Trial launches of ABO-101 for primary hyperoxaluria type 1

The first patient has been dosed in the phase 1/2 redePHine trial (NCT06839235), exploring ABO-101, an investigational gene editing therapy for the treatment of patients with primary hyperoxaluria type 1 (PH1), Arbor Biotechnologies announced in a news release.¹

The first patient in the trial received ABO-101 at the Mayo Clinic. No serious adverse events (AEs) were reported in the 28-day dose-limiting toxicity period following dosing, and thus the safety board for the study has recommended that the trial proceed with dosing.

“Preclinical data support the potential for ABO-101 to be a one-time therapy for patients living with PH1, who currently rely on lifelong medication, such as siRNA therapies, and for whom historically the only long-lasting treatment option was a combined liver and kidney transplant,” said Dan Ory, MD, chief medical officer of Arbor Biotechnologies, in the news release from the company.¹ “As Arbor’s first clinical trial, this study marks an important milestone in our commitment to advancing innovative genetic medicines into the clinic for people living with PH1 and other rare genetic diseases.”

In total, the open-label redePHine trial plans to enroll up to 23 adult and pediatric patients with PH1.² Patients are currently being enrolled across clinical trial sites in the US, with plans to open additional sites in the UK and Europe in the third quarter of 2025, the company reported.

The first study period in the trial will consist of 2 parts. In part 1, adult patients will receive ascending doses of ABO-101 to identify a recommended phase 2 dose (RP2D). In part 2, pediatric patients (aged 6 to 17) will receive the RP2D to further assess the safety, tolerability, and preliminary efficacy of the therapy in these patients. The study will then proceed to period 2 of the trial, which will include long-term monitoring.

To be eligible for enrollment, patients must be aged 18 to 64 years for part A or 6 to 17 years in part B. Additionally, all patients need to have a 24-hour urinary oxalate excretion (UOx) of at least 0.7 mmol/24 hours/1.73m², an eGFR of at least 30 mL/min/1.73², and a weight of 90 kg or lower.

The primary end point for the study is safety, assessed by the incidence and severity of treatment-emergent AEs and serious AEs. Secondary outcome measures include the percent change in 24-hour UOx from baseline to 6 months, the absolute change in UOx corrected for body surface area, the percent change in plasma glycolate from baseline to 6 months, and the change in eGFR from baseline to 12- and 24-months.

Primary completion of the trial is expected in March 2029.

About ABO-101

ABO-101 is an investigational liver-directed gene editing therapy intended to be a one-time treatment for PH1, according to the company. The therapy is designed to reduce expression of the HAO1 gene in the liver and thus decrease oxalate production. In February 2025, the FDA granted an orphan drug designation and rare pediatric disease designation to ABO-101 for the treatment of patients with PH1.³

Preclinical data on ABO-101 were presented at the American Society of Gene and Cell Therapy 27th Annual Meeting in Baltimore, Maryland and at the American Society of Nephrology (ASN) 2024 Kidney Week in San Diego, California. Overall, the data demonstrated the proof-of-pharmacology and efficacy of ABO-101 in non-human primates.^4,5

The investigators found that ABO-101 was able to specifically target the HAO1 gene and preserve genomic integrity following gene editing. According to the presentation at ASN Kidney Week, HAO1 gene editing was achieved in approximately 60% of whole liver tissue, which was correlated with a greater than 2 times increase in serum glycolate.⁵

In a preclinical model, in vivo editing of the HAO1 gene led to a therapeutically relevant reduction in urinary oxalate. Additionally, increases in gene editing led to dose-dependent reductions in glycolate oxidase enzyme activity and increases in serum glycolate levels.

Multiple doses of ABO-101 also appeared to be well tolerated in the non-human primates.

Based on these findings, the authors concluded, “Taken together, these results provide in vivo proof of pharmacology for a gene editing approach and support further advancement of ABO-101 towards the clinic as a potential treatment for PH1.”

REFERENCES

1. Arbor Biotechnologies announces first patient dosed at Mayo Clinic in the redePHine phase 1/2 study of ABO-101, an investigational gene editing treatment for primary hyperoxaluria type 1. News release. Arbor Biotechnologies Inc. July 30, 2025. Accessed July 30, 2025. https://arbor.bio/arbor-biotechnologies-announces-first-patient-dosed-at-mayo-clinic-in-the-redephine-phase-1-2-study-of-abo-101-an-investigational-gene-editing-treatment-for-primary-hyperoxaluria-type-1/

2. Phase 1/​2 study of ABO-101 in primary hyperoxaluria type 1 (redePHine). ClinicalTrials.gov. Last updated May 25, 2025. Accessed July 30, 2025. https://clinicaltrials.gov/study/NCT06839235

3. Arbor Biotechnologies announces FDA Orphan Drug and Rare Pediatric Disease Designations Granted to ABO-101 for the treatment of primary hyperoxaluria type 1 (PH1) and upcoming presentations at the 20th Congress of the International Pediatric Nephrology Association (IPNA). News release. Arbor Biotechnologies Inc. February 5, 2025. Accessed July 30, 2025. https://arbor.bio/arbor-biotechnologies-announces-fda-orphan-drug-and-rare-pediatric-disease-designations-granted-to-abo-101-for-the-treatment-of-primary-hyperoxaluria-type-1-ph1-and-upcoming-presentations-at-the-20t/

4. 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. News release. Arbor Biotechnologies. May 9, 2024. Accessed July 30, 2025. https://arbor.bio/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/

5. Yan W, Ditommaso T, Kuefner M, et al. Development of ABO-101, a novel gene editing therapy for primary hyperoxaluria type 1. American Society of Nephrology (ASN) 2024 Kidney Week Meeting. October 23-27. San Diego, California. Abstract TH-OR88. Accessed July 30, 2025. https://www.asn-online.org/education/kidneyweek/2024/program-abstract.aspx