Addressing Unmet Needs in End Stage Kidney Disease With Genetically Modified Porcine Kidney Transplant
David-Alexandre Gros, MD, the chief executive officer of Eledon Pharmaceuticals, discussed the company’s collaboration with EGenesis.
David-Alexandre C. Gros, MD
Credit: Eledon
EGenesis's EGEN-2784 is a porcine kidney that features a number of genetic modifications intended to prevent rejection in human patients, and is under evaluation for the treatment of end-stage kidney disease. In February 2025, the company announced that it had successfully completed its second in-human transplant of EGEN-2784. Notably, the transplants were carried out with the use of Eledon Pharmaceuticals’ tegoprubart, an investigational monoclonal antibody intended to improve the efficacy and safety of kidney transplants.
Shortly after the announcement, CGTLive® interviewed David-Alexandre C. Gros, MD, Eledon’s chief executive officer, to get his insight on the news. Gros discussed unmet needs in kidney disease and organ transplant and how EGenesis and Eledon's products are intended to help address these unmet needs.
CGTLive: Can you give some background context about end-stage kidney disease and the unmet needs in organ transplantation?
David-Alexandre C. Gros, MD: End stage kidney disease is when a kidney stops functioning. It is a large problem in the United States, with hundreds of thousands of people who are now living with end stage kidney disease. There are 2 solutions today. One is dialysis, which we're all familiar with, but the problem with dialysis is multiple-fold. The first is that it's quite expensive. Today dialysis in the US costs in the range of $150,000 per year. It also comes at a very high personal cost for patients. Patients on dialysis typically have to spend multiple hours sitting in a dialysis center every other day, which obviously has significant personal costs. Finally, the third issue with dialysis is the outcomes. The outcomes are actually quite poor. The average person on dialysis in the United States has a life expectancy of under 5 years. That's really striking since, if you think about it, we do better with most cancers today than we're doing with end stage kidney disease.
One of the best options for patients with end stage kidney diseases is to get an organ transplant. These can be organs that come from either living donors, typically family members, or what we call deceased donors, people who die, very often from trauma such as car accidents, and then donate their organs to save other people. Today, the average kidney transplant allows a normal lifestyle—one doesn't have to go to a dialysis center—and it allows the organs survive an average of 10 to 15 years.
In terms of the unmet need in organ transplantation, it's both around the efficacy and around the safety. The current standard of care cornerstone immunosuppression that we use in the United States is a class of drug called a calcineurin inhibitor, and specifically a drug called tacrolimus. Tacrolimus has been the standard and was approved in 1994. Now, as you know, there are very few things that we do in our lives, let alone very few things that we do in medicine, that have pretty much not evolved in over 3 decades, but yet that is what we're facing in transplantation medicine. If we look at kidney transplantation in particular, the first need is for a novel therapy to better protect the kidneys so that they can survive longer. The average age of transplant in the US is only 51 so if you think about it, if the average organ is only surviving 10 to 15 years, that means that for most people receiving a transplant, if 20, 30, 40, 50, or even 60 years old, for them to live a regular lifespan they're going to need multiple kidney transplants. Obviously, we don't have enough kidneys to begin with, and so they may never be able to get that second kidney transplant. As a result, being able to allow organs to survive longer and to function longer would likely extend people's lives and would reduce the need for repeat kidneys, which would make more kidneys available for first time kidney recipients. That would help shorten the organ gap.
So why is it that the average organ only survives up to 15 years? Ironically, the reason for that is the very same drug that we're using to protect the kidney, these calcineurin inhibitors: tacrolimus. That's because tacrolimus has a large number of side effects. In particular, tacrolimus is both directly toxic to kidneys, as well as indirectly toxic to kidneys. It's directly toxic to kidneys as a nephrotoxin, and it's indirectly toxic to kidneys in that it causes both hypertension and diabetes. That is a further irony, since the 2 most common reasons why people need a kidney transplant to begin with are hypertension and diabetes. To give you a sense of the impact of that, if we look at patients that have had a heart transplant, and they go into that with healthy kidneys, about 1 in 10 or 1 in 11 of these patients are going to need a kidney transplant within a decade; 1 in 10 or 1 in 11 will be in end stage kidney disease. The reason they're going into end stage kidney disease, again, is not because of their heart disease. It's because of the drug that we're giving to protect their transplanted heart that both directly and indirectly ends up destroying their native kidneys.
What we're working on and what we're looking to solve is to develop instead of a 1994 immunosuppressant, is a 2030 very targeted version of a novel immunosuppressant—one that could be both more effective at protecting the kidneys, as well as one that can be safer than what we see today with tacrolimus.
What is EGenesis's EGEN-2784, and how is it meant to address this unmet need?
As I mentioned, we have a high level of unmet need in terms of the number of available organs for transplants every year. This is particularly true with kidney diseases. In kidney transplantation today, for every 6 people that we transplant every year, 1 dies waiting for a transplant that they do not get. In fact, we have a waiting list for organs today that has about 100,000 people on it in the United States. As we think about how we can help address that organ shortage, there are there really 3 ways.
One is to make more people donate their organs, but that's obviously been tried every year for a long time, and that's very hard to do. A second way is to allow transplants to function longer so that fewer people need repeat transplants, which is, as I mentioned earlier, one of the things that we're looking to do with tegoprubart. The third way is to find a whole new source of kidneys.
That potential new source of kidneys could be using animal organs, and in particular pig organs, to replace human organs. While 5 or 10 years ago, this would have sounded like science fiction, today it is happening. We've now put organs, both hearts and kidneys, from pigs into humans. The procedure that was done a few weeks back but was announced last week at Mass General Hospital, was the second time that EGenesis—so they're the biotechnology company that is manufacturing that organ, that is growing those pigs—it was the second time that EGenesis had put a kidney from their humanized pigs into a human. Tegoprubart, our drug, was used as one of the core immunosuppressants to allow that to be possible.
There are 2 companies that are in the lead of developing these organs: United Therapeutics and EGenesis. For us, we've now done pig to human transplants (xenotransplants) with both of these companies. We did a pig heart into a human with United Therapeutics and we've now done the 2 EGenesis kidneys that have gone into humans.
