PROVIDING PATIENTS WITH ANOTHER CHANCE AT LIFE.

We selected our programs to unlock the next frontier of genetic medicine.

Overview

Our programs are currently focused on developing in vivo gene insertion therapies for the treatment of rare pediatric liver diseases: indications where traditional gene therapy approaches have failed to produce durable responses, given the rapid cell division in children’s livers. We will initially focus on developing ARCUS^®-mediated therapeutic candidates, but we will continually evaluate new technologies and new therapeutic areas.

Therapeutic area

Discovery

Preclinical

Phase 1/2

Phase 2

Knock-in Programs

Dual AAV with ARCUS Nuclease

OTC

Citrullinemia Type 1

PKU

Preclinical OTC

Discovery Citrullinemia Type 1

Discovery PKU

LNP/ Nuclease/ AAV

Multiple programs under evaluation

Discovery Undisclosed indication

Partnered Program

Wang, L., et al. Meganuclease targeting of PCSK9 in macaque liver leads to stable reduction in serum cholesterol. Nat Biotechnol 36, 717-725 (2018). https://doi.org/10.1038/nbt.4182
Breton, C., et al. ITR-Seq, a next-generation sequencing assay, identifies genome-wide DNA editing sites in vivo following adeno-associated viral vector-mediated genome editing. BMC Genomics 21, 239 (2020). https://doi.org/10.1186/s12864-020-6655-4
Wang, L., et al. A mutation-independent CRISPR-Cas9-mediated gene targeting approach to treat a murine model of ornithine transcarbamylase deficiency. Sci Adv 6:eaax5701. (2020). https://doi.org/10.1126/sciadv.aax5701

Breton, C., et al. Increasing the Specificity of AAV-Based Gene Editing through Self-Targeting and Short-Promoter Strategies. Mol Ther 29, 1047-1056 (2021). https://doi.org/10.1016/j.ymthe.2020.12.028
Wang, L., et al. Long-term stable reduction of low-density lipoprotein in nonhuman primates following in vivo genome editing of PCSK9. Mol Ther 29, 2019-2021 (2021). https://doi.org/10.1016/j.ymthe.2021.02.020

Urea Cycle Disorders

The urea cycle is a series of biochemical reactions that converts highly toxic ammonia – a waste product of protein metabolism – to urea. In individuals affected with a urea cycle disorder, the gene coding for one of the critical enzymes in the cycle has lost function. Without the functional enzyme, the effects are devastating. Ammonia builds up in the bloodstream, causing brain damage, coma and eventually death.

Using our gene editing technology, we are currently pursuing long-lasting treatments for two urea cycle disorders: ornithine transcarbamylase (OTC) deficiency and citrullinemia type 1 (argininosuccinate synthase or ASS deficiency).

Additional Disorders

In addition to urea cycle disorders, we are advancing our gene editing technologies in other liver disorders. Our initial focus is phenylketonuria (PKU), an inborn deficiency in phenylalanine hydroxylase (PAH), which is the enzyme needed to metabolize the amino acid phenylalanine. This is a life-threatening disease that, when left untreated, leads to severe developmental delays in children.