Xenotransplantation has long existed on the fringes of modern medicine—scientifically intriguing, ethically complex, and, for decades, largely out of reach. Yet the need it seeks to address has never been abstract. Across the transplant landscape, the gap between available organs and the number of patients waiting continues to widen, creating an urgent and persistent crisis. For those on transplant lists, time becomes something far more punishing, shaped by uncertainty, declining health, and the rising cost of simply staying alive.

In recent years, however, xenotransplantation has begun to move from theory into practice. In 2022 and 2023, groundbreaking compassionate-use cases saw genetically modified pig hearts transplanted into humans with end-stage heart failure. While these early procedures did not achieve long-term survival, they marked a critical turning point—demonstrating feasibility and opening the door to expanded clinical use for patients with no remaining options.

Mike Curtis, PhD, president and CEO of eGenesis, is using this emerging clinical framework to expand xenotransplantation to more patients, beginning with the most complex cases and steadily progressing toward broader populations. Central to this approach is his belief that success does not have to mean permanence—sometimes, extending life itself is a meaningful therapeutic outcome. This philosophy is reflected in a recent kidney xenotransplant case in which a patient maintained renal function for nine months, offering not a cure but a critical bridge to future interventions with significant implications for survival.

In this episode of Behind the Breakthroughs, Curtis explores the history of xenotransplantation and shares insights from the company’s pioneering case studies, emphasizing a shift in perspective: xenotransplantation is evolving from a last-resort measure into a viable and scalable clinical strategy.

This interview has been edited for length and clarity.

 

IPM: What significant milestones has eGenesis reached since you joined roughly five years ago?

Curtis: When I joined the company, the goal was to establish the genetics for the first generation of donors that we want to take to the clinic. Part of that selection was based on outcomes in the non-human primate. We had set a goal to get to at least one year of post-transplant outcome that would give us enough data to say we have a reasonable chance of success clinically. That took us probably four years to get to that data set. We published it in Nature in 2023, where we showed that we could get porcine kidneys out to two years.

I think what changed for us at eGenesis was the first two heart transplants at Maryland. At the same time that we were advancing and developing our clinical donor, United had produced a donor, and Mohammad Mohiuddin and Bart Griffith at Maryland did the first-ever porcine heart transplants in people. Mr. Bennett and Mr. Fossett were the two recipients.

The outcomes were not great. They were less than two months, and those two gentlemen passed away. But what it triggered in us and our colleagues at Mass General was that these transplants were done under expanded access. These were patients who had really run out of options. They were not going to get a human heart and were imminently facing mortality. We took that and asked whether we could do the same with a kidney. Is there a case to be made for a patient in kidney disease who has run out of treatment options? We know enough now about outcomes in monkeys to say we have the potential to give a patient a chance.

That led to the identification of Rick Slayman. Rick was imminently going to lose dialysis. If you lose access to dialysis with kidney disease, you will pass away within a few weeks. When we met Rick, he was trying to figure out which hospice he would go to. He agreed to join the study. We petitioned the FDA, and they agreed it was the right balance of potential risk and benefit.

That was the beginning of what led us to where we are now. Opening the door under expanded access where the risk-benefit makes sense. Rick passed away on day 51 following an arrhythmia post-transplant, but the kidney was performing beautifully. Rick was out of the hospital, at home, living a relatively normal life. He was dialysis-independent for 51 days.

When we went back to the FDA, we said we need to go into healthier patients with less comorbidity so we can really test outcomes. That led to a three-patient expanded access study at Mass General, where Mr. Tim Andrews was the first patient.

If you take a step back and look at the field, the work by Mohiuddin and Griffith on the heart was a direct inspiration for what has been done in the kidney. It showed us that the expanded access pathway is useful. We now have a registration trial, which we call a phase-less trial or a Phase I/II/III trial. In transplant, especially xenotransplant, there’s no dose range finding. Once you do the transplant, you let it go as long as it can. It’s a unique development path where you can learn a tremendous amount from a small number of patients.

Over the past couple of years, starting with Mr. Bennett, we’ve defined the path to test cross-species transplantation in the clinic. In some ways, we’re not relying as much on non-human primate studies anymore. There’s still a minimum bar, but now that we have a clinical path, the door for the second generation is wide open.

 

IPM: What do you mean by second generation?

Curtis: When we developed what we call 2784—the kidney currently in the clinic—we also had other versions with different genetic profiles. Those performed a bit better in monkeys. The question is whether we should test those people. One thing we don’t fully understand is the relationship between outcomes in non-human primates and people. We already know immunosuppression in primates is not predictive of what we need in people. But you still need a minimum bar in primates, and you can see differences between genetic designs.

Another factor is feedback from our first four recipients. The rejection mechanisms we observe inform what we do next in engineering. We always knew there would be an iterative loop. We didn’t expect to be in it this early. Four patients into the first trial, we’re already learning enough to inform next-generation designs.

 

IPM: Has the regulatory relationship between eGenesis and the FDA regarding xenotransplantation changed under the various presidential administrations?

Curtis: No. The first expanded access cases were done under the previous administration. The reviewers and medical directors are the same people. They are highly motivated to help patients with organ failure.

The thinking around expanded access and controlled trials hasn’t changed. We’ve had strong collaborators at the FDA who want this to become a reality while ensuring safety and efficacy.

One advantage in kidney disease and heart failure is that endpoints are very clear. When kidneys fail, it’s obvious. Dialysis outcomes are measurable and comparable to transplant. We often use the analogy of parachutes—you don’t need a control group to know they work.

We effectively have a historical control group of 550,000 dialysis patients. That gives us a strong baseline. The agency understands this and holds us to a standard that makes sense for these indications. In our field, the agency has been excellent, and we’ve asked them not to change anything.

 

IPM: What’s unique about regulatory interactions in xenotransplantation compared to established drug modality?

Curtis: We don’t assume we know what the FDA will say. Six years ago, we had no idea we’d get here this way. We expected a traditional path: primate studies, a small Phase I trial, then Phase II. Expanded access changed that. We were open-minded enough to recognize it might be a better path. We ask fundamental questions every day. This is a brand-new therapeutic area. We’re about two years ahead of where we expected to be because of this approach. As we scale, we have to keep iterating based on clinical data, patient feedback, FDA input, and payer considerations.

There’s no fixed playbook. When hiring, there’s no one with xenotransplant experience—it doesn’t exist. Same for manufacturing. We leverage expertise from agriculture but are solving entirely new problems.

 

IPM: How does organ size vary from porcine donor to porcine donor, and which porcine organs are most suitable for xenotransplantation?

Curtis: The top three are kidney, heart, and liver. In order of difficulty: kidney, heart, liver. Kidneys and hearts are more similar to humans. Liver is harder due to its complex synthetic functions. That’s why our liver program is perfusion-based. Beyond those, we’re working on porcine islets. Then lung, which is probably the hardest due to immune reactivity. Ultimately, we envision five organs: kidney, heart, liver, islets, and lung. There are also possibilities like bone, blood, and skin, though markets are smaller.

We’ve been building manufacturing capacity. Across two Midwest facilities, we can produce 400–500 pigs per year, with about 150 at clinical grade. This matches our clinical needs. Our kidney registration trial is 33 patients, plus expanded access cases—roughly 50 animals total. Liver studies are similar. Over the next 12–18 months, we need 100–120 animals. Production is well aligned. We can scale up or down as needed, though there’s a natural lag.

We selected the Yucatan pig, about 150 pounds fully grown. Its organs are well matched to human size. Other groups use larger pigs, requiring genetic modification to control size. We avoid that by starting with the right breed. Kidney and heart are the most straightforward. Liver is more complex. Neural tissue is far more challenging and not a near-term focus. We’re focused on solving organ transplantation first. If we eliminate transplant waitlists, that’s already transformative.

 

IPM: What does success look like for an individual xenotransplantation?

Curtis: Mr. Andrews was dialysis independent for 271 days. Then we performed a nephrectomy. He returned to dialysis for 12 weeks, and 46 days ago, he received a human kidney. He represents what we’re trying to achieve. He wasn’t doing well on dialysis but was otherwise healthy. We stabilized him for nine months, and he successfully transitioned to a human transplant. This “bridge to transplant” model could extend survival and increase transplant success. Alternatively, patients could keep the porcine kidney long-term.

The key question is how long dialysis independence needs to be to be clinically meaningful. When people hear about nephrectomy, they think “failure.” But it may not be. In Mr. Andrews’ case, it enabled a successful human transplant. We’re still early—only four cases. Our focus now is determining the immunosuppression needed to achieve one year or more. We’re confident we’ll get there; the question is how much further we can go.

 

IPM: Have you treated female patients?

Curtis: Yes, the fourth case was a female patient. There’s no gender selection—it depends on who is eligible and willing. She’s doing well at 105 days post-transplant. (Note: this podcast episode was recorded on March 6, 2026).

 

IPM: What are the near-term milestones at eGenesis?

Curtis: Continued execution. The key milestone is establishing immunosuppression for the kidney registration trial, which we aim to start this year. We’re also enrolling patients in liver perfusion studies and aiming for expanded access heart transplants next year. 2026 is about building human data sets to support a product within two years.

 

IPM: How does eGenesis do patient recruitment for xenotransplantation?

Curtis: This is systematic and built on decades of research. It may seem sudden, but it’s not. We always prioritize patients. We must believe we can help them. Early cases had mixed outcomes, but now we’re seeing the vision. What’s striking is how routine the surgery has been. Surgeons say it’s similar to a standard transplant. Patients are often discharged quickly. That wasn’t guaranteed. Each success builds confidence and momentum.

 

IPM: What aspect of the work at eGenesis do you think is underappreciated?

Curtis: Pathogen screening. We rigorously monitor both animals and patients. So far, results are clean, but we remain cautious. We’re only four cases in. There’s still a lot to learn, but the systems we’ve built are working well.