Intellia and Regeneron Announce Updated Phase 1 Clinical Data for NTLA-2001 Demonstrating Dose-Dependent, Deep and Sustained Reduction in TTR Protein Levels

On March 1, Intellia Therapeutics and Regeneron Pharmaceuticals announced the latest Phase 1 clinical trial data for their in vivo genome editing candidate therapy, NTLA-2001. The results showed that all doses were well tolerated, with mean reductions of 86% and 93% in serum levels of the target protein in the two highest dose groups. Across all four dose groups, the degree of reduction also demonstrated dose dependency.

NTLA-2001 Targets Transthyretin Amyloidosis (ATTR). Patients with this disease produce misfolded transthyretin proteins in the liver due to specific mutations in the TTR gene. As these proteins accumulate in the body, they may cause severe symptoms in multiple tissues, including the heart and nerves.

As an innovative therapy for gene editing within the body, NTLA-2001 uses lipid nanoparticles (LNP) to deliver a CRISPR gene editing system targeting the TTR gene into the human body, enabling liver-specific knockout of the TTR gene, thereby reducing the expression of TTR protein and decreasing the accumulation of pathogenic proteins. The press releases from these two companies also noted that this therapy is the first systematically administered CRISPR/Cas9 candidate gene therapy for precise editing of human genes. In June of last year, the first clinical results of NTLA-2001 were announced, drawing global industry attention.

▲Mechanism of Action of NTLA-2001 (Image Source: Reference [2])

Today's news disclosed more clinical trial data to the industry —— these data come from 15 patients who were divided into four different dose groups and received intravenous infusion treatment of NTLA-2001. Subsequently, the researchers evaluated the changes in TTR protein levels in their serum relative to the baseline and found that the reduction in TTR protein was dose-related.

After 28 days of treatment, TTR protein levels were reduced by 52%, 87%, and 86% in the groups receiving doses of 0.1 mg, 0.3 mg, and 0.7 mg per kilogram of body weight, respectively (each group consisted of 3 individuals). In the treatment group receiving 1.0 mg per kilogram of body weight (6 individuals), the reduction in TTR protein reached 93%. The press release also noted that during follow-up intervals ranging from 2 to 12 months, the reduction in serum TTR protein levels remained stable.

▲NTLA-2001 Durability Data (Source: Intellia Therapeutics Official Website)

NTLA-2001 Was Well Tolerated Overall in All Four Dose Groups, with the Most Common Adverse Events Being Headache, Infusion-Related Reactions, Back Pain, Rash, and Nausea; No Clinically Significant Liver Findings Were Observed.

According to the plan of this clinical trial, in the first quarter of this year, the researchers will further expand the treatment group. Intellia also plans to release more clinical data at a medical conference later this year. We look forward to hearing more good news from this innovative therapy!

References:

[1] Intellia and Regeneron Announce Updated Phase 1 Data Demonstrating a Single Dose of NTLA-2001, Investigational CRISPR Therapy for Transthyretin (ATTR) Amyloidosis, Resulted in Rapid, Deep and Sustained Reduction in Disease-Causing Protein, Retrieved February 28, 2022, from https://www.prnewswire.com/news-releases/intellia-and-regeneron-announce-updated-phase-1-data-demonstrating-a-single-dose-of-ntla-2001-investigational-crispr-therapy-for-transthyretin-attr-amyloidosis-resulted-in-rapid-deep-and-sustained-reduction-in-disease-causing-301491764.html

[2] Gillmore et al., (2021). CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. The New England Journal of Medicine, DOI: 10.1056/NEJMoa2107454

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