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POWER: Immune Genetics Implemented as an IO Clinical Biomarker Germline genetic score (PRS) for hypothyroidism risk separates survival probability Phase 3 trial failure → Withdrawal of triple-negative breast cancer indication Atezolizumab+Nab-Paclitaxel 181/451 Placebo+Nab-Paclitaxel 208/451 Percentage of Patients PMID: 30345906; PMID: 34099659 100- 90- 80- 70- 60- 50- 40- 30- 20- 10- 0- 0 T 3 No. of Events/ No. of Patients -6 9 12 Median Overall Survival (95% CI) mo 21.3 (17.3-23.4) 17.6 (15.9-20.0) 15 Stratified hazard ratio for death, 0.84 (95% CI, 0.69-1.02) P=0.08 N~900 HR~0.84 18 Months 21 Atezolizumab+nab-paclitaxel 2-Yr Rate of Overall Survival (95% CI) % Placebo+nab-paclitaxel 24 42.1 (34.3-49.9) 39.7 (33.2-46.3) 27 30 33 36 N~150 HR~0.62 Survival probability 1.0 0.9- 0.8- 0.7 0.6- 0.5- 0.4 0.3 0.2 0.1 0.0 Strata PRS(hypoT)=below median+ PRS(hypoT)=above median 0 100 200 Number at risk 737 Atezo (PD-L1) + Chemotherapy ~15 months 266 #5 60 ~26 months 20 14 10 900 580 Copyright © 2024 23and Me, Inc. 1000 1100 1200 1300 1400 5 10 14 13 23andMe 11

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