Efficacy and Safety of AG10 in Subjects with Transthyretin Amyloid Polyneurophathy

Inclusion Criteria:

• Be male or female ≥18 to ≤90 years of age;

• Have Stage I or II symptoms (polyneuropathy disability [PND] ≤IIIa) of ATTR-PN andan established diagnosis of ATTR-PN as defined by physical exam findings and/orneurophysiological test findings consistent with the diagnosis of ATTR-PN;

• Have an NIS of 5 to 130 (inclusive) during screening;

• Have a nerve conduction studies (NCS) score [sum of the sural sensory nerve actionpotential (SNAP), tibial compound muscle action potential (CMAP), ulnar SNAP, ulnarCMAP, and peroneal CMAP] of ≥2 points during screening. NCS is a component ofmNIS+7;

• Have a mutation consistent with ATTR-PN either documented in medical history orconfirmed by genotyping obtained at Screening prior to randomization. *No genetictesting is needed for subjects who are recipients of domino liver transplants;

• Have an anticipated survival of ≥2 years

• Have Karnofsky performance status ≥60 %;

Exclusion Criteria:

• Had a prior liver transplantation or is planning to undergo liver transplantationwith a wild-type organ graft as treatment for symptomatic ATTR-PN during the studyperiod.

Note: Recipients of a "domino" liver transplant from an ATTR-PN donor who have developed ATTR-PN mediated by their graft are allowed under this protocol, as long as re-transplantation to treat ATTR-PN is not planned during the study period and meets all other eligibility criteria;

• Has sensorimotor or autonomic neuropathy not related to ATTR-PN; for example,autoimmune disease or monoclonal gammopathy, malignancy, or alcohol abuse;

• Has Vitamin B-12 levels below the lower limit of normal (LLN);

• Has clinical evidence of untreated hyper/hypothyroidism;

• Has leptomeningeal TTR amyloidosis;

• Has Type 1 diabetes;

• Has had Type 2 diabetes for ≥5 years;

• Has active hepatitis B or C or known human immunodeficiency virus (HIV) infection;

• Has NYHA heart failure classification >Class II

• Had a malignancy within 2 years, except for basal or squamous cell carcinoma of

• Is currently undergoing treatment for ATTR-PN with patisiran, inotersen, or othergene silencing agents, marketed drug products lacking a label indication for ATTR-PN (e.g., diflunisal, doxycycline), natural products or derivatives used as unproventherapies for ATTR-PN (e.g., green tea extract, tauroursodeoxycholic acid [TUDCA]/ursodiol), within 14 days, or 90 days for patisiran and 180 days forinotersen prior to dosing. Prior to screening, tafamidis, if already prescribed topotential subjects as part of their established background therapy, is allowed atthe labeled dosage and administration of 20 mg/day for the treatment of ATTR-PNwith, i in the opinion of the Investigator, evidence of disease progression while ontafamidis treatment