Arbor Biotechnologies has announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for ABO-101, a gene-editing therapeutic targeting primary hyperoxaluria type 1 (PH1). This clearance paves the way for the redePHine Phase 1/2 study, which will assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ABO-101 in adult and pediatric patients with PH1. The advancement of ABO-101 represents a significant step forward in addressing the unmet medical needs of individuals affected by this rare genetic disorder.
PH1 is a rare genetic disorder resulting from enzyme deficiencies in the liver, leading to excessive oxalate production. This overproduction can result in kidney stones, end-stage kidney disease, and systemic oxalosis. Current treatments are limited, and many patients face significant morbidity and mortality. ABO-101 offers a novel approach by utilizing a CRISPR-based mechanism to knock down the HAO1 gene in the liver, aiming to provide a durable reduction in oxalate levels. Preclinical data have demonstrated specific and lasting in vivo HAO1 editing, with therapeutic reductions in urinary oxalate observed in PH1 models.
ABO-101: A Novel CRISPR-Based Therapeutic Approach
ABO-101 is designed as a one-time gene-editing therapy, utilizing lipid nanoparticles (LNPs) licensed from Acuitas Therapeutics. These LNPs encapsulate messenger RNA encoding a novel Type V CRISPR Cas12i2 nuclease and an optimized guide RNA specifically targeting the human HAO1 gene. The therapy aims to correct the underlying genetic defect in PH1, offering a potentially curative treatment option. The CRISPR-Cas12i2 system allows for precise and efficient editing of the HAO1 gene, reducing oxalate production at its source.
Clinical Development and Future Prospects
The upcoming redePHine Phase 1/2 study will be crucial in evaluating the clinical profile of ABO-101. The study's primary endpoints will focus on assessing the safety and tolerability of the gene-editing therapy, while secondary endpoints will evaluate pharmacokinetics, pharmacodynamics, and preliminary efficacy in reducing oxalate levels. The trial will enroll both adult and pediatric patients with PH1, providing valuable data across different age groups affected by the disease.
"We’re excited to advance ABO-101 to the clinic as a potential first-in-class treatment for PH1, addressing a high unmet need," said Dan Ory, M.D., Chief Medical Officer of Arbor. Kim Hollander, Executive Director of The Oxalosis and Hyperoxaluria Foundation, emphasized the significance of this milestone for the PH1 community, highlighting it as a groundbreaking opportunity in genomic medicine.
With the FDA's clearance of the IND application, Arbor Biotechnologies is poised to begin clinical trials, potentially bringing a transformative therapy to patients suffering from PH1. The development of ABO-101 underscores the promise of gene-editing technologies in addressing rare genetic disorders and improving patient outcomes.
