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

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 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

Intellia Therapeutics Announces Anticipated 2025 Milestones and Strategic Reorganization to Prioritize the Advancement of its Late-Stage Programs, NTLA-2002 and Nexiguran Ziclumeran (nex-z) (GlobeNewswire) - "Phase 3 HAELO study evaluating NTLA-2002 for HAE to complete enrollment in the second half of 2025; Company plans to submit a Biologics License Application in the second half of 2026....Anticipated cost savings, including a net workforce reduction of approximately 27% in 2025, support company operations into 1H 2027 and through anticipated, first commercial launch in the U.S. Nex-z for ATTR amyloidosis: Dose the first patient in the pivotal Phase 3 MAGNITUDE-2 trial for ATTRv-PN in 1Q25. Enroll at least 550 patients cumulatively within the MAGNITUDE trial for ATTR-CM."

Commercial • Enrollment closed • FDA filing • Amyloidosis • Hereditary Angioedema

Intellia Therapeutics Announces FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted to Nexiguran Ziclumeran (nex-z) for the Treatment of Hereditary Transthyretin (ATTR) Amyloidosis with Polyneuropathy (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...for the treatment of hereditary transthyretin (ATTR) amyloidosis with polyneuropathy (ATTRv-PN)."

FDA event • Amyloidosis • CNS Disorders

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

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

MTT.01: Meet the Trialists: nex-Z and BPROAD (AHA 2024) - "Join this informal time of conversation and Q&A with the trialists of BPROAD and nex-z"

Meet the Trialist: Nexiguran ziclumeran (nex-z, also known as NTLA-2001), an investigational in vivo CRISPR-based therapy for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM): interim report of the Phase 1 study (AHA 2024) - No abstract available

P1 data • Preclinical • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Discussant: nex-z, also known as NTLA-2001 (AHA 2024) - No abstract available

Late-breaking abstract • Cardiovascular

Nexiguran ziclumeran (nex-z, also known as NTLA-2001), an investigational in vivo CRISPR-based therapy for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM): interim report of the Phase 1 study (AHA 2024) - P1 | "A single dose of nex-z was well-tolerated and was associated with consistently deep, rapid, and durable reductions in serum TTR. Compared with the well-established natural history of the disease, this interim 12-month data update provides the first evidence that a CRISPR-based therapy can favorably impact functional capacity and clinical biomarkers known to be indicative of ATTR-CM disease progression."

Late-breaking abstract • P1 data • Preclinical • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

CRISPR-Cas9 Gene Editing with Nexiguran Ziclumeran for ATTR Cardiomyopathy. (PubMed, N Engl J Med) - P1 | "In this phase 1 study involving patients with ATTR-CM, treatment with a single dose of nex-z was associated with transient infusion-related reactions and consistent, rapid, and durable reductions in serum TTR levels. (Funded by Intellia Therapeutics and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT04601051.)."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

NEJM at AHA - CRISPR-Cas9 Gene Editing with Nexiguran Ziclumeran for ATTR Cardiomyopathy. (PubMed, N Engl J Med) - No abstract available

Journal • Cardiomyopathy • Cardiovascular

On the Pulse of Gene Therapy: Continuing Progress in Cardiovascular Disease - "'While this therapy NTLA-2001 does not necessarily target the myocardium, it is for a cardiac indication. So, this makes it essentially the first phase 3 trial that we've run across...It does signal an important milestone for us is that we are crossing over to that to that space of development [for which there have been many years of development] for different products in the hematology space and in other areas, but not really in cardiology,' Masri, who is an investigator on the nex-z program, said."

Media quote

Intellia Therapeutics Announces Third Quarter 2024 Financial Results and Highlights Recent Company Progress (GlobeNewswire) - "Intellia announced today that the U.S. Food and Drug Administration (FDA) has cleared its nex-z Investigational New Drug (IND) application to initiate the MAGNITUDE-2 pivotal Phase 3 trial for ATTRv-PN...The Company expects to initiate patient enrollment in the MAGNITUDE-2 study at ex-U.S. sites by year-end."

Trial status • Amyloidosis • CNS Disorders • Metabolic Disorders

ATTRv-PN Arm Results (GlobeNewswire) - P1 | N=72 | NCT04601051 | Sponsor: Intellia Therapeutics | "Across patients who received a dose of 0.3 mg/kg or higher (n=33), the mean serum TTR reduction was 91% and the mean absolute residual serum TTR concentration was 20 µg/mL at month 12. With 16 patients who have reached 24 months of follow-up, all patients continued to show a sustained response with no evidence of a waning effect over time. It is anticipated that greater TTR reduction may lead to a greater clinical benefit in patients with ATTRv-PN...Favorable trends indicating stability or improvement were observed in patients with ATTRv-PN based on evaluation of multiple clinical measures, including Neuropathy Impairment Score (NIS), modified Neuropathy Impairment Score (mNIS+7) and modified BMI (mBMI)."

P1 data • Amyloidosis • CNS Disorders

ATTR-CM Arm Results (GlobeNewswire) - P1 | N=72 | NCT04601051 | Sponsor: Intellia Therapeutics | "At month 12, the mean serum TTR reduction was 90%, and the mean absolute residual serum TTR concentration was 17 µg/mL. With 11 patients who have reached 24 months of follow-up, all patients continued to show a sustained response with no evidence of a waning effect over time...In newly reported data of multiple markers of disease progression, patients treated with nex-z showed evidence of disease stabilization or improvement at month 12 compared to baseline. This evidence was observed despite the high proportion of patients enrolled with advanced or severe disease, as indicated by 50% classified as New York Heart Association (NYHA) Class III, 31% variant ATTR-CM, as well as elevated baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) and poor functional status."

P1 data • Amyloidosis • CNS Disorders

Ahmad Masri, MD, MS: Establishing Proof-of-Concept of Gene Editing in ATTR-CM (YouTube) - "HCPLive spoke with Ahmad Masri, MD, MS...about how nex-z's phase 1 tiral data has provided proof-of-concept for the therapy. Masri also shared his excitement for the future findings of the ongoing phase 3 MAGNITUDE trial."

Video

A Phase 3 Study of NTLA-2001 in ATTRv-PN (clinicaltrials.gov) - P3 | N=50 | Not yet recruiting | Sponsor: Intellia Therapeutics

New P3 trial • Amyloidosis • Cardiac Amyloidosis • CNS Disorders • Genetic Disorders • Metabolic Disorders • Pain

Intellia Therapeutics Announces Two Upcoming Investor Events in November 2024 (GlobeNewswire) - "Intellia will also host an investor webcast to review new data from the ongoing Phase 1 study of nexiguran ziclumeran (nex-z, also known as NTLA-2001), following a late-breaking oral presentation at the 2024 American Heart Association (AHA) Scientific Sessions, taking place November 16-18 in Chicago, Illinois."

Late-breaking abstract • P1 data • Amyloidosis • CNS Disorders