**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Mathew S. Maurer, Department Of General Cardiology, Columbia University Irving Medical Center, New York, NY

**Main Body of the Abstract**
Background: ATTR amyloidosis is a progressive condition most commonly presenting as cardiomyopathy and/or polyneuropathy. Current disease-modifying treatments require repeat administration, presenting a significant burden and leaving patients at risk for disease progression/death. NTLA-2001, an investigational, in vivo, CRISPR-based, one-time gene editing therapy, has been administered to 72 participants in an ongoing phase 1 study (NCT04601051) with interim data demonstrating a favorable safety profile, with rapid, consistent, and durable reductions of serum transthyretin to low levels  following a single intravenous infusion ≥0.3 mg/kg.
Methods: MAGNITUDE (NCT06128629) is a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled study evaluating NTLA-2001 in approximately 765 patients with ATTR-CM. Eligible patients are ages 18-90 with mutant or wild-type ATTR-CM, NYHA class I-III, NT-proBNP ≥1000 pg/mL (≥2000 pg/mL for participants with atrial fibrillation), and symptoms of heart failure optimally managed and clinically stable ≤28 days of administration of study drug. Stratification is by NAC stage, TTR genotype (mutant vs wild-type), and concomitant tafamidis use. Patients will be randomized 2:1 to a single 55-mg intravenous infusion of NTLA-2001 or placebo. The primary endpoint is a composite of CV‑related mortality and frequency and timing of CV events; secondary endpoints are change from baseline to 18-month serum TTR and KCCQ-OS score. Exploratory endpoints include change in 6-minute walk distance, NT-proBNP, and ATTR-Quality of Life score. Patients will undergo serial echocardiography and CMR imaging (select sites). Safety will be evaluated throughout. Minimum follow-up is 18 months, with the majority estimated to have ≥30 months follow-up at time of primary analysis.



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Mathew S. Maurer, Department Of General Cardiology, Columbia University Irving Medical Center, New York, NY

**Main Body of the Abstract**
**Background:** ATTR amyloidosis is a progressive condition most commonly presenting as cardiomyopathy and/or polyneuropathy. Current disease-modifying treatments require repeat administration, presenting a significant burden and leaving patients at risk for disease progression/death. NTLA-2001, an investigational, _in vivo,_ CRISPR-based, one-time gene editing therapy, has been administered to 72 participants in an ongoing phase 1 study (NCT04601051) with interim data demonstrating a favorable safety profile, with rapid, consistent, and durable reductions of serum transthyretin to low levels  following a single intravenous infusion ≥0.3 mg/kg.
**Methods:** MAGNITUDE (NCT06128629) is a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled study evaluating NTLA-2001 in approximately 765 patients with ATTR-CM. Eligible patients are ages 18-90 with mutant or wild-type ATTR-CM, NYHA class I-III, NT-proBNP ≥1000 pg/mL (≥2000 pg/mL for participants with atrial fibrillation), and symptoms of heart failure optimally managed and clinically stable ≤28 days of administration of study drug. Stratification is by NAC stage, TTR genotype (mutant vs wild-type), and concomitant tafamidis use. Patients will be randomized 2:1 to a single 55-mg intravenous infusion of NTLA-2001 or placebo. The primary endpoint is a composite of CV‑related mortality and frequency and timing of CV events; secondary endpoints are change from baseline to 18-month serum TTR and KCCQ-OS score. Exploratory endpoints include change in 6-minute walk distance, NT-proBNP, and ATTR-Quality of Life score. Patients will undergo serial echocardiography and CMR imaging (select sites). Safety will be evaluated throughout. Minimum follow-up is 18 months, with the majority estimated to have ≥30 months follow-up at time of primary analysis.



Design and rationale for MAGNITUDE, a phase 3, randomized, placebo-controlled trial of NTLA-2001, a CRISPR-based gene editing therapy, in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) PC104 (#152)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.