1. THAOS Status Update: Demography and Genotypes
Dr Bryan Shapiro

3. 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

4. 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

5. Cumulative Subject Enrollment

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

7. Global Patient Distribution
147
1143
Data as of Sept 2017

8. 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

9. 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

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

11. % 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

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

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

14. *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

15. 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

16. 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