Piotr Witkowski, MD, PhD, is a professor of surgery in the Transplantation Institute at the University of Chicago.

Piotr Witkowski, MD, PhD

All 12 Tegoprubart Recipients Off External Insulin Following Islet Implant in Pilot Study

All 12 patients treated with tegoprubart following islet cell transplant for 

 in Eledon’s investigator-initiated trial have successfully discontinued external insulin, according to new data.

Presented at the American Diabetes Association (ADA) Scientific Sessions 2026 in New Orleans, Louisiana, by Piotr Witkowski, MD, PhD, associate professor of surgery in the Transplantation Institute and director of the Pancreatic and Islet Transplant Program at the University of Chicago, these data reflect a potentially groundbreaking shift in islet transplantation strategy.

“These data are very reassuring, and I attribute this to the mechanism of action and the fact that this is provided intravenously on a regular basis,” Witkowski told 

 in an exclusive interview. “Our patients did not skip any doses, and they tolerated treatment very well, and because they tolerate it so well, they don’t hesitate to continue. They really appreciate the outcome because they have the clear benefit of not taking insulin again.”

Tegoprubart is a humanized monoclonal antibody that selectively inhibits CD40 ligand (CD40L). This ligand is a co-stimulatory molecule involved in the activation of T cells. Tegoprubart is simultaneously being investigated for xenotransplantation, liver and kidney allograft transplantation, and amyotrophic lateral sclerosis.

This investigator-initiated pilot study investigated a total of 12 adult patients, all of whom had long-standing T1D. These patients had a median T1D duration of around 33 years and a mean HbA1c of roughly 8% prior to transplantation. Their median body mass index (BMI) was 25.1 kg/m2 with a range of 19.4-29.9 kg/m2. Median daily baseline insulin was 47.5 U, with a range of 35-90 U.

Prior to transplantation, patients began induction therapy with daily thymoglobulin 1.5 mg/kg and solumedrol 1 mg/kg. The day before transplantation, patients received tegoprubart 20 mg/kg as a 1-hour infusion, with repeat doses occurring on days 0, 1, 3, 7, 14, 21, and 28. These repeat doses were then lengthened to 3-week intervals. Patients also received etanercept 50 mg on day 0, with 25 mg administered on days 3, 7, and 10. Mycophenolic acid 720 mg was administered twice daily following induction.

Witkowski and colleagues noted rapid improvement in glycemic control after transplantation, with stable islet graft function observed across the cohort. All 12 patients were successfully removed from insulin therapy with no rejection episodes and no de novo donor-specific HLA antibodies. Additionally, among the included patients, roughly 3-5 times more transplanted islets survived and took hold versus those treated with tacrolimus, a common immunosuppressant. The team also recorded no kidney or nerve damage and no high blood pressure, all common side effects of tacrolimus.

“Seeing these exciting results, Eledon has committed to continue clinical trials and to organize and begin the next steps of clinical testing of tegoprubart,” Witkowski said. “The problem is that all of this transplantation, and the procedure itself, hasn’t been made available to patients. So, in parallel to the trials, we are working on adjusting the regulations, allowing cadaveric islet transplantation, to be reimbursable in the US.”

Editors’ Note: Witkowski reports no relevant disclosures.

Witkowski P. Anti-CD40L to Induce Graft Survival and Function in Islet Allotransplantation. Presented at the American Diabetes Association (ADA) Scientific Sessions 2026, New Orleans, LA. June 5-8, 2026.

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

Williams L. Tegoprubart islet transplantation achieves insulin independence in type 1 diabetes. 

. June 19, 2026. Accessed July 10, 2026. 

https://www.springermedicine.com/type-1-diabetes/ada-2026/tegoprubart-islet-transplantation-insulin-independence-t1d/52747112

Herrick B. All 12 Clinical Trial Participants Off External Insulin: New Data on Tegoprubart Continues to Impress. Breakthrough T1D. June 7, 2026. Accessed July 10, 2026. 

https://www.breakthrought1d.org/news-and-updates/tegoprubart-islet-transplant-all-participants-off-external-insulin/

Videos

Piotr Witkowski, MD, PhD, discusses the CD40L inhibitor’s efficacy in improving outcomes for patients with T1D undergoing islet transplant.

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 

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.

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.

“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 

 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.

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.

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%.

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.

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.”

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

Brooks A. Tegoprubart Enables Insulin Independence in Type 1 Diabetes Islet Transplantation Study. 

. March 16, 2026. Accessed March 24, 2026. 

Witkowski discusses the data presented at ATTD 2026, highlighting the investigative anti-CD40L monoclonal antibody in facilitating insulin independence.

Piotr Witkowski, MD, PhD

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