Kidney Week

Abstract: TH-PO1296

First-in-Human Study of SK-09, a Novel Transient Receptor Potential iChannel-5 Inhibitor: Safety, Tolerability, and Pharmacokinetics in Healthy Participants

Session Information

• Late-Breaking Research Posters
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Ying, Du, Consun Pharmaceutical Group Limited, Guangzhou, Guangdong, China

Du Ying, MD, PhD

• Wong, Gloria Yee Man, Q-Pharm Pty Ltd., Herston, Queensland, Australia

Gloria Yee Man Wong, PhD

Background

Overactivation of the TRPC5-Rac1 pathway drives cytoskeletal dysfunction, podocyte injury, proteinuria and glomerulosclerosis. SK-09, a novel highly selective TRPC5 inhibitor in first-in-human (FIH) trials, has shown potent target inhibition and renoprotective efficacy in preclinical models, supporting its continued clinical development for glomerular diseases.

Methods

This FIH trial (NCT07267026) comprised single-ascending-dose (SAD) (20-500 mg), multiple-ascending-dose (MAD), and food-effect (FE) studies. SAD/MAD studies used a randomized, double-blind, placebo-controlled design in healthy adults (3:1 active-to-placebo; 8 subjects/cohort: 6 SAD, 3 MAD cohorts) for safety, tolerability, PK and PD. The FE part used a randomized, open-label, two-period crossover design to assess the food effect on safety, tolerability and PK after a single 150 mg dose.

Results

Initial data from four SAD cohorts (20, 50, 100 and 200 mg) showed rapid absorption, non-linear dose-proportional exposure, and biphasic elimination. Plasma concentrations declined rapidly within 12 hours postdose, followed by a slower terminal phase that was prolonged at higher doses (Figure 1A).
Following a single 200 mg dose in healthy subjects, plasma C_max exceeded the IC₅₀ for hTRPC5 inhibition (15.15 ng/mL after correction for protein binding and molecular weight). In a DOCA/Salt-induced FSGS rat model, SK-09 dose-dependently reduced glomerulosclerosis and preserved podocyte integrity (Figure 1B–D).
SK-09 was well tolerated, with no serious/severe adverse events; most AEs were mild. Higher-dose SAD and MAD cohorts are ongoing to further characterize PK/PD, safety and therapeutic exposure range.

Conclusion

SK-09 showed rapid absorption, dose-related exposure, and prolonged terminal phase exposure at higher doses in healthy adults. A single 200 mg dose achieved plasma exposure above the adjusted IC₅₀ for human TRPC5 inhibition, supporting target engagement with favorable safety/tolerability. These findings support continued development of SK-09 for glomerular diseases.

Funding

• Commercial Support – Consun Pharmaceutical Group