Intellia’s CRISPR Therapy Shows Durable Efficacy for Three Years in ATTR Amyloidosis

CAMBRIDGE, Mass.–September 25, 2025 – Intellia Therapeutics, Inc. announced compelling longer-term follow-up data from its ongoing Phase 1 study of nexiguran ziclumeran (nex-z), a CRISPR-based investigational therapy for hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). The results, presented at the 5th International ATTR Amyloidosis Annual Meeting in Baveno, Italy, and simultaneously published in the New England Journal of Medicine, show that a single dose of nex-z achieves deep and durable reduction of the disease-causing protein, TTR, for up to three years.

Nex-z, which utilizes CRISPR/Cas9 gene editing technology, is designed to be a one-time treatment that inactivates the TTR gene in the liver, thereby halting the production of the misfolded transthyretin (TTR) protein that builds up in the body.

Deep and Consistent TTR Reduction

The data confirms the sustained therapeutic effect of the single-dose treatment:

• Durable Knockdown: Patients who received a single dose of 0.3 mg/kg or higher ($n=33$) maintained a mean serum TTR reduction of 92% at 24 months.
• Three-Year Data: Among the 12 patients who reached 36 months of follow-up, the mean serum TTR reduction remained consistently deep at 90%.

Intellia CEO John Leonard, M.D., emphasized that these consistent and deep reductions in TTR are expected to translate to better patient outcomes.

Clinical Improvement Trends Emerge

Beyond the biomarker data, the study showed favorable trends in key clinical and functional measures, suggesting the therapy may be halting or reversing disease progression:

• Neuropathy Improvement: At the 24-month mark, 13 out of 18 assessed patients (72%) showed a clinically meaningful improvement (a $\ge 4$ point improvement) on the mNIS+7 (modified Neuropathy Impairment Score +7) assessment. This included patients who had been progressing on prior standard-of-care treatments.
• Functional Stability: Across all 36 patients, mean values for secondary endpoints like modified body mass index (mBMI), Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) questionnaire, and the neurodegeneration biomarker NfL (neurofilament light chain) all trended toward disease improvement.
• Disability Scores: Notably, 89% of patients showed improvement or stability in their Polyneuropathy Disability (PND) scores through 24 months compared to baseline.

The therapy was generally well tolerated across all doses, with the most common treatment-related adverse events being mild or moderate infusion-related reactions.

Phase 3 Trial Underway

Intellia’s pivotal Phase 3 MAGNITUDE-2 trial for ATTRv-PN is now enrolling rapidly, with patient enrollment completion expected in the first half of 2026. The trial is a randomized, double-blind, placebo-controlled study designed to further evaluate nex-z’s efficacy and safety. Intellia anticipates submitting a biologics license application (BLA) for the therapy by 2028.

ATTR amyloidosis is a rare, progressive, and fatal disease caused by the buildup of misfolded TTR protein, leading to severe complications in the nerves, heart, and digestive system. There are an estimated 50,000 people worldwide living with the hereditary form of the disease.