SPR301 is a potential best-in-class gene therapy candidate that delivers a more stable, rationally engineered version of GCase, the enzyme deficient in Parkinson’s disease patients with GBA1 mutations
Preclinical studies show SPR301 reaches key regions of the brain, leading to substantially greater reduction of toxic substrates compared to delivery of wildtype GCase
Initiating Investigational New Drug (IND)-enabling studies to support advancement of SPR301 into a Phase 1/2 clinical trial in 2026
LONDON, December 3, 2024 – Spur Therapeutics today announced that it has selected a lead development candidate in its gene therapy program for a genetically defined subset of Parkinson’s disease characterized by mutations in the GBA1 gene. The mutations cause a deficiency in the enzyme glucocerebrosidase (GCase), leading to the accumulation of α-synuclein and subsequent death of neuronal cells that are hallmarks of Parkinson’s disease.
The development candidate, SPR301, uses the AAV9 capsid, a proven gene-delivery vehicle known for its broad distribution across the brain, to deliver GCase85, a rationally engineered version of the GCase enzyme with enhanced stability compared to wildtype GCase. In preclinical studies, SPR301 successfully delivered GCase85 to critical regions of the brain and demonstrated substantially higher GCase activity and greater α-synuclein reduction than an AAV9 construct delivering wildtype GCase.
“GBA1 mutations greatly increase the risk of developing Parkinson’s disease and are associated with earlier onset, more severe symptoms, and higher likelihood of progression to dementia,” said Henning Stennicke, PhD, Spur’s Chief Scientific Officer. “By delivering our more stable GCase85 to key cells in the brain, we believe SPR301 can counteract the reduced GCase activity caused by these mutations, potentially providing a gene therapy that alters the course of disease and changes the lives of people with GBA1 Parkinson’s disease.”
“SPR301 marks an important step toward our vision to bring transformative new gene therapies to more patients, addressing more prevalent diseases and expanding our impact,” said Michael Parini, Spur’s Chief Executive Officer. “The preclinical data we’ve seen so far highlight SPR301’s potential to change the way we approach Parkinson’s disease. Based on these data, we are initiating IND-enabling studies to support the advancement of SPR301 into a Phase 1/2 trial in 2026. We are committed to working closely with the Parkinson’s disease community to advance this novel gene therapy candidate and work toward a future where GBA1 Parkinson’s disease can be better managed and, ultimately, cured.”
Spur’s Parkinson’s disease program builds on the company’s work in Gaucher disease, which also results from mutations in the GBA1 gene. As in Parkinson’s, the GBA1 mutations lead to a deficiency of the GCase enzyme and the accumulation of toxic substrates. Spur’s scientists developed GCase85 as part of their work on FLT201, the company’s clinical-stage gene therapy program in Gaucher disease type 1. Data from the ongoing Phase 1/2 clinical trial of FLT201 has shown significant reductions in accumulated substrate, compelling signs of clinical benefit, and a favorable safety and tolerability profile.
As part of its strategy to optimize therapies for specific diseases, Spur scientists further enhanced SPR301 for expression and distribution of GCase85 in the brain and selected the AAV9 capsid, which is better suited for delivery to the brain than the capsid used in FLT201.
Preclinical data supporting the selection of SPR301 include:
- An order of magnitude higher GCase activity in vitro and in vivo compared to an AAV9 construct delivering wildtype GCase (AAV9-wtGase).
- Efficient distribution to target cells within regions of the brain affected by Parkinson’s disease, including the substantia nigra.
- Broader GCase distribution than AAV9-wtGcase when directly injected into the brain in GCase-deficient mice, with dose-dependent substrate reduction.
- Wider therapeutic window, with 25-fold lower dose showing substrate reduction equivalent to high-dose AAV9-wtGCase and higher doses showing further reductions, potentially allowing for greater efficacy at doses with a favorable safety profile.
- Greater reduction of α-synuclein in vitro compared to AAV9-wtGCase in neuronal cells.
About GBA1 Parkinson’s Disease
Parkinson’s disease impacts the nervous system, resulting in tremors and difficulty walking or moving, as well as anxiety, depression, and cognitive impairments. Symptoms often emerge slowly and get progressively worse over the years. There is no cure, and symptomatic treatments become less effective over time. Between 5% and 15% of people with Parkinson’s disease have mutations in the GBA1 gene. These mutations are the most common genetic risk factor for Parkinson’s disease and are associated with earlier disease onset of disease, more severe symptoms, and an increased risk of dementia.
About Spur Therapeutics
Spur Therapeutics is a clinical-stage biotechnology company focused on developing life-changing gene therapies for debilitating chronic conditions. By optimizing every component of its product candidates, Spur aims to unlock the true potential of gene therapy to realize outsized clinical results. Spur is advancing a breakthrough gene therapy candidate for Gaucher disease, a potential first-in-class gene therapy candidate for adrenomyeloneuropathy and a preclinical gene therapy candidate for Parkinson’s disease, as well as a research strategy to move gene therapy into more prevalent diseases, including forms of dementia and cardiovascular disease. Expanding our impact, and advancing the practice of genetic medicine.
Toward life-changing therapies, and brighter futures. Toward More™
For more information, visit www.spurtherapeutics.com or connect with Spur on LinkedIn and X.
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