SEEKING TO PROVIDE PATIENTS WITH ANOTHER CHANCE.

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

Overview

Our programs focus on in vivo targeted gene insertion therapies for rare pediatric neurometabolic diseases — areas where traditional gene therapy approaches have not demonstrated durable benefit, particularly in children, where rapid liver cell division can limit long-term effectiveness.

We prioritize diseases in which targeted gene insertion may offer a novel therapeutic approach by addressing the underlying genetic cause.

Our current efforts are centered on liver-directed therapies, where targeted editing has the potential to enable sustained gene expression and meaningful, long-term benefit.

Program

Discovery

Preclinical

Phase 1

Phase 2

Phase 3

Dual AAV with ARCUS Nuclease

Ornithine Transcarbamylase Deficiency (OTC)

ECUR-506*

Phase 1 Ornithine Transcarbamylase (OTC) - neonatal onset*

Lead Program: ECUR-506

ECUR-506 is an investigational variant-agnostic, in vivo targeted gene insertion therapy. It utilizes two adeno-associated virus (AAV) vectors with the same capsid but different payloads: one delivers a functional copy of the gene encoding the OTC enzyme, and the other delivers the gene encoding the ARCUS® nuclease, which creates a targeted insertion site within the well-characterized PCSK9 gene locus. iECURE has licensed the ARCUS® nuclease from Precision BioSciences.

ECUR-506 has received the following regulatory designations:

  • Orphan Drug Designation (FDA and EMA)
  • Rare Pediatric Disease Designation (FDA)
  • Fast Track Designation (FDA)
  • Regenerative Medicine Advanced Therapy (RMAT) Designation (FDA)
  • Innovation Passport to enter the Innovative Licensing and Access Pathway (ILAP) in the United Kingdom (MHRA)
  • Chemistry, Manufacturing, and Controls (CMC) Development and Readiness Pilot (CDRP) Program (FDA)

Citrullinemia Type 1 (CTLN1)

Discovery Citrullinemia Type 1 (CTLN1)

Phenylketonuria (PKU)

Discovery Phenylketonuria (PKU)

*ECUR-506 is cleared for clinical trials by the U.S. Food and Drug Administration (FDA), U.K. Medicines & Healthcare products Regulatory Agency (MHRA), Australian Therapeutic Goods Administration (TGA) and European Union (EU) and the European Economic Area (EEA) under the EU Clinical Trial Regulation by the Spanish Agency of Medicines and Medical Devices (AEMPS).

Expanded Access Policy

For more information on the ongoing clinical trial in OTC deficiency please visit OTC-HOPE.com

Selected Supporting Publications

  • Greig, J.A., Martins, K.M., Breton, C. et al. Integrated vector genomes may contribute to long-term expression in primate liver after AAV administration. Nat Biotechnol (2023). https://doi.org/10.1038/s41587-023-01974-7

  • 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

Urea Cycle Disorders

The urea cycle is the body’s natural process for clearing ammonia, a waste product formed when protein is broken down. Normally, ammonia is converted into urea and safely eliminated. In individuals with a urea cycle disorder (UCD), a genetic change in one of the enzymes disrupts this process, causing ammonia to accumulate in the bloodstream.

Excess ammonia is highly toxic to the brain and can lead to severe neurological injury, coma, or death. These disorders often present in infancy and are a key group within rare neurometabolic diseases. While current treatments can help manage ammonia levels, they do not address the underlying genetic cause.

Using our genome editing approach, we are pursuing long-lasting treatments for two UCDs: ornithine transcarbamylase (OTC) deficiency, the most common UCD and often the most severe form in male infants, and citrullinemia type 1 (argininosuccinate synthase or ASS deficiency).

Additional Disorders

Beyond urea cycle disorders, we are advancing our technologies in other rare neurometabolic conditions, including Phenylketonuria (PKU). PKU is caused by changes in the gene encoding phenylalanine hydroxylase (PAH), an enzyme required to break down the amino acid phenylalanine. When PAH function is impaired, phenylalanine can accumulate to harmful levels in the blood, potentially leading to neurological injury if not carefully managed.