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)

Polyneuropathy Inclusion Criteria:

1. Male and/or female participants 18 to 80 years of age inclusive, at the time of signing the informed consent
2. Diagnosis of polyneuropathy (PN) due to transthyretin (TTR) amyloidosis (ATTR)
3. Must have a body weight of at least 45 kilograms (kg) at Screening visit
4. Lack of access to approved treatments for ATTR and/or progression of hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) despite use of approved treatment for ATTRv-PN

Cardiomyopathy Inclusion Criteria (UK only):

1. Male and/or female participants 18 to 90 years of age inclusive, at the time of signing the informed consent
2. Diagnosis of transthyretin (ATTR) amyloidosis with cardiomyopathy, classified as hereditary ATTR amyloidosis with cardiomyopathy (ATTRv-CM) or wild type cardiomyopathy (ATTRwt-CM).
3. Must have a body weight of at least 45 kilograms (kg) at Screening visit
4. New York Heart Association (NYHA) Class I-III heart failure
5. At least 1 prior hospitalization for heart failure and/or clinical evidence of heart failure.
6. Able to complete ≥150 meters on the 6-minute walk test (6-MWT) during the Screening period.

Polyneuropathy Exclusion Criteria:

1. Amyloidosis attributable to non-TTR protein, e.g., amyloid light-chain (AL) amyloidosis
2. Known leptomeningeal transthyretin amyloidosis

Use of any of the following TTR-directed therapy for ATTR within certain timeframe:

1. Patisiran
2. Inotersen
3. Vutrisiran
4. Tafamidis
5. Diflunisal
6. Doxycycline and/or tauroursodeoxycholic acid
7. Any other investigational agent for the treatment of ATTRv-PN:

Other protocol defined Inclusion/Exclusion criteria may apply




Cardiomyopathy Exclusion Criteria (UK only):



1. Amyloidosis attributable to non-TTR protein, e.g., amyloid light-chain (AL) amyloidosis
2. Known leptomeningeal transthyretin amyloidosis



Use of any of the following TTR-directed therapy for ATTR within certain timeframes:



1. Patisiran
2. Inotersen
3. Vutrisiran
4. Tafamidis
5. Diflunisal
6. Doxycycline and/or tauroursodeoxycholic acid
7. Investigational TTR stabilizer (e.g., AG-10)
8. Participants with heart failure that in the opinion of the investigator is caused by ischemic heart disease, hypertension, or uncorrected valvular disease and not primarily due to transthyretin amyloid cardiomyopathy.
9. Participants with a history of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular (AV) nodal or sinoatrial (SA) nodal dysfunction for which a pacemaker is indicated but will not be placed. Pacemaker or defibrillator placement, initiation of or change in anti-arrhythmic medication within 28 days prior to study drug administration.

Other protocol defined Inclusion/Exclusion criteria may apply