Arbor Biotechnologies to Present Data on CNS Programs and Platform Advances at the American Society of Gene and Cell Therapy (ASGCT) 28th Annual Meeting
- Presentations demonstrate progress in advancing portfolio of CNS gene editing programs in SOD1 ALS and first data presented on company’s Angelman syndrome program
- Data showcase specificity characterization of Arbor’s proprietary type V nucleases to have 10-fold greater sensitivity in off-target detection
- Identification and characterization of first RT editor packageable in a single AAV
CAMBRIDGE, MA – May 15, 2025 – Arbor Biotechnologies, Inc., a biotechnology company discovering and developing the next generation of genetic medicines, today announced the presentation of four posters showcasing Arbor’s commitment to CNS diseases of high unmet need and advances in proprietary gene editing technology at the American Society of Gene and Cell Therapy (ASGCT) 28th Annual Meeting, taking place May 13-17 in New Orleans, Louisiana.
CNS Program Presentations
Presented data demonstrated preclinical proof-of-concept for Arbor’s proprietary type V gene editing platform, which enables delivery of the nuclease and guide construct in a single AAV capsid, in amyotrophic lateral sclerosis (ALS) with superoxide dismutase 1 (SOD1) mutations. In vitro and in vivo data detailed the identification and characterization of nuclease and guide constructs targeting SOD1 that efficiently reduced SOD1 protein levels while maintaining low off-target liability. Assessment of top performing editing constructs in a fast-progressing preclinical mouse model of ALS prevented a decline in muscle function which is indicative of motor neuron preservation. Moreover, an ongoing survival study demonstrated an extension of survival by approximately 100 days compared to controls.
Arbor’s presentations at the meeting included the first public presentation of its differentiated gene editing approach to potentially enable long-term treatment of Angelman syndrome by reactivating the paternal copy of the UBE3A gene, which is normally silenced in Angelman patients. The gene editing approach was able to restore UBE3A protein levels in Angelman patient-derived neurons to or above levels found in neurotypical control neurons or greater. In a novel multi-electrode array assay, developed to evaluate neuron activity, Arbor demonstrated the ability to reverse the hyperexcitability and hypersynchrony phenotype demonstrated in Angelman syndrome neurons to levels observed in neurotypical control neurons.
“We are excited to share our progress in advancing our type V gene editing platform beyond the liver into two CNS diseases of high unmet medical need,” said John Murphy, Ph.D., Chief Scientific Officer at Arbor. “These data support the continued development of these programs toward the clinic as novel therapeutic approaches with the potential to durably improve patient outcomes.”
Arbor’s Gene Editing Platform Presentations
Building on an earlier oral presentation highlighting preclinical data for ABO-101 in PH1, a separate presentation further elaborated on the in-depth on- and off-target assessment of Arbor’s proprietary engineered Cas12i2 type V nuclease. Data presented showed the consistency of Arbor’s engineered Cas12i2 to generate 5-20 nucleotide deletions. The similarity between on- and off-target editing patterns enabled Arbor to develop and validate a robust statistical method for off-target analysis. The limit of detection of the verification workflow was shown to be 0.012%, which is 10-fold more sensitive than the industry standard for detection of off-target editing for Cas9-based programs. Arbor showcased this approach in the off-target analysis for ABO-101, with 80% on-target editing and no off-target edits detected above 0.1% in primary human hepatocytes (PHH) and human splenic endothelial cells (HSEC).
An additional presentation detailed the first identification and characterization of novel small reverse transcriptase (RT) editors deliverable via a single adeno-associated virus (AAV) vector. Arbor demonstrated robust engineering of the small RT editors (sRTE) to substantially improve RT editing activity and broader targetability with the ability to make precise corrections in induced motor neurons.
“The advances in our platform technology support the sustainability of our gene editing discovery and development platform at Arbor,” said Devyn Smith, Ph.D., Chief Executive Officer at Arbor. “The ability to increase the sensitivity of our off-target detection allows more rigorous evaluation of the specificity and safety profile of our nucleases prior to entering the clinic. In addition, our identification of, what is to our knowledge the first small RT editors capable of being delivered via single AAV, allows us to further expand potential therapeutic targets for future development.”
Details for the poster presentations are as follows:
Title: A compact RT editor built from the metagenome
Abstract Number: 1100
Session: Wednesday Poster Reception
Session Date and Time: Wednesday, May 14, 2025, 5:30-7:00 PM CDT
Location: Poster Hall, Hall I2
Presenter: Dan Brogan, PhD
Title: Disruption of UBE3A-ATS by Gene Editing with a Type V CRISPR-Cas Enzyme as a treatment for Angelman Syndrome
Abstract Number: 1549
Session: Thursday Poster Reception
Session Date and Time: Thursday, May 15, 2025, 5:30-7:00 PM CDT
Location: Poster Hall, Hall I2
Presenter: Adele Bubnys, PhD
Title: Type V CRISPR nuclease edit patterns enable highly sensitive off-target detection
Abstract Number: 1637
Session: Thursday Poster Reception
Session Date and Time: Thursday, May 15, 2025, 5:30-7:00 PM CDT
Location: Poster Hall, Hall I2
Presenter: Ivan Kristanto
Title: Preclinical development of AAV mediated gene editing for SOD1-ALS using a Type V CRISPR-Cas enzyme
Abstract Number: 1923
Session: Thursday Poster Reception
Session Date and Time: Thursday, May 15, 2025, 5:30-7:00 PM CDT
Location: Poster Hall, Hall I2
Presenter: Amrutha Pattamatta, PhD
About ABO-101
ABO-101 is a novel, investigational gene editing medicine designed to be a one-time liver-directed gene editing treatment that results in a permanent loss of function of the HAO1 gene in the liver to reduce PH1-associated oxalate production. ABO-101 is currently being evaluated for PH1 in the redePHine Phase 1/2 clinical study (NCT06839235). PH1 is a rare genetic disorder in which enzyme deficiencies in the liver lead to the overproduction and buildup of oxalate, resulting in kidney stones eventually leading to end stage kidney disease and systemic oxalosis. ABO-101 is designed to knock down HAO1 gene expression in the liver, thereby providing durable reduction in oxalate production. ABO-101 consists of a lipid nanoparticle (LNP), licensed from Acuitas Therapeutics, encapsulating messenger RNA expressing a novel Type V CRISPR Cas12i2 nuclease and an optimized guide RNA which specifically targets the human HAO1 gene.
About Arbor Biotechnologies, Inc.
Arbor Biotechnologies™, a clinical stage, next-generation gene editing company based in Cambridge, MA, is advancing a pipeline of novel gene editing therapeutics to address a wide range of genetic conditions – from the ultra-rare to the most common genetic diseases. The company’s unique suite of optimized gene editors, which is capable of approaches ranging from gene knockout, excisions, reverse transcriptase editing, and large gene insertion, goes beyond the limitations of early editing technologies to unlock access to new gene targets and has fueled a robust pipeline of first-in-class assets focused on diseases of high unmet need. With Arbor’s lead program, ABO-101 for the treatment of primary hyperoxaluria type 1, progressing into clinical trials, the company continues to focus its research and development efforts on genomic diseases of the liver and CNS for which there are no existing functional cures. For more information, please visit: arbor.bio.
Media Contact:
Peg Rusconi
Deerfield Group
prusconi@nulldeerfieldgroup.com