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, from collaborative research with the Chinese Academy of Medical Sciences, provide mechanistic insights into how HTD1801 may preserve kidney function in patients with Type 2 Diabetes Mellitus (T2DM) and early chronic kidney disease (CKD).
HTD1801 is a first-in-class anti-inflammatory metabolic modulator (AIMM) targeting the AMPK-NLRP3 axis. In completed Phase III trials (SYMPHONY-1 and 2), HTD1801 significantly improved renal function in T2DM patients with baseline eGFR of 60–90 mL/min/1.73m². Treatment resulted in 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. These findings suggest HTD1801 may differentiate from existing therapies by potentially delaying or preventing disease progression.
The new preclinical study explored the mechanistic basis for these clinical observations. 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 the inflammatory marker phosphorylated NF-kB and the apoptosis executioner caspase-3. In a diabetic nephropathy (DN) 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.
Dr Filip Surmont, Chief Medical Officer of HighTide Therapeutics, presented the findings. He stated, "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."
The findings are particularly important given the high unmet need in CKD, which affects approximately 850 million people worldwide. Current therapies primarily manage symptoms or slow progression, but few offer disease modification. HTD1801's dual mechanism—activating AMPK and inhibiting NLRP3 inflammasome—addresses key pathways in metabolic dysfunction and inflammation that drive kidney disease. The company plans to continue advancing clinical development of HTD1801 across CKD and related indications.
For more information about HighTide Therapeutics and its pipeline, visit www.hightidetx.com.
