2-Year Phase 1b Tegoprubart Preserves Kidney Function in Transplant Recipients, With Eliezer Katz, MD

2-year phase 1b results from the first adult de novo kidney transplant recipients treated with tegoprubart as the core immunosuppressive agent showed preserved kidney function, no episodes of acute rejection, and an acceptable safety profile.1

The findings were presented at the American Society of Transplant Surgeons (ASTS) Winter Symposium, January 22–25, 2026, in Phoenix, AZ, and highlight the potential for non-calcineurin inhibitor-based immunosuppression.1

Currently, the standard of care for kidney transplant immunosuppression in the United States is a calcineurin inhibitor–based regimen with tacrolimus and mycophenolate. Overall, > 90% of patients are maintained on these 2 agents, with or without corticosteroids.2,3

Tacrolimus is a potent immunosuppressive drug used primarily to prevent organ rejection in transplant recipients. It acts as a calcineurin inhibitor, binding to FKBP12 to block T-cell activation and IL-2 production. While highly effective, neurotoxic effects are common, including hand tremors, insomnia, and headaches. Long-term tacrolimus use is associated with nephrotoxicity, supporting continued evaluation of noncalcineurin inhibitor–based regimens.2,3

“Calcineurin inhibitors are very effective at preventing rejection, but they come at a significant cost,” said Eliezer Katz, MD, Chief Medical Officer of Eledon Pharmaceuticals, in an interview with HCPLive. “Beyond nephrotoxicity, calcineurin inhibitors can damage pancreatic islet cells, leading to diabetes, and cause neurologic side effects such as tremor, brain fog, insomnia, and headaches. They are also associated with hypertension and cardiovascular effects. Patients are grateful that their graft is functioning, but many are still suffering from these side effects.”

Tegoprubart, a humanized monoclonal antibody, selectively inhibits CD40 ligand (CD154), a co-stimulatory molecule in T-cell activation. The investigational drug has the potential to enter the treatment landscape as a non–calcineurin inhibitor immunosuppressive option, with sustained preservation of kidney function observed through 24 months.¹

To investigate tegoprubart, Katz and colleagues conducted a multicenter, phase 1b, single-arm trial, enrolling adults who were Epstein–Barr virus (EBV)–seropositive, had low levels of panel-reactive antibodies, and had no donor-specific antibodies (DSAs) at screening before receipt of their first kidney transplant from a living or deceased donor.1

On the day of transplantation, all patients received induction with rATG ≤6 mg/kg and maintenance therapy with intravenous tegoprubart (20 mg/kg, administered on days 1, 7, 14, 21, and 28 post-transplantation). After this, every 21 days, patients received mycophenolate and corticosteroids.1

The primary safety endpoints included the incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs). If a patient experienced > 1 adverse event with the same preferred term, they were counted once for that term.1

At 12 and 24 months, exploratory endpoints included the incidence of biopsy-proven acute rejection, graft failure, de novo DSA formation, and mean estimated glomerular filtration rate (eGFR). Patients who completed 12 months of treatment were offered enrollment in an open-label extension study.1

Overall, 8 patients completed 12 months of treatment and continued into the extension study. The mean (standard deviation [SD]) treatment duration with tegoprubart was 29.50 (5.42) months, with 7 of the 8 patients completing at least 24 months of treatment.1

“Tegoprubart has a different mechanism of action. It offers the possibility of achieving effective immunosuppression without many of these side effects, as we demonstrated in a phase 2 study that we recently presented at Kidney Week in Houston in early November,” explained Katz. “The fundamental difference is specificity. Tacrolimus is a small molecule taken orally, and its effects are distributed throughout the body. Because calcineurin plays a role in many cellular processes, inhibiting it affects virtually every organ system, which explains the wide range of side effects.”

Over 24 months, tegoprubart had an acceptable safety profile. All patients experienced ≥1 TEAE, while SAEs were reported for 3 patients, and AESIs were reported for 7 patients. No cases of biopsy-proven acute rejection, de novo DSA, delayed graft function, or graft loss were reported.1

Investigators observed that functional eGFR levels were restored within 1 month after transplantation and generally maintained over 24 months. At 12 and 24 months, mean (SD) eGFRs were 67.0 (19.85) mL/min/1.73 m² and 74.2 (24.91) mL/min/1.73 m², respectively.1

Tegoprubart is also advancing through additional clinical programs, including the Phase 2 BESTOW trial in kidney transplantation and early investigator‑initiated studies in islet cell transplant rejection, with further data and regulatory guidance expected as development continues.1

References

1. E. Katz, T. Coates, J. Gill2, et al. Long-Term Outcomes of a Phase 1, Single-Arm Cohort of De Novo Kidney Transplant Recipients Treated with Tegoprubart, an Anti-CD40L Antibody, as the Core Immunosuppression Regimen. Poster presented at: American Society of Transplant Surgeons (ASTS) Winter Symposium. January 22-25, 2026; Phoenix, AZ.

2. Araya AA, Tasnif Y. Tacrolimus. PubMed. Published May 29, 2023. https://www.ncbi.nlm.nih.gov/books/NBK544318/

3. Laskow DA, Neylan JF, Shapiro RS, Pirsch JD, Vergne-Marini PJ, Tomlanovich SJ. The role of tacrolimus in adult kidney transplantation: a review. Clinical transplantation. 1998;12(6):489-503. https://pubmed.ncbi.nlm.nih.gov/9850440/