Good morning, ladies and gentlemen, and welcome to the American Transplant Congress data update call. At this time, all lines are in a listen-only mode. Following the presentation, we will conduct a question-and-answer session. If at any time during this call you require immediate assistance, please press star zero for the operator. This call is being recorded on Monday, June 22, 2026. I would now like to turn the conference over to Paul Little, Chief Financial Officer. Please go ahead.
Good morning, everyone, and thank you for joining our BESTOW long-term data update conference call. I'm joined on today's call by David-Alexandre Gros, Chief Executive Officer, Steven Perrin, our President and Chief Scientific Officer, and David Hovland, our Chief Regulatory Officer. Earlier today, Eledon issued a press release detailing the updated clinical results presented at the American Transplant Congress. You may access the release and this presentation under the Investors tab on our company's website at eledon.com. I would like to remind everyone that statements made during this conference call relating to Eledon's expected future performance, future business plans, or future events or plans may include forward-looking statements as defined under the Private Securities Litigation Reform Act of 1995. All such forward-looking statements are intended to be subject to the safe harbor protection provided by the Reform Act.
Actual outcomes and results could differ materially from these forecasts due to the impact of many factors beyond the control of Eledon. Eledon expressly disclaims any duty to provide updates to its forward-looking statements, whether as a result of new information, future events, or otherwise. Participants are directed to the risk factors set forth in Eledon's reports filed with the U.S. Securities and Exchange Commission. Now it is my pleasure to pass the call to our CEO, Dr. David-Alexandre Gros. DA.
Thank you, Paul, and thank you all for joining. Turning to slide three, we can see our programs with tegoprubart truly becoming a drug in a pipeline asset. Let me start by pointing out a few areas of progress in our programs before we dive into the new data. First, we have progressed our subcutaneous formulation of tegoprubart and have already completed a healthy volunteer study. We now expect to begin testing this formulation in transplant patients early next year. This formulation will allow us to present more options to patients and to physicians in terms of how they prefer to use TEGO. Second, we have a new indication where we have begun clinical trials, and that is in kidney transplant tolerance induction. This is being run as an investigator-sponsored trial at the Massachusetts General Hospital here in Boston, and two patients have already been transplanted.
In terms of agenda for this call, I will start by reviewing the long-term kidney transplant data presented at ATC, starting with kidney function as measured by eGFR, followed by acute rejection and the different effects of rejection that seem to be seen on kidneys treated with tegoprubart or tacrolimus, followed by safety update, and lastly followed by patient-reported outcomes. As you will see, this data now clearly demonstrates the emerging advantages of using tegoprubart for kidney transplantation, including, one, higher kidney function, it reaching statistical superiority at 18 months. Two, no rejections in the tegoprubart arm after six months post-transplant versus ongoing rejections in the tacrolimus arm. Three, higher kidney function in patients that experienced a rejection on TEGO and remained on TEGO versus patients that experienced a rejection on TAC or that were switched to TAC after TEGO.
Four, in terms of safety, we previously presented black-and-white safety differences between TAC and TEGO in the first year of post-transplant. Today we'll discuss CNS, kidney, and GI-related adverse events that continue to be seen more frequently in the TAC arm. Five, for the first time, we are going to show patient-reported outcomes at 52 weeks where we saw improvements favoring TEGO on two different validated measures of symptom burden. We'll wrap up the kidney transplant discussion by discussing regulatory feedback in our phase III plans. Afterwards, we will cover exciting data from our islet cell transplantation program, where 12 of 12 patients with high-risk type 1 diabetes have been able to achieve normal blood glucose levels along with insulin independence. This data was first presented at ADA a few weeks ago, subsets were subsequently presented here at ATC yesterday in an oral presentation.
Turning to slide four, we are in the long-term extension phases for both our phase II and our phase I-b kidney transplant studies designed to examine the use of tegoprubart as part of a calcineurin-free regimen. In both of these studies, patients received antithymocyte globulin, also called ATG, as induction therapy, followed by TEGO, mycophenolate, and a corticosteroid taper for chronic maintenance therapy. The phase II study also included a control arm with tacrolimus instead of tegoprubart alongside mycophenolate and steroids. Note that in the phase II BESTOW study, patients had a choice at the end of the 52 weeks whether to continue on tegoprubart in the long-term extension or switch to tacrolimus. 96% of patients chose to remain on TEGO, which is a very high percentage and one that shows how satisfied the patients were with their therapy.
Turning to slide five, we have been focusing on two efficacy endpoints. The first efficacy endpoint is the historical approvable endpoint in kidney transplantation, as well as the endpoint that the FDA has guided us to use as our primary endpoint for our upcoming phase III study. That endpoint is a non-inferiority composite endpoint consisting of biopsy-proven acute rejection, graft loss, and death. Please remember that although rejection in common parlance is used to mean graft loss, from a medical perspective, they are not the same. Rejection here refers to an immune flare, whereby the immune system recognizes the kidney graft as foreign. In the first year post-transplant, acute rejection typically refers to T-cell-mediated rejection, which is treated with steroids or ATG, and despite being part of the endpoint, is only poorly correlated with long-term organ function and survival. The second efficacy endpoint is eGFR.
While this is not an approvable endpoint, it was the primary endpoint that we used in our phase II BESTOW study. That was because eGFR is the best single predictive variable in terms of kidney graft function and survival. As is true in other kidney conditions, the higher a patient's eGFR, in other words, the higher their kidney function, the longer they are likely to have that kidney function. In transplantation, a higher eGFR has also been associated with lower rates of subsequent hospitalizations. The graph on this slide on the right is the latest published large natural history paper on post-transplant eGFR. The study included nearly 5,000 patients followed for six years. The red line are patients taking a CNI, with a vast majority of those patients taking tacrolimus.
This line decreases over time because the tacrolimus is eating away at the patient's kidney function as a result of the drug's direct toxicity. It's a nephrotoxin, as well as the drug's indirect toxicity, since tacrolimus causes both hypertension and diabetes. Turning now to slide six. This slide is showing long-term eGFR between the TAC and TEGO arms. The x-axis is time as measured in months, and the y-axis is kidney function, in other words, eGFR. The numbers on the x-axis are the numbers of patients at every time point. These numbers decline with time as a result of the staggered enrollment into the study. In other words, it's not that patients are dropping out of the study between months 18 and 24. It's just that most of the patients that made it to 18 months post-transplant have not yet made it to 24 months post-transplant.
Looking at the graph, one can see patients on tegoprubart on average have higher mean eGFRs at every time point post-transplant, with the curves separating after 12 months, resulting in a statistically significant difference of over 12 mL per minute at 18 months. Also, there is a trend upwards for patients on TEGO during the long-term extension versus a slight downward trend for tacrolimus. Turning to slide seven. In this Kaplan-Meier curve, we are looking at the probability of biopsy-proven acute rejection over time. The x-axis is measured in days. The numbers under the x-axis represent the number of patients still in the study that have not had an episode of bPAR at that time.
You'll note that these numbers are correct, but they appear slightly different from the numbers in the prior slide, since the prior slide numbers do not exclude patients after they have had a bPAR episode, as long as they remain in the study. We are happy to report that there have been no cases of bPAR in the TEGO arm after six months, with the patients being the longest on therapy, now nearly 1,000 days post-transplant. In the tacrolimus arm, over 9% of patients have had a total of seven cases of bPAR after six months, including two patients that experienced acute rejection after one year post-transplant. These two patients were one patient that had a recurrent case of mixed T-cell-mediated and antibody-mediated rejection, and a second patient that experienced their first acute rejection, which was antibody-mediated.
Of note, late acute active antibody-mediated rejection carries materially worse prognosis than acute T-cell-mediated rejection in the first six months post-transplant. Since early-treated T-cell-mediated rejection is largely reversible, while later antibody-mediated rejection is a type of rejection that can cause graft loss. Looking at the graft, one sees an obvious question, which is: How do these patients do after they experience a bPAR episode? What happens to their kidney function? Was there a difference between how patients did on one therapy versus another? In other words, could kidneys recover differently depending on what type of immunosuppression is being used? Turning to slide eight, we can see what happened with TEGO and TAC. Here, we're looking at eGFR over time, where the y-axis is again eGFR and the x-axis is time measured in months.
There are three lines here because when a patient on TEGO in the trial had a bPAR event, the treating physician had the choice whether to keep the patients on TEGO or to switch the patients to TAC. On this slide, the dark blue line are patients on TEGO who remained on TEGO after their bPAR episode. The light blue line are patients who were on TEGO and were switched to TAC at the time of their bPAR. The orange line are patients who were on TAC to begin with and thus remained on TAC after bPAR. As one can clearly see, patients on TEGO demonstrate higher eGFRs after every time point. Note also the upward eGFR curve over time for TEGO, again suggesting that kidneys continue to recover function.
As a result, the difference in eGFR between patients treated on TEGO who remained on TEGO after the rejection episode and those on TAC who experienced a rejection in their first year post-transplant increased from 15 mL per minute at 12 months to about 25 mL per minute at 21 months. Patients who were on TEGO and were switched to TAC post-rejection also had lower eGFRs at 12 months versus those who had a bPAR but remained on TEGO. Turning to slide nine, we see the long-term data from the single-arm phase I-b study. This long-term data is very similar to what we just saw in the phase II. This study was launched before the phase II BESTOW study, so we have patients that are out further, including two patients that are already out three years.
First thing to note is that, again, there were no incidents of bPAR in this population after six months. In terms of eGFR, the middle tan line are patients that were on TEGO and did not experience a rejection. The dark blue line on top are patients who experienced a rejection and remained on TEGO, and the light blue line on the bottom are patients who were switched to tacrolimus after they experienced a rejection. Once again, we can see the advantages of being on TEGO and remaining on TEGO versus switching to TAC. Let's switch our attention to safety, starting on slide 10. Here, we are looking at the safety and tolerability data that we previously presented towards the end of last year regarding how patients were doing in the first year.
This slide is a summary slide. It includes all of the AEs that were frequent, in other words, that were seen at least 5% of the time in one or both arms, where one of the arms also demonstrated twice the risk or greater of having that AE versus the other arm. The teal color text represents AEs that were seen more than twice as often in the tacrolimus arm, and the black represents the one AE that was seen more often in the TEGO arm. I'll start with the proteinuria that was seen more often and remind everyone that this was dipstick proteinuria. It was not done in the central lab. This proteinuria started and ended at varying times.
There was some slight ties to this proteinuria if patients had an immune source of their underlying kidney disease. All of these proteinuria resolved by themselves without needing therapy, and none of them appeared to impact kidney function. In the time post year one, we have not seen a single case of proteinuria in the long-term extension study. In terms of the side effects from TAC, many of these obviously continue over time so that patients that had tremors, patients that had developed hypertension, or patients that became diabetics continued to have their symptoms into the second year. If somebody developed diabetes, they were not cured of their diabetes as they entered their second year post-transplant. If we flip to the next slide to look at safety and tolerability in the second year, what we are listing here are the new AEs.
Patients that had ongoing hypertension or ongoing diabetes that they had developed in the first year as the result of being on tacrolimus are not being counted again on this slide. Overall, as you'll see, in terms of number of events, it's relatively similar between TAC and TEGO, maybe with a slight advantage towards TEGO. Once one looks at the same analysis that we did in the first year, frequent AEs where one arm had twice the risk, we saw some higher levels of CMV or BK reactivation in the TEGO arm, and that reactivation was measured in terms of DNAemia. I would note that all of this viremia was controlled, typically either using an antiviral for CMV or by decreasing the dose of MMF. We did not see any end-organ disease or syndrome in either arm.
On the tacrolimus arm, we saw twice as much herpes zoster as we did in TEGO. We continued to see the CNS effects and the CNS signal very strongly with multiple times the new reported incidents in the TAC arm versus TEGO. We also saw more acute kidney injury, about three times more acute kidney injury in the TAC arm, which might be associated with the decreased kidney function that we reported earlier. Finally, a GI side effect, diarrhea, became very clear this time around. Tacrolimus GI side effects are well known. Interestingly, in the first year, almost one in three or about one in three patients in the tacrolimus arm had developed diarrhea, and in the second year, one in five did. In terms of other AEs or other things to note, we had an equal amount of discontinuations in each arm.
We did have a death in the tegoprubart arm. This was tied to a cardiovascular event in a patient that had a history, including obviously a history of kidney disease, and this death was not attributed to drug, and we did not have graft loss in either arm. Importantly, we did not see a single case of PML or PTLD in either arm. We have now had about 200 humans exposed to TEGO, and to date, we have not seen PML or PTLD, which could be, from a competitive perspective, an important differentiating factor. We are very encouraged by this ongoing difference in safety and tolerability favoring TEGO. Moving to slide 12.
This is a slide that was not originally in the deck. Yesterday during ATC, I sat on a panel where a patient presented this slide, and I asked her afterwards to be able to use the slide today and got her permission to do so. This is a young lady in her 20s who was describing what it's like to be nine years post-transplant, including what the side effect burden of the tacrolimus that she is taking is like. This is her slide. Here you can see how these AEs that we've been discussing over the past two slides aren't just numbers on a page but can have a tremendous effect on a person's quality of life. As you can note, just her title, the side effects of her taking tacrolimus infiltrate into everything that she does. In other words, they infiltrate into her whole life.
I won't read everything. Even with her tremors, she was working in a dialysis clinic, and she needed to be able to insert sharp needles into patients. She noted how difficult that is when one has a tremor, including creating levity by talking about how she would scare the patients when they would see her with her tremor. Obviously, leading to a very difficult position for a young person trying to establish themselves in their field. Similarly, she explained how debilitating her brain fog or her headaches could be, and how often she is getting headaches that can force her to stay at home.
Finally, the diarrhea we just discussed, these GI issues, for her, lead her to rethink how it is that she eats and how it is that she travels, since she needs to take into consideration the TAC effects on her GI system, including not eating if she has to travel because of what might happen if she's been eating. Switching to the next slide. We are excited today to present what we think are the first patient-reported outcomes in a controlled study versus CNIs. Here you are seeing two different symptom burden scales that were examined. The first one is the MTSOSD scale, and that is a scale that is looking at post-transplant symptoms occurrence and symptoms distress. That scale looks not only at how frequently side effects like tremor might occur, but also how severe the side effect is.
The second scale is the KDQOL scale, which is the Kidney Disease Quality of Life scale, with that title being self-explanatory. In both of those, tacrolimus showed a statistically inferior change from baseline over time versus TEGO. With the MTSOSD, patients on TEGO were doing better over time. They improved in terms of how the patients reported they were feeling, as can be seen by the decreasing numbers on TEGO. In fact, patients on TAC are pretty much flat and at the end have a slight uptick. The clinically meaningful differences here are considered to be about 10 points. As you can see, between week 25- 52, the patients in the TEGO arm overall continued to improve. By week 52, there was not only a statistical difference between the two arms, but one that was also clinically meaningful.
For KDQOL, one notes that for some of these, the numbers are very similar between the two arms. For kidney disease, burden of kidney disease, or the kidney disease effect on daily life, and that makes sense because these patients had a kidney transplant. However, when it comes to overall quality of life in terms of the symptoms and the problems that the patients are facing, we see again a statistical and clinically meaningful difference between TEGO and TAC, favoring TEGO. I will note that in the TAC arm, under the mental component subset, the numbers get worse. That, in other words, over 52 weeks, patients reported a downward trend on that scale for the mental component, which is of course consistent with the side effect profile of TAC that we were just discussing.
Moving on to slide 14. We continue to be on track, as we've previously guided, to begin launching our phase III study towards the end of this year. The study will be a 52-week prospective, global, multicenter, active controlled randomized phase III trial. The study will look very much like the phase II study, but it will be significantly bigger. We plan to enroll approximately 600 patients in two arms, that they'll be randomized one-to-one. The induction therapy will be the same, as will the maintenance therapy, with one arm being on TAC and another one being on TEGO. The primary endpoint will be the triple endpoint that I just mentioned, this efficacy failure endpoint consisting of bPAR graft loss and death. Of course, we will look at key secondary endpoints, including eGFR, so kidney function, which we'll measure at 12, 24, and 36 months.
Safety, including the diabetes, new onset diabetes, delayed graft function, all of the neurotoxicity of TAC, hypertension, including crises and diarrhea, we will include patient-reported outcomes in this study as well. We have discussed this with the U.S. FDA, we have received clearance from the U.S. FDA to proceed with our phase III study. Moving on to islet cell transplantation. The patient population that we're studying here is a high-risk patient population. As we know, there are 1.5-2 million patients living with T1D living in the U.S. today. Of these, about 12% experience what is called recurrent severe hypoglycemic events. A severe hypoglycemic event is defined as a patient's blood sugar falling so low that they need third-party assistance in order to help rescue them and get their blood sugars back to normal.
The way recurrent severe hypoglycemia is defined is by at least two episodes requiring this third-party assistance within the past 12 months. This is also how the FDA defines recurrent severe hypoglycemic episodes. These patients are some of the patients that have the highest risk of diabetes complications, and as you'll see, ironically, many of these patients not only get very low blood sugars, but paradoxically, they keep their blood sugars very high as well, that they have high A1C. In other words, over time, they not only have all the risks associated with getting very low blood sugars, they also have all of the complications associated with having high blood sugar. The procedure itself can be seen on slide 17. It is a non-invasive procedure in terms of the fact that it's done by interventional radiology.
In our study, we are taking donor cells from deceased donors, so people that have donated their organs. The pancreas is removed. It is placed into a machine that purifies and isolates the islets. The islets are then put into an IV bag and infused by the interventional radiologist directly into the portal vein of the liver. They then flow into the liver, where they engraft and begin to make insulin. Moving on to the next slide, 18, we can see our phase I/II study. This is an investigator-sponsored trial that is being done at the University of Chicago. The design is an open-label, single-dose, 52-week study. It's the same dose that we're using in kidney transplantation, and we have now transplanted 12 patients. Here, induction therapy is the same, using ATG.
The chronic maintenance therapy is slightly different since we're not using corticosteroids because of the fact that these patients are diabetic. In terms of the endpoint as we think about the future, I'm happy to announce today that we have been ahead of schedule and so have already begun interacting with the agency, so the FDA, about this program. From these interactions, we anticipate that in a registrational path study, the primary endpoint would be a composite of, one, insulin independence, which the FDA is defining as six out of 12 months without the need for insulin, with the patients maintaining an HbA1c below seven while not using insulin. Two, the complete absence of the severe hypoglycemic events that we just discussed. On the next slide 19, we can see the demographics of the 12 patients in the study. There was more females than males.
As you'll see, the patients are adults, 42 years old on average, and they have had diabetes for a long time, 29 years on average. These aren't patients that are new to diabetes. These aren't patients that don't know how to manage their diabetes. All of these patients, in order to get into the study, needed to have optimized care for their diabetes. One of these patients, as an example, was a cardiologist, and obviously as a cardiologist, he knows how to manage diabetes. Yet this individual once had a severe hypoglycemic event while driving his car and ended up having a car accident as a result. It's not that these are patients that don't know how to manage their diabetes. These are patients that despite being able to get the best diabetes care for them, they continue to have these recurrent severe hypoglycemic events.
You'll note that the baseline A1C is high at about an eight on average, as is the average baseline insulin that some patients are on. Seven of the patients required one transplant in order to get off insulin, and five of the patients required two transplants in order to fully get off exogenous insulin. In those five patients, three of them, that was principally due to the body mass of those patients. These were larger patients, as you can see, with about a 30 BMI that required a high level of insulin. A transplant from one individual just wasn't large enough, wasn't sufficient to produce the insulin that they needed. Moving on to the next slide. We can see how the patients did. A few things to note. The first one is that every single patient was able to achieve insulin independence.
Also, every single patient was able to achieve a non-diabetic HbA1c, and on average, the patients saw a 2.6% reduction in HbA1c versus their baseline, which is a very large improvement. Of note, 11 of the 12 patients achieved a non-diabetic HbA1c within about two months after their transplant. If you look at the lines, you'll see that in terms of the FDA endpoint, basically all 11 of these 12 patients achieved that endpoint of being below the seven within about four weeks. The effects that we're seeing here are not only dramatic, but they're very fast. In terms of severe hypoglycemic events after transplant, in all 12 of these patients, we have not seen a single case of a severe hypoglycemic event after transplant.
These patients have all gone from getting them sometimes frequently and very frequently to no longer having to worry about them at all. Moving on to slide 21, we are now looking at the engraftment rates, the calculated engraftment rates post-transplant. This is comparing the 12 patients on TEGO to six historical patients that were chosen by the principal investigators as comps from the University of Chicago. You can see that we're seeing a higher engraftment rate for patients that are on TEGO versus patients that are on TAC. Intuitively, that makes sense. We know that TAC is toxic to the insulin-producing cells in the pancreas.
As we just discussed a little while ago in terms of the kidney transplant study, patients that received the kidney transplant and were on TAC, one in six patients that did not have diabetes at the time of their transplant developed diabetes by the end of their first year as a result of this toxicity. Here we're seeing the toxicity in terms of what it means with engraftment rates. TEGO, we assume by not having the toxicity is allowing for greater engraftment and greater cellular function of the transplant itself. Moving on to the next slide. We are now looking at the effect of tacrolimus over time on the kidneys of these transplanted patients. On the left-hand side of the slide, we can see the data from a study for the Lantidra product. Lantidra are approved deceased donor islet cells.
In their registrational study, they saw what is on the left-hand side of this slide, which is decreasing kidney function over time. On the right, you can see for nine of our patients that were examined by Dr. Witkowski, their eGFR over time. Once again, we're not seeing a negative effect of TEGO on kidney function. In fact, we're seeing signs of the opposite. The green line are patients that had lower eGFR, so slightly lower kidney function at the time of their transplant, probably due to the ongoing diabetes that these patients have. Once their diabetes was able to be under control, although these are small ends, there does appear to be a trend where those kidneys are recovering function.
We have done one compassionate use patient that was on tacrolimus after having had an islet cell transplantation, that patient could no longer tolerate the tacrolimus because it was destroying their kidneys. After that patient was switched from TAC to TEGO, they quickly began recovering their kidney function as well. In terms of safety in the study, the safety continues to look very good similarly to the kidney transplant study. Here, all 12 patients were able to achieve a stable islet graft function, to rapidly improve their blood glucoses, to live without severe hypoglycemic events. We did not see any signs of rejection or any de novo specific antibodies. Importantly, as opposed to what the investigator reports seeing in his patients with CNIs, as we discussed, we did not see any kidney toxicity, but we have not seen any neurotoxicity, GI tox, hypertension, or thromboembolic events on TEGO.
The TEGO patients did experience some non-severe infections, but all of them could be controlled by lowering the dose of the mycophenolate. As such, we're highly encouraged by these results, look forward to advancing the program in islet cell as well. As I mentioned, for kidney transplantation, we are looking forward to our target of initiating our phase III late this year as we seek to provide a new treatment alternative to standard of care with tacrolimus that has barely changed in over three decades. When taken together with our clinical progress in islet cell, in xeno, and now as we enter tolerance induction, we as a team, and Eledon as a company, continue to build momentum in the transplant space in pursuit of our mission of one transplant per life. With that, I will now ask the operator to begin our Q&A session. Operator?
Ladies and gentlemen, we will now begin the question and answer session. If you wish to ask a question, please press star, then the number one on your telephone keypad. If you would like to withdraw, just press star, then the number two. We'll just pause for a brief moment to compile the Q&A roster. Your first question comes from Thomas Smith from Leerink Partners. Please go ahead.
Hey, guys. Good morning. Congrats on these updated data. Thanks so much for taking our questions. On the phase III plans in renal transplant, it sounds like you have FDA feedback to proceed here. Could you talk a little bit about what the gating factors are to getting this study started in the second half of the year? Do you need other international regulator feedback? Is it more logistical considerations around site activation or some other factor?
Yeah. Thanks for the question, Tom. This is Steven Perrin. It's a great question. Right now, with the regulatory feedback that we have, it's all logistical. It's basically about launching a global phase III study, which will take some time. We're anticipating launching the study and getting a first patient in by the end of the year.
Got it. Thanks. That's helpful. I just wanted to ask about the latest.
Sorry, I was just going to add and to remind you that we raised money late last year in order not to slow down. As we were waiting for this data and as we were having FDA discussions, we're able to continue planning for the phase III full speed ahead. We now have the FDA feedback in hand, and we haven't lost any momentum in terms of our ability to get the study up and running.
Got it. That makes sense. I just wanted to ask about the latest status on iBox. I didn't see it mentioned on the phase III slide, just wondering if you could give us an update there, are you still expecting to incorporate this into the phase III design?
Sure. For that, I'll turn it over to Dave.
Yeah. Thanks for the question. We are planning at this point to include iBox as a secondary endpoint in our phase III design.
So far.
Yeah.
The FDA.
Yeah.
Ask us to incorporate it as a co-primary, as an example. The FDA has not permitted that to be the case. In fact, in our discussions at least, the FDA was much more focused on eGFR as opposed to iBox.
Understood. That makes sense. Just one question, if I could, on the islet cell program. Truly remarkable data there. Just wondering in the initial feedback that you've got from the agency, and I guess in thinking through some of the implications of this planned composite primary endpoint, could you just talk about perhaps thresholds that the FDA is looking for that you might need to show on this composite endpoint that could potentially enable approvability there?
Sure. Preliminary guidance from the FDA aligns with precedent In regards to the approvals that have been granted to date, one in particular that DA mentioned, the Lantidra approval, but also publicly available information regarding programs that have been given a go-ahead to proceed towards a BLA. The numbers that are shown in our slides align exactly with that precedent and publicly available guidance from the agency.
Right. That's, in other words, the endpoint. We assume, or we estimate that overall the FDA is going to want to see about 40- 50 patients in the program. The FDA did not give us a specific number in terms of what's the percentage of patients that need to not have severe hypoglycemic events, or that need to be able to be off insulin for at least six months while maintaining an HbA1c less than 7%. Although obviously, right now, our success rate of achieving that appears to be very high. The path forward there is going to be twofold. I think in the near term, we are going to look to help establish manufacturing, if you will, of deceased donor cells. Today, as you saw, the deceased donor cells do need to be purified out.
We will look to establish one or potentially two sources for these cells. Once we have done so, which should take about 18 months, we could then use the data from those cells to show comparability to the patients that we've already done with FDA.
Subsequently to that, be able to quickly finish enrolling the 40- 50 patients that we would need.
Makes sense. All right, guys. Thanks so much. Great to see all the progress here. Congrats again on these updates.
Thank you, Tom.
The next question comes from Pete Stavropoulos from Cantor Fitzgerald. Please go ahead.
Hi, guys, congrats on the data, thank you for taking our questions. A couple from me. For the patient-reported outcomes that measure symptom burden, can you just help us understand what those outcomes mean for patient experience and what is considered clinically meaningful?
Sure. The patients' reported outcomes look at how patients are feeling as well as in the MTSOSD includes specifically the side effects that patients may be experiencing because of their medication. In what is commonly considered clinically meaningful for the MTSOSD is 10 points. A decrease of 10 points is considered meaningful for the patient. In the KDQOL, in any one of the groups, an improvement or a difference of five points is considered clinically meaningful. We show that clinical and statistical difference in both with the MTSOSD at week 52, overall, and that includes, again, the specifically drug-induced AEs. For KDQOL, when it comes to symptoms and problems, we show a benefit. There, that's an increase in the number where we get to a treatment difference of about six points.
Sorry, I had to unmute myself. Any color that you can provide, like feedback-wise from investigators who treated both patients with TEGO as well as TAC in this study, any feedback in terms of the AE profile, the patient experience for both actually, kidney transplant as well as islet cell?
Yeah, sure. Great question, Pete. This is Steven Perrin. Yeah, we have heard from a lot of our investigators that the AE profile of TEGO is better in their mind than what they typically see on TAC. As you know, TAC is an incredibly difficult drug to manage with daily dosing because of its very narrow therapeutic index. When they see problems where they have to change levels of TAC due to infections or leukopenia, it's very challenging to monitor levels of TAC daily, and it's challenging for both the physician and the patient. Whereas with TEGO, it's in every three-week IV infusions. Biologics tend to be a little bit easier to manage in that regard. As DA reviewed in the presentation here, we're just seeing an overall better AE side effect profile than TAC, both at 12 months as well as in the long-term data.
The similar story for islet cell transplant, we're even seeing fewer side effects thus far, albeit in a smaller patient population than our kidney study. So far the data's looking very encouraging.
I'll add that for patients now, one can see their experiences online. We've now had patients. We live in a new world where people will post how it is that they're doing. Patients have posted their experiences on TEGO on all sorts of social media platforms. These are not condoned by Eledon, but obviously in today's environment, it's the reality of running a clinical trial. What's striking looking at these patients is how well they're feeling, and they talk about it. You can see them get an infusion of TEGO and talking about how it doesn't interfere with their day, and they feel great, and they're able to work through the infusion. You can hear them talk about the absence of side effects and how much better their life is post-transplant.
Last question from me is for the islet cell, the data that you just mentioned are sort of well-known among both, I guess, patients and investigators and many physicians. At ATC, they're fully aware of the outcomes of the data to date. Just curious to hear the overall interest in the program and importantly patient interest in this program, either interest conveyed directly to you guys or through the principal investigator.
There is a tremendous amount of interest in the diabetes program. This can be seen again online just by the sheer volume of people talking about TEGO and talking about the islet cell data. There was a post, as an example, on Facebook, with one of the patients talking about how well she was doing, and that post was seen 2.5 million times within the first 24 hours after she posted it. It was seen overall, the woman who posted it said that her post had been seen over 4 million times total. When it comes to the study itself, to date, we have received over 1,000 inquiries from patients asking to be a part of the study. I think the data has made it into the community.
Patients are aware, and there is a tremendous amount of interest in what we are doing here. It shows just how large this unmet need is.
All right. That's great to hear. Thank you for taking our questions, and again, congratulations on these outcomes.
Thank you.
Your next question comes from the line of Vamil Divan from Guggenheim. Please go ahead.
Great. Thanks for taking our question. Yeah, let me add my congrats also. This looks really like a nice update here. Two questions if I could. One, just going back to slide six in the presentation. You see that sort of meaningful drop-off in the tacrolimus arm on eGFR as we get to the 24-month mark. I know the number of patients out there is smaller, but anything specific you can comment on in terms like why we're seeing such a sudden drop there in the tacrolimus arm? The second question, which we've gotten from investors a lot too, is just your thoughts around. Sorry if I missed this in the comments, been juggling a few different piece of news this morning, but just around you're potentially looking at a switch study.
Opportunity where maybe patients still starting on tacrolimus for the first three months or six months and then switch over to TEGO after that to avoid the longer-term toxicity with tacrolimus. Not sure if you mentioned it this morning, but if there's any color you could add on potentially looking at that from a regulatory perspective. Thank you.
Sure. Thank you, Vamil. To answer your first question regarding slide six, and for folks trying to follow along, this is the slide that's showing eGFR over time. The reason you're seeing a decrease in month 24, is probably tied to the low N, so that the patients that are on TAC at that time are probably just doing a bit worse than the patients that have not made it out 24 months. We would expect that that number would have some reversion towards the mean as the remainder of the patients reach the 24-month time point. In terms of your question number two, which is switch, and I think what you are asking is why don't we use tacrolimus in combination with TEGO in year one. The reason for that would be in order to reduce the short-term rate of biopsy-proven acute rejection.
Those rejections that we're seeing in the first six months. The reason why we're not combining with TAC and we're running a TAC-free regimen, is because the moment you start to use TAC, you then get into all of the TAC side effects. From a rejection perspective, as you saw, today, the advantage from a numerical perspective long term, becomes negligible. In terms of the impact of rejections over time, again, as we discussed earlier, patients on TEGO are doing better than the patients on TAC. If you experience a rejection on TEGO, the impact on the kidney does not appear to be the same as the impact on TAC. We already know that experiencing rejection in the first six months, even on TAC, is not associated with long-term organ survival or function.
It's hard to see, if you will, the advantage of adding the TAC in order to try to slightly reduce some early rejection in the first six months. However, the downside is very clear. The downside is going to be all of the AEs that we're seeing, including the increased delayed graft function and the associated costs of longer inpatient dialysis post-transplant, as well as the whole suite of AEs that we observed in the first year. If we give TAC for six months, we're going to have patients become diabetics, and those patients will remain diabetics for the rest of their lives. We're going to have patients begin to experience the brain fog, the tremors, the headaches, the hypertension, and some of that will continue even after the TAC is discontinued.
From our perspective, doing a short-term combination would probably not lead to good safety efficacy trade-off. Now, a switch could be interesting longer term in terms of switching patients that are already on tacrolimus and are experiencing these AEs and trying to switch them to TEGO in order to relieve them as much as possible of the side effects. As I mentioned, we've now done that using compassionate use for one patient that had had an islet cell transplantation. The feedback from the agency earlier had been that the agency wanted us to start with a de novo study before doing a switch study. We recognize that switch is a very large market. There are probably 250,000- 270,000 Americans today taking tacrolimus. That could be a large opportunity if those patients started to switch to TEGO.
That would be a new indication, and that would require another phase III. From a life cycle management, that is something that we can consider to pursue over time, but that is something that we would start, and we would need to start after we started our phase III in de novo.
Okay. All right. Thanks for the information, and congrats again. Thank you.
Thank you, Vamil.
Your next question comes from Rami Katkhuda from LifeSci Capital. Please go ahead.
Hey, guys. Wanted to pass along my congrats on the update as well. Thank you for taking my questions. I guess in the phase III kidney transplant study, what non-inferiority margin has the FDA accepted for the composite endpoint? Then more broadly, how are you thinking about ATG induction doses? Is that going to be standardized across the board?
Thank you, Rami. Great question. The FDA has not given us a final non-inferiority margin. As you know, the last drug that was approved, which was belatacept, had a 20% non-inferiority margin. The FDA has told us that they considered the exact non-inferiority margin to be a review issue since it would be due or tied to the ultimate advantages, or lack thereof, of being on TEGO versus TAC. The reason that Bela was able to get a 20% margin was because Bela was showing significant advantages from a safety perspective versus TAC. In our discussions, we discussed an 18% non-inferiority margin with the agency, and the agency did not tell us that was not an approvable margin, although we do not have spine plates as an example around that margin.
We are powering our study around that 18% non-inferiority margin, and it allows us at the 600 patients or so to have a 90% power to reach non-inferiority if, from an efficacy failure perspective, we were within 8%. That's a net 8% versus tacrolimus. In other words, 12% versus 20%. 15% versus 23%.
Got it. We found it particularly impressive that no bPAR events were observed with TEGO after month six. I guess, can you provide more color about the clinical importance of late rejection events, and could this become an important differentiator if reproduced ultimately in phase III?
Great question, Rami. This is Steve. Historically, the biggest issues with TAC post 12 months is not T-cell-mediated rejection, which is fairly treatable with steroids or ATG. It's antibody-mediated rejection, which is much more challenging, and mixed rejections as well, that tend to have poor prognoses. Post 12 months, we anticipate that we're going to continue to see those on the TAC arm based on historical data. The nice thing about costimulatory blockade, and again, we have some lessons learned from belatacept, although CD40 ligand in preclinical models is superior to belatacept's activity here. The direct mechanism of action of blocking CD40 ligand is to block germinal center formation and B cell maturation, therefore, it should have a direct impact on decreasing the incidence of antibody-mediated rejection longer term after graft function.
We're hoping to see that not only in the long-term extension data, but also in the phase III.
Here it's DA again. At ATC, we're presenting the data both in the poster as well as in the oral session. At the poster, physician after physician commented on the fact that we were not seeing acute rejection after six months. People definitely found it striking.
Awesome. Thanks, and congrats again.
Thank you.
Your next question comes from Robert LeBoyer from Noble Capital Markets. Please go ahead.
Good morning. Congratulations on both sets of data that you presented today. My question has to do with the iBox measure. You had mentioned that the FDA won't require it in your trial. I was expecting to hear something from the agency as to its acceptability as an endpoint or some kind of comments or decisions or opinions on iBox as a measure. Have there been any communications or signals or anything expected from the agency on that?
Thank you for the question, Robert. It's DA. The FDA had initially guided or was supposed to provide an answer, I believe it was about 60 days ago, has not yet done so. In other words, the FDA is behind there. We don't obviously have perfect insight into what is going on at the agency and how the agency is talking to the consortium that is advocating for iBox. From our perspective, we now have an agreed-upon endpoint with the FDA. iBox, if you recall, for us was an upside because it would have been an additional endpoint that if we hit, would allow us to get an extended claim on our label in terms of superiority. Right now it does not, based on our discussions, appear that will be the case, at least for our study.
If the agency changes its mind and approves that endpoint, it's something that we might be able to add in the future to our study as needed. Let me turn over to Steve.
Yeah. Hi, Robert. Great question. There was a session here yesterday at ATC that was hosted by TTS. The tone in the room was a little bit disappointed that they haven't received that feedback at 60 days. They have petitioned the FDA with some letters to try to formally push a decision forward. The FDA at this point, according to the session yesterday that TTS hosted, the FDA has not gotten back to them with feedback yet.
Okay. Yeah. I think the FDA is supposed to, but not yet done so. I think that sums it up quite well. The second question I had was on the islet cell program, and you touched on the manufacturing and the standardization of the islet cells themselves. I was wondering about the actual administration, and you mentioned that a radiologist would be administering the cells by IV through the portal vein. I was wondering how standard of a practice that is and whether there's any additional training or any additional risk of variation or whether this is something that's refined to practice and routine for this specialty or whether this is something that is unique to the trial.
Hi, Robert. This is Steven Perrin. A great question. I think you asked two. One about manufacturing and our path forward there, and the second one about how routine the surgical procedure is. This procedure goes back decades, and the insertion of cells into the portal vein is a very routine procedure. It's done not only in the U.S., which is a little bit less common here, just because historically islet cells haven't been approved by the FDA as an organ, but as a drug product. Globally, as an example, thousands of these transplants are done in Europe. It's been approved in Canada for a very long time, as well as Australia, Japan, and other countries. This is a very routine surgical procedure that we don't anticipate issues with training or anything like that. You should be able to roll it out fairly seamlessly.
As far as your first question, I think Eledon's strategy there is very similar to what you've seen us do with xenotransplantation. We've collaborated and worked with any xenotransplant company, including United Therapeutics, as well as eGenesis. Preclinically, we have global collaborations all over the world in non-human primates using other types of genetic pig organs as well. We're agnostic to it. We'll supply TEGO to protect those organs because we think it's superior to CNI in that regard, and it's clearly become one of the best ways to prevent xenotransplant rejection. Our strategy in islet cell is very similar.
We're going to support and obviously listen to the guidance from the agency historically that you need a robust manufacturing process and whether that's a collaboration partnership with Lantidra, which is already an approved product that we could jump into a larger phase II, III design much more quickly than in parallel setting up our own manufacturability. We're agnostic to other cell types coming down the line as well, be it embryonic stem cells or induced pluripotent stem cells as well. If a cell-based company has a robust technology to differentiate cells into pancreatic islet cells and they need immunoprotection, we're happy to partner with them and provide tegoprubart for that. If you've seen, we've done that with both Sernova, as well as Nucleix. Our strategy in xeno and islet cell is very, very similar in that regard.
Okay, great. Thank you very much.
Thank you.
There are no further questions. I'll turn the call back over to Dr. David-Alexandre Gros.
Thank you, operator. Thanks everyone for joining today. Appreciate everyone's time and interest, and we'll end the call.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.