Tegoprubart Improves Glycemic Control Following Islet Transplantation for T1D, With Piotr Witkowski, MD, PhD

On March 16, 2026, Eledon Pharmaceuticals announced updated results from an investigator-initiated trial of the investigative anti-CD40L monoclonal antibody tegoprubart in patients undergoing allogeneic islet transplant for long-standing type 1 diabetes (T1D).1

Presented at the Advanced Technologies and Treatments for Diabetes (ATTD) conference in Barcelona, Spain, from March 11-14, 2026, these data build on previously released data highlighting the drug’s efficacy in both immunosuppression and insulin independence at 4 weeks post-transplant.1

Pancreatic islet transplantation is a minimally invasive procedure created to provide blood glucose control in T1D while minimizing insulin dependence. Clinicians isolate pancreatic islets containing insulin-producing beta cells from the pancreas of an organ donor and infuse these cells into the liver via a small catheter. The cells then lodge in small blood vessels in the liver and produce insulin.1

“The patient still needs to take anti-rejection immunosuppression medication following implantation,” Piotr Witkowski, MD, PhD, professor of surgery in the Transplantation Institute at the University of Chicago, told HCPLive in an exclusive interview. “However, the toxicity of this immunosuppression medication has been a major barrier to this therapy; to that end, we have been testing a new medication, tegoprubart, and the results are really promising, with almost no toxicity.”

Tegoprubart is a humanized monoclonal antibody designed to selectively inhibit CD40 ligand, a co-stimulatory molecule in T cell activation. In addition to islet transplantation, tegoprubart is currently being explored for kidney allograft transplantation, xenotransplantation, liver allograft transplantation, and amyotrophic lateral sclerosis.2

This pilot study investigated a total of 12 adults with long-standing T1D who underwent allogeneic islet transplant at UChicago Medicine. These patients had a median T1D duration of roughly 33 years and a mean hemoglobin A1c of roughly 8% before transplantation. Participants were given tegoprubart as part of a calcineurin inhibitor-free immunosuppression regimen.1

Ultimately, Witkowski and colleagues saw rapid improvement in glycemic control after transplantation. Stable islet graft function was observed across the cohort, with all 10 patients who were >4 weeks post-transplant achieving both insulin independence and a most recent HbA1c of <6%. Among those 10 patients, the mean most recent HbA1c was roughly 5.35%.1

Tegoprubart-based immunosuppression was largely well-tolerated during the trial, with reported adverse events successfully treated through lowering of the mycophenolic acid dose where necessary. Additionally, investigators reported no rejection episodes, and no patients developed de novo donor-specific HLA antibodies. No evidence of nephrotoxicity, hypertension, or neurotoxicity, all of which are commonly associated with tacrolimus-based immunosuppression regimens, was observed.1

These advancements are particularly significant because patients with T1D in America have limited access to islet transplantation therapy. Current guidelines refer to human islets as a drug rather than an organ for transplantation, meaning they are regulated by the US Food and Drug Administration (FDA) rather than the Health Resources and Services Administration (HRSA). This means that islets currently require a stringent Biologics License Application (BLA).

“One key point I would like to add is that, although we’ve been optimizing islet transplantation for over 20 years, it is still not available to patients with T1D in the US because of outdated regulations,” Witkowski said. “And we, as a transplant community, experts in the field, are advocating for a regulatory update, so that we can help more patients and progress the field faster.”

References

1. Eledon Pharmaceuticals. Eledon Announces Updated Data from Investigator-Initiated Islet Transplant Trial of Tegoprubart in Patients with Type 1 Diabetes at UChicago Medicine. March 16, 2026. Accessed March 24, 2026. https://ir.eledon.com/news-releases/news-release-details/eledon-announces-updated-data-investigator-initiated-islet

2. Brooks A. Tegoprubart Enables Insulin Independence in Type 1 Diabetes Islet Transplantation Study. HCPLive. March 16, 2026. Accessed March 24, 2026. https://www.hcplive.com/view/tegoprubart-enables-insulin-independence-in-type-1-diabetes-islet-transplant-study