Intellia Therapeutics (NTLA) Study Update summary

Study background and design

• Phase I open-label studies evaluated Nexi/nexiguran ziclumeran (nex-z), an in vivo CRISPR/Cas9 gene editing therapy, for ATTR amyloidosis, including both cardiomyopathy (ATTR-CM) and hereditary polyneuropathy (ATTRv-PN) arms.

• 36 ATTR-CM patients enrolled, many with severe disease (50% NYHA class III, 31% hereditary form); ATTRv-PN cohort included early-stage and severely impaired patients, some previously treated with patisiran.

• Single-dose therapy administered intravenously; primary endpoints were safety, tolerability, and TTR reduction.

• No concurrent use of other disease-modifying therapies during the study.

• Secondary endpoints included cardiac/neuropathy biomarkers, functional capacity, imaging, and quality of life.

Key efficacy results

• Nexi/nex-z achieved rapid, deep, and durable TTR reduction (mean 89–91% at day 28 or 12 months, sustained up to 24 months).

• 80–81% of ATTR-CM patients showed stability or improvement in NT-proBNP, troponin T, and six-minute walk test at 12 months.

• 92% of ATTR-CM patients had no change or improvement in NYHA class at 12 months, with 72% of NYHA III patients improving.

• ATTRv-PN patients had mean 91% TTR reduction at 12 months, with favorable trends in neuropathy scores (NIS, mNIS+7) and mBMI.

• Functional and structural cardiac/neuropathy parameters remained stable or improved; quality of life improved.

Safety and tolerability

• Nexi/nex-z was generally well tolerated in both ATTR-CM and ATTRv-PN arms; most adverse events were mild or moderate infusion reactions and transient liver enzyme elevations.

• Serious adverse events were mainly related to underlying disease; only one death in each cohort, both unrelated to treatment.