AviadoBio announced the completion of the second dose cohort in its Phase 1/2 ASPIRE-FTD clinical trial, evaluating its investigational gene therapy AVB-101 for people living with frontotemporal dementia (FTD) with GRN gene mutations. The company plans to initiate dosing for a third cohort in Q3 2025 and expects to share early biomarker data in 2026. The announcement was made at the Association for Frontotemporal Degeneration (AFTD) annual caregiver conference in Denver on May 1, 2025.
The ASPIRE-FTD trial is actively recruiting participants across multiple sites in the United States, Spain, Poland, Sweden, and the Netherlands, with additional countries expected to join soon. This milestone represents significant progress in addressing a devastating neurodegenerative condition with limited treatment options.
Novel Delivery Approach Targets Brain Regions Affected by FTD
AVB-101 employs an innovative delivery method to overcome one of the major challenges in treating central nervous system diseases: the blood-brain barrier. The investigational gene therapy is administered via a neurosurgical procedure directly to the thalamus—a key hub with widespread projections across the brain, including the frontal and temporal cortex regions most affected in FTD-GRN.
"This delivery method bypasses the blood-brain barrier and the pial membrane that separates the brain from the cerebrospinal fluid, targeting therapy precisely where needed while potentially reducing required dosage and limiting systemic exposure," explained David Cooper, M.D., Chief Medical Officer of AviadoBio.
Pre-clinical data indicate that AVB-101 delivered to the thalamus can increase progranulin levels in cortical brain tissue, potentially restoring physiological function in people with FTD-GRN. The therapy contains a correct (non-mutated) version of the GRN gene and is designed to restore progranulin levels in the brain, which could slow or stop disease progression.
Encouraging Safety Profile Emerging
The completion of the second cohort marks the sixth patient dosed with AVB-101 in the trial. According to Dr. Cooper, the first cohort demonstrated an encouraging safety profile.
"In the first cohort, we did not see any clinically significant safety findings through follow-up of up to 52 weeks and did not require any immunosuppression prophylactically or reactively," he noted.
This safety profile is particularly significant for gene therapies, which can sometimes trigger immune responses requiring immunosuppressive treatment.
Addressing a Significant Unmet Need
Frontotemporal dementia is a devastating neurodegenerative disorder that primarily affects the frontal and temporal lobes of the brain, regions responsible for personality, behavior, and language. FTD with GRN mutations represents a genetic subtype of the disease with particularly rapid progression and limited treatment options.
Lisa Deschamps, CEO of AviadoBio, emphasized the company's commitment to the FTD community: "We're proud to share this important milestone with the FTD community, who continue to inspire our commitment to advancing research for therapies that may slow or stop the progression of this devastating disease. People living with FTD-GRN and their families remain at the heart of everything we do."
Trial Design and Future Outlook
The ASPIRE-FTD study is an open-label, multi-center Phase 1/2 trial designed to evaluate both the safety and preliminary efficacy of AVB-101. Eligible patients receive a one-time administration of the gene therapy delivered as a set of MRI-guided infusions into the thalamus during a minimally invasive stereotactic neurosurgical procedure.
AVB-101 has received orphan designation from both the U.S. Food and Drug Administration (FDA) and the European Commission, highlighting the significant unmet need in this patient population. Additionally, AviadoBio has entered into an option agreement with Astellas Pharma Inc. for a worldwide exclusive license for the development and commercial rights to AVB-101 in FTD-GRN and other indications.
As the trial progresses to its third cohort later this year, the company anticipates sharing early biomarker data in 2026, which could provide crucial insights into the therapy's mechanism of action and potential efficacy.
Founded on pioneering research from King's College London and the UK Dementia Research Institute, AviadoBio is backed by several prominent investors, including New Enterprise Associates, Monograph Capital, F-Prime Capital, Johnson & Johnson Innovation, and Astellas Pharma, among others.
