AviadoBio Announces Initiation of Phase 1/2 Clinical Trial Evaluating AVB-101 in People With Frontotemporal Dementia With GRN Mutations

AviadoBio recently announced it has initiated the Phase 1/2 ASPIRE-FTD clinical study of its investigational gene therapy, AVB-101, in people with frontotemporal dementia (FTD) with mutations in the progranulin (GRN) gene.

ASPIRE-FTD is an open-label, multi-center study designed to evaluate the safety and preliminary efficacy of AVB-101 in patients with FTD-GRN. In the study, AVB-101 will be delivered as a one-time treatment into the thalamus via a stereotactic neurosurgical procedure at expert neurosurgical centers throughout Europe and the US.

“FTD is a devastating form of early-onset dementia and there are currently no disease-modifying treatments available,” said Lisa Deschamps, Chief Executive Officer. “The initiation of our company’s first clinical trial demonstrates our commitment to developing and delivering potential transformative gene therapies for those living with neurodegenerative disorders such as FTD.”

“While it is known that progranulin protein supplementation is possible using gene therapy, effective brain distribution remains challenging primarily because of the brain’s anatomy,” said David Cooper, MD, Chief Medical Officer. “Our aim is to use intrathalamic delivery to facilitate biodistribution of the PGRN protein to the areas of the cortex impacted by FTD. AVB-101 has already shown great promise in preclinical studies, and we now look forward to this important next step in its clinical development.”

Preclinical safety and biodistribution data following intrathalamic delivery to non-human primates demonstrate good tolerability and widespread progranulin expression in brain tissues. These data will be presented at the 30th Annual European Society of Gene & Cell Therapy (ESGCT) meeting in Brussels, Belgium Oct. 24-27, 2023.

People with FTD who have disease-causing GRN mutations produce a reduced amount of progranulin protein. AVB-101 has been designed as a potential one-time therapy to halt disease progression by delivering a functional copy of the GRN gene to restore appropriate progranulin levels to the affected areas of the brain.

AVB-101 is delivered using a minimally-invasive, stereotactic neurosurgical procedure directly to the part of the brain called the thalamus. The thalamus has extensive connections to other parts of the brain, including the frontal and temporal lobes, which play a critical role in FTD and the symptoms that impact patients and their families. This targeted delivery method aims to limit the treatment to the brain where it is needed most, thereby reducing the dose required and the potential systemic exposure. More information about the ASPIRE-FTD study can be found at https://clinicaltrials.gov/study/NCT06064890.

FTD is a devastating form of early onset dementia that typically leads to death within 7 to 13 years of symptom onset and 3 to 10 years from diagnosis. People with FTD commonly experience personality changes, behavioral disturbance, loss of language, apathy, and reduced mobility.

FTD is a leading cause of dementia in people under the age of 65 with an estimated prevalence at any one time of up to 4.6 cases per 1,000 of people. FTD typically strikes younger than Alzheimer’s disease and the majority of FTD cases occur between 45 and 68 years of age. Given the early onset, FTD has a substantially greater impact on work, family, and finances than Alzheimer’s disease. Genetic FTD cases account for about one-third of cases and are associated with autosomal dominant mutations in three genes, including the GRN (progranulin) gene. Approximately 11,000 people in the US and EU5 are living with FTD-GRN with approximately 2,200 new cases per year. Some FTD cases may be misidentified, and diagnostic delay is common. As disease education, genetics knowledge, and research and treatment options grow, these numbers are expected to increase.

AviadoBio’s mission is to develop and deliver potentially transformative gene therapies for people living with devastating neurodegenerative diseases such as frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). With our deep understanding of the brain and suite of proprietary gene therapy platforms and delivery technologies, AviadoBio is working relentlessly to overcome the challenges of delivering the right drug to the right place. Its innovative, neuroanatomy-led approach is designed to maximize the therapeutic potential of gene therapy to halt or potentially reverse neurodegenerative diseases. AviadoBio was founded on pioneering research from King’s College London and the UK Dementia Research Institute and has a leadership team with extensive gene therapy development, delivery, and commercialization experience which uniquely positions the Company for success in bringing transformative medicines to patients.

AviadoBio’s investors include New Enterprise Associates (NEA), Monograph Capital, F-Prime Capital, Johnson & Johnson Innovation – JJDC, Inc. (JJDC), Dementia Discovery Fund (DDF), Advent Life Sciences, EQT Lifesciences, and LifeArc. For more information, visit www.aviadobio.com.