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

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

Current and emerging treatment options for transthyretin amyloid cardiomyopathy. (PubMed, Heart) - "Treatments available in clinical practice include TTR stabilisers (tafamidis and acoramidis), which prevent the dissociation of TTR tetramer into monomers and oligomers that subsequently form amyloid fibrils, and gene-silencing therapies (patisiran, inotersen and vutrisiran), which suppress the hepatic synthesis of TTR, which is the amyloid precursor protein. Novel treatment strategies that are at various stages of development include Clustered Regularly Interspaced Short Palindromic Repeats-Cas9 gene-editing technology (nexiguran ziclumeran), which, if successful, offers the prospect of a single-dose treatment, and monoclonal (cormitug and ALXN220) and pan-amyloid antibodies (AT-02) that seek to target and remove amyloid fibrils that have deposited in the myocardium...The success of ATTR-specific disease-modifying therapies has already altered the treatment landscape and changed the perception of ATTR amyloidosis from a progressive and fatal disease to one that is..."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • APP

Panel discussion - CRISPR gene editing with nexiguran ziclumeran in ATTR cardiomyopathy: treatment effect in hereditary vs. wild-type disease (HEART FAILURE 2025) - No abstract available

Late-breaking abstract • Cardiomyopathy • Cardiovascular

Discussant review - CRISPR gene editing with nexiguran ziclumeran in ATTR cardiomyopathy: treatment effect in hereditary vs. wild-type disease (HEART FAILURE 2025) - No abstract available

Late-breaking abstract • Review • Cardiomyopathy • Cardiovascular

CRISPR gene editing with nexiguran ziclumeran in ATTR cardiomyopathy: treatment effect in hereditary vs. wild-type disease (HEART FAILURE 2025) - No abstract available

Late-breaking abstract • Cardiomyopathy • Cardiovascular

Intellia Announces Positive Two-Year Follow-Up Data from Ongoing Phase 1 Study of Nexiguran Ziclumeran (nex-z), in Patients with Hereditary Transthyretin (ATTR) Amyloidosis with Polyneuropathy at Peripheral Nerve Society Annual Meeting (GlobeNewswire) - P1 | N=72 | NCT04601051 | Sponsor: Intellia Therapeutics | "Deep, durable and consistent reductions in TTR were sustained at two years, following a one-time dose of nex-z; Clinically meaningful improvements in ATTRv-PN related outcomes observed at 24 months compared to baseline, including in patients who were previously progressing on patisiran; Continue to observe generally favorable safety and tolerability data in the full Phase 1 cohort with no new drug-related adverse events within the follow-up period...Enrollment continues to progress well in MAGNITUDE-2, which is designed to measure clinical outcomes (including mNIS+7) and evaluate how a single dose of nex-z can lead to reduction in serum TTR, to potentially support a BLA submission by 2028"

FDA filing • P1 data • Trial status • Amyloidosis • Cardiomyopathy

Intellia Therapeutics Announces First Quarter 2025 Financial Results and Highlights Recent Company Progress (GlobeNewswire) - "Enrollment in the global Phase 3 MAGNITUDE trial is progressing ahead of the Company’s target projections and anticipates enrollment to exceed 550 total patients by year-end...In April, the Company announced the first patient was randomized and dosed with nex-z in the global Phase 3 MAGNITUDE-2 study. Intellia expects enrollment to be completed in 2026....Intellia expects to present longer-term data from both ATTR-CM and ATTRv-PN patients in the Phase 1 study in the second half of 2025. The data will include updated measures of clinical efficacy and safety."

Enrollment status • P1 data • Amyloidosis • Cardiomyopathy • CNS Disorders

Etiological Treatment of Cardiac Amyloidosis: Standard of Care and Future Directions. (PubMed, Curr Heart Fail Rep) - "The standard of care for ATTR-CA include agents capable of selectively stabilizing the precursor protein (e.g., tafamidis), whereas the plasma cell clone is the main target of chemotherapy for AL-CA...Recent data from ATTRibute-CM led to the approval of acoramidis, whereas patisiran received refusal based on the APOLLO-B trial. Novel CRISPR-Cas9-based drugs (i.e., NTLA-2001) hold great potential in the setting of ATTR-CA...However, the investigation of monoclonal antibodies targeting misfolded ATTR (e.g., PRX004, NI301A) or AL (e.g., birtamimab, anselamimab) has led to encouraging results. Various cutting-edge strategies are being tested for treatment of CA and may change the prognostic landscape of this condition in the next years."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiovascular • Hematological Disorders

Intellia Therapeutics Announces First Patient Dosed in the MAGNITUDE-2 Phase 3 Study of Nexiguran Ziclumeran (nex-z), a One-Time Gene Editing-Based Treatment for Transthyretin (ATTR) Amyloidosis with Polyneuropathy (GlobeNewswire) - "Intellia Therapeutics, Inc...today announced the first patient has been dosed in MAGNITUDE-2, a global, pivotal Phase 3 trial of nexiguran ziclumeran (nex-z) for the treatment of hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN)....Intellia expects to present longer-term data from the Phase 1 studies of nex-z for both polyneuropathy and cardiomyopathy later this year. The company plans to submit a biologics licensing application (BLA) for ATTRv-PN by 2028."

FDA filing • P1 data • Trial status • Amyloidosis • Cardiomyopathy

Intellia Therapeutics Announces FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted to Nexiguran Ziclumeran (nex-z) for the Treatment of Transthyretin (ATTR) Amyloidosis with Cardiomyopathy (GlobeNewswire) - "Intellia Therapeutics, Inc...today announced that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to nexiguran ziclumeran (nex-z, also known as NTLA-2001) for the treatment of transthyretin (ATTR) amyloidosis with cardiomyopathy (ATTR-CM)."

FDA event • Cardiac Amyloidosis • Cardiomyopathy

Intellia Therapeutics Announces Fourth Quarter and Full-Year 2024 Financial Results and Highlights Recent Company Progress (GlobeNewswire) - "NTLA-2002...Intellia expects to present longer-term data from the ongoing Phase 1/2 study in 2025...Nexiguran ziclumeran...Intellia expects to present longer-term data from both ATTR-CM and ATTRv-PN patients in the Phase 1 study in 2025."

P1 data • P1/2 data • Amyloidosis • Cardiomyopathy • Cardiovascular • Hereditary Angioedema

New therapies to treat cardiac amyloidosis. (PubMed, Curr Opin Cardiol) - "The therapeutic landscape for ATTR-CM and AL-CM is rapidly evolving, driven by novel therapies targeting diverse mechanisms. Ongoing clinical trials promise to further refine the standard of care and improve outcomes for patients with cardiac amyloidosis."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiovascular