Cardiomyopathy Clinical Trials

• Participant must be ≥ 18 years to ≤ 85 years at the time of signing the informed consent.

• Participants who have a diagnosis of ATTR-CM with either wild-type or variant TTR genotype based on 1 of the following:

‣ Endomyocardial biopsy with confirmatory TTR amyloid typing OR

⁃ Grade 2 or 3 cardiac uptake on 99mTc scintigraphy in the absence of monoclonal gammopathy OR

⁃ Grade 2 or 3 cardiac uptake on 99mTc scintigraphy AND confirmatory TTR amyloid typing in the presence of monoclonal gammopathy.

• NYHA Class I to III at Screening and life expectancy of ≥ 1 year as per the Investigator's judgement.

• End-diastolic IVST ≥ 12 mm on echocardiography.

• NT-proBNP ≥ 600pg/mL for participants without ongoing atrial fibrillation/flutter at Screening or NT-proBNP ≥ 1200pg/mL for participants with ongoing atrial fibrillation/flutter at Screening.

• Able to complete symptom-limited maximal CPET at Screening based on the following test criteria:

‣ Able to exercise to near exhaustion during CPET as exhibited by RER ≥ 1.0 during symptom-limited CPET conducted during screening.

⁃ If participant does not achieve RER ≥1.0, the CPET may be repeated once, at least 48 hours but less than 2 weeks (but before randomization) after the initial test.

• Treated according to locally recognised guidelines on standard-of-care treatment for patients with HF. Therapy should have been individually optimised and stable for ≥ 4 weeks (except diuretics) and include, unless contraindicated or not tolerated, treatment of high BP (targeting SBP \< 130 mmHg as suggested in 2022 American College of Cardiology/American Heart Association/Heart Failure Society of America HF guidelines), and ischaemic heart disease.

• Willingness to adhere to daily self-administered vitamin A supplementation (3000 IU).