Fig. 5: TBI-223 clinical translation, comparison to linezolid and dose selection.

Shaded areas show 95 percentile intervals and solid lines represent means. Each panel compares linezolid (red) to TBI-223 administered either daily (light blue) or twice daily (navy). A Comparison of monotherapy PK-PD model shown by concentration-response and predicted decrease in CFU. B Combination PK-PD results including concentration-response and predicted change in CFU from baseline over seven days. C Dose-response of LZD and TBI-223 with top and bottom axis aligned to compare suggested low and high doses of linezolid and TBI-223. D Predicted time to culture conversion defined by bacterial compartment reaching <1 bacteria for TBI-223 without dose adjustments and real-world ZeNix data (600 mg QD arm). E Lesion coverage is defined as lesion-specific drug concentrations above the respective lesion target concentration for each hour, Fig. S8. Each colored square represents 1 h that a drug is above its respective PD target. Empty blocks show drug concentration below the relevant monotherapy PD target and blue and navy blocks represent hours above target concentration for TBI-223 2400 mg daily and 1200 mg twice daily respectively and red blocks for linezolid (LZD). The selected monotherapy PD targets for TBI-223 were MIC for uninvolved lung (2 mg/L), macrophage IC₉₀ for cellular lesions (4.2 mg/L), and caseum MBC₉₀ for caseum (46.8 mg/L), Table 2: Potency targets.