Intellia Therapeutics, Inc. and Regeneron Pharmaceuticals, Inc. announced additional positive interim data from an ongoing Phase 1 study of their lead investigational in vivo genome editing candidate, NTLA-2001, which is being developed as a single-dose treatment for transthyretin (ATTR) amyloidosis. The data were presented in an oral presentation at the European Association for the Study of the Liver (EASL) International Liver Congress™ 2022, taking place June 22 – 26 in London. The presentation included extended follow-up data from 15 patients with hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN) treated across four single-ascending dose cohorts in Part 1 of the study. Results demonstrated sustained durability of serum transthyretin (TTR) reduction through the last measured timepoint in the ongoing observation. These data support NTLA-2001's continued development as a potential one-time treatment to permanently inactivate the TTR gene and reduce the disease-causing protein. At the highest dose evaluated, treatment with NTLA-2001 at 1.0 mg/kg resulted in a 93% mean and 98% maximum serum TTR reduction by day 28 across the six patients treated. With longer-term follow-up data now available, these deep reductions continue to be sustained through six months, with an observed mean reduction of 93%. Additionally, three patients in the 1.0 mg/kg cohort have reached nine months in the follow-up period with no evidence of a loss in TTR reduction after a single dose. In the 0.7 mg/kg dose cohort, the 86% mean serum TTR reduction observed at day 28 also remained durable through six months. Further, in the 0.1 and 0.3 mg/kg cohorts, patients have now reached 12 months of follow-up, and a durable response to treatment continues to be observed. Notably, patients in the 0.3 mg/kg cohort sustained an 89% mean serum TTR reduction at 12 months. At all four dose levels, NTLA-2001 was generally well tolerated through the follow-up period (median follow-up of 10 months). The majority of adverse events were mild in severity with 73% (n = 11) of patients reporting a maximal adverse event severity of Grade 1. There was a single possibly related serious adverse event of vomiting (Grade 3) reported in a patient with concomitant medical history of gastroparesis in the 1.0 mg/kg dose group. The most frequent adverse events included headache, infusion-related reactions, back pain, rash and nausea. All infusion-related reactions were considered mild, resolving without clinical sequelae. The safety and activity profile of NTLA-2001 observed in Part 1 indicates that NTLA-2001 has a favorable therapeutic window. These data combined with pharmacokinetic modeling and simulation data support the utilization of a fixed dose of 80 mg in Part 2, which is anticipated to yield similar exposures to the 1.0 mg/kg dose. Dosing is ongoing in Part 2, the single-dose expansion cohort of the polyneuropathy arm. The Phase 1 study, run by Intellia as the program's development and commercialization lead as part of a multi-target collaboration with Regeneron, is evaluating NTLA-2001 in patients with either ATTRv-PN or ATTR amyloidosis with cardiomyopathy (ATTR-CM). The cardiomyopathy arm, evaluating NTLA-2001 across patients classified with New York Heart Association (NYHA) Class I - III heart failure, is ongoing. The companies plan to present the first interim data from the cardiomyopathy arm in the second half of 2022. Enrollment across both ATTRv-PN and ATTR-CM patient populations is expected to complete in 2022.