4D Molecular Therapeutics, Inc. and Arbor Biotechnologies, Inc. announced a strategic partnership focused on advancing new AAV-based gene-editing therapies for central nervous system (CNS) diseases with high unmet medical needs in both rare and common disease populations. 4DMT and Arbor will co-develop and co-commercialize up to six AAV-delivered CRISPR/Cas-based therapeutic candidates, with the costs and profits shared evenly based on mutually agreed plans. Arbor will lead research, development and, if approved, commercialization efforts on the first product candidate in the collaboration, which will address a molecular target implicated in amyotrophic lateral sclerosis (ALS).

4DMT will lead research, development and, if approved, commercialization efforts on the second product candidate (target and disease to be disclosed at a future date). Arbor utilizes its artificial intelligence and machine learning, or AI/ML, driven discovery engine and protein engineering capabilities to identify and optimize genomic editors with the potential to treat a broad range of genetic diseases. Arbor?s proprietary portfolio of novel genomic editors has therapeutic potential due to, among other things, their unique cut patterns and protospacer adjacent motifs (PAMs).

The PAMs, for example, may enable Arbor to access greater than 93% of all sites in the human genome which allows it to target nearly any genetic locus. The small size of Arbor?s genomic editing technology allows the use of additional delivery mechanisms with their high specificity, which can enable improved safety profiles. Arbor also has expertise in CNS biology, CNS drug development and CNS therapeutic development.

4DMT?s proprietary invention platform, Therapeutic Vector Evolution, has yielded customized and evolved, highly targeted AAV vectors in ophthalmology, pulmonology and cardiology that have demonstrated differentiation compared to naturally occurring AAVs in clinical studies. Initial evidence includes strong clinical activity in wet age-related macular degeneration (wet AMD) with low dose, intravitreal delivery using the R100 vector (4D-150 product candidate), and unprecedented transgene expression was achieved in the lungs of people with cystic fibrosis using the A101 vector (4D-710 product candidate). 4DMT has utilized its platform to invent customized AAV vectors for CNS tissues, and these vectors will be deployed in the partnership.

In addition, the partnership will leverage 4DMT?s AAV product design and engineering, manufacturing, clinical and regulatory development expertise.