lonvoguran ziclumeran (NTLA-2002) / Intellia Therap - LARVOL DELTA

Attack-Free and Long-Term Prophylaxis-Free Status Following Treatment With Lonvoguran Ziclumeran in Hereditary Angioedema (ACAAI 2026) - No abstract available

Late-breaking abstract • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Four-Year Durability/Safety of Lonvoguran Ziclumeran (Lonvo-z) 50 mg in Patients With Hereditary Angioedema (ACAAI 2026) - No abstract available

Clinical • Late-breaking abstract • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Intellia Therapeutics Announces FDA Acceptance of Biologics License Application with Priority Review for Lonvoguran Ziclumeran (Lonvo-z) for Hereditary Angioedema (HAE) (Yahoo Finance) - "FDA sets Prescription Drug User Fee Act (PDUFA) date of March 10, 2027....The BLA is supported by positive data from Intellia’s global Phase 3 HAELO clinical trial, which was fully enrolled with 80 patients in just nine months and was designed to evaluate the efficacy and safety of a one-time 50 milligram dose of lonvo-z in adults and adolescents aged 16 years and older with Type 1 or Type 2 HAE."

FDA filing • PDUFA • Priority review • Hereditary Angioedema

Current and future therapies for bradykinin-mediated angioedema (PubMed, Dermatologie (Heidelb)) - "On-demand treatment options include plasma-derived and recombinant C1 inhibitor (C1INH) concentrates, the bradykinin B2 receptor antagonist icatibant, and, more recently, the first orally available plasma kallikrein inhibitor, sebetralstat...LTP therapies include subcutaneous and intravenous C1INH preparations, the oral kallikrein inhibitor berotralstat, the anti-kallikrein monoclonal antibody lanadelumab, the factor XIIa inhibitor garadacimab, and the antisense oligonucleotide donidalorsen. Currently under development are the oral bradykinin B2 receptor antagonist deucrictibant, which is intended for both on-demand treatment and long-term prophylaxis in different formulations, long-acting antibodies, such as navenibart, and CRISPR/Cas9-based gene-editing therapies, such as NTLA-2002 with potential functional curative properties. In particular, orally available and long-acting therapies are expected to improve adherence, self-management, and quality of life in..."

Journal • Review • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

LONVOGURAN ZICLUMERAN: a CRISPR-CAS9-BASED GENE THERAPY FOR THE TREATMENT OF HEREDITARY ANGIOEDEMA. (PubMed, Expert Opin Investig Drugs) - "A single administration has produced sustained reductions in plasma kallikrein levels and HAE attack frequency. Although long-term follow-up is ongoing, current evidence supports its potential as the first one-time disease-modifying treatment for HAE and a landmark advance in CRISPR-based therapeutics."

Journal • Review • Cardiovascular • Complement-mediated Rare Disorders • Gene Therapies • Genetic Disorders • Hereditary Angioedema

Lonvoguran Ziclumeran - In Vivo CRISPR Gene Editing in Hereditary Angioedema. (PubMed, N Engl J Med) - P3 | "Among patients with hereditary angioedema, a single intravenous infusion of lonvo-z resulted in a significantly lower rate of hereditary angioedema attacks than placebo. (Funded by Intellia Therapeutics; HAELO ClinicalTrials.gov number, NCT06634420.)."

Journal • Preclinical • Back Pain • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hereditary Angioedema • Infectious Disease • Musculoskeletal Pain • Pain • Respiratory Diseases

HAELO: A Phase 3 Study to Evaluate NTLA-2002 in Participants With Hereditary Angioedema (HAE) (clinicaltrials.gov) - P3 | N=80 | Active, not recruiting | Sponsor: Intellia Therapeutics | N=60 ➔ 80

Enrollment change • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Intellia Therapeutics Initiates Rolling Submission of Biologics License Application to FDA for Lonvoguran Ziclumeran (lonvo-z) as a One-Time Treatment for Hereditary Angioedema (GlobeNewswire) - "Expect to complete BLA submission in second half of 2026; anticipate launch in first half of 2027, if approved....The trial met its primary and all key secondary endpoints, demonstrating that a one-time dose of lonvo-z led to freedom from both HAE attacks and the use of ongoing therapy for most patients during the six-month primary observation period."

FDA filing • Launch US • P3 data: top line • Hereditary Angioedema

Status of Current Clinical Trials on Therapy for Hereditary Angioedema (IMMUNOLOGY 2026) - "The sole drug in phase 4 is CSL312 (Garadacimab), a fully human IgG4 monoclonal antibody targeting activated factor XIIa. Drugs in phase 3 include: NTLA-2002, a single-dose intravenous gene therapy targeting inactivation of the KLKB1 gene; Navenibart, an IgG1 monoclonal antibody inhibiting activated kallikrein; OCTA-C1-INH, a virus-inactivated, nanofiltrated, highly purified concentrate of C1-INH derived from pooled human plasma; ADX-324, an siRNA therapy to reduce hepatic production of prekallikrein (PKK); Donidalorsen, an antisense oligonucleotide targeted against hepatic PKK mRNA; Sebetralstat and berotralstat, both plasma kallikrein inhibitors that reduce production of bradykinin; and deucrictibant, a competitive bradykinin B2 receptor antagonist. Advances in gene therapy, biologics, RNA interference therapeutics, and improved replacement strategies hold promise for transforming both rescue and prophylactic management for HAE. Ongoing evaluation of safety,..."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Gene Therapies • Hereditary Angioedema • AVEN

NTLA-2002 in Adults With Hereditary Angioedema (HAE) (clinicaltrials.gov) - P1/2 | N=37 | Active, not recruiting | Sponsor: Intellia Therapeutics | Trial completion date: Mar 2026 ➔ Jul 2026

Trial completion date • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Long-Term Durability and Safety of Lonvoguran Ziclumeran (Lonvo-z, NTLA-2002) 50mg in Patients With Hereditary Angioedema (AAAAI 2026) - P1/2 | "Updated data will be presented. Conclusions With up to 2 years of follow-up, a one-time treatment with lonvo-z 50mg led to robust, sustained reductions in HAE attacks without the need for LTP with an acceptable safety profile."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Infectious Disease • Respiratory Diseases

Evolving Treatment Goals to Achieve Freedom From Attacks and Long-Term Prophylaxis Following a One-Time Treatment With Lonvoguran Ziclumeran (Lonvo-z; NTLA-2002) (AAAAI 2026) - P1/2 | "Conclusions Lonvo-z 50mg uniquely enabled 90% of patients with HAE to be both attack-free and LTP-free. This milestone may enable patients to achieve their goals, alleviating the burden of living with HAE."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

HAELO Phase 3 clinical data for lonvo-z in HAE expected by mid-2026; BLA submission in second half of 2026; anticipated U.S. launch in first half of 2027 (Intellia Therapeutics)

FDA filing • Launch US • P3 data • Hereditary Angioedema

CRISPR-Cas9 gene editing for hereditary angioedema: current treatments and emerging therapies. (PubMed, Ann Med Surg (Lond)) - "However, concerns about long-term safety, off-target effects, ethical implications, and accessibility remain. CRISPR-based therapeutics such as NTLA-2002 represent a paradigm shift in the management of HAE and underscore the broader potential of in vivo gene editing for genetic disorders."

Journal • Review • Cardiovascular • Complement-mediated Rare Disorders • Dermatology • Gene Therapies • Genetic Disorders • Hereditary Angioedema • Immunology • Urticaria

Safety/Tolerability of a One-Time Infusion of Lonvoguran Ziclumeran (Lonvo-z NTLA-2002) for Hereditary Angioedema (ACAAI 2025) - P1/2 | "Four patients received treatment for IRRs: dexamethasone (n=3), acetaminophen (n=2), and ibuprofen (n=2). Most IRRs occurred shortly after infusion and resolved same day. All patients received the full dose of lonvo-z."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Two-Year Durability/Safety of One-Time Lonvoguran Ziclumeran (Lonvo-z NTLA-2002) 50mg in Patients With Hereditary Angioedema (ACAAI 2025) - P1/2 | "Plasma kallikrein reductions were deep and durable. Lonvo-z has the potential to be a one-time treatment for HAE."

Clinical • Late-breaking abstract • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hereditary Angioedema • Pulmonary Embolism • Respiratory Diseases

Clinical Development Plans (Intellia Therapeutics) - "Intellia’s global Phase 3, randomized, double-blind, placebo-controlled HAELO trial is ongoing to assess the safety and efficacy of lonvo-z at the 50 mg dosage. The Company announced today the HAELO trial has successfully completed screening ahead of schedule, with over half of the patients being screened in the United States. The study is no longer recruiting and Intellia will provide an update on enrollment in the future...Intellia expects to submit a biologics license application (BLA) in 2026 to support the Company’s plans for a U.S. launch in 2027."

FDA filing • Launch US • Trial status • Hereditary Angioedema

Intellia Therapeutics Announces Positive Three-Year Data from Phase 1 Trial of Lonvoguran Ziclumeran (lonvo-z) in Patients with Hereditary Angioedema (HAE) at the European Academy of Allergy and Clinical Immunology Congress (Intellia Therapeutics) - P1/2 | N=37 | NCT05120830 | Sponsor:Intellia Therapeutics | "In the Phase 1 portion of the study, a one-time dose of 25 mg (N=3), 50 mg (N=4) or 75 mg (N=3) of lonvo-z was administered via intravenous infusion and plasma kallikrein protein levels were measured along with HAE attacks. At the time of the February 12 data cutoff, patients were attack-free and treatment-free for a median of nearly two years. With up to three years of follow-up, a single dose of lonvo-z led to a mean reduction in monthly HAE attack rate of 98% over the study period, compared to pre-treatment baseline. For all 10 patients, deep, dose-dependent and durable reductions in plasma kallikrein protein continued to be observed through the latest assessment...New and longer-term data from the Phase 2 portion of the ongoing Phase 1/2 study is planned to be presented in the second half of 2025."

P1/2 data • Hereditary Angioedema

HAELO: A Phase 3 Study to Evaluate NTLA-2002 in Participants With Hereditary Angioedema (HAE) (clinicaltrials.gov) - P3 | N=60 | Active, not recruiting | Sponsor: Intellia Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

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

CRISPR-Based NTLA-2002 Improves Quality of Life in Patients With Hereditary Angioedema (AAAAI-WAO 2025) - P1/2, P3 | "No serious adverse events were reported with NTLA-2002. Conclusions With a one-time treatment of NTLA-2002, patients experienced clinically meaningful improvements in QOL, providing the first evidence of a CRISPR-based therapy favorably impacting QOL measures in patients with HAE."

Clinical • HEOR • Late-breaking abstract • Cardiovascular • Complement-mediated Rare Disorders • Genetic Disorders • Hereditary Angioedema

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

Distinguished Industry & Late-breaking Oral Abstracts - Session 1 (ACAAI 2024) - "Learning Objectives Objective 1: Discuss lebrikizumab’s efficacy up to 52 weeks among patients with atopic dermatitis with or without atopic comorbidities. Observe that participants with hereditary angioedema treated with a single dose of NTLA-2002 in Phase 2 of a Phase 1/2 study saw robust, sustained reductions in attacks and plasma kallikrein levels, with no new safety signals...To educate on the efficacy and safety of Dupilumab in a randomized, placebo-controlled, double-blind 24-week phase 3 trial compared dupilumab to placebo treatment in omalizumab-naive patients with symptomatic CSU despite standard-of-care H1-antihistamines treatment (up to 4-fold approved dose)...Understand the efficacy and safety profile for barzolvolimab from the first large, randomized placebo-controlled study to achieve a successful outcome for chronic inducible urticaria. This data allows advancement of the program to registrational studies."

Late-breaking abstract • Allergic Rhinitis • Atopic Dermatitis • Cardiovascular • Chronic Spontaneous Urticaria • Complement-mediated Rare Disorders • Conjunctivitis • Dermatitis • Dermatology • Hereditary Angioedema • Immunology • Inflammation • Ocular Infections • Ocular Inflammation • Ophthalmology • Urticaria

RESULTS FROM A PHASE 2, RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF CRISPR-BASED THERAPY NTLA2002 FOR HEREDITARY ANGIOEDEMA (ACAAI 2024) - P1/2 | "A single dose of NTLA-2002 25mg or 50mg led to robust, sustained reduction in attacks and total plasma kallikrein levels and was well-tolerated with no new safety signals."

Clinical • Late-breaking abstract • P2 data • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hereditary Angioedema • Infectious Disease • Pain

CRISPR-Based Therapy for Hereditary Angioedema. (PubMed, N Engl J Med) - P1/2 | "NTLA-2002 administered in a single dose of 25 mg or 50 mg reduced angioedema attacks and led to robust and sustained reduction in total plasma kallikrein levels in patients with hereditary angioedema. These results support continued investigation in a larger phase 3 trial. (Funded by Intellia Therapeutics; ClinicalTrials.gov number, NCT05120830; EudraCT number, 2021-001693-33.)."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Genetic Disorders • Hereditary Angioedema • Infectious Disease • Pain