Tegoprubart Sustains Increased eGFR Longterm Compared to Tacrolimus

Long-term follow-up from the phase 2 BESTOW extension study found that kidney transplant recipients treated with tegoprubart maintained increased estimated glomerular filtration rate (eGFR) compared with those receiving tacrolimus, with the difference remaining statistically significant at 18 months.

The findings, presented at the American Transplant Congress 2026, provide additional follow-up on whether CD154-directed immunomodulation with tegoprubart may offer a strategy to reduce reliance on calcineurin inhibitor-based regimens, which remain the standard of care in kidney transplantation but are associated with long-term toxicities, including nephrotoxicity.

For transplant clinicians, the ongoing challenge is balancing effective rejection prevention with preservation of kidney function over the lifetime of the graft. Tacrolimus remains highly effective at preventing rejection, but cumulative exposure has been associated with complications including calcineurin inhibitor nephrotoxicity, metabolic effects, and other adverse events.

“Even the best of kidneys over time tend to have damage and scar formation,” said Andrew Adams, MD, PhD, professor of surgery and chief of the division of transplantation at the University of Minnesota. “Some of that traces directly to the immunosuppressive therapy itself.”

Targeting the CD154 Pathway

Tegoprubart is an investigational monoclonal antibody targeting CD154 (CD40 ligand), a pathway involved in T-cell activation and immune responses that contribute to organ rejection.

“Interrupting that pathway with an antibody like tegoprubart can prolong survival, and it does so in a very specific way so that we don't see the side effects that traditional immunosuppression tends to bring along,” Adams said.

BESTOW Extension Findings

Among patients who completed 12 months of treatment in BESTOW, 96% of tegoprubart-treated patients and 86% of tacrolimus-treated patients entered the long-term extension study. Mean follow-up reached 21 months, including 89 patients followed through 18 months.

Kidney function, measured by eGFR, remained higher among tegoprubart-treated patients at each reported time point. At month 18, mean eGFR was 74 mL/min/1.73 m² with tegoprubart compared with 61 mL/min/1.73 m² with tacrolimus (P < .05).

Biopsy-proven acute rejection (BPAR) events after 6 months were not observed among tegoprubart-treated patients, compared with 7 events (9.4%) among patients receiving tacrolimus. Among patients who experienced rejection, those who remained on tegoprubart had higher observed mean eGFR compared with tacrolimus-treated patients, with the difference increasing from approximately 15 mL/min/1.73 m² at 12 months to approximately 25 mL/min/1.73 m² at 21 months in an exploratory analysis.

Patient-reported outcomes also favored tegoprubart at 52 weeks. Tegoprubart-treated patients reported lower symptom burden on the Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD-59R) and higher scores on the KDQOL-36 Symptoms and Problems domain compared with tacrolimus-treated patients.

Safety and Next Steps

During long-term follow-up, several adverse events occurred less frequently in the tegoprubart group compared with the tacrolimus group, including headache, extremity pain, falls or loss of balance, acute kidney injury, and diarrhea.

No graft loss, progressive multifocal leukoencephalopathy, post-transplant lymphoproliferative disorder, BK or CMV nephropathy/disease, or new malignancies were reported in the tegoprubart cohort. One death occurred in the tegoprubart arm and was not attributed to study treatment.

Following an FDA End-of-Phase 2 meeting, Eledon Pharmaceuticals plans to initiate a phase 3 kidney transplant program in late 2026. The planned phase 3 study will evaluate non-inferiority versus tacrolimus at 52 weeks using a composite endpoint of biopsy-proven acute rejection, graft loss, and death.

Although the BESTOW extension data represent the longest reported follow-up for tegoprubart in kidney transplantation to date, larger phase 3 studies will be needed to determine whether the observed eGFR advantage translates into improved long-term transplant outcomes.

Editor’s Note: Adam’s reports relevant disclosures Eledon Pharmaceuticals, Miromatrix, and Sanofi.

References

1. Eledon Pharmaceuticals, Inc. Eledon presents long-term extension phase 2 BESTOW results at American Transplant Congress showing sustained higher kidney function and improved patient-reported outcomes with tegoprubart compared with tacrolimus. News release. GlobeNewswire. June 22, 2026. Accessed July 10, 2026. https://www.globenewswire.com/news-release/2026/06/22/3315172/0/en/eledon-presents-long-term-extension-phase-2-bestow-results-at-american-transplant-congress-showing-sustained-higher-kidney-function-and-improved-patient-reported-outcomes-with-tego.html

2. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9(suppl 3):S1-S155.