Figure 5. In silico simulation (ISS) model validation and simulated urinary oxalate (UOx) lowering subsequent dietary oxalate removal by SYNB8802.

1. Validation of simulated UOx excretion against clinical data. Simulated UOx on a free‐living diet and on 3 days of a high‐oxalate diet (dark blue). Observed UOx on a free‐living diet and on 3 days of a high‐oxalate, low‐calcium (HOLC) diet (light blue); points and error bars represent mean and standard deviation, respectively, across 30 simulated healthy subjects.
2. Simulated UOx and UOx reduction for healthy subjects consuming 200 mg/day dietary oxalate without SYNB8802 and with 1 × 10¹¹, 2 × 10¹¹, and 5 × 10¹¹ SYNB8802 cells TID over 10 days. Points represent simulations under a baseline assumption of dietary oxalate absorption in healthy subjects (Holmes et al, 2001) (See Materilas and Methods for a detailed description). Error bars represent a simulated range of dietary oxalate absorption (two simulations: 0.75× baseline and 1.25× baseline).
3. Simulated UOx and UOx reduction for enteric hyperoxaluria patients consuming 200 mg/day dietary oxalate without SYNB8802 and with 1 × 10¹¹, 2 × 10¹¹, and 5 × 10¹¹ SYNB8802 cells TID over 10 days. Points represent simulations under a baseline assumption of increased dietary oxalate absorption in HOX patients (4× healthy absorption). Error bars represent a simulated range of increased dietary oxalate absorption (two simulations: 3× healthy absorption and 5× healthy absorption).
4. Simulated UOx reduction for enteric hyperoxaluria patients after 5 days dosing with 1 × 10¹¹, 2 × 10¹¹, and 5 × 10¹¹ SYNB8802 cells TID as a function of dietary intake of oxalate. Solid curves represent simulations under a baseline assumption of increased dietary oxalate absorption in HOX patients (4× healthy absorption). Shaded regions represent a simulated range of increased dietary oxalate absorption (two simulations: 3× healthy absorption and 5× healthy absorption).