Eledon’s anti-CD40 antibody tegoprubart sustained kidney function benefits over tacrolimus through 18 months in the Phase 2 BESTOW program, with no late rejection events and a favorable safety profile, supporting Phase 3 development in transplantation.
Written By: Shaik Yasmeen, PharmD
Reviewed By: Pharmacally Editorial Team
Tegoprubart demonstrated sustained kidney function benefits over tacrolimus through 18 months in the Phase 2 BESTOW clinical program (NCT05983770), with no biopsy-proven acute rejection reported after six months of treatment. The long-term data, presented at the 2026 American Transplant Congress (ATC), strengthen the case for Eledon Pharmaceuticals’ anti-CD40 antibody as a potential alternative to calcineurin inhibitor-based immunosuppression ahead of Phase 3 development.
Anti-CD40 Therapy Targets Safer Long-Term Immunosuppression
Tegoprubart is an investigational monoclonal antibody that blocks the CD40-CD40L costimulatory pathway, suppressing immune activation without the nephrotoxicity commonly associated with calcineurin inhibitors such as tacrolimus.
Improving long-term graft survival while reducing treatment-related toxicity remains a major unmet need in kidney transplantation, where lifelong immunosuppression often contributes to declining kidney function and adverse effects.
BESTOW Extension Demonstrates Sustained Kidney Function Benefit
Among patients completing the first 12 months of the Phase 2 BESTOW study, 96% of tegoprubart-treated patients and 86% of tacrolimus-treated patients enrolled in the long-term extension. At the data cutoff, mean follow-up reached 21 months, with some patients followed for up to 33 months.
Kidney function, measured by estimated glomerular filtration rate (eGFR), remained consistently higher with tegoprubart throughout follow-up. At 18 months, patients receiving tegoprubart achieved a statistically significant mean eGFR of 74 mL/min/1.73 m², compared with 61 mL/min/1.73 m² in the tacrolimus arm, representing an approximately 12 mL/min/1.73 m² advantage (p<0.05).
No biopsy-proven acute rejection (BPAR) occurred in tegoprubart-treated patients after the first six months post-transplant. In contrast, seven of the eleven rejection events reported in the tacrolimus arm occurred after six months, including active antibody-mediated rejection and recurrent T-cell-mediated rejection.
Patients receiving tegoprubart also reported significantly lower symptom burden at 52 weeks, with improvements on both the Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD-59R) and the Kidney Disease Quality of Life-36 Symptoms and Problems assessment. An exploratory analysis further suggested better preservation of kidney function among tegoprubart-treated patients who experienced rejection compared with similar patients receiving tacrolimus.
Long-term findings from the earlier Phase 1b study were consistent with the Phase 2 results, with no rejection episodes observed after six months and one patient remaining on therapy for approximately 3.5 years.
Favorable Long-Term Safety Profile
Long-term safety remained favorable for tegoprubart. Neurological and kidney-related adverse events, including headache, extremity pain, falls, acute kidney injury, and diarrhea, occurred less frequently than with tacrolimus.
Investigators also reported no graft loss, progressive multifocal leukoencephalopathy (PML), post-transplant lymphoproliferative disorder (PTLD), BK or CMV nephropathy, new malignancies, or treatment-related proteinuria in the tegoprubart arm. One death occurred but was considered unrelated to study treatment.
Eledon CEO David-Alexandre C. Gros, MD, said the sustained kidney function benefit, absence of late rejection events, favorable safety profile, and improved quality-of-life measures reinforce confidence as the program advances into Phase 3. Transplant surgeon Andrew Adams, MD, PhD, noted that preserving kidney function while reducing long-term treatment burden remains one of the field’s most important goals, making these findings clinically meaningful.
Phase 3 Program Planned for Late 2026
Following a successful FDA End-of-Phase 2 meeting, Eledon plans to initiate its Phase 3 kidney transplantation program in late 2026. The pivotal study will evaluate tegoprubart against tacrolimus using a 52-week composite primary endpoint of biopsy-proven acute rejection, graft loss, and death, while incorporating lessons from the BESTOW program on long-term graft function, rejection control, and patient-reported outcomes.
What Does This Mean for Patients?
For kidney transplant recipients, these results suggest that tegoprubart may provide long-term protection for the transplanted kidney while reducing some of the drawbacks associated with tacrolimus-based immunosuppression. Patients treated with tegoprubart maintained better kidney function through 18 months, experienced no biopsy-proven acute rejection after the first six months, and reported fewer treatment-related symptoms than those receiving tacrolimus.
Although tegoprubart remains investigational and is not yet approved for clinical use, the encouraging Phase 2 results support its potential as a new maintenance immunosuppressive therapy. If the upcoming Phase 3 trial confirms these findings and regulatory approval is obtained, tegoprubart could offer kidney transplant recipients a treatment option that helps preserve graft function while improving long-term quality of life.
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About the Writer
Shaik Yasmeen (LinkedIn) is a Pharm.D graduate with interests in clinical pharmacy, pharmacovigilance, and medical writing. She has gained experience through hospital clinical postings, patient case reviews, case presentations, and literature evaluation. Passionate about evidence-based healthcare, she is committed to creating accurate and engaging medical content while continuously expanding her professional knowledge.