Chinese participants with:

• sUA ≥ 480 μmol/L with gout;

• sUA ≥ 480 μmol/L without gout but with comorbidities;

• sUA ≥ 540 μmol/L.

• Ruzinurad superior to placebo at 5 mg and 10 mg doses;

• 32.5–61.5% of patients achieved target sUA, ≤ 360 μmol/L;

• Highest with ruzinurad 10 mg.

• Incidence of TEAEs similar among groups;

• No serious TEAEs;

• Incidence of gout flares requiring intervention similar among groups.

Chinese participants with:

• sUA ≥ 480 μmol/L with gout;

• sUA ≥ 480 μmol/L without gout but with comorbidities;

• sUA ≥ 420 μmol/L for ≥ 3 months and diagnosed hyperuricemia;

• sUA ≥ 540 μmol/L.

Ruzinurad plus febuxostat in one of three regimens:

• Ruzinurad 10 mg + febuxostat 80 mg;

• Ruzinurad 10 mg + febuxostat 40 mg;

• Ruzinurad 5 mg + febuxostat 20 mg;

• Oral QD for 4 weeks.

• Target sUA (≤ 360 μmol/L) achieved in 75.0–96.6% of patients;

• Highest with ruzinurad 10 mg + febuxostat 40 mg;

• sUA percentage reduction of 41.8–‍63.7% across doses;

• Highest with ruzinurad 10 mg + febuxostat 40 mg.

• Incidence of TEAEs similar among groups;

• Serious treatment-related TEAE occurred in 1 (1.1%) patient (acute kidney injury);

• Safety profile comparable across groups.

• Patients with gout and subcutaneous tophi;

• Baseline sUA was 9.1–9.6 mg/dL across treatment groups.

After 3 months (primary endpoint):

• Mean sUA reduced to 4.5–6.1 mg/dL, highest with allopurinol alone;

• 46–86% achieved sUA < 6 mg/dL, most on pozdeutinurad 75 mg;

• 23–69% achieved sUA < 5 mg/dL, most on pozdeutinurad 50 mg + allopurinol.

After 6 months:

• 29% (n = 4) of patients in the pozdeutinurad 75 mg group achieved resolution of ≥ 1 tophus [vs. 8% (n = 1)] each in other groups;

• Total urate crystal volume reduced by 17–32%, greatest in pozdeutinurad 50 mg + allopurinol group.

• No serious TEAEs;

• No kidney or liver abnormalities observed;

• Gout flare was the most common TEAE, occurring less frequently in pozdeutinurad groups than allopurinol group.

In participants with mild or moderate renal impairment, after a single 100 mg dose:

• Only mild increases in plasma exposure compared with those with normal renal function;

• Maximum sUA reductions were similar to those in participants with normal renal function (approximately 50–60%).

In participants with mild or moderate renal impairment, after multiple 50 mg doses:

• Similar plasma exposure as in those with normal renal function;

• At steady state, approximately 53% reduction in sUA in both groups.

• Median sUA reduced from 8.6 to 3.5 mg/dL with 75 mg and to 5.0 mg/dL with 50 mg pozdeutinurad, with no change in the placebo group;

• 89%, 82%, 63%, and 29% of patients on 75 mg achieved sUA < 6, < 5, < 4, and < 3 mg/dL respectively, in the 75 mg group;

• In the 50 mg group, 78%, 50%, and 8% of patients achieved < 6, < 5, and < 4 mg/dL, respectively.

• No serious AEs;

• AEs were mild or moderate;

• 65 gout flare incidents, evenly distributed among groups;

• Pozdeutinurad was well tolerated, with no dose adjustments needed.

Western (Study 1) patients with gout and sUA > 6.5 and ≤ 10 mg/dL; Japanese (Study 2) patients with gout sUA ≤ 10 mg/dL, and either:

• sUA ≥ 7 mg/dL with gout;

• sUA ≥ 8 mg/dL without gout but with comorbidities;

• sUA ≥ 9 mg/dL without gout and complications.

• Placebo for 24 weeks;

• Verinurad 5 mg for 24 weeks;

• Verinurad 5 mg for 2 weeks then 10 mg for 22 weeks;

• Verinurad 5 mg for 2 weeks, 10 mg for 2 weeks, then 12.5 mg for 20 weeks;

• All QD, all oral.

Least squares mean (± SE) percentage change in sUA from baseline:

• Study 1: 1.2 ± 2.9 for placebo, and –17.5 ± 2.8, –29.1 ± 2.8, –34.4 ± 2.9 for verinurad 5, 10, and 12.5 mg, respectively;

• Study 2: –2.4 ± 2.5, –31.7 ± 2.5, –51.7 ± 2.6, and –55.8 ± 2.5, respectively;

• Difference from placebo was significant for each verinurad dose in both studies (p < 0.0001).

• TEAEs have similar frequency among groups;

• Renal TEAEs were more common with verinurad than placebo.

• Maximum decrease in sUA from baseline occurred 8–12 hours after dosing, and ranged from: 52–77% for verinurad + febuxostat vs. 42% for febuxostat 40 mg alone; 62–82% for verinurad vs. 55% for febuxostat 80 mg alone;

• Verinurad + febuxostat decreased sUA dose-dependently;

• Urinary uric acid excretion rate was similar to baseline for verinurad + febuxostat, and reduced from baseline with febuxostat alone;

• Verinurad plasma exposure was dose-dependent, and comparable with/without febuxostat.

• No drug-drug interactions;

• Verinurad well tolerated;

• No clinically meaningful changes in laboratory values.

• Complex treatment arms: verinurad at doses 2.5–20 mg + febuxostat either 40 or 80 mg, in one of four different sequences, all oral, QD, and for 4 weeks;

• Eight treatment sequences, including allopurinol 300 mg + verinurad at doses 2.5–20 mg, orally QD, or allopurinol alone at 300 mg QD, or 600 mg BID orally for 5 weeks.

• Maximum decrease in sUA from baseline occurred 7–12 hours after dosing, and ranged from: 47–74% for verinurad + allopurinol groups; 40–54% for allopurinol alone groups;

• Verinurad + allopurinol decreased sUA dose-dependently;

• Verinurad had no effect on allopurinol plasma pharmacokinetics, but decreased oxypurinol C_max by 19–32% and AUC_last by 21–39%.

• Verinurad + allopurinol was well tolerated;

• No serious TEAEs, AE-related withdrawals, or renal AEs;

• No clinically meaningful change in laboratory values.

• Study 1 (low-dose): Epaminurad 0.25, 0.5, 1, or 2 mg, or placebo;

• Study 2 (high-dose): Epaminurad 3, 5, 7, 10 mg, or placebo;

• All given orally, QD for 15 days.

Mean (± SD) sUA changes were dose-dependent, ranging from:

• −3.3 to −29.5 (vs. −4.0 for placebo) among epaminurad groups in Study 1;

• −28.3 to −54.3 (vs. −1.2 for placebo) among epaminurad groups in Study 2.

• AEs occurring in ≥ 10%: Study 1: arthralgia, pain; Study 2: gout, arthralgia;

• Most AEs were mild;

• No difference in frequency of AEs between placebo and epaminurad groups;

• Two serious AEs, neither causally related.

• Epaminurad 6 or 9 mg or febuxostat 40 or 80 mg, or placebo;

• All oral, given for 20 weeks, followed by a 28-week open-label extension in which patients can receive epaminurad 6 or 9 mg.

• ABP-671 2, 4, or 8 mg/day (single daily dose or divided into two doses per day) or placebo in successive ascending doses;

• 4-week dose evaluation period.

• ABP-671 significantly reduced sUA levels compared to placebo and baseline at all dose levels tested;

• sUA levels < 6 mg/dL were achieved by 6 (75.0%), 5 (62.5%), 7 (100%), 7 (87.5%), 7 (100%), and 8 (100%) participants in the 1 mg BID, 2 mg QD, 2 mg BID, 4 mg QD, 4 mg BID, and 8 mg QD cohorts, respectively.

• ABP-671 (3 dose levels, not published), allopurinol, or placebo;

• 28 weeks.