A novel immune therapy called tegoprubart made by Eledon Pharmaceuticals and being tested in kidney transplant patients has the potential to help beta cell transplants survive in people with type 1 diabetes (T1D) with fewer side effects. The first data from this Breakthrough T1D-funded study suggests it does. The study was presented at the 5th Annual International Pancreas and Islet Transplant Association/Harvard Stem Cell Institute/Breakthrough T1D Stem Cells Summit.
The need for a better drug regimen
Organ transplants are a wonder of modern medicine, but they require the use of immunosuppressive drugs. These drugs have serious side effects. They include but are not limited to an increased risk of infections and malignancies. They are also toxic to the kidneys, nerves, and islet cells themselves.
This is one reason that islet transplants, which follow the Edmonton Protocol, are only an option for people with hypoglycemia unawareness who have had severe hypoglycemic events. (Another reason is the extremely limited supply of deceased donor islets.) Today, Breakthrough T1D and researchers across various disciplines are working on developing novel and more targeted drugs. They goal: develop drugs that can inhibit the immune response to transplanted cells, like pancreatic islets, with more tolerable, or milder, side effects.
If the more serious side effects can be prevented, a much larger population of people with T1D could have access to this therapy. That is, assuming we have a larger supply of cells to transplant.
Enter tegoprubart
Tegoprubart is an immune therapy (anti-CD40 ligand) manufactured by Eledon Pharmaceuticals. It helps limit the body’s immune response.
It works by inhibiting CD-40L, a protein involved in the immune system. By blocking this protein, the drug interferes with how immune cells communicate with each other. It also increases the number of T regulatory cells, which suppress the body’s immune response.
This drug is currently in a phase 3 clinical trial in kidney transplants conducted by Eledon Pharmaceuticals. Results to date indicate that it has the potential to be a less toxic option to keep transplanted organs and cells, like islet cells, alive and healthy post-transplant.
Early results from new study are positive—and more data is needed
Breakthrough T1D is funding longtime collaborator Dr. Piotr Witkowski at the University of Chicago to use Eledon Pharmaceutical’s drug, tegroprubart, as an alternative to traditional immunosuppressives in people with T1D and severe hypoglycemia who have received deceased donor islet transplants.
Per Eledon Pharmaceutical’s press release:
- The first two out of three subjects treated with tegoprubart as part of an immunosuppression regimen to prevent transplant rejection achieved insulin independence. They remained insulin-free, with glucose control in the normal range.
- The third subject was recently transplanted. They reduced insulin dosage by 60% within three days post-transplant.
- Islet engraftment in the first two subjects with tegoprubart was three to five times higher than engraftment in three subjects receiving standard-of-care tacrolimus-based immunosuppression.
- Treatment with tegoprubart was well tolerated.
This news is exciting and has the potential to be life-changing for people with T1D. Removing the 24/7, 365-day-a-year burden of T1D without toxic side effects through curative therapies is our goal.
However, the data is only in two people to date. We look forward to seeing data from more transplants in the future.
How this fits into our strategy for cures
Breakthrough T1D is laser-focused on cell therapies, which implant insulin-producing cells into the bodies of people with T1D. Our ultimate goal is an unlimited, or allogenic, supply of cells derived from stem cells. These cells can be transplanted into anyone living with T1D without the use of chronic immunosuppressives.
In other words, we need two things: a unlimited cell source and a non-toxic way to keep the cells healthy.
Incredible recent progress has been made toward both of these goals. For example, in Vertex’s VX-880 study, they are using stem-cell-derived islets, and the 11/12 recipients are fully insulin-independent after 1 year. Individuals in this study are on the traditional post-transplant immunosuppressive regimen. (The study is ongoing and has expanded enrollment to 37 people.)
Breakthrough T1D, Vertex, and others are also working on how to keep the cells safe using a combination of encapsulation, gene editing, and other tactics. Several of these studies are in clinical trials.
Tegoprubart can potentially be a viable tactic to keep these cells functional durably. That’s why we’re funding the study along with the Cure Alliance. It’s also why the T1D Fund invested in Eledon Pharmaceuticals several months ago and again on October 29.
What we’re saying
“Breakthrough T1D is proud to fund and support this research and is encouraged by the tegoprubart study showing that patients who received islet transplants with a tacrolimus-free immunosuppressive regimen are making insulin again,” said Breakthrough T1D Chief Scientific Officer Sanjoy Dutta, Ph.D. “Islet replacement therapies are a key priority for Breakthrough T1D, and we’re committed to driving research that moves us toward a world where these therapies are available to the broader T1D community. Achieving this requires novel approaches to keep transplanted cells functional with a tolerable immunosuppression regimen. These results are an important step toward that goal, and we look forward to seeing additional data.”
Read more in the press release.
