VQ-101 Show Promise in Interim Phase 1 Data for GBA-Parkinson Disease Treatment

Jim Sullivan, PhD

(Credit: Vanqua Bio)

New positive interim results from the phase 1a portion of a trial assessing investigational VQ-101 (Vanqua Bio), an orally administered brain-penetrant allosteric activator of glucocerebrosidase (GCase), showed that treatment with the agent resulted in target engagement in health volunteers across single and multiple ascending doses. Based on these findings, the company plans to proceed with the phase 1b portion of the trial among patients with Parkinson disease (PD), with data anticipated in 2025.¹

In the phase 1a portion trial, VQ-101 activated lysosomal GCase by over 75% in single dose cohorts and had sustained activation after multiple doses. These results went beyond the study’s initial target engagement goal of 50% activation, instructed by human genetics, and the company’s preclinical studies with patient-derived dopaminergic neurons in which 50% activation of GCase demonstrated a significant blockade of the accumulation of insoluble alpha synuclein, known as a pathologic hallmark of the movement disorder.

“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 data reflect the considerable efforts of an experienced team that is passionate about making a difference in the lives of people living with PD,” Jim Sullivan, PhD, cofounder and CEO at Vanqua Bio, said in a statement.¹ “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. We are pleased to advance to the Phase 1b portion of the study in patients with PD.”

In previous research, the therapy has been shown to activate lysosomal GCase in a live-cell assay across in vitro, ex vivo, and in vivo settings, and block the buildup of insoluble alpha synuclein in patient-derived neurons. Performed at the Centre for Human Drug Research in the Netherlands, the phase 1b portion of the study will include 28-day, randomized, double-blind, placebo-controlled treatment with multiple ascending doses of VQ-101 among patients with PD with and without GBA mutations.

READ MORE: Extended-Release Amantadine Shows Reduction in Dyskinesia Severity for Parkinson Disease

Additional findings from the phase 1a portion revealed that VQ-101 reached significant levels in the cerebrospinal fluid (CSF), with mean CSF-to-unbound plasma ratios of at least 1, indicating full central nervous system penetration. Notably, in both the single and multiple ascending dose cohorts, the therapy was well-tolerated in participants, with researchers not reporting any dose-limiting or serious adverse events. Overall, all of the observed treatment-emergent adverse events were considered as mild or moderate in nature and there were no study discontinuations because of adverse events. Vanqua Bio noted that detailed data from this portion of the phase 1 trial will be presented at a future medical conference.

In preparation for advancing VQ-101 into later-stage clinical studies, the company has announced the appointment of Maurizio Facheris, MD, as its new CMO. Jesse M. Cedarbaum, MD, FAAN, the company’s acting CMO, will continue to support Vanqua Bio as a senior clinical advisor. “We are grateful for Jesse’s contributions to Vanqua’s progress and are pleased that he will remain a key part of the Vanqua team,” Sullivan said in a statement.¹ “Maurizio brings first-hand experience of taking PD therapies from early phase development to approval and will be an excellent addition to our team.”

Prior to joining Vanqua Bio, Facheris served as senior medical director of neuroscience development at AbbVie, where he led the clinical development of PD therapies, including the successful approval of foslevodopa/foscarbidopa (Vyalev) for subcutaneous infusion. Previously, he was the senior associate director of research programs at the Michael J. Fox Foundation for Parkinson’s Research. Facheris earned his MD from the University of Brescia in Italy and completed his neurology residency at the University of Milano.

REFERENCES
1. Vanqua Bio Announces Positive Interim Results from Phase 1 Clinical Trial of VQ-101, an Orally Administered, Brain-Penetrant, Allosteric Activator of GCase for the Treatment of GBA-Parkinson’s and Related Disorders. News Release. Vanqua Bio. Published October 9, 2024. Accessed November 14, 2024. https://www.vanquabio.com/vanqua-bio-announces-positive-interim-results-from-phase-1-clinical-trial-of-vq-101-an-orally-administered-brain-penetrant-allosteric-activator-of-gcase-for-the-treatment-of-gba-parkinsons/