RARE Daily

Intellia Reports Positive Phase 1 Clinical Data of In Vivo CRISPR Therapy for HAE

June 12, 2023

Rare Daily Staff

Intellia Therapeutics reported positive interim results from the phase 1 portion of the ongoing phase 1/2 study of NTLA-2002, its experimental in vivo CRISPR candidate in development as a single-dose treatment for the rare, autoimmune disorder angioedema.

Hereditary angioedema (HAE) is characterized by severe, recurring, and unpredictable inflammatory attacks in various organs and tissues of the body, which can be painful, debilitating, and life-threatening. Current treatment options often include life-long therapies, which may require chronic intravenous or subcutaneous administration as often as twice per week, or daily oral administration to ensure constant pathway suppression for disease control. Despite chronic administration, breakthrough attacks still occur.

NTLA-2002 is the first single-dose investigational treatment being explored in clinical trials for the potential to continuously reduce kallikrein activity and prevent attacks in people living with HAE. NTLA-2002 is a wholly owned investigational CRISPR therapeutic candidate designed to inactivate the kallikrein B1 (KLKB1) gene, which encodes for prekallikrein, the kallikrein precursor protein.

NTLA-2002 is Intellia’s second investigational CRISPR therapeutic candidate to be administered systemically, by intravenous infusion, to edit disease-causing genes inside the human body with a single dose of treatment. Intellia’s proprietary non-viral platform deploys lipid nanoparticles to deliver to the liver a two-part genome editing system: guide RNA specific to the disease-causing gene and messenger RNA that encodes the Cas9 enzyme, which together carry out the precision editing.

The data were shared in a late-breaking presentation at the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress 2023, being held June 9-11 in Hamburg, Germany.

“After a single dose of our investigational CRISPR-based therapy, patients living with hereditary angioedema experienced durable elimination of their attacks. We are thrilled to see that the earliest-dosed patients are attack free for approximately a year or longer, with NTLA-2002 demonstrating a very favorable safety profile,” said Intellia President and CEO John Leonard. “These remarkable attack rate reductions have been consistent, even in patients with the most severe symptoms. While early, these unprecedented interim data from the phase 1 study continue to reinforce our belief that NTLA-2002 could be a potential functional cure for people with hereditary angioedema.

In the phase 1 portion of the study, single doses of 25 mg, 50 mg, and 75 mg of NTLA-2002 were administered via intravenous infusion, and HAE attacks and plasma kallikrein protein levels were measured for each patient. The first analysis of HAE attack rates occurred at the end of the pre-specified 16-week primary observation period. HAE attacks and plasma kallikrein protein levels will continue to be assessed through the end of the study.

Photo: Intellia President and CEO John Leonard

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