Astellas Pharma Inc. and AviadoBio Ltd have announced a strategic collaboration focused on developing AVB-101, a gene therapy candidate for frontotemporal dementia with progranulin mutations (FTD-GRN). The agreement, potentially valued at $2.2 billion, aims to address the significant unmet need in treating this devastating neurodegenerative disease. Astellas will make a $20 million equity investment in AviadoBio and up to $30 million in upfront payments for the option to license AVB-101.
AVB-101: A Novel Gene Therapy Approach
AVB-101 is an investigational adeno-associated virus (AAV)-based gene therapy designed to deliver a functional copy of the GRN gene to the brain, restoring appropriate progranulin levels. Progranulin, an 88kDa protein, is essential for neuronal survival and function, and mutations in the GRN gene are a known cause of FTD. Approximately 5-10% of FTD patients exhibit low progranulin concentrations in their serum.
The therapy is administered via a minimally invasive, stereotactic neurosurgical procedure directly to the thalamus, a brain region with extensive connections to the frontal and temporal lobes. This targeted delivery method aims to safely and effectively cross the blood-brain barrier, delivering treatment directly to the areas most affected by FTD while minimizing systemic exposure.
Clinical Significance and Unmet Need
Frontotemporal dementia is an often unrecognized and misdiagnosed early-onset dementia with a poor prognosis, typically leading to death within 3 to 13 years of diagnosis. Patients experience a rapid decline in executive function, including attention control, working memory, and problem-solving, as well as uncharacteristic behaviors, loss of language, apathy, and reduced mobility. It is the second most prevalent form of young-onset dementia.
"AVB-101 represents a truly innovative approach to the treatment of FTD-GRN and has the potential to be part of the next generation of gene therapy products through the creation of this agreement," said Adam Pearson, chief strategy officer, Astellas.
Currently, there is no cure or effective treatment for FTD. Medicines used to treat Alzheimer’s disease have not shown benefit in FTD patients. Existing treatments focus on managing behavioral symptoms with antidepressants and antipsychotics.
Collaboration Details and Future Milestones
Under the terms of the agreement, Astellas will have the option to receive a worldwide exclusive license for the development and commercialization rights to AVB-101 in FTD-GRN and other potential indications. In addition to the upfront investment, AviadoBio is eligible to receive up to $2.18 billion in license fees and milestone payments, plus royalties, if Astellas exercises its option.
The ongoing Phase I/II ASPIRE-FTD trial (started enrollment in April 2024) is evaluating the safety and efficacy of AVB-101 in patients with FTD-GRN. The multicenter study is actively enrolling participants.
"As we complete dosing of the first cohort of patients in our Phase I/II ASPIRE-FTD trial of AVB-101, we are excited about the potential of this collaboration to help address the unmet need that exists today in frontotemporal dementia," said Lisa Deschamps, CEO, AviadoBio. "This strategic collaboration will combine our promising gene therapy candidate for FTD-GRN and delivery expertise with Astellas’ global capabilities in development and commercialization of gene therapies."
