THAOS Status Update: Demography and Genotypes Dr Bryan Shapiro

Participating THAOS sites 54 active sites in 17 countries registered to THAOS 7 sites selected and in start-up but not initiated 1 site initiated but no enrollment as yet Data as of Sep 2017

Total of 54 active sites in 17 countries Country No. of active sites Argentina 2 Belgium 1 Brazil Bulgaria Canada Denmark France 3 Germany 4 Italy Japan Korea Mexico Netherlands Portugal Spain 7 Sweden USA 18 TOTAL 54 4 countries discontinued from THAOS: Cyprus, Israel, Turkey, Taiwan

Cumulative Subject Enrollment

Cumulative Enrollment – Sites with Subjects Detailed data not available 2008/2011

Global Patient Distribution 147 1143 Data as of Sept 2017

Subject Distribution at Enrollment (as of August 01, 2017) Val122Ile n=160, 62.7% Wild type   n=469, 13.8% Val30Met   n=2138, 73.0% Leu111Met n=19, 7.5% Cardiacd   n=255, 34.7% All patients enrolled in THAOS N=3399a Thr60Ala n=69, 27.1% Mutationb   n=2930, 86.2% Non-Val30Met   n=734, 25.1% Ile68Leu n=7, 2.7% Other   n=479, 65.3% Heterozygous, non-specificc   n=58, 2.0% [a] This STROBE represents patients with signed data using the 01AUG2017 data cut [b] Genetic mutation in the gene that codes TTR but which does not lead to a TTR disease. [c] Reported TTR mutation but missing specific genotype details. [d] Cardiac mutations include: Val122Ile, Leu111Met, Thr60Ala, and Ile68Leu. Data as of 01 August 2017

Countries and contributions to THAOS (%): 21 countries, 3,399 subjects Others: Belgium Bulgaria Canada Cyprus Israel Netherlands South Korea Taiwan Turkey Data as of 01 August 2017

Spectrum of Genotypes (%) N=3399 62.9% Other 89 mutations affecting 226 patients Data as of 01 August 2017

% of patients with TTR mutation Most Common TTR Mutations 2017 (101 different mutations in 2930 subjects) Mutation Total % of patients with TTR mutation Cumulative % Val30Met 2138 73.0% Val122Ile 160 5.5% 78.4% Thr60Ala 69 2.4% 80.8% Ser50Arg 68 2.3% 83.1% Glu89Gln 62 2.1% 85.2% Phe64Leu 36 1.2% 86.5% Ser77Tyr 28 1.0% 87.4% Ile107Val 24 0.8% 88.2% Gly47Ala 22 89.0% Val20Ile 20 0.7% 89.7% Leu111Met 19 90.3% Glu89Lys 14 0.5% 90.8% Val28Met 13 0.4% 91.2% DelVal122 11 91.6% Ser52Pro 10 0.3% 92.0% Heterozygous: 58 subjects 85 different mutations reported in 9 or fewer patients 11

Genotypic Spectrum in Val30Met “Endemic” Regions Japan (N=119) Brazil (N=198) Portugal (N=1367) Sweden (N=180) Data as of 01 August 2017

Spectrum of Disease in USA N=648 *Other 33 mutations affecting 40 patients Data as of 01 August 2017

*Other 42 mutations affecting 69 patients Spectrum of Disease in Europe (excluding Portugal and Scandinavia) N=650 Other Mutations (16.7) Wild Type (18.3) Val30Met (31.9) Ile68Leu (6.0) Glu89Gln (6.6) *Other 42 mutations affecting 69 patients Data as of 01 August 2017

Spectrum of Mutations in Latin America N=359 Other Mutations (16.7) Wild Type (18.3) Val30Met (31.9) Ile68Leu (6.0) Glu89Gln (6.6) Data as of 01 August 2017

Spectrum of Mutations in Asia N=137 Other Mutations (16.7) Wild Type (18.3) Val30Met (31.9) Ile68Leu (6.0) Glu89Gln (6.6) Data as of 01 August 2017