RARE Daily

4DMT and Arbor Bio Partner to Collaborate on Genetic Medicines for CNS Diseases

January 3, 2024

Rare Daily Staff

4D Molecular Therapeutics and Arbor Biotechnologies entered a strategic partnership focused on advancing new AAV-based gene-editing therapies for central nervous system 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.

“Gene editing technology continues to rapidly advance and we believe the safe and efficient delivery of these potentially transformative therapies can address CNS diseases of high unmet need,” said David Kirn, co-founder and CEO of 4DMT. “Arbor is at the forefront of this rapid innovation, and they have discovered and optimized gene editing payloads that are compact enough to be delivered within a single AAV vector. This collaboration provides us with the opportunity for next-generation gene editing capabilities and CNS products, while simultaneously allowing us to maintain our focus on clinical development in large market ophthalmology and pulmonology.”

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), a progressive neurodegenerative disease in which the motor neurons atrophy and die, resulting in loss of the ability to speak, move, eat and, eventually, breathe. 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-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). Arbor says the PAMs, for example, may enable Arbor to access greater than 93 percent 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.

“CNS disorders include some of the most devastating diseases, many of which have a genetic origin. The technology to effectively edit the underlying genetic mutations within these diseases did not exist until an AAV compatible genomic editing technology was developed. Utilizing our expansive toolbox of AAV compatible genomic editors, we aim to advance the development of potential lifesaving therapies for CNS diseases,” said Devyn Smith, CEO of Arbor. “4DMT’s proprietary, customized, and evolved AAV vectors potentially provide the best delivery vehicles for our gene editing payloads to target select regions of the brain that we believe could provide meaningful benefits to patients in both rare and large CNS patient populations.”

Financial details of the collaboration were not disclosed.

Photo: Devyn Smith, CEO of Arbor

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