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In January 2025, Tim Andrews was non-ambulatory, in a wheelchair, and on dialysis with little hope of not only getting a kidney transplant but also of living much longer. He’d lost all hope and felt like his life was going to end on dialysis and that he had already done his favorite things—fishing, spending time with grandsons, and seeing the Boston Red Sox in person. In June, Andrews threw the first pitch in Fenway Park for a Boston Red Sox home game. That was made possible by receiving a kidney transplant from a genetically modified pig. Today, Andrews is the longest surviving person with a pig organ.
Andrews isn’t the only person seeing transformational results. A second individual, Bill Stewart, who was on dialysis, received a kidney xenotransplant a little under three months ago and, just a few weeks ago, completed a two-hour bike ride. Although the outcomes of these two procedures are impressive, there are more than 800,000 Americans and millions worldwide who suffer from end-stage kidney disease (ESKD), only 28,000 of whom received human kidney transplants, the gold standard, in 2024 as a result of the severe organ shortage. For those unable to receive a transplant, dialysis remains the only option, which has a five-year mortality rate exceeding 50%, higher than that of the most common cancers. Now, some of them will have the opportunity to receive a pig kidney in hopes of improving their health and lengthening their lives.
Today, eGenesis announced that the FDA has approved an IND for EGEN-2784, the company’s genetically modified pig kidney, that supports a Phase I/II/III study designed to assess safety, tolerability, and efficacy at 24 weeks post-transplant in patients with ESKD who are age 50 or older, dialysis-dependent, and on the kidney transplant waitlist. EGEN-2784 is eGenesis’ lead candidate for kidney transplantation.
President and chief executive officer at eGenesis, Mike Curtis, PhD, told Inside Precision Medicine, “Even in one patient, you see this massive change, and it helps you realize the potential here—it embodies the whole vision. These little acts really add together to show just what the transformative potential is of this technology, and here we go right now. It’s one of those things where it happens slowly and quickly. It’s rolling. We’re off and running into the registration, which is amazing.”
Leonardo V. Riella, MD, PhD, medical director for kidney transplantation; lead surgeon Tatsuo Kawai, MD, PhD, director of the Legorreta Center for Clinical Transplant Tolerance; and Nahel Elias, MD, surgical director for kidney transplantation, led the team at Massachusetts General Hospital (MGH).
A half-century in the making
The dream of xenotransplantation stretches back more than half a century. In the 1960s, surgeons attempted chimpanzee and baboon kidney transplants in desperate patients, with limited survival times. The most famous early case was that of Baby Fae in 1984, who received a baboon heart at Loma Linda University. She survived for 21 days, a record at the time, but her death underscored the immense immunological barriers.
In the 1990s and early 2000s, research focused on the genetic engineering of pigs, seen as more practical organ donors than primates. Knockout pigs lacking certain antigens were developed, and incremental progress was made in non-human primate models. Still, until the past few years, no one had achieved long-term survival in a living human.
The recent wave of successful pig kidney and heart transplants represents the culmination of decades of trial, error, and incremental innovation. CRISPR gene editing, advanced immunosuppression protocols, and improved surgical techniques have converged to turn xenotransplantation from science fiction into tangible clinical practice.
EGEN-2784 carries three classes of genetic modifications designed to improve compatibility and support long-term function in human recipients: elimination of three glycan antigens to prevent hyperacute immune rejection; insertion of seven human transgenes to regulate immune response, reduce inflammation, improve coagulation compatibility, and regulate complement activation; and inactivation of endogenous retroviruses within the porcine genome to enhance safety. eGenesis is the only company developing organs with all three classes of edits to optimally address safety and efficacy. Without genetic modification, a porcine kidney would be immediately rejected by the human immune system.
eGenesis is not alone in the race to make xenotransplantation a clinical reality. Revivicor, a subsidiary of United Therapeutics, supplied the genetically modified pig hearts used in landmark procedures at the University of Maryland, where surgeons transplanted hearts into two living patients in 2022 and 2023. While those patients survived for weeks to months, the cases highlighted both the promise and the challenges of pig-to-human transplantation.
NYU Langone Health and the University of Alabama at Birmingham (UAB) have also advanced the field, performing pig kidney transplants in brain-dead human recipients to study immune responses and organ function. These academic efforts provided critical proof-of-concept data that helped de-risk subsequent living patient transplants.
Yet eGenesis has differentiated itself through the breadth of its gene-editing strategy. By combining multiple modifications—removing antigens, adding human genes, and inactivating porcine retroviruses—the company aims to address the key safety and efficacy concerns that have historically limited xenotransplant progress. This comprehensive approach may give EGEN-2784 an edge in achieving durable, complication-free outcomes.
From expanded access to IND Clearance
Back in 2024, eGenesis did the first-ever porcine kidney transplant on a living patient with Richard Slayman. That summer, eGenesis met with the FDA about extending the expanded access approach to a three-patient trial. That was approved in December of 2024, and Andrews was treated as the first patient of that study shortly thereafter in January 2025.
“What was really compelling about Mr. Andrews relative to Mr. Slayman is that Mr. Andrews had relatively less comorbidity, but he was still declining pretty quickly on dialysis, which was the impetus to get him into the trial,” Curtis said. “He’s 222 days post-transplant today. Then we treated Mr. Bill Stewart in June. He was the second patient of that three-patient study, and he’s 82 days post-transplant today. The experiences of those three patients have demonstrated to us and the FDA that, first, the early post-transplant period is quite consistent.”
According to Curtis, the transplants were pretty uneventful, which is exactly what you want to hear in these situations—no news is good news. All three patients were discharged relatively shortly after the transplant, and so much of the focus is on post-transplant care, managing the patients to have successful long-term outcomes. Curtis said that the combination of their non-human primate (NHP) data eGenesis published in a 2023 Nature study, plus the expanded access data, led to the filing for a registration trial with the FDA this summer, which has been cleared and could begin as early as mid-2029.
Curtis said, “When you look at the three patients who have been treated so far and this idea of one-off, I think Mr. Andrews and Mr. Stewart are more like our registration population than Mr. Slayman. So Mr. Slayman was going to lose dialysis; he had extensive vascular disease, and he was really much closer to death than Mr. Andrews or Mr. Stewart. Mr. Andrews or Stewart would qualify for our registration trial. So they’re essentially the first two patients in the registration study.”
The FDA approved a 33-patient trial, with three patients in part one and then 30 patients in part two. Part one will be done at Mass General. In the first part of that study, eGenesis will continue to have a 12-week sentinel period between patients.
“If you look at Mr. Andrews’ transplant in January and Mr. Stewart’s in June, we’re holding this sentinel period to understand how the patients do post-transplant. By this time next year, we’ll have treated a total of seven patients, three of them on the new registration trial. What’s really important for us is understanding that post-transplant care before we transfer it to another transplant center.”
The next four transplants will all be done at MGH with the same team that’s done Slayman, Andrews, and Stewart. That will set eGenesis up really well to transfer the transplant protocol to additional transplant centers to enroll the rest of the registration trial, which will expand to single-digit numbers of centers to receive the 30 patients. The fact that all three patients have been men thus far is simply a result of chance. Men and women are equally eligible over 50, up to two years on dialysis, and have a low chance of getting a transplant in the next five years.
“When you look at the number of patients who have reached out to the team at MGH to participate, it’s well over 200 patients,” said Curtis. “The beauty of the eligibility criteria, which are generally at a high level, is that we’re looking at patients over 50 who have been on dialysis for at least two years but have a very low likelihood of getting an allo in the next five years—that’s a lot of patients. This is why we’re so pleased with it. The FDA agreed and understands the risk that these patients face.”
It’s a very high mortality risk for older patients on dialysis: a 50% mortality risk on dialysis in five years. That is a risk that rivals most cancers.
“The sooner we can get those patients into a transplant, the better, and unfortunately, because there’s such an organ shortage, most of those patients will never see a transplant and will die on dialysis,” said Curtis. “Some of the older patients don’t even list because they know there’s no chance of getting a transplant. So why fool yourself? We’re thrilled with the eligibility criteria. It’s relatively healthy patients early in their disease progression that have the best chance for a favorable transplant outcome.”
Beyond the kidney
For patients like Tim Andrews and Bill Stewart, pig kidney transplants have already transformed daily life—from wheelchairs and dialysis machines to baseball fields and bike rides. For eGenesis, FDA clearance of the IND for EGEN-2784 marks a decisive step toward large-scale clinical evaluation and, eventually, regulatory approval.
The coming years will test whether genetically engineered pig kidneys can reliably match the performance of human organs. If they can, xenotransplantation may one day eliminate the transplant waiting list and save the lives of hundreds of thousands worldwide suffering from ESKD. However, Curtis’s vision extends beyond the kidney to other organs where the supply for transplantation—currently the gold standard of care—is far too limited.
This is the second IND approved this year for eGenesis. Back in April, the FDA approved their IND for the liver perfusion product.
“We will now have two products in the clinic; we expect to treat our first patient with liver perfusion in the fourth quarter,” said Curtis. “If you look at the history of eGenesis, we are now preparing to run trials that are going to realize the vision of the company, which was to transform the treatment of solid organ failure. The trial that we just got approved for the kidney has the potential to allow us to bring this technology to thousands of patients, and to us, that’s incredible.”
While kidneys have so far led the way in terms of stable long-term outcomes, hearts remain the most symbolically powerful—and challenging—xenotransplant target. The first living patient to receive a genetically modified pig heart was David Bennett Sr. at the University of Maryland Medical Center in January 2022. Bennett survived two months before succumbing to complications, but his case marked a watershed moment, proving that a pig heart could sustain human life. A year later, in September 2023, surgeons at Maryland transplanted a second pig heart into Lawrence Faucette, a Navy veteran with end-stage heart failure who was ineligible for a human heart transplant. Faucette lived for six weeks, demonstrating incremental progress in both surgical approach and post-transplant management. These pioneering heart recipients, though their survival times were shorter than those seen with kidney xenotransplants, opened the door for continued development.
The relative success of pig kidneys—where patients like Tim Andrews and Bill Stewart are now living active, independent lives—underscores that the kidney may prove to be the first xenotransplant organ to achieve widespread clinical adoption. But researchers believe lessons learned from kidney studies, particularly in immunological management and gene editing, will accelerate the heart program as well. Curtis said, “I think the progress that we made in the kidney—that’s a very strong foundation to bring heart into the clinic as early as next year.”
If eGenesis and other developers can achieve in hearts what they are beginning to demonstrate in kidneys, the implications for treating end-stage organ disease could be nothing short of transformative.