Abstract: SA-PO0852
Exploratory Protein Biomarkers and Urinary Extracellular Vesicle microRNA Changes After TRPC6 Inhibition with Apecotrep in FSGS
Session Information
- Glomerular Diseases: Management, Evolving Strategies, and Practice-Changing Advances
October 24, 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
- Kretzler, Matthias, Department of Medicine, Nephrology and Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States
- Maas, Monika, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
- Delic, Denis, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
- Ju, Wenjun, Department of Medicine, Nephrology and Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States
- Eddy, Sean, Department of Medicine, Nephrology and Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States
- Lang, Benjamin, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
- Zwick, Matthias, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
- Steubl, Dominik, Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
- Anders, Fabian, Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
- Soleymanlou, Nima, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut, United States
- Trachtman, Howard, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, United States
Background
Focal segmental glomerulosclerosis (FSGS) is characterized by podocyte injury, proteinuria and potential kidney failure. Transient receptor potential cation channel subfamily C member 6 (TRPC6) dysregulation, including gain-of-function mutations, leads to podocyte loss. In Phase 2, apecotrep, an oral TRPC6 inhibitor, reduced proteinuria in primary FSGS and TRPC6-variant FSGS (NCT05213624; Trachtman et al. The Lancet 2026). Urinary protein biomarkers and urinary extracellular vesicle (uEVs) microRNAs (miRNAs) were analyzed to explore biomarker patterns in response to TRPC6 inhibition across key disease processes in FSGS.
Methods
Urinary protein biomarkers were quantified by validated immunoassays in evaluable patients. A mixed model for repeated measures (MMRM) was used to estimate biomarker changes between pooled apecotrep dose groups and placebo over time. UEV miRNA was quantified by small RNA sequencing. MiRNAs of interest were identified based on fold-change ≥1.5 and p≤0.05 significance thresholds when comparing placebo-corrected end of treatment values to baseline.
Results
MMRM analyses showed directional protein biomarker changes over 12 weeks in pooled apecotrep dose groups vs. placebo (35 active/7 placebo). Urinary markers of podocyte injury, inflammation, tubular injury and tissue remodeling generally declined over time, across biomarker domains relevant to FSGS pathophysiology (Table 1). Patients with ≥25% urinary protein-creatinine ratio (UPCR) reduction showed increased miRNA expression of 12 miRNAs and decreased expression of 25 miRNAs. UPCR correlated positively with miRNA-542-5p (r=0.42; p=0.032) and negatively with miR-455-5p (r=-0.48; p=0.020).
Conclusion
This exploratory analysis indicates changes across disease-relevant biomarkers in FSGS in response to TRPC6 inhibitor treatment. Observations are consistent with apecotrep’s therapeutic potential in reducing proteinuria in FSGS. MiRNA analyses also reveal UPCR-associated expression patterns. Findings require confirmation in ongoing pivotal trial.
Acknowledgment
Medical writing support for the preparation of this abstract was provided by Iqra Farooq, BSc, and Eve Blumson, PhD, of OPEN Health Communications, and funded by Boehringer Ingelheim, in accordance with Good Publication Practice (GPP) guidelines (www.ismpp.org/gpp-2022).
Funding
- Commercial Support – Boehringer Ingelheim