Preclinical Evidence for PH1 Gene Therapy

John Murphy, PhD
Credit: Arbor Biotechnologies

Tia DiTommaso, PhD
Credit: Arbor Biotechnologies

Arbor Biotechnologies is currently developing ABO-101, a lipid nanoparticle (LNP)-delivered Cas12i2-based gene editing therapy, for the treatment of primary hyperoxaluria type 1 (PH1). Notably, the first patient was recently dosed in a newly launched phase 1/2 clinical trial for the gene therapy (redePHine; NCT06839235).

At the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting, held May 13 to 17, 2025, in New Orleans, Louisiana, Tia DiTommaso, PhD, the senior director of preclinical pharmacology Arbor Biotechnologies, presented preclinical data supporting the move of ABO-101 into clinical trials. At the conference, CGTLive® interviewed DiTommaso and John Murphy, PhD, the chief scientific officer of Arbor Biotechnologies, to learn more.

CGTLive: Can you give some background context about Arbor's presentations at ASGCT this year?

John Murphy, PhD: Arbor has had a number of presentations at ASGCT this year. One that we'll highlight in this video is one from Tia De Tomaso on our PH1 program, which is our first approved investigational new drug (IND) application and will be start a clinical trial in the near future. We also have a number of presentations on our central nervous system (CNS) programs: one for amyotrophic lateral sclerosis (ALS) targeting SOD1, which is the cause of familial ALS, and one for Angelman syndrome looking at gene editing to reverse the loss of UBE3A in Angelman syndrome. Then we have a presentation that's really companion to Tia's looking at the off-target effects of editing in the PH1 program and showing that we have a very clean profile off-target. Then finally, we have a presentation on a novel technology for small RT editors.

What were some of the key points from Arbor's presentation on ABO-101?

Tia DiTommaso, PhD: ABO-101 is a clinical stage program now, but what we were talking about at ASGCT was a lot of the nonclinical data that supported the advancement of ABO-101 into the phase 1/2 trial. We showed data in primary cell types showing that ABO-101 is really specific to the target cell type. We also showed data in mice looking at the pharmacology that ABO-101 can drive, and we found that we were able to substantially reduce oxalate levels, which is one of the disease biomarkers. We show that we can see a really durable effect with a single administration of ABO-101 out to a year, and also in juvenile mice, through their development into adults. We also show that ABO-101 is really efficacious as well as tolerable in nonhuman primates (NHPs).

John Murphy, PhD: One thing to add to what Tia said: the juvenile study is very important because it's disease that affects patients from very early in life and we hope to eventually treat very young patients.

How would you summarize the big picture implications that you would want doctors and the broader healthcare community to take away from that?

John Murphy, PhD: I think there are a number of implications here. One of the things, clearly, is what we want to do really is treat patients once and have them be sustained, a treatment that works for life—so it's a one-and-done treatment. The work that we've done preclinically shows that we have durability, both over the course of basically the lifetime of a mouse, and also as they mature from infants or very young mice until full maturity. It's also very critical that's safe. So we've really shown in a number of nonclinical species, tolerability. Then also, one of the key things for gene editing is that you edit the gene you want and nothing else and we've done very thorough studies to give us confidence that's what we're doing with our product.

Are there any challenges in this program that still need to be addressed or future plans that you can discuss?

Tia DiTommaso, PhD: One of the things that we spent a lot of time working up and doing really carefully was the off-target analysis. As John mentioned, showing that ABO-101 was very, very specific was something that was really important to us to advance it from a safety perspective. We spent a good amount of time working up the right assays in the lab to do to give us confidence and predict that specificity. One of the things that we highlighted in my presentation, but also in one of our posters, is that we're able to look really, really deeply into the cells that we treat. We can see at ultra low levels any edits that might be unwanted in other places. We've done a lot of extensive characterization aided by a lot of development work that shows really good specificity of ABO-101.

John Murphy, PhD: I think that the next steps for the program is entry into the clinic. We help to dose our first patient in the very near future. The way we will do this is we'll start with adults and do dose escalation to find an optimal dose, and then go into younger patients, where we think we could have the most benefit.

Is there anything else you want to share?

John Murphy, PhD: As Tia discussed, we've learned a lot from this program about analyzing both the on-target and off-target safety of our products and we'll extend that into our next products in the CNS realm and beyond.

This transcript has been edited for clarity.

Click here to view more coverage of the 2025 ASGCT Annual Meeting.

REFERENCE
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 September 2, 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/