Changes in T-cell parameters. (A) Mean CD4⁺ and CD8⁺ senescent T-cell percentages (CD57⁺) over time. n values for baseline, D29, D57, and D85 for each group are as follows: leniolisib, CD4⁺, 18, 15, 16, and 15; placebo, CD4⁺, 9, 9, 7, and 8; leniolisib, CD8⁺, 19, 16, 19, and 16; and placebo, CD8⁺, 10, 9, 7, and 8. (B) Mean CD4⁺ and CD8⁺ PD-1⁺ T-cell percentages over time. n values for baseline, D29, D57, and D85 for each group are as follows: leniolisib, CD4⁺, 19, 17, 20, and 16; placebo, CD4⁺, 10, 9, 7, and 8; leniolisib, CD8⁺, 17, 14, 16, and 16; and placebo, CD8⁺, 10, 9, 7, and 7. (C) Mean CD4⁺ and CD8⁺ T-cell percentages over time. n values for baseline, D29, D57, and D85 for each group are as follows: leniolisib, CD4⁺, 19, 17, 20, and 16; placebo, CD4⁺, 10, 9, 7, and 8; leniolisib, CD8⁺, 19, 17, 20, and 16; and placebo, CD8⁺, 10, 9, 7, and 8. (D) Mean naïve (CD45RA⁺CD62L⁺) CD4⁺ and CD8⁺ T-cell percentages over time. n values for baseline, D29, D57, and D85 for each group are as follows: leniolisib, CD4⁺, 18, 17, 20, and 16; placebo, CD4⁺, 10, 9, 8, and 7; leniolisib, CD8⁺, 19, 17, 19, and 17; and placebo, CD8⁺, 10, 9, 7, and 8. Note that reference ranges are greater than graph axis, CD4⁺, 49.3% to 72.0%; CD8⁺, 48.6% to 87.5%.²⁷ (E) Mean CD4⁺ and CD8⁺ terminally differentiated effector memory T-cell percentages (CD45RA⁺CD62L^-) over time. n values for baseline, D29, D57, and D85 for each group are as follows: leniolisib, CD4⁺, 18, 17, 19, and 16; placebo, CD4⁺, 10, 9, 7, and 8; leniolisib, CD8⁺, 19, 17, 20, and 16; and placebo, CD8⁺, 10, 9, 7, and 8. (F) Mean serum CXCL13 level over time. n values for baseline, D29, D57, and D85 for each group are as follows: leniolisib, 21, 20, 21, and 21; and placebo, 10, 10, 10, and 9. Baseline was calculated as the average of D−1 and 1. All patients from the safety analysis set with measurements are included in the figures. Reference ranges are from personal communication (A-B; Manish Butte, University of California, Los Angeles, written communication, 29 March 2022), the literature (C-E), or laboratory (F).²⁷ In (A-E), gray boxes indicate reference ranges for CD4⁺ cells, and dotted lines indicate reference ranges for CD8⁺ cells. In (F), gray box indicates reference range. Error bars are SEM.