Innovation in Transplant Immunosuppression With Tegoprubart, With John Gill, MD

Results from the phase 2 BESTOW trial suggest tegoprubart, a novel anti-CD40L monoclonal antibody from Eledon Pharmaceuticals, provides comparable efficacy and superior safety to tacrolimus as the core immunosuppressant in de novo kidney transplant recipients.

Presented at the American Society of Nephrology (ASN) Kidney Week 2025, the multicenter, randomized, open-label study enrolled 127 patients undergoing kidney transplantation, who were randomized 1:1 to receive tegoprubart 20 mg/kg intravenously every 3 weeks or tacrolimus, both in combination with rabbit anti-thymocyte globulin induction, corticosteroids tapered to 5 mg by day 28, and mycophenolate. The primary endpoint was estimated glomerular filtration rate (eGFR) at 12 months, serving as a proxy for long-term graft function.

“The Phase 2 results presented at ASN Kidney Week highlight the potential of tegoprubart to deliver strong graft function after kidney transplantation, while avoiding the long-term toxicities often associated with current standard of care,” said Andrew Adams, MD, PhD, Professor of Surgery and Chief, Division of Transplantation, John S. Najarian Surgical Chair in Clinical Transplantation, Department of Surgery, University of Minnesota. “It’s been more than a decade since we’ve seen true innovation in transplant immunosuppression. These data offer real hope that patients may soon have a transformative therapy that improves their health outcomes and overall quality of life.”

Among patients who completed treatment, mean eGFR at month 12 was 69 mL/min/1.73 m² in the tegoprubart arm compared to 66 mL/min/1.73 m² with tacrolimus. Across all subgroups, including donor type, donor age, and degree of human leukocyte antigen mismatch, tegoprubart demonstrated consistently higher eGFR values, with differences favoring tegoprubart of approximately 3–5 mL/min/1.73 m².

The composite efficacy endpoint, which was defined as death, graft loss, biopsy-proven acute rejection [BPAR], or loss to follow-up, showed non-inferiority for tegoprubart, with rates of 22.2% vs 17.2% for tacrolimus. BPAR occurred in 20.6% of tegoprubart-treated patients and 14.1% of those receiving tacrolimus, though most episodes were mild (Banff IA–IIB) and responsive to standard therapy.

Additionally, tegoprubart demonstrated a distinct safety advantage relative to tacrolimus, showing markedly lower rates of key calcineurin inhibitor–related toxicities. Compared to tacrolimus, tegoprubart was associated with lower incidences of new-onset diabetes (1.6% vs 10.9%), hyperglycemia (9.5% vs 21.9%), hyperkalemia (11.1% vs 26.6%), tremor (1.6% vs 25.0%), and delayed graft function (14.3% vs 25.0%). Investigators also pointed out rates of serious adverse events and opportunistic infections were comparable between groups (52–56% and ~68%, respectively), with no new safety signals observed.

For more on the study, check out our interview with phase 1 trial investigator John Gill, MD, MS, professor of medicine at The University of British Columbia.

Editors’ Note: Gill reports no relevant disclosures.

References:

1. Eledon Pharmaceuticals. Eledon Presents Phase 2 BESTOW Trial Results for Tegoprubart for the Prevention of Rejection in Kidney Transplantation at the American Society of Nephrology’s Kidney Week 2025 Annual Meeting. Published November 6, 2025. Accessed November 21, 2025. https://ir.eledon.com/news-releases/news-release-details/eledon-presents-phase-2-bestow-trial-results-tegoprubart

2. Adams AB, Tedesco-Silva H, Potter S, et al. Efficacy and Safety of Tegoprubart for the Prevention of Rejection in Kidney Transplantation: Results from the Phase 2 BESTOW Trial. Presented at: ASN Kidney Week. Houston, Texas. November 5-9, 2025.