Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy

This Phase 3 prospective, randomized, multicenter, parallel-group study will evaluate the
efficacy and safety of AG10 800 mg in subjects with symptomatic Transthyretin Amyloid
Cardiomyopathy (ATTR-CM) for a total of 30 months of blinded, placebo-controlled treatment.

At the end of 12 months of treatment (Part A) efficacy of AG10 will be assessed through
analyses of the functional endpoint, 6 Minute Walk Test, and the health-related Quality of
Life endpoint, heart failure-specific instrument Kansas City Cardiomyopathy Questionnaire.

At the end of 30 months of treatment (Part B) efficacy of AG10 will be further assessed
through analysis of all-cause mortality and frequency of cardiovascular-related
hospitalization.

All subjects who complete 30 months of blinded, placebo-controlled treatment may be eligible
to participate in an open label extension study of long-term AG10 treatment.

Inclusion Criteria:

- Have an established diagnosis of ATTR-CM with either wild-type TTR or variant TTR
genotype

- Have a history of heart failure evidenced by at least one prior hospitalization for
heart failure or clinical evidence of heart failure without prior heart failure
hospitalization manifested by signs or symptoms of volume overload or elevated
intracardiac pressures or heart failure symptoms that required or require ongoing
treatment with a diuretic.

- New York Heart Association (NYHA) Class I-III symptoms due to ATTR cardiomyopathy.

- On stable doses of cardiovascular medical therapy

- Completed ≥150 m on the 6MWT on 2 consecutive tests

- Biomarkers of myocardial wall stress, NT-proBNP level ≥300 pg/mL

- Have left ventricular wall (interventricular septum or left ventricular posterior
wall) thickness ≥13 mm

Exclusion Criteria:

- Had acute myocardial infarction, acute coronary syndrome or coronary
revascularization, or experienced stroke within 90 days

- Has hemodynamic instability

- Likely to undergo heart transplantation within a year of screening

- Confirmed diagnosis of primary (light chain) amyloidosis

- Biomarkers of myocardial wall stress, NT-proBNP level ≥7000 pg/mL pg/mL

- Measure of kidney function, eGFR by MDRD formula < 15 mL/min/1.73 m2

- Current treatment with other investigational agents for the treatment of ATTR-CM

- Current treatment with calcium channel blockers or digitalis