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Dongbao Zixing (Hangzhou) Biopharmaceutical Co., Ltd., a wholly owned subsidiary of Tonghua Dongbao Pharmaceutical Co., Ltd. ("the Company" or "Tonghua Dongbao"), recently completed a Phase IIa pivotal clinical trial on its dual-target inhibitor for gout (THDBH151 Tablets) and produced a clinical trial report. The results demonstrate that the trial has reached its primary endpoint.

Key clinical trial results:

• THDBH151 tablets showed good safety and tolerance in Chinese patients with gout. The overall incidence of      adverse events was similar to placebo.

• In gout patients, once-daily oral administration significantly reduced blood uric acid levels, with a clear dose-response relationship.

• By the end of Week 4, the 150 mg dose of THDBH151 demonstrated efficacy comparable to febuxostat at its highest clinical dose of 80 mg, in reducing blood uric acid and achieving target levels of ≤6 mg/dL and ≤5mg/dL.

• On Day 28, the 150 mg dose of THDBH151 achieved a greater average reduction in blood uric acid over 0–24 hours compared to the 80 mg dose of febuxostat (49.3% vs. 43.4%).

• The proportion of subjects experiencing at least one gout flare during the study was lower in the THDBH151 150 mg group than in the febuxostat 80 mg group (10.0% vs. 24.1%).

Gout and hyperuricemia treatment is a key focus and priority within the Company's endocrine and metabolism portfolio. This dual inhibitor is among the Company's key investigational novel drugs for gout/hyperuricemia treatment and is the first XO/URAT1 dual inhibitor for gout that has entered the Phase II clinical trial stage in China. Results from the Phase IIa clinical trial show that once-daily THDBH151 tablets provide clear uric acid–lowering efficacy over short-term treatment, with good safety and tolerance, a low incidence of gout flares, and a feasible titration regimen. Based on its favorable benefit-risk profile, the Company is advancing related research as planned.

Phase IIa Clinical Trial Results of THDBH151 Tablets (XO/URAT1 Dual Inhibitor for Gout)

After securing approval from the National Medical Products Administration (NMPA), the THDBH151 tablets successfully completed the Phase I clinical trial and the Company has launched "a multicenter, randomized, double-blind, double-dummy, febuxostat-and-placebo-controlled Phase IIa clinical study to evaluate the safety, tolerance, preliminary clinical efficacy, and pharmacokinetic/pharmacodynamic characteristics of THDBH151 tablets in adult patients with gout." The study evaluated the short-term (4-week) efficacy and safety of different titration regimens of THDBH151 tablets.

The study has concluded, and the final report was recently completed. The results show that the pharmacokinetic profile of THDBH151 tablets in gout patients is similar to that observed in healthy individuals, supporting the suitability of once-daily dosing. In gout patients, once-daily oral administration significantly reduced blood uric acid levels, with a clear dose-response relationship. By the end of Week 4, the 150 mg dose of THDBH151 demonstrated efficacy comparable to febuxostat at its highest clinical dose of 80 mg, in reducing blood uric acid and achieving target levels of ≤6 mg/dL and ≤5 mg/dL. Blood uric acid levels also continued to decline with longer treatment duration. The study further evaluated the 24-hour uric acid–lowering effect and the stability of drug activity. On Day 28, the 150 mg dose of THDBH151 achieved a greater average reduction in blood uric acid over 0–24 hours compared to the 80 mg dose of febuxostat (49.3% vs. 43.4%). The study also evaluated the 1-week efficacy of THDBH151 at doses of 150 mg and 100 mg. Compared with febuxostat at 40 mg, a commonly used clinical dose, THDBH151 at 150 mg achieved a greater reduction in blood uric acid from baseline, while the 100 mg dose demonstrated a comparable effect.

Most subjects in the study were gout patients with poor responses to prior uric acid-lowering therapy, with baseline blood uric acid levels ranging from 9.46 to 9.99 mg/dL. Nearly half of the subjects had experienced three or more gout flares in the past year. The findings suggest that THDBH151 tablets are effective in subjects with different baseline characteristics and gout flare histories during short-term treatment. By simultaneously inhibiting XO and URAT1, the drug shows potential for more stable and sustained blood uric acid control compared with febuxostat.

THDBH151 tablets showed good safety and tolerance in Chinese patients with gout. The overall incidence of adverse events was similar to placebo. No treatment-related serious adverse events were reported, and no subjects discontinued or withdrew due to treatment-related adverse events. The proportion of subjects experiencing at least one gout flare during the study was lower in the THDBH151 150 mg group than in the febuxostat 80 mg group (10.0% vs. 24.1%).

About THDBH151 Tablets (XO/URAT1 Inhibitor for Gout)

THDBH151 tablet is a dual-target XO/URAT1 inhibitor for gout. Due to its special mechanism of action, it can both reduce uric acid production by inhibiting xanthine oxidase (XO) and increase uric acid excretion by inhibiting the uric acid reabsorption by URAT1 transporter in the renal tubules. This mechanism improves efficacy and reduces side effects, leading to significantly higher medication adherence. THDBH151 has the potential to become the best-in-class drug of its kind. There are no similar products available on the market in China or worldwide.

About Gout and Hyperuricemia

The prevalence of gout and hyperuricemia has obviously increased in China, especially among young people, in recent years. According to the Chinese Guidelines for the Treatment of Hyperuricemia and Gout (2019) and data from the 6th national population census conducted by the National Bureau of Statistics, the overall prevalence of hyperuricemia in China is 13.3%, with approximately 177 million patients, while the overall prevalence of gout is 1.1% with about 14.66 million patients. Hyperuricemia has become the fourth most common metabolic disorder, following diabetes, hypertension, and hyperlipidemia. Gout has also become the second most common metabolic disease after diabetes.

A Frost & Sullivan analysis reveals that the number of people in China with hyperuricemia and gout will continue to increase, respectively reaching 239 million and 52.2 million in 2030, and the Chinese gout drug market is expected to grow to RMB 10.8 billion. There are two main treatments for gout and hyperuricemia: inhibiting uric acid production and increasing uric acid excretion.