Arbor Biotechnologies has received FDA clearance for its Investigational New Drug (IND) application for ABO-101, a CRISPR-based gene editing therapy targeting primary hyperoxaluria type 1 (PH1). This clearance paves the way for a Phase 1/2 clinical trial, named redePHine, to evaluate the safety and efficacy of ABO-101 in adults and children with PH1.
ABO-101: A Novel CRISPR-Based Therapeutic Approach
ABO-101 utilizes a lipid nanoparticle (LNP) delivery system, licensed from Acuitas Therapeutics, to deliver mRNA encoding a novel Type V CRISPR Cas12i2 nuclease and a guide RNA specifically targeting the human HAO1 gene. The therapy aims to inactivate HAO1 in the liver, reducing the overproduction of oxalate that characterizes PH1.
Dan Ory, MD, Chief Medical Officer of Arbor Biotechnologies, stated, "We are thrilled to advance ABO-101 to the clinic as we believe it has the potential to be a first-in-class treatment for PH1, a rare disease with a high unmet need, and reinforces the promise of our precisely tailored gene editing approach."
Addressing the Unmet Needs in PH1 Treatment
PH1 is a rare genetic disorder resulting from enzyme deficiencies in the liver, leading to the overproduction and accumulation of oxalate. This excess oxalate can cause kidney stones, kidney damage, and eventually end-stage kidney disease and systemic oxalosis. Current standard of care includes Alnylam Pharmaceuticals’ lumasiran (Oxlumo), an siRNA therapy also targeting HAO1. However, lumasiran requires regular dosing and may present tolerability issues for some patients, highlighting the need for new therapeutic options.
Kim Hollander, Executive Director of the Oxalosis and Hyperoxaluria Foundation (OHF), noted, "Arbor’s innovative CRISPR-based approach represents a groundbreaking opportunity in genomic medicine, with the potential to transform the lives of patients with PH1."
Preclinical Evidence and Clinical Trial Design
Preclinical data presented at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting demonstrated ABO-101's potential to safely lower oxalate levels. The redePHine Phase 1/2 trial will assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ABO-101 in adult and pediatric patients with PH1. The trial is expected to begin in the first half of 2025.
John Murphy, PhD, Chief Scientific Officer of Arbor Biotechnologies, explained that ABO-101 aims to block the conversion of glycolate to glyoxylate, an intermediate in oxalate production, through gene editing. This approach is supported by the observation that individuals lacking the targeted enzyme are generally healthy, suggesting a favorable safety profile.
Regulatory Designations and Future Directions
In addition to the IND clearance, the FDA has granted ABO-101 orphan drug designation (ODD) and rare pediatric disease designation (RPDD). These designations provide incentives such as tax credits, exemption from certain regulatory application fees, potential market exclusivity, and eligibility for a pediatric priority review voucher upon approval.
