HIGHTIDE-B (02511) announced positive results from its Phase III HARMONY trial (NCT06415773), a head-to-head comparison between HTD1801 and dapagliflozin in patients with type 2 diabetes (T2DM). The study met its primary endpoint, with HTD1801 demonstrating superior improvements in multiple key cardiometabolic indicators compared to dapagliflozin. The data reaffirm HTD1801's ability to target the root causes of T2DM, delivering comprehensive cardiometabolic benefits.

HARMONY was a randomized, double-blind, active-controlled Phase III study (N=369) evaluating the efficacy and safety of HTD1801 versus dapagliflozin in adult T2DM patients with inadequate glycemic control after metformin treatment. The primary endpoint was the change in HbA1c from baseline at 24 weeks (non-inferiority margin: 0.4%). Secondary endpoints included multiple cardiometabolic markers.

Key findings: - **Primary Endpoint Achieved**: HTD1801 showed a least squares (LS) mean change in HbA1c of -1.12% at 24 weeks, compared to -0.93% for dapagliflozin (LS mean difference: -0.20%; 95% CI: -0.37 to -0.03; P < 0.001). - **Superior Secondary Outcomes**: HTD1801 significantly outperformed dapagliflozin in reducing LDL-C and non-HDL-C, with fewer patients requiring additional or intensified statin therapy. It also demonstrated better improvements in other cardiometabolic markers, including a higher proportion of patients achieving HbA1c <7.0% and greater reductions in Lp(a). - **Safety Profile**: HTD1801 exhibited favorable safety and tolerability, with a serious adverse event rate of 3.8% (vs. 4.4% for dapagliflozin). The most common adverse events were mild-to-moderate gastrointestinal reactions, with no severe hypoglycemia reported.

HTD1801 uniquely targets T2DM’s core pathological mechanisms by modulating both metabolic and inflammatory pathways, offering broader clinical benefits than SGLT2 inhibitors like dapagliflozin. Following the SYMPHONY-1 and SYMPHONY-2 trials, HARMONY marks HTD1801’s third successful Phase III study, reinforcing its potential as a foundational therapy for cardiorenal metabolic (CKM) diseases. HIGHTIDE-B plans to submit a New Drug Application (NDA) for HTD1801 this year.