The 52-week data from these two Phase III clinical trials demonstrate the durability of response and highlight the comprehensive long-term clinical benefits of HTD1801 in patients with T2DM. HighTide plans to submit a new drug application (NDA) for HTD1801 as a treatment for T2DM to the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) later this year.

SYMPHONY-1 (NCT06350890) and SYMPHONY-2 (NCT06353347) are randomized, double-blind, placebo-controlled, Phase III clinical trials designed to evaluate the efficacy and safety of HTD1801 in adults with T2DM and inadequate glycemic control despite diet and exercise (SYMPHONY-1; N=408) or with Metformin (SYMPHONY-2; N=551). The primary endpoint in both studies was the change in glycated hemoglobin (HbA1c) from baseline with HTD1801 compared to placebo after 24 weeks of treatment. Patients were eligible to continue in a 28-week OLE during which all patients received HTD1801; Durability of response across efficacy endpoints was evaluated based on the change from baseline to Week 52.

Efficacy observed during the 24-week double-blind period was durable and maintained with longer-term treatment through 52 weeks in both studies

SYMPHONY-1 (HTD1801 as monotherapy): At week 24, the reduction from baseline in HbA1c with HTD1801 (-1.3%) was superior to placebo. HbA1c reductions were maintained in patients who continued receiving HTD1801 (-1.2% at Week 52). Placebo patients who switched to HTD1801 saw a reduction in HbA1c of -1.3% at Week 52, substantiating the double-blind phase findings.

SYMPHONY-2 (HTD1801 as an add-on therapy to Metformin): At week 24, the reduction from baseline in HbA1c with HTD1801 (-1.2%) was superior to placebo. HbA1c reductions were sustained in patients who continued receiving HTD1801 (-1.1% at Week 52). Placebo patients who switched to HTD1801 saw a reduction in HbA1c of -1.2% at Week 52, also substantiating the double-blind phase findings.

In both studies, the durability of effect on other cardiometabolic and renal endpoints was maintained at 52 weeks, suggesting comprehensive advantages of HTD1801 beyond glycemic control with long-term treatment.

In both studies, the proportion of patients receiving HTD1801 during the double-blind phase who achieved target HbA1c<7.0% was sustained through Week 52. The lipid-lowering effects observed during the double-blind phase, including significant reductions in low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C), were also maintained. Long-term HTD1801 treatment also led to continued reductions in key inflammatory biomarkers, including gamma-glutamyl transferase (GGT) and high-sensitivity C-reactive protein (hs-CRP), both associated with cardiovascular risk in patients with T2DM.

Notably, while estimated glomerular filtration rate (eGFR) remained stable in the overall population, the improvement of eGFR in patients with mild renal impairment at Week 24 was preserved at Week 52. These data highlighting the potential renal benefit of HTD1801 will be presented at a forthcoming scientific meeting.

Favorable safety and tolerability profile

Overall, long-term safety and tolerability were favorable and consistent with the double-blind phase. The types and severity of AEs did not increase with continued HTD1801 treatment compared to newly initiated HTD1801 treatment.

“The robust 52-week results from these trials reinforce that HTD1801 may represent a novel and truly differentiated therapeutic option for patients with T2DM,” said Dr. Linong Ji, Lead Principal Investigator, former Vice President of the International Diabetes Federation (IDF), and Director of the Peking University Diabetes Center and the Department of Endocrinology and Metabolism at Peking University People’s Hospital. “As a first-in-class new molecular entity, HTD1801 is an anti-inflammatory metabolic modulator (AIMM) with a dual mechanism of action, AMP kinase activation and NLRP3 inflammasome inhibition, distinct from existing therapies. Its unique profile is designed not only to lower blood glucose, but also to improve lipid metabolism, exert anti-inflammatory effects, and potentially enhance renal function, supporting its potential as a backbone therapy to address the cardiovascular-kidney-metabolic (CKM) syndrome by targeting the underlying drivers of diabetes and diabetes-related complications. In addition, the unique mechanism allows for potential of combination treatments”

“We extend our deepest gratitude to the patients who participated in these pivotal studies,” said Dr. Liping Liu, Founder, Chairperson, and CEO of HighTide Therapeutics. “Given the progressive nature of T2DM, durability of effect is a key determinant of long-term therapeutic success. The sustained beneficial effects of HTD1801 on metabolic, inflammatory, and renal parameters help reduce the risk of both microvascular and macrovascular complications. We look forward to sharing results from our Phase III head-to-head study with dapagliflozin, and will continue to explore HTD1801’s potential to deliver patients with chronic metabolic diseases a truly comprehensive, long-term treatment solution.”

About Type 2 Diabetes Mellitus (T2DM)

According to the International Diabetes Federation (IDF), 589 million adults (ages 20-79) were living with diabetes in 2024, and this number is projected to grow to 853 million (representing 1 in 8 adults) by 2050, of these, around 90% are T2DM cases. China has the largest population of diabetes patients worldwide, estimated to be 148 million in 2024, and projected to grow to 168 million in 2050. Diabetes is a global societal burden leading to over 6 million deaths per year. To address this urgent challenge, there is a critical need for innovative therapies that can deliver comprehensive clinical benefits for patients worldwide.

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 foundation therapy in CKM disease management.