-day, randomized, double-blind, placebo-controlled trial with multiple ascending doses of VQ-101 in Parkinson's disease patients, both with and without GBA mutations.
Additional Phase 1a Findings
Further results from the Phase 1a trial indicated that VQ-101 reached significant levels in the cerebrospinal fluid (CSF), with mean CSF-to-unbound plasma ratios of at least 1, suggesting full central nervous system penetration. The therapy was well-tolerated, with no dose-limiting or serious adverse events reported. All treatment-emergent adverse events were considered mild or moderate, and there were no study discontinuations due to adverse events. Detailed data from the Phase 1a trial will be presented at a future medical conference.
Leadership Changes
In preparation for advancing VQ-101 into later-stage clinical studies, Vanqua Bio has appointed Maurizio Facheris, MD, as its new CMO. Jesse M. Cedarbaum, MD, FAAN, will continue to support Vanqua Bio as a senior clinical advisor. Facheris previously served as senior medical director of neuroscience development at AbbVie, where he led the clinical development of Parkinson's disease therapies, including the approval of foslevodopa/foscarbidopa (Vyalev) for subcutaneous infusion. He also held a position at the Michael J. Fox Foundation for Parkinson’s Research.
