AviadoBio Presents Preclinical Data at ASGCT 2022 Demonstrating that AVB-101 Represents a Novel and Promising Approach to Treatment of Frontotemporal Dementia
• Intrathalamic delivery of AVB-101 achieved broad biodistribution in the brain, with no vector detected in the liver or progranulin in the serum
• AVB-101 demonstrated efficacy by rescuing disease pathology in progranulin-deficient mouse model
• AviadoBio plans to initiate clinical activities for AVB-101 later this year
London, UK; May 17, 2022 — AviadoBio, a pioneering, pre-clinical stage gene therapy company focused on developing and delivering transformative medicines for people with neurodegenerative disorders, today presents preclinical data on its investigational, one-time, adeno-associated virus (AAV) gene therapy, AVB-101 (AVB-PGRN), in an oral presentation at the American Society of Gene & Cell Therapy annual meeting (ASGCT 2022).
The data being presented are from pre-clinical studies with AVB-101 to treat frontotemporal dementia with GRN mutations (FTD-GRN). Mutations in the GRN gene encoding progranulin (PGRN) cause FTD-GRN and the supplementation of PGRN has been hypothesised as a potential therapeutic approach. In pre-clinical pharmacology studies, AVB-101 administration via intrathalamic injection, in a progranulin-deficient mouse model, demonstrated neuronal specific PGRN brain expression and reduction in disease pathology.
“The data from these studies are highly compelling and give us great confidence in the potential of precision micro-dosing of AVB-101 to effectively treat FTD by delivering a functional copy of the GRN gene to the right areas of the CNS to impact disease progression while minimizing off target expression and distribution. The findings from the biodistribution studies are particularly exciting, demonstrating that effective and targeted distribution of a gene therapy is possible via intrathalamic injection. We look forward to continuing our clinical studies as we move ever closer to addressing the unmet need in FTD,” said Prof. Chris Shaw, Co-founder and Chief Scientific and Clinical Advisor, AviadoBio.
Patients with FTD-GRN experience profound subcortical and cortical degeneration, so the ability to treat these regions is critically important for therapeutic success. AviadoBio’s targeted approach takes advantage of existing neuronal networks to achieve maximal biodistribution with low doses of viral vector. AviadoBio presented data from pre-clinical studies in a large animal model that underwent intrathalamic delivery of AVB-101 and demonstrated widespread cortical and subcortical distribution of PGRN. Importantly, no PGRN or AVB-101 vector was detected in the serum and liver respectively, thus potentially minimizing off-target tissue effects.
“The results from these studies represent a further important milestone for AviadoBio, and for FTD patients who currently have limited or no viable treatment options. We believe that our novel, neuroanatomy-led approach to gene therapy helps to address the challenges of gene therapy for neurodegenerative diseases. We look forward to initiating the next phase of our clinical studies later this year,” said Lisa Deschamps, CEO, AviadoBio.
The oral presentation, entitled “Intrathalamic Delivery of AVB.PGRN Rescues Pathology in Grn Null Mice and Achieves Widespread Cortical Expression in a Large Animal Model without Expression in the Liver”, will be presented by AviadoBio Co-Founder and Chief Scientific and Clinical Advisor, Professor Chris Shaw, today at 3:45pm (EST). The presentation will form part of the session “Applications of Improved Gene Therapy Methods in Neurologic Disorders” and will be followed by a Q&A discussion.
The abstract (number 468) can be viewed here.
At AviadoBio, our mission is to transform the lives of people living with neurodegenerative disorders by developing and delivering transformative gene therapies for diseases including frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The Company’s technology is based on pioneering research from King’s College London and the UK Dementia Research Institute. AviadoBio’s unique platform combines next-generation gene therapy design with deep neuroscience expertise and a novel neuroanatomy-led approach to drug delivery. AviadoBio’s investors include New Enterprise Associates (NEA), Monograph Capital, Advent Life Sciences, EQT Lifesciences, Dementia Discovery Fund (DDF), F-Prime Capital, Johnson & Johnson Innovation – JJDC, Inc. (JJDC), and LifeArc.
The company is developing AVB-101 for patients with FTD-GRN. AVB-101 is an investigational AAV gene therapy designed to slow or stop disease progression by delivering a functional copy of the GRN gene throughout the central nervous system to restore progranulin levels.
About Frontotemporal Dementia (FTD) and FTD with GRN mutations (FTD-GRN)
Frontotemporal dementia (FTD) is of the second most common form of dementia in people under the age of 65 after Alzheimer’s disease. It affects 50,000 to 60,000 patients in the U.S. and over 100,000 in the E.U. Approximately one third of FTD cases are familial and linked to autosomal dominant mutations in three genes including the granulin gene (GRN) and FTD-GRN represents 5-10% of all patients with FTD. Progressive degeneration of the frontal and temporal lobes of the brain is characteristic of FTD, and is associated with progressive decline of behaviour, decision-making, language and emotion, typically leading to death within 7-10 years of diagnosis. There are currently no approved treatments to stop or slow the progression of FTD or FTD-GRN.