Arbor Biotech Showcases ABO-101 Data at ASGCT Annual Meeting

Arbor Biotechnologies®, a pioneering biotechnology company specializing in the discovery and development of advanced genetic medicines, showcased significant preclinical data at the 2024 American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting in Baltimore, Maryland. Among the highlights was the presentation of preclinical efficacy and pharmacology data for ABO-101, a novel gene editing therapeutic intended for treating primary hyperoxaluria type 1 (PH1).

In his statement, Devyn Smith, Ph.D., Chief Executive Officer of Arbor, emphasized the company's commitment to enhancing CRISPR-Cas gene editing technologies through its proprietary nuclease discovery and development platform. This platform is pivotal in identifying and optimizing new gene editing tools, thereby translating them into potentially life-changing therapeutics. Arbor's robust pipeline addresses various liver and central nervous system (CNS) conditions, including PH1 and amyotrophic lateral sclerosis (ALS).

The key presentation at ASGCT featured in vivo data demonstrating the therapeutic potential of ABO-101 specifically designed to target PH1. The data showed precise targeting of the HAO1 gene in the liver, maintaining genomic integrity post-editing. Moreover, the preclinical model of PH1 revealed effective in vivo editing of HAO1, leading to a significant reduction in urinary oxalate levels. Notably, ABO-101 was well tolerated across multiple doses in non-human primates (NHPs). The efficacy and pharmacology of ABO-101 were validated through NHP studies, which showed efficient HAO1 editing, reduced glycolate oxidase activity, and increased serum glycolate levels. These compelling results support the continued clinical development of ABO-101.

Another important presentation discussed preclinical data indicating the effectiveness of Arbor’s novel type V nucleases in preventing aberrant splicing of the STMN2 gene, which is implicated in ALS. In cellular models, human motor neurons, and STMN2 transgenic mice, the disruption of the STMN2 motif increased the full-length STMN2 mRNA and decreased levels of aberrantly spliced STMN2 mRNA. This suggests that targeted deletions using novel nucleases could correct splicing errors in STMN2, signifying a promising therapeutic approach for ALS patients with TDP43 proteinopathy.

Arbor also presented data on its innovative platform for discovering and optimizing new nucleases. The presentation detailed the identification and enhancement of a compact type V nuclease, ABR-004. Using structure-guided design, Arbor improved the activity and specificity of this CRISPR-Cas type V-L system, resulting in potent and therapeutically relevant silencing of the PCSK9 gene in mice and NHPs. This highlights the potential for broader therapeutic applications and underscores Arbor’s capability in developing next-generation gene editing tools.

David Cheng, Arbor’s Chief Technology Officer, participated in a scientific symposium discussing the transformative role of artificial intelligence (AI) in the discovery and development of genomic medicines. His presentation underscored the impact of AI on cell and gene therapy advancements.

Arbor Biotechnologies, co-founded by Feng Zhang and David Walt, integrates CRISPR technology with sophisticated AI-driven discovery, high-throughput screening, and protein engineering. This combination has produced an expansive arsenal of gene editing tools aimed at treating a wide range of genetic diseases, from ultra-rare conditions to common genetic disorders. With a strategic focus on genomic diseases of the liver and CNS, Arbor is progressing towards clinical trials for its lead program targeting PH1 and is actively seeking partnerships to expand the application of its novel nuclease technology across various therapeutic areas.

Through these efforts, Arbor Biotechnologies aims to realize the full potential of gene editing, advancing the treatment landscape for genetic diseases and pioneering the next generation of genomic medicines.