nexiguran ziclumeran (NTLA-2001) / Intellia Therap, Regeneron - LARVOL DELTA

Cardiac Outcomes Following a Single Dose of Nexiguran Ziclumeran in Patients with Transthyretin Amyloidosis with Cardiomyopathy or Hereditary Transthyretin Amyloidosis with Polyneuropathy: A Phase 1 Analysis (AHA 2026) - "Abstract is embargoed at this time."

Clinical • P1 data • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Long-Term Follow-Up (LTFU) of Subjects Dosed With NTLA-2001 (clinicaltrials.gov) - P=N/A | N=72 | Enrolling by invitation | Sponsor: Intellia Therapeutics | Recruiting ➔ Enrolling by invitation

Enrollment status • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • CNS Disorders

Disease-Modifying Therapies for Hereditary Transthyretin Amyloidosis with Polyneuropathy: Current Status and Future Perspectives. (PubMed, Neurol Ther) - "These therapies include TTR stabilizers, such as tafamidis, diflunisal, and acoramidis, as well as RNA-silencing agents, such as patisiran, vutrisiran, inotersen, and eplontersen, which reduce hepatic production of TTR and slow disease progression...Emerging gene-editing approaches, including CRISPR-based therapies like NTLA-2001, may provide a one-time treatment and long-term disease control, representing a promising future direction for managing ATTRv-PN...These include high treatment costs, limited global accessibility, uncertainty regarding optimal treatment selection and sequencing, and the need for long-term real-world, patient-centered outcome data. This review summarizes current disease-modifying therapies for ATTRv-PN, compares their mechanisms and clinical evidence, and discusses unmet needs and future research directions, with the aim of providing a practical and comprehensive overview for clinicians treating patients with ATTRv-PN."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Developmental Disorders • Gene Therapies • Pain • Transplantation

Long-Term Follow-Up (LTFU) of Subjects Dosed With NTLA-2001 (clinicaltrials.gov) - P2/3 | N=72 | Recruiting | Sponsor: Intellia Therapeutics | Phase classification: P ➔ P2/3

Phase classification • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • CNS Disorders

CMR outcomes following one-time in vivo CRISPR editing with nexiguran ziclumeran in patients with ATTR-CM: phase 1 results (HEART FAILURE 2026) - "Conclusions In this Phase 1 cohort with a high proportion of hereditary ATTR-CM (including genotypes typically associated with rapid CMR progression), a single dose of nex-z was associated with stability of cardiac structure, function and amyloid burden over 2 years. These findings support the potential of gene editing to alter the natural history of amyloid deposition and disease progression in ATTR-CM."

P1 data • Preclinical • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Nexiguran Ziclumeran (Nex-z) for Transthyretin (ATTR) Amyloidosis (GlobeNewswire) - "Patient screening activities are advancing in...MAGNITUDE and MAGNITUDE-2 Phase 3 clinical trials....Intellia plans to complete patient enrollment in MAGNITUDE-2 in the second half of 2026."

Trial status • Amyloidosis

MAGNITUDE-2: A Phase 3 Study of NTLA-2001 in ATTRv-PN (clinicaltrials.gov) - P3 | N=60 | Recruiting | Sponsor: Intellia Therapeutics | Active, not recruiting ➔ Recruiting

Enrollment open • Amyloidosis • Cardiac Amyloidosis • CNS Disorders • Genetic Disorders • Metabolic Disorders • Pain

MAGNITUDE: A Phase 3 Study of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM) (clinicaltrials.gov) - P3 | N=1200 | Recruiting | Sponsor: Intellia Therapeutics | Active, not recruiting ➔ Recruiting

Enrollment open • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Process underway to reactivate global sites for MAGNITUDE-2 Phase 3 clinical trial of nex-z in ATTRv-PN; enrollment completion expected in second half of 2026 (Intellia Therapeutics)

Trial status • Amyloidosis

FDA engagement ongoing to resolve clinical hold on MAGNITUDE Phase 3 clinical trial of nex-z in ATTR-CM (Intellia Therapeutics)

FDA event • Amyloidosis • Cardiomyopathy

Intellia Therapeutics…announced that the U.S. Food and Drug Administration (FDA) has removed the clinical hold on the Investigational New Drug application (IND) for the MAGNITUDE Phase 3 clinical trial of nexiguran ziclumeran (nex-z) for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) (GlobeNewswire) - "The clinical holds on the INDs for MAGNITUDE and MAGNITUDE-2 were imposed by the FDA on October 29, 2025, following the observation of Grade 4 liver transaminases and increased total bilirubin in a patient who was dosed with nex-z in MAGNITUDE that met the trial’s protocol-defined pausing criteria....For MAGNITUDE, additional exclusion criteria are being incorporated for patients with a recent history of cardiovascular instability and those with ejection fraction <25% at the time of screening....MAGNITUDE is a randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of nex-z in approximately 1,200 patients with ATTR-CM."

FDA event • Trial status • Amyloidosis • Cardiomyopathy

Intellia Therapeutics Announces FDA Lift of Clinical Hold on MAGNITUDE-2 Phase 3 Clinical Trial in ATTRv-PN (GlobeNewswire) - "The company plans to provide an update once alignment has been achieved on the path forward for this program....The company has aligned with the FDA on certain study modifications and mitigation measures related to MAGNITUDE-2 that include enhanced safety monitoring of liver laboratory tests."

FDA event • Trial status • Amyloidosis • Cardiomyopathy • Cardiovascular • CNS Disorders

Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NTLA-2001 in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy (ATTRv-PN) and Patients With Transthyretin Amyloidosis-Related Cardiomyopathy (ATTR-CM) (clinicaltrials.gov) - P1 | N=72 | Completed | Sponsor: Intellia Therapeutics | Active, not recruiting ➔ Completed | Trial completion date: Aug 2026 ➔ Sep 2025

Trial completion • Trial completion date • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • CNS Disorders • Pain

Nanoparticle-enhanced CRISPR delivery: paving the path for in vivo tumor gene editing. (PubMed, Ann Med Surg (Lond)) - "The NTLA-2001 trial demonstrated the first successful use of lipid nanoparticles for in vivo CRISPR delivery in humans, paving the way for potential applications in oncology...This letter highlights current progress, ongoing challenges, and the need for transparent, globally coordinated development. Nanoparticle-enhanced CRISPR delivery has the potential to bring genetic precision therapy from the laboratory to the clinic, offering a new avenue for durable and accessible cancer care."

Journal • Preclinical • Oncology • Solid Tumor

MAGNITUDE: A Phase 3 Study of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM) (clinicaltrials.gov) - P3 | N=1200 | Active, not recruiting | Sponsor: Intellia Therapeutics | Recruiting ➔ Active, not recruiting | N=765 ➔ 1200

Enrollment change • Enrollment closed • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

MAGNITUDE-2: A Phase 3 Study of NTLA-2001 in ATTRv-PN (clinicaltrials.gov) - P3 | N=50 | Active, not recruiting | Sponsor: Intellia Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Amyloidosis • Cardiac Amyloidosis • CNS Disorders • Genetic Disorders • Metabolic Disorders • Pain

Updated Phase 1 Clinical Trial Outcomes of CRISPR Gene Editing With Nexiguran Ziclumeran In Patients With Transthyretin Amyloidosis With Cardiomyopathy (AHA 2025) - P1 | "ConclusionsA single dose of nex-z was well-tolerated and associated with consistently rapid, deep, and durable reductions in serum TTR. Compared with the natural history of the disease, these data suggest that a CRISPR-based therapy can favorably impact functional capacity, clinical biomarkers known to be indicative of ATTR-CM disease progression and potentially reduce adverse clinical outcomes including mortality."

Clinical • P1 data • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Intellia Therapeutics Presents Positive Longer-Term Phase 1 Data of Nexiguran Ziclumeran (nex-z) in Patients with Transthyretin (ATTR) Amyloidosis with Cardiomyopathy (GlobeNewswire) - "Across all patients, a one-time treatment of nex-z led to consistently rapid, deep and sustained serum TTR reduction, regardless of baseline levels, through the latest follow-up. All patients continued to show a sustained response with no evidence of a waning effect over time. Among the nine patients who reached 36 months of follow-up, the mean serum TTR reduction was 87% (mean absolute serum TTR level of 22.9 µg/mL [mean 95% CI, 16.0 to 29.8]), consistent with the overall cohort at month 24....At 24 months, NT-proBNP and hs-Troponin T, which are markers known to be associated with disease progression, showed stability or improvement in 70% and 85% of patients, respectively...The analysis showed patients receiving a one-time treatment with nex-z had an all-cause mortality rate of 3.9 per 100 patient-years, while the matched cohort had an all-cause mortality rate of 12.7 per 100 patient-years (HR 0.27, p=0.009)."

P1 data • Amyloidosis • Cardiomyopathy

Recent Updates About Nexiguran Ziclumeran (nex-z) for Transthyretin (ATTR) Amyloidosis (GlobeNewswire) - "On November 10, 2025 at the 2025 American Heart Association (AHA) Scientific Sessions, longer-term data will be presented in a late-breaker oral session from the company’s ongoing Phase 1 clinical trial in patients with ATTR-CM."

P1 data • Cardiac Amyloidosis • Cardiomyopathy

Patient with liver damage in Intellia trial dies (STAT)

Trial status • Amyloidosis • Cardiomyopathy

Intellia Therapeutics Provides Update on MAGNITUDE Clinical Trials of Nexiguran Ziclumeran (nex-z) (GlobeNewswire) - "Intellia Therapeutics...announced that the company has temporarily paused patient dosing and screening for its MAGNITUDE and MAGNITUDE-2 Phase 3 clinical trials of nex-z for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN), respectively...The patient was hospitalized, is being closely monitored and is receiving medical intervention. Intellia is consulting with experts, considering potential risk mitigation strategies and engaging with regulatory authorities....As of today, more than 650 patients with ATTR-CM are enrolled in MAGNITUDE, and 47 patients with ATTR-PN are enrolled in MAGNITUDE-2. Over 450 of these patients are estimated to have been dosed with nex-z."

Trial suspension • Amyloidosis • Cardiomyopathy • CNS Disorders

Transthyretin amyloid cardiomyopathy: from cause to novel treatments. (PubMed, Eur Heart J) - "Transthyretin (TTR) stabilizers, such as tafamidis and acoramidis, mitigate amyloid formation by promoting the native tetrameric conformation of circulating TTR, thereby slowing functional decline and prolonging survival. Similarly, TTR gene silencers inhibit hepatic TTR synthesis, and gene-editing therapy with nexiguran ziclumeran offers an additional strategy to reduce amyloid production...Promisingly, monoclonal antibodies targeting TTR amyloid are under development, with early clinical trials suggesting that this passive immunotherapy may reverse disease progression and improve heart function. Ultimately, optimal management of ATTR-CM will require further elucidation of the complex interplay between amyloid formation, its structural and functional impacts, its clearance mechanisms, and the potential for myocardial reverse remodelling."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Nexiguran Ziclumeran Gene Editing in Hereditary ATTR with Polyneuropathy. (PubMed, N Engl J Med) - P1 | "A single administration of nex-z in patients with ATTRv-PN was associated with rapid, deep, and durable reductions in serum TTR levels. The results support further investigation of nex-z to treat ATTRv-PN. (Funded by Intellia Therapeutics and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT04601051.)."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiovascular • CNS Disorders • Endocrine Disorders • Pain • NEFL

Intellia Therapeutics Announces Positive Longer-Term Phase 1 Data for Nexiguran Ziclumeran (nex-z) in Patients with Hereditary Transthyretin (ATTR) Amyloidosis with Polyneuropathy (Intellia Therapeutics) - "Deep, durable and consistent TTR reductions continue to be observed. Across patients who received a one-time dose of 0.3 mg/kg or higher (n=33), the mean serum TTR reduction at 24 months was 92% (corresponding mean absolute serum TTR level of 17.3 g/mL [Mean 95% CI, 12.5 – 22.2]). Among the 12 patients who had reached 36 months of follow-up, the mean serum TTR reduction was 90% (corresponding mean absolute serum TTR level of 20 g/mL [Mean 95% CI, 11.2 – 28.8])....Nex-z has been generally well tolerated as of the data cutoff date across all patients and at all dose levels tested."

P1 data • Amyloidosis • Genetic Disorders

Intellia Therapeutics to Present Longer-Term Data from the Ongoing Phase 1 Clinical Trial of Nexiguran Ziclumeran (nex-z) for the Treatment of Hereditary Transthyretin (ATTR) Amyloidosis with Polyneuropathy (GlobeNewswire)

P1 data • Amyloidosis • Genetic Disorders