These data reinforce HTD1801’s potential to target the metabolic drivers of Type 2 diabetes mellitus progression while delivering cardiometabolic benefits
ROCKVILLE, MD and SHENZHEN, CHINA – [Dec 1, 2025] – HighTide Therapeutics, Inc. (2511.HK), a biopharmaceutical company specializing in the development of multifunctional, multi-targeted therapies for chronic metabolic diseases, today reported positive topline results from its Phase III HARMONY trial, demonstrating that HTD1801 achieved the primary endpoint of this trial, with superior improvements in key cardiometabolic markers in patients with type 2 diabetes mellitus (T2DM) compared to dapagliflozin.
HARMONY (NCT06415773) is a randomized, double-blind, active-controlled, Phase III clinical trial evaluating the efficacy and safety of HTD1801 compared with dapagliflozin in adults with T2DM inadequately controlled with metformin (N=369). The primary endpoint assessed the change in HbA1c from baseline to Week 24 versus dapagliflozin, with a non-inferiority margin of 0.4%. Gated secondary endpoints included multiple cardiometabolic markers.
- The Phase III head-to-head trial met its primary endpoint: HTD1801 achieved a –1.12% LS mean reduction in HbA1c at Week 24, compared with –0.93% for dapagliflozin (LS mean difference –0.20%; 95% CI –0.37 to –0.03; P < 0.001).
- HTD1801 met gated secondary endpoints, demonstrating superior reductions in LDL-C and non-HDL-C with lower rate of statin intensifications compared with dapagliflozin. HTD1801 also delivered superior improvements in other cardiometabolic markers, including a higher proportion of patients reaching HbA1c < 7.0%, and a greater reduction in Lp(a).
- The safety and tolerability profile of HTD1801 was favorable, with serious adverse events reported in 3.8% of patients versus 4.4% for dapagliflozin; the most common side-effects were mild to moderate gastrointestinal events, and no severe hypoglycaemia occurred in the HTD1801 arm.
Collectively, these results indicate that HTD1801 may offer broader clinical benefits than SGLT2 inhibitor, targeting the underlying metabolic and inflammatory drivers of T2DM. The HARMONY study is the third consecutive successful Phase III trial of HTD1801, following SYMPHONY-1 and SYMPHONY-2, underscoring its strong potential as a foundational therapy in cardiovascular-kidney-metabolic (CKM) disease management. HighTide Therapeutics plans to submit a New Drug Application (NDA) for HTD1801 later this year.
“The HARMONY study demonstrated the superiority of HTD1801 over the SGLT2 inhibitor dapagliflozin in glycemic control. It also led to a greater reduction in atherogenic LDL-C and further reduced the need for statin therapy, compared with dapagliflozin— an agent with established cardiorenal protective effects.” said Dr. Linong Ji, Lead Principal Investigator; former Vice President of the International Diabetes Federation (IDF); and Director of both the Peking University Diabetes Center and the Department of Endocrinology and Metabolism, Peking University People’s Hospital. “These results indicated that HTD1801 may have greater potential in improving the treatment of ASCVD. We look forward to bringing this novel treatment option to patients as soon as possible.”
“These results from the HARMONY study mark another important milestone in our global HTD1801 development program,” said Liping Liu, Ph.D., Founder, Chairperson, and CEO of HighTide Therapeutics. “With three successful Phase III studies now completed, HTD1801 continues to demonstrate its potential as a first-in-class, multifunctional therapy that addresses the complex metabolic and inflammatory drivers of T2DM. HTD1801 could complement—or even extend beyond—the benefits of SGLT2 inhibitors, offering a more comprehensive approach to managing patients with T2DM.”
About HTD1801
HTD1801 is a first-in-class new molecular entity that targets the residual risks underlying cardiovascular–kidney–metabolic (CKM) diseases. It is an orally delivered, anti-inflammatory metabolic modulator (AIMM) that, as a single molecule, exerts a unique dual mechanism of action through activation of AMP Kinase and inhibition of the NLRP3 inflammasome, two complementary pathways that mitigate metabolic dysfunction. Multiple global clinical studies have demonstrated the comprehensive benefits of HTD1801, including improved insulin sensitivity, glycemic control, lipid lowering, renal protection, weight reduction, hepatic improvement, and anti-inflammatory effects. Collectively, these findings support the potential of HTD1801 to serve as a foundational therapy in CKM disease management.
About HighTide Therapeutics
HighTide Therapeutics, Inc. (2511.HK) is a biopharmaceutical company dedicated to developing multifunctional, multi‐targeted therapies for chronic metabolic diseases, with a strategic emphasis to address the residual risks of cardiovascular-kidney-metabolic (CKM) syndrome. The company focuses on delivering breakthrough treatments that generate comprehensive, multi-organ benefits for patients worldwide. HighTide has built an innovative, globally integrated pipeline of proprietary assets and advanced multiple clinical programs across chronic metabolic diseases. The company’s lead asset, HTD1801, has received two Fast Track designations and one Orphan Drug designation from the US Food and Drug Administration (FDA), and has been selected for China’s National Major Science and Technology Project for Significant New Drug Development.
For more information, please visit www.hightidetx.com. Contact: pr@hightidetx.com