Arbor Biotechnologies Presents Data Supporting Clinical Development of ABO-101 and Robust Potential of Platform to Enable Therapeutic Programs at the American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting

  • Presented data which, along with ongoing IND-enabling studies, demonstrate efficacy and pharmacology of ABO-101 in non-human primates (NHPs), supporting continued development as a potential novel gene editing therapy for patients with primary hyperoxaluria type 1 (PH1)
  • Other presentations include preclinical evidence of editing in the central nervous system (CNS) using novel CRISPR-Cas systems, signaling potential for an effective STMN2-targeting gene editing approach for amyotrophic lateral sclerosis (ALS)
  • Data demonstrate applicability of Arbor’s platform to identify and optimize new nucleases, including a novel type V nuclease ABR-004, and fuel a robust portfolio of gene editing programs spanning indications in the liver and CNS

CAMBRIDGE, MA – May 9, 2024 – Arbor Biotechnologies®, a biotechnology company discovering and developing the next generation of genetic medicines, today presents preclinical data demonstrating the potential of ABO-101, its novel gene editing therapeutic designed to address primary hyperoxaluria type 1 (PH1), as well as its broader discovery capabilities and their application to enable novel gene editing therapeutics in a suite of presentations at the 2024 American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting in Baltimore, Maryland.

“At Arbor, we are building upon the potential of CRISPR-Cas approaches by leveraging our proprietary nuclease discovery and development platform to enable efficient identification and optimization of novel gene editing tools for a focus on translation of these tools into therapeutics,” said Devyn Smith, Ph.D., Chief Executive Officer of Arbor. “This approach has fueled our robust pipeline of genetic medicines which address a range of liver and CNS indications, including PH1 and ALS. The data presented at ASGCT reinforce the vast potential of our approach and demonstrate the tremendous progress we have made advancing our platform and programs toward the clinic.”

In an oral presentation, Arbor shares in vivo data that highlights the therapeutic potential of its lead program, ABO-101, to address PH1. The data show highly specific targeting of the HAO1 gene in the liver and preservation of genomic integrity upon editing. The results further demonstrate efficient in vivo editing of HAO1 in a preclinical model of PH1, which resulted in a corresponding, therapeutically relevant reduction in urinary oxalate. ABO-101 was well tolerated in nonhuman primates (NHPs) at multiple doses. NHP data confirmed the efficacy and pharmacology of ABO-101, with efficient editing of HAO1 yielding reduced glycolate oxidase activity and increased serum glycolate. Together, this strong preclinical data package and the ongoing IND-enabling studies support continued advancement of ABO-101 toward clinical evaluation.

Preclinical data shared in a poster presentation confirm that novel type V nucleases, discovered and optimized using Arbor’s discovery platform, can prevent aberrant splicing of STMN2, providing preclinical evidence of editing in CNS cells. In vitro studies in cellular models and human motor neurons and in vivo studies in STMN2 transgenic mice showed that STMN2 motif disruption increased full-length STMN2 mRNA and decreased mRNA levels for the aberrantly spliced novel exon of STMN2 (Exon 2A). These results show that leveraging a novel nuclease capable of achieving targeted deletions can reverse aberrant splicing of STMN2 and demonstrate the therapeutic potential for an effective gene editing approach for sporadic ALS in patients with TDP43 proteinopathy.

The company also highlights the potential of its end-to-end nuclease discovery and optimization platform in a third presentation outlining the identification of a unique, compact type V nuclease. Arbor used structure-guided design to enhance activity and specificity of a compact CRISPR-Cas type V-L system identified via metagenomic search. The resulting nuclease, ABR-004, demonstrated the ability to achieve potent, therapeutically relevant silencing of PCSK9 in mice and non-human primates, signaling opportunities for future development for broader therapeutic applications. The data demonstrate the feasibility of applying Arbor’s discovery and targeted nuclease optimization capabilities to develop new gene editing tools with the potential to power the next generation of genomic medicines.

David Cheng, Chief Technology Officer at Arbor, also participated in the scientific symposium, delivering a presentation on the significance and future of AI in the discovery and development of new genomic medicines as part of a session titled The Impact of Artificial Intelligence (AI) on CGT.

 

Details for the presentations are as follows:

Scientific Symposium: The Impact of Generative Artificial Intelligence (AI) on CGT

Presentation Title: Generative AI Progress and Applications for Cell and Gene Therapies

Session Date and Time: Wednesday, May 8, 2024, 8:00-8:25 am ET

Location: Room 318-323

Presenter: David R. Cheng

 

Oral Presentation Title: Development Of ABO-101, A Novel Gene Editing Therapy For Primary Hyperoxaluria Type 1

Abstract Number: 165

Session Date and Time: Thursday, May 9, 2024, 2:00-2:15 pm ET

Location: Room 307-308

Presenter: Tia DiTommaso, PhD

 

Oral Presentation Title: Identification and Engineering of ABR-004, a Compact, High-fidelity Nuclease for Therapeutic Gene Editing

Abstract Number: 150

Session Date and Time: Thursday, May 9, 2024, 1:30-1:47 pm ET

Location: Ballroom 3

Presenter: Jeffrey Haswell, PhD

 

Poster Title: Disruption of Aberrant Splicing of STMN2 by Gene Editing with a Type V CRISPR-Cas Enzyme as a Potential Treatment for ALS

Abstract Number: 1598

Session Date and Time: Friday, May 10, 2024, 12:00-7:00 pm ET

Location: Exhibit Hall

Presenter: Jace Jones-Tabah, PhD

 

About Arbor Biotechnologies®

Arbor Biotechnologies is a next-generation gene editing company based in Cambridge, MA. Combining the promise of CRISPR with advanced computational AI-driven discovery, high throughput screening, and robust protein engineering approaches, our co-founders Feng Zhang and David Walt laid the groundwork for our proprietary discovery engine, which has yielded an extensive toolbox of gene editors, far exceeding the number of editors published in the literature to date. We envision a future of gene editing that extends beyond simple knockdowns to include precision writing, precise excisions and large insertions. This affords us the potential to treat a broad spectrum of patients, from ultra-rare to the most common genetic diseases. Guided by a deep understanding of the molecular basis of disease and our access to a unique suite of optimized editors, we are rapidly advancing our discovery-stage programs with an initial focus on genomic diseases of the liver and CNS for which there are no existing functional cures. As we advance toward the clinic with our lead program in primary hyperoxaluria type I, we look to expand our strategic partnerships around in vivo gene editing across multiple therapeutic areas and ex vivo cell therapy programs to broaden the reach of our novel nuclease technology. For more information, please visit: arbor.bio

 

Media Contact:

Peg Rusconi

Verge Scientific Communications

prusconi@nullvergescientific.com