HighTide Therapeutics, Inc. (2511.HK) presented new findings on the renoprotective effects of its lead candidate HTD1801 in an oral presentation at the 63rd European Renal Association (ERA) Congress in Glasgow, UK. The data, drawn from completed Phase III trials (SYMPHONY-1 and 2) and mechanistic studies, demonstrate that HTD1801 significantly improves renal function in patients with Type 2 Diabetes Mellitus (T2DM) and reduced kidney function.
In the Phase III trials, patients with baseline eGFR of 60–90 mL/min/1.73m² treated with HTD1801 experienced a mean increase of +3.08 mL/min/1.73m² in eGFR after 52 weeks (95% CI: 0.46–5.70), without evidence of hyperfiltration or fluid retention. This suggests that HTD1801 may differentiate from existing therapies by potentially delaying or preventing disease progression in chronic kidney disease (CKD).
The mechanistic studies, conducted in collaboration with the research team led by Academician Jiandong Jiang at the Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, explored the underlying biological basis. In glucose- and palmitic acid-induced podocyte injury models, HTD1801 significantly preserved podocyte viability and inhibited apoptosis. It also restored expression of key podocyte structural proteins nephrin and podocin, while reducing levels of inflammatory marker phosphorylated NF-kB and apoptosis executioner caspase-3. In a diabetic nephropathy model, HTD1801 demonstrated dose-dependent improvements in renal architecture, reduced tubular injury scores, attenuated renal inflammatory and fibrotic changes, and drove a robust decrease in 24-hour urinary microalbumin.
HTD1801 is a first-in-class anti-inflammatory metabolic modulator (AIMM) targeting the AMPK-NLRP3 axis. As a single molecule, it activates AMP Kinase and inhibits the NLRP3 inflammasome, two complementary pathways that mitigate metabolic dysfunction. The compound has shown comprehensive benefits in multiple global clinical studies, including improved insulin sensitivity, glycemic control, lipid lowering, renal protection, weight reduction, hepatic improvement, and anti-inflammatory effects.
“This study provides the first evidence into the renoprotective effects of HTD1801 at the podocyte and glomerular levels. The convergence of clinical and preclinical data further supports the disease-modifying potential of HTD1801 and its ability to target fundamental pathophysiologic processes in CKD or other renal diseases,” said Dr Filip Surmont, Chief Medical Officer of HighTide Therapeutics. “We will continue advancing the clinical development of HTD1801 across CKD and related indications to provide more treatment options for patients worldwide.”
The findings have significant implications for the treatment of cardiovascular–kidney–metabolic (CKM) diseases, a growing global health burden. HTD1801's potential to serve as a foundational therapy in CKM disease management could reshape treatment paradigms, offering a multifunctional approach that addresses multiple risk factors simultaneously. Business leaders in the biopharmaceutical sector should note that HighTide's progress positions HTD1801 as a potential first-in-class therapy for CKD, a market with high unmet need. For more information, visit www.hightidetx.com.
