Core Insights - Intellia Therapeutics announced promising three-year follow-up data from the Phase 1 portion of its ongoing Phase 1/2 study for lonvoguran ziclumeran (lonvo-z) in patients with hereditary angioedema (HAE) [1][2] - All 10 patients in the Phase 1 study were attack-free and treatment-free for a median of nearly two years, demonstrating the potential of lonvo-z as a one-time therapy [2][6] - The global Phase 3 HAELO trial has completed screening ahead of schedule, with over half of the patients screened in the United States [4][6] Clinical Results - A single dose of lonvo-z led to a mean reduction in monthly HAE attack rate of 98% compared to pre-treatment baseline [2][6] - Patients showed deep, dose-dependent, and durable reductions in plasma kallikrein protein levels throughout the study [2][6] - The treatment was well tolerated, with the most frequent adverse events being infusion-related reactions, which were mostly Grade 1 and resolved without complications [3][6] Development Plans - The ongoing Phase 3 HAELO trial is randomized, double-blind, and placebo-controlled, assessing the safety and efficacy of lonvo-z at the 50 mg dosage [4][5] - Intellia plans to submit a biologics license application (BLA) in 2026, aiming for a U.S. launch in 2027 [4][8] - New data from the Phase 2 portion of the ongoing Phase 1/2 study is expected to be presented in the second half of 2025 [4][10] About Lonvo-z - Lonvo-z is based on CRISPR/Cas9 technology and aims to prevent HAE attacks by inactivating the kallikrein B1 (KLKB1) gene [8] - The therapy has received multiple regulatory designations, including Orphan Drug and RMAT Designation from the FDA [8][9] - Intellia is focused on leveraging gene editing technology to develop novel therapies that address unmet medical needs [9]

Core Insights - Intellia Therapeutics announced positive two-year follow-up data from the Phase 1 trial of investigational nexiguran ziclumeran (nex-z) for hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN) [1][2] - The data presented at the 2025 Peripheral Nerve Society Annual Meeting indicates that a single dose of nex-z leads to significant reductions in serum TTR levels and improvements in neuropathic impairment measures [2][5] ATTRv-PN Results - In the dose-escalation portion (N=15), the mean Neuropathy Impairment Score (NIS) improved by -2.0 at Month 12 and -4.5 at Month 24 [4] - In the dose expansion portion (N=21), the mean NIS improved by -2.1 at Month 12 and -5.2 at Month 24 [4] - The overall mean change in modified NIS +7 (mNIS+7) was -0.6 at Month 12 and -8.5 at Month 24 [4] - Among patients previously on patisiran, the mean mNIS+7 change was -6.3 at Month 12 and -6.5 at Month 24 [4] - The Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) score improved by -3.5 at Month 12 and -8.5 at Month 24 [4] - Neurofilament light chain (NfL) showed a reduction of -8.6% at Month 12 [4] Safety and Tolerability - Nex-z demonstrated generally favorable safety and tolerability with no new drug-related adverse events reported during the follow-up period [5][7] - The most common treatment-related adverse events were mild to moderate infusion-related reactions, which did not lead to discontinuations [7] Clinical Program and Future Prospects - The ongoing Phase 1 trial is a multi-center study evaluating nex-z in adults with hereditary ATTR amyloidosis [8] - The Phase 3 MAGNITUDE-2 trial is designed to measure clinical outcomes and evaluate the efficacy of a single dose of nex-z, with a potential biologics license application submission by 2028 [5][9] - Nex-z is based on CRISPR technology and aims to be the first one-time treatment for ATTR amyloidosis by inactivating the TTR gene [10]