Advancing a vaccine targeting genetic amyotrophic lateral sclerosis (C9orf72 ALS) to the clinical stage

Introduction

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is triggered by protein aggregation in the brain and spinal cord motor neurons, leading to respiratory failure within 2-5 years. The best available drug extends life by approximately 3 months. ALS strikes about 1 in 500 people, mostly for unknown reasons, but 5-10% of cases in Caucasians are caused by a mutation in the C9orf72 gene.

Background

We have shown that this mutation leads to the expression of large aggregating poly-Glycine-Alanine (poly-GA), which triggers downstream pathology. We developed a poly-GA peptide vaccine that reduces aggregates and largely prevents motor deficits in a mouse model.

Vaccine Efficacy

When starting vaccination in already symptomatic mice, our vaccine reduces neuronal damage to a similar extent. Since regular lifelong vaccination is required to maintain sufficient antibody levels, GA-VAX is an attractive business case in the orphan disease space with:

• ~2500 prevalent C9orf72 ALS cases in the US, DE, IT, FR, ES, UK.
• ~9000 mutation carriers at risk to develop the disease within 10 years who could benefit even more from our approach.

Joint Venture

A joint venture established by Intravacc and DZNE will bring together the right resources to advance this promising treatment approach towards clinical evaluation.

Contributions

• Intravacc contributes know-how for the production and clinical development of peptide/carrier conjugate vaccines.
• DZNE provides in-depth knowledge of disease pathology as well as all necessary model systems and assays.

Next Steps

Together, we will set up GMP manufacturing for the antigen and conduct pivotal toxicology and efficacy studies in animals in accordance with regulatory requirements by EMA and FDA. This will allow us to compile a clinical trial application in C9orf72 ALS patients.

Funding Strategy

In addition, we will use this data package to raise capital for the phase 1 trial from a patient organization or investor for further de-risking or, preferentially, directly partner with a larger pharma company to bring GA-VAX to the market.