Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by protein aggregation in the motor neurons of the brain and spinal cord that leads to respiratory failure within 2-5 years. The best available drugs extend life by ~3 months. ALS affects about 1 in 500 people in their lifetime, mostly for unknown reasons, but 5-10% of cases in Caucasians are caused by a mutation in the C9orf72 gene. We have shown that this mutation leads to the expression of large aggregating poly-glycine-alanine (poly-GA), which triggers downstream pathology. We have developed a poly-GA peptide vaccine that reduces aggregates and largely prevents motor deficits in a mouse model. Remarkably, our vaccine reduces neuronal damage to a similar extent when administered in already symptomatic mice, underscoring the vaccine’s potential both for treatment and prevention.
Since regular lifelong vaccination is required to maintain sufficient antibody levels, GA-VAX represents an attractive business case in the orphan disease space with ~2500 prevalent C9orf72 ALS cases in the United States, Germany, Italy, France, Spain, and the United Kingdom. The ~9000 mutation carriers at risk of developing the disease within 10 years could benefit even more from our approach. C9orf72 patients developing frontotemporal dementia (FTD), a related neurodegenerative disease, are an additional market. Our highly complementary industry/academia team has all the expertise and resources to advance this promising treatment approach towards clinical evaluation. Intravacc contributes world-class manufacturing capabilities and clinical development expertise for peptide/carrier conjugate vaccines, while DZNE provides extensive knowledge of disease pathology, alongside advanced preclinical models and assays. Together, we aim to optimize the antigen, establish scalable manufacturing processes, and conduct rigorous preclinical evaluations aligned with EMA and FDA regulatory frameworks.
This will allow us to prepare a clinical trial application in C9orf72 ALS patients. In addition, we will use this data package to raise capital for the Phase 1 trial from a patient organization or investor to further de-risk the project or partner with a larger pharmaceutical company to bring GA-VAX to market. By advancing GA-VAX towards clinical application, we aim to create a meaningful impact on the lives of C9orf72 patients and provide a scalable model for addressing other neurodegenerative diseases through active immunization.
