Eledon announces data for islet transplant recipients treated with tegoprubart

Eledon Pharmaceuticals (ELDN) announced data for the first three islet transplant recipients treated with an immunosuppression regimen that includes tegoprubart, the Company’s investigational anti-CD40L antibody, for prevention of islet transplant rejection in subjects with type 1 diabetes. The investigator-initiated trial, conducted by the research team at the University of Chicago Medicine’s Transplantation Institute, demonstrated potentially the first human cases of insulin independence achieved using an anti-CD40L monoclonal antibody therapy without the use of tacrolimus, the current standard of care for prevention of transplant rejection. The first two subjects achieved insulin independence and normal hemoglobin A1C levels, a measure of average blood glucose, post-transplant. The third subject, who recently received an islet transplant, decreased insulin use by more than 60% three days following the procedure and continues on an insulin independence trajectory. Subjects on study received islet transplants combined with induction therapy, mycophenolate mofetil, and tegoprubart, given every third week by intravenous infusion. The first two subjects achieved insulin independence and presented stable islet graft function at approximately three months and six months post-transplant, respectively. Islet engraftment, measured by graft function standardized to the number of islets infused, was three to five times higher than three comparable subjects outside this study who received tacrolimus-based immunosuppression, suggesting treatment with tegoprubart is less toxic to transplanted islets resulting in improved graft survival and function. Treatment was generally well tolerated in all subjects with no unexpected adverse events or hypoglycemic episodes. After initial islet transplant, the first participant reduced insulin requirements by over 60% and normalized blood glucose control. The first patient then achieved insulin independence approximately two weeks after the second islet transplantation procedure. The data are being featured in an oral presentation at the International Pancreas and Islet Transplantation Association, Harvard Stem Cell Institute, and Breakthrough T1D 5th Annual Summit on Stem Cell Derived Islets on Tuesday, October 29, 2024.The first participant was a 42-year-old female with a baseline weight of 88 kg/194 lbs. At 90 days post-transplant, the participant’s HbA1c level improved to 6.0% and daily insulin dose decreased to 16 units per day. After 16 weeks, the participant received a second islet transplant, and approximately two weeks later achieved insulin independence, maintaining improved HbA1c levels of 5.4% afterwards. The second participant was a 30-year-old female with a baseline weight of 50 kg/110 lbs. This patient stopped insulin support four weeks after the islet transplant. Her HbA1c levels improved to 5.8% and below starting at seven weeks after the transplant. The third participant was a 37-year-old male with a baseline weight of 92 kg/203 lbs with a baseline HbA1C of 9.3%. This patient was discharged home on day three post-transplant, requiring 29 units of insulin. The treatment was generally well tolerated in all subjects with no unexpected adverse events, severe hypoglycemic episodes, or graft rejection.