- AVB-101 is an investigational gene therapy designed to halt disease progression by delivering a functional copy of the progranulin (GRN) gene to restore progranulin protein levels in the brain
- Intrathalamic delivery of AVB-101 in non-human primates was well tolerated and led to broad biodistribution of progranulin expression in the brain
- AviadoBio recently announced the initiation of the Phase 1/2 ASPIRE-FTD clinical study evaluating AVB-101 in people with frontotemporal dementia with GRN mutations
AviadoBio, a pioneering gene therapy company dedicated to developing and delivering potentially transformative medicines for neurodegenerative disorders, announced today the presentation of preclinical safety and biodistribution data on AVB-101 at the 30th annual European Society of Gene and Cell Therapy (ESGCT) Congress in Brussels.
AVB-101 is an investigational, adeno-associated virus (AAV) gene therapy in development for patients with frontotemporal dementia (FTD) with disease-causing mutations in the GRN gene, known as FTD-GRN. These mutations lead to deficient production of the protein progranulin (PGRN). AVB-101 is designed to normalize PGRN levels in the areas of the cortex most impacted by FTD, while restricting PGRN expression to neurons and enhancing secretion efficiency to minimize the required dose of vector.
At all doses studied, AVB-101 showed good tolerability and widespread PGRN expression in the brain tissues of non-human primates at three and six-months post-treatment.
"We are excited to present at ESGCT our preclinical data on a novel gene therapy for people with FTD-GRN. Infusion of AVB-101, containing the GRN gene, directly into the thalamus boosts progranulin protein production and secretion into the cortex. This approach has the potential to restore progranulin protein levels throughout the brain and address the needs of patients with FTD-GRN," said Prof Christopher E. Shaw, Chief Scientific Officer and Co-Founder. "As we begin enrollment in our Phase 1/2 ASPIRE-FTD trial, these data reinforce our belief in AVB-101 as a potential one-time, disease-modifying treatment for patients with this devastating disease."
AVB-101 Six-month Preclinical Safety and Biodistribution Data Following Intrathalamic Delivery to Cynomolgus Monkeys Demonstrates Good Tolerability and Widespread Progranulin Expression in Brain Tissues
Presenter: Carlos Miranda, AviadoBio Ltd
Poster Number: 30
Highlights from this study include:
- AVB-101 delivered by intrathalamic infusion constitutes a novel and promising approach to address unmet medical needs in FTD-GRN, with the Phase 1/2 clinical trial (ASPIRE-FTD) currently open in Europe.
- Intrathalamic delivery of AVB-101 was well tolerated at all doses tested, with no mortality or observable clinical adverse events seen.
- Results showed that human progranulin (hPGRN) was most abundant in the thalamus, a key hub for biodistribution in the brain, but also detected throughout the brain.
- AVB-101 increased hPGRN levels in the temporal and frontal lobes, the cortical regions most severely affected by FTD-GRN.
- Vector genomes (VGs) were minimal or undetectable in most visceral tissues, and hPGRN expression was restricted to the central nervous system (CNS).
- Levels of PGRN in the cerebrospinal fluid (CSF) showed a dose-dependent increase, offering a potential biomarker of vector transduction and expression in the CNS.
About Frontotemporal Dementia (FTD) and FTD with GRN mutations (FTD-GRN)
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 may have a substantially greater impact on work, family, and finances than Alzheimer's disease. Genetic FTD cases account for about one-third of cases and is associated with autosomal dominant mutations in three genes, including the GRN (progranulin) gene. Approximately 11,000 people in the U.S. 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.
About AviadoBio
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, please visit www.aviadobio.com and follow us on X @AviadoBio and LinkedIn at AviadoBio. More information about the ASPIRE-FTD study can be found at https://clinicaltrials.gov/study/NCT06064890.
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