On June 2, 2024, Intellia Therapeutics, a gene-editing therapy company founded by CRISPR pioneer and Nobel laureate Jennifer Doudna, released long-term follow-up data from the Phase 1 stage of its ongoing Phase 1/2 study. The study focuses on NTLA-2002, an LNP-mRNA in vivo gene editing therapy for the rare genetic disorder hereditary angioedema (HAE).
In the earliest treated patients, more than two years of extended follow-up data further strengthen the potential of NTLA-2002 as a functional cure for hereditary angioedema (HAE). Among 10 patients, 8 remained completely attack-free during the latest follow-up after the 16-week primary observation period, including those with the most severe symptoms. A single dose of NTLA-2002 reduced the monthly HAE attack rate by an average of 98%, with all patients having an average follow-up time of over 20 months. Patients who discontinued prophylactic treatment did not require long-term prophylaxis after receiving NTLA-2002. Good safety and tolerability were observed across all dose levels.
This long-term follow-up data suggest that NTLA-2002 could become the first one-time treatment for hereditary angioedema (HAE), achieving the goal of "one treatment, lifelong cure."
NTLA-2002 is an in vivo CRISPR gene editing candidate therapy that utilizes lipid nanoparticles (LNPs) to deliver the CRISPR-Cas9 gene editing system via mRNA. This approach targets the KLKB1 gene to permanently suppress the production of kallikrein, which in turn inhibits bradykinin production. Excessive bradykinin is associated with hereditary angioedema (HAE) attacks.
On March 2, 2023, Intellia Therapeutics announced that the FDA had approved the Investigational New Drug (IND) application for NTLA-2002. This marks the first FDA-approved in vivo CRISPR gene editing therapy delivered by LNPs for human clinical trials.
BOC RNA offers comprehensive LNP-mRNA services for the development and delivery of mRNA therapeutics, ensuring efficient and stable encapsulation. Additionally, our CRISPR Gene Editing support services provide cutting-edge solutions for precise gene modification and research applications.
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Hereditary angioedema (HAE) is a rare genetic disorder affecting approximately 1 in 50,000 people. It is characterized by severe, recurrent, and unpredictable inflammation across various organs and tissues, causing significant pain, disability, and potentially life-threatening conditions. Current treatments generally involve lifelong therapy, with options including biweekly chronic intravenous or subcutaneous injections, or daily oral medications. Despite ongoing treatment, breakthrough attacks still occur. Inhibiting kallikrein is a clinically validated strategy for preventing HAE.
NTLA-2002 is Intellia's second in vivo CRISPR gene editing therapy, designed to evaluate its safety, tolerability, pharmacokinetics, and pharmacodynamics in adults with Type I or Type II HAE. This includes assessing kallikrein activity levels in plasma and HAE attack rates. The Phase 1 clinical trial was an open-label, dose-escalation study aimed at determining various dose levels of NTLA-2002, while the Phase 2 trial will involve randomized, placebo-controlled evaluations.
On November 12, 2022, Intellia released mid-term data from the Phase 1/2 trials of NTLA-2002 for treating HAE. The data from 10 patients receiving different doses (25mg, 50mg, 75mg) showed significant reductions in pathogenic kallikrein levels, with decreases of 64%, 81%, and 92% at weeks 32, 22, and 16, respectively.
Moreover, the data demonstrated that HAE attack frequency significantly decreased after a single dose, with attack rates dropping by an average of 91% and 78% for the 25mg and 75mg dose groups, respectively, from week 1 to week 16. Most adverse events were mild, and the therapy showed promise for sustained relief. Long-term follow-up data revealed an average monthly attack rate reduction of 98% and a 99% reduction in moderate to severe attacks. With a median follow-up time of 20.1 months, the therapy achieved robust and enduring reductions in HAE attack rates. In two patients with the most severe HAE symptoms, attacks were completely eliminated during the follow-up period.
NTLA-2002 has demonstrated a dose-dependent, robust, and sustained reduction in plasma kallikrein levels, with average decreases of 60% (25mg, 88 weeks), 88% (50mg, 72 weeks), and 95% (75mg, 88 weeks). The therapy was well-tolerated across all dose levels, with most adverse events being mild and resolving within two days. No dose-limiting toxicities or serious adverse events were observed, and no clinically significant laboratory abnormalities were noted.
Intellia has completed enrollment for the Phase 2 study at 25mg and 50mg doses and plans to report the primary results mid-year, with detailed findings expected at the end-of-year medical meetings. The company aims to launch a pivotal Phase 3 trial for NTLA-2002 in the second half of 2024, pending regulatory feedback, with plans to submit for FDA approval in 2026.
LNPs provide efficient encapsulation, protect mRNA from degradation, and enable targeted delivery to cells, improving expression levels and experimental reproducibility in gene editing and mRNA studies.
Custom mRNA allows researchers to quickly generate precise sequences with desired modifications, enabling rapid testing of gene function, protein expression, or delivery strategies without repeated cloning steps.
Effective gRNA design requires selecting target sequences with high specificity, minimal off-target potential, and compatibility with delivery platforms, ensuring efficient and accurate gene editing outcomes.
Yes, we provide scalable LNP encapsulation, multiplexed gRNA synthesis, and parallel mRNA production, enabling high-throughput screening or multiple experimental conditions efficiently.
They allow precise gene modulation, transient or stable protein expression, and rapid testing of gene regulatory networks, helping researchers investigate molecular pathways with minimal experimental variability.
All products undergo sequence verification, purity assessment, and analytical characterization to ensure high stability, reproducibility, and performance in laboratory applications.
