Clinical Data

1. Generally consistent with what has been seen with selective SGLT2 inhibitors in type 2 diabetes, study participants randomized to Zynquista experienced a modest initial reduction in eGFR that quickly stabilized. In the pooled analysis, the placebo-corrected least squares mean change from baseline in eGFR was −2.0 mL/min/1.73 m2 (p = 0.010) and −0.5 mL/min/1.73 m2 (p = 0.52) for the 200 mg and 400 mg doses, respectively. Importantly, in the subset of patients (n = 370) with off drug follow-up laboratory records, defined as 7 days after last dose, eGFR returned to baseline for study participants randomized to Zynquista, but not to placebo, with a placebo-corrected LS mean change from baseline to off drug records of +3.0 mL/min/1.73 m2 (p = 0.031) and +2.7 mL/min/1.73 m2 (p = 0.045) for Zynquista 200 mg and 400 mg, respectively.
   
   
2. Zynquista demonstrated meaningful effects on markers of hemoconcentration and plasma uric acid, where biochemical changes have been linked to cardiorenal protection associated with SGLT2 inhibitors. Mean serum hematocrit increased from 41.9% at baseline to 43.8% at Week 12 for Zynquista 200 mg and from 42.0% to 44.0% for Zynquista 400 mg. Relative to placebo, the LS mean difference was 1.8% and 1.9% for Zynquista 200 mg and 400 mg, respectively (p < 0.0001, for both). These changes persisted throughout the 52-week trial at both Zynquista doses (p < 0.0001). Mean baseline serum albumin concentrations were similar, at approximately 4.3 g/dL for all groups. LS mean serum albumin increased 0.06 g/dL and 0.07 g/dL with Zynquista 200 mg and 400 mg, respectively, at Week 4 (p < 0.0001, for both). At Week 52, placebo-corrected LS mean change was 0.03 g/dL (p = 0.036) for Zynquista 200 mg and 0.03 g/dL (p = 0.053) for Zynquista 400 mg. Zynquista also significantly reduced uric acid throughout 52 weeks (p < 0.001). The placebo-corrected LS mean change in serum uric acid was 20.29 mg/dL and 20.42 mg/dL (p < 0.0001 for both) at 4 weeks and 20.17 mg/dL (p = 0.0003) and 20.28 mg/dL (p < 0.0001) at 52 weeks for Zynquista 200 mg and 400 mg, respectively.
   
   
3. Zynquista demonstrated consistent lowering of blood pressure and urinary albumin-to-creatinine ratio (UACR). Systolic blood pressure difference was −2.9 and −3.6 mmHg (p < 0.0001 for both doses) for Zynquista 200 mg and Zynquista 400 mg, respectively, placebo-adjusted. Diastolic blood pressure changed by −1.4 (p = 0.0033) and −1.6 mmHg (p = 0.0008) placebo-adjusted. Of note, in patients whose current blood pressure targets were above and below 130/80 mmHg, the impact of Zynquista was comparable and resulted in clinically relevant blood pressure lowering. As for UACR, in patients with baseline UACR ≥30 mg/g, UACR decreased by 23.7% (p = 0.054) and 18.3% (p = 0.18) for Zynquista 200 mg and 400 mg, respectively, versus placebo.