Good afternoon, ladies and gentlemen, and welcome to the Eledon Pharmaceuticals updated Phase Ib D ata Conference Call. At this time, all lines are in listen-only mode. Following the presentation, we will conduct a question- and- answer session. If you would like to ask a question at that time, please press Star, one on your phone. If at any time during this call you require any assistance, please press zero for the operator. This call is being recorded on Wednesday, August 6, 2025. I will now like to turn the conference over to Paul Little, Chief Financial Officer of Eledon. Please go ahead. Good afternoon, and thank you for joining Eledon's Phase Ib Data Update Conference Call. I am joined on today's call by Dr. David-Alexandre Gros, our Chief Executive Officer, Steven Perrin, our President and Chief Scientific Officer, and Dr. Eliezer Katz, our Chief Medical Officer. Earlier today, Eledon issued a press release detailing the updated results presented at the World Transplant Congress from our ongoing phase Ib trial of tegoprubart in kidney transplantation. 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 prospects, 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 SEC. Now it is my pleasure to pass the call to our CEO, Dr. David-Alexandre Gros. DA. Thank you, Paul, and thank you everyone for joining today. It is a pleasure to reconnect with everyone on what is a beautiful day here in San Francisco, where we are wrapping up the World Transplant Congress. This has been a big week for Eledon at the meeting where we have continued to show tegoprubart's potential. We started the week by reporting that a third kidney xenotransplant was performed at Mass General and that the patient is doing well with good kidney function. We then presented some non-human primate preclinical liver transplant data, which we believe is sufficient to begin approaching regulatory bodies regarding a potential liver transplant clinical trial. We also sponsored a seminar that was attended by 344 people on kidney transplant trial endpoints and how the field is evolving to long-term predictive endpoints. Finally, of course, we presented our phase Ib data today, which is what we'll focus on and cover on this call. Of note, our phase Ib data, after we presented it, was chosen by the organizers to be highlighted during the closing ceremonies. Elie will walk through the trial design and the safety, after which Steve will walk through the results, and I will then come back on to wrap and to take questions. As you'll see, this is an important trial in that it is the first, an update on the first study using tego as the cornerstone immunosuppression in de novo kidney transplantation. You'll see that tego had a good safety and was well tolerated, and importantly, that it resulted at 12 months in good eGFRs as well as good scores when it comes to abbreviated iBOX, which we will dive into and is a predictor of five-year kidney graft survival. With that, let me turn the microphone over to Elie to go into study design and safety. Good afternoon. It's, as DA said, a very exciting week for us. This morning, the 52 weeks open-label single-arm study of tegoprubart in de novo kidney transplantation was presented in oral presentation by the senior author, Dr. John Gill from Vancouver. As you see here, if you look at the left side, our included in exploring criteria, we enroll in this study in a representative population for de novo kidney transplant patients, adult patients, EBV positive and DSA negative. The exclusion was mainly related to ischemic time, more than 30 hours, older age of the donor above 65, and we excluded marginal donor DCDs and ECDs. Primary endpoint was safety and pharmacokinetics, and secondary endpoint involved, of course, patient and graft survival, biopsy-proven acute rejection, eGFR, and other biomarker for injury and rejection risk, and also, of course, pathological examination of the graft. We also included exploratory endpoint, as DA mentioned, which is the abbreviated iBOX. All patients on the study were on immunosuppression regimens to include ATG i nduction with tegoprubart, corticosteroids, and MPA. We have two cohorts in the study. Cohort one, 19 patients that were on 20 mg per kg of tegoprubart, and they were treated with up to 6 mg per kg of thymoglobulin. The second, cohort two, tegoprubart dose was reduced to 10 mg per kg, and ATG was up to 4.5 mg per kg. The tegoprubart regimen included dosing depends on the cohort on day one, day seven, day 14, day 21, day 28, and then every three weeks after that. Day three was only given on the cohort two. Patients were followed until month 12, and then they have the opportunity to go to our extension study that enrolled the patient for a long-term follow-up. Just to add a little bit of detail about the regimen. When we started the first few patients, the first 13 patients of cohort one, we were actually mandated by regulatory authorities to start with the high dose of 6 mg per kg of thymoglobulin. Following this cohort, after we gained experience and we felt that we got a relatively good safety profile, we decided to reduce to what was being used more in the transplant community. We went to up to 4.5 mg per kg of ATG, and in cohort two, we mandated 4.5 mg per kg of ATG. As far as the methodology, this is, as you understand, compiled data from the two cohorts with a total of 32 patients. We summarized all the safety by the standard summarization of safety data. All the biopsies were reviewed by central pathologists, and the diagnosis is based on central pathology. The kidney function was assessed by eGFR that was calculated based on the CKD EPI formula and presented the same. iBOX score was calculated according to the published methodology. This is pretty complex, but can be found anywhere. All the data is as of July 9th, 2025. Patient characteristics of the 32 patients, as you see here, the mean age was 52.9. Regular distribution as far as race. What's important to notice here is the HLA matching that actually 56% of the patients had an HLA mismatch of more than five, which basically put them in relatively high risk immunologically wise. The median donor age was 47 years. As far as living donation versus deceased donor, we have about 75% living donor and 25% deceased donor. Next, please. I talked about HLA. I did. Last point that I think I mentioned is the HLA. 56% of our patients were more than five mismatch, which put this patient to be relatively on a high risk immunologically. This is patient disposition as far as July 9th. As you see, in blue is the cohort one and in red is the cohort two. We have 13 patients that complete the study, 41%. 13 patients are still ongoing and still in the follow-up period of up to month 12. Six patients discontinue, two due to rejection, two due to the patient decision, one due to polyomavirus viremia, and one due to hemorrhage that led to acute kidney injury. This was a post-transplant severe hemorrhage that was complicated by perinephric hematoma and led to kidney function deterioration, and the investigator decided to take the patient off the study. This is the overall treatment emergent event that is not related specifically to the drug. As you see here, we have a relatively representative distribution of the viral infection with a BK viremia of 25%. It's important to note that we have only one BK nephropathy. All the other seven cases were viremia only. CMV, we have only 19% or six cases, but all those viremia, none of those end-stage organ disease. EBV, we didn't see any infection with EBV, and of course, because of that, none of the PTLD. We had two cases of skin malignancy that are very common in patients post kidney transplantation. We had two thrombotic events. Both of those were determined by our DMC, our safety board, and by the investigator to be unrelated to the drug. One of them was in a patient whose diagnosis of deep vein thrombosis was missed for a certain period. With lymphoceles around the kidney, who developed deep vein thrombosis, eventually developed a pulmonary embolism. He remained on the study and is doing very well. The other case is a case of deep vein thrombosis, again associated with lymphoceles around the transplant kidney. He also stayed on the drug and is doing also very well. We have three cases of tremor in the study. Two of them actually happened only when the patient was switched from tegoprubart to tacrolimus. One of them on tegoprubart was a transient event of tremor in a patient who has pre-existing carpal tunnel syndrome. The treatment emergent event by cohort, as you see here, is just here to present you by cohort one, cohort two that are the same point that I made before relevant here, and we can move forward. Rejection episodes. We had a total of six rejection episodes, 19%. Four of them happened in the deceased donor and two in the living donor. Again, it's important to mention here the HLA mismatch that we have four patients where we have five, one patient with a six mismatch, and one three. So it's pretty high immunological risk patients. The other important point to make here is that 75% of these patients were on a lower than recommended dosing of ATG. In red, you see here all the four patients that got induction therapy with less than optimum ATG level dosing, and it's important to note in the related to the rejection. Of the three rejections, another point which is very important is that three of the patients with rejection remained on the study, remained on tegoprubart, were treated, and are doing very well up to 12 months. The other three were switched to tacrolimus based on investigator decision, one of them based on patients that chose to go to the tacrolimus arm. Thank you, Elie. Yeah, with that, we'll turn over to Steve to talk about the efficacy. Before we do, I'll just add a quick note on the rejection episodes. What stood out here was obviously the fact that most of these rejections occurred in the patients that received low dose anti-thymocyte globulin. Obviously, a phase Ib trial is one where we're learning about how to use tegoprubart. What we found is that similar to prior experience with other co-stimulatory blockades, induction and T cell depletion up front is very important. When we had patients in this study that received low or very low doses of anti-thymocyte globulin induction, these patients were at higher risk of experiencing a rejection episode. Hence, when we looked to bring and to examine a lower dose of tegoprubart at 10 mg per kg, we made sure that the dosing there would be at a higher level, so 4.5 mg per kg. Steve, let me turn it over to you to talk about our eGFRs and our abbreviated iBOX. Thank you, DA and Elie. What we're showing here is the longitudinal kidney function data from the entire group of patients in the phase I that Elie described. Kidney function here is measured by eGFR. You can see that within a month post-transplant, we restore kidney function quite rapidly. What's most important is if you look at the 12-month endpoint, our eGFRs at 12 months are at 68. Much like we presented a year ago with initial 13 patients of data, we continue to have excellent kidney function out at 12 months from this group of patients that we've been following in the phase I study. The dashed red line is eGFR from historical data representing mean eGFR at 12 months on CNIs. As Dr. Katz mentioned, this is breaking out the rejections versus not rejections, again looking at kidney function longitudinally over time. As you can see with the darker blue line with gray shading, those are the 26 participants that did not have any rejection. At 12 months, they had an eGFR of 66 and they remained on tegoprubart throughout the entire study. The lighter blue line above that's shaded is the three patients that had a rejection but stayed on tegoprubart after the rejection. As you can see, at 12 months, they had an eGFR of 73, which is even better than the subjects that did not experience a rejection. Not surprisingly, the three patients that had a rejection decided to switch over to tacrolimus as shown in orange, much like what's been described historically in the literature for CNIs. The kidneys don't perform very well after rejections when on CNIs and have a mean eGFR at 12 months of only 34. Finally, wrapping up eGFR, you can see what we did here is we broke eGFR into the two cohorts. Cohort one, again reminding you the 20 mg per kg tegoprubart cohort, and cohort two was at 10 mg per kg. As you can see, there is a dip in eGFR in the cohort two that starts around day 154. This is really just due to the small number of patients. There's only a couple of patients out that far at this point in cohort two. Ironically, for people that remember when we presented data last year on 13 patients, our first couple of patients at that point in time had shown a swing up in their eGFRs out at the end of the study. That's because those first couple of patients had very good kidney functions. In cohort two here, ironically, the first couple of participants that enrolled are some of the poorest kidney functions that we've seen thus far. We actually are guiding and think that over time this will again collapse towards the mean of the high 60s. I'm showing you the historical tacrolimus data with the dashed red line. Switching over to iBOX, just to give a little bit of background here on what iBOX is for people that have not been following the field. iBOX was originally developed by Alex Lupi and colleagues in Europe to develop a tool so that both patients and doctors could follow patient care over a long period of time. It was a tool to utilize commonly collected clinical data that may be utilized to predict long-term graft survival. A consortium took over the guidance of iBOX called the Transplant Therapeutic Consortium or TTC a couple of years ago with the objective of initiating a process to qualify iBOX to global healthcare authorities as a reasonably likely surrogate endpoint to predict five-year graft survival with 12 months of data post-transplant. They have already received approval in Europe as a secondary endpoint in clinical trials for kidney transplant. They've been working closely with the FDA over the last few years, are in the final stages of qualification there, to either approve iBOX as a secondary endpoint or possibly even as a co-primary endpoint, which could thus be utilized as an accelerated approval. The agency is guided that we should hear some of their thoughts on the utilization of iBOX in kidney transplant in the second half of next year. What is an iBOX? As I mentioned, it's typical. In April of next year. In April of next year. Hopefully, they will hit that target. iBOX is, as I mentioned, typical clinical data that's collected from patients post-kidney transplant. It's made up of eight different outcomes, if you will, that are weighted as part of the iBOX calculation and formula. Four of them are not associated with a 12-month biopsy. Those are eGFR, time since transplant, DSA, and proteinuria. In the full iBOX, it also includes a 12-month biopsy with four different parameters that are looking at characterization of immune cell infiltrate and any type of damage, pathological damage to the kidney at 12 months. Interestingly enough, biopsy-proven rejection, which has been a long-term component of composite endpoints, is not included in iBOX because that is not a very good predictor of long-term graft survival when looking at 12-month data. That's captured in that table that's up in the upper right-hand corner of this slide. Here, we're looking at the C statistics from a ROC curve where a ROC curve measures two different groups with both for reproducibility of data between the two groups. If it's a random chance that the two models are identical, the C statistic tends to be about 0.5. A C statistic between 0.7 and 0.8 is considered statistically significant. A C statistic above 0.8 is considered to be a very strong predictor of the model. As you can see, BPAR, as I just mentioned, has a C statistic of only 0.57, which means it's actually a random and not very good predictor of long-term graft survival with one-year data. You can see both the full and the abbreviated iBOX are 0.8, which means they're very strong predictors of what five-year graft survival would look like with one-year data. The consortia, based on historical data that I'll show you in a second, that they use to build the model and validate the model is guiding that an iBOX score with a difference of - 0.4 between the two groups at 12 months is statistically significant and meets a threshold of minimal clinically important difference between the groups and also would predict about a 5% difference in five-year graft survival. This slide here is actually showing the abbreviated iBOX calculations from the patients that have reached 12 months in our phase I study. The blue graphs are the historical data sets that I alluded to that were used to, A, build the model and then, B, validate the model over time. You can see that the two BELATACEPT studies are in this analysis. They're the ones that are called BENEFIT and BENEFIT-EXT. The BELATACEPT cohorts, as you can see, are the darker blue. In the BENEFIT study, they had an iBOX score of minus 3.68 and in the extension minus 0.29. The lighter shade boxes are the CNI control arms from those studies. You can see they're significantly less, meeting that 0.4 difference between the two groups. You can see that there are similar types of analyses between other cohorts that we use for validation that include mTOR inhibitors plus and minus CNI. Our two groups of patients, both the on-treatment with an N of 12 as well as the intent-to-treat group with an N of 15, are shown in orange. The darker one being the on-treatment, which had an iBOX score of - 4.11. The ITT group had an iBOX score of - 3.75. Albeit these are low numbers of patients in our study at this point, it's a very exciting result that we're seeing such positive iBOX differentiation compared to other treatment groups that are out there. With scores of minus 3.75- minus 4.11, that would predict a five-year graft survival of more than 96%. Thank you, Steve. In order to begin to conclude and summarize, if we look back at the past few years since we started what is now Eledon, tegoprubart has continued to perform as expected. We've gone from having preclinical data to then showing early clinical data in kidney transplantation, first with only three subjects, then last year at ATC with 13 subjects overall and only two that had made it out a year. Now we have 32 subjects in the study and a dozen that have remained on drug and made it through the year. Overall, as I said, tegoprubart continues to do what we expected that it would. From a safety and tolerability perspective, the profile continues to look good and supportive. In terms of efficacy, whether we look at eGFR or whether we look at the abbreviated iBOX score, which is now evolving as one of the most important endpoints in the space, tegoprubart continues to demonstrate that it can protect the kidneys very well, leading to high scores, which should suggest improved five-year survival versus current standard of care. This is what is really needed today. We have gotten quite good at allowing transplanted organs to survive one year, but what we need to do is to change how long those organs can function and survive so that ideally patients could keep their organs for their whole lives as opposed to the way it is today where organs typically fail within 10- 15 years after transplant. Patients may require two or three transplants during their lifetime since the average age of transplant is only 50 in order to live a regular life. To give you a sense of how meaningful a 5% change in graft survival would be, what would it mean if we were to be able to continue to show an improvement of 0.4 in terms of the abbreviated iBOX score or above, I'd like to compare kidney transplant death on the waitlist to cancer. Overall today, there are about 5,000 Americans that die every year waiting for a kidney that they don't get. In other words, there are about 30,000 transplanted kidneys being performed every year so that for every kidney transplant that gets performed, every sixth that gets performed, there is one person that dies waiting for a kidney that they don't get. This death on the transplant waiting list is greater numerically than what we see in terms of mortality every year in this country from cancers, like whether it's thyroid or cervical or anal. If we imagine a world hypothetically where one was able to improve five-year survival by 5%, then that would mean that one out of every transplant that would have failed would be able to survive to those five years. In other words, out of the 30,000 transplants or so being done every year, if 5% of them made it to five years now, then 1,500 people would not need repeat transplants. As we know, transplanted organs don't get thrown away. These 1,500 organs would be able to be used by these individuals that today are waiting for a kidney transplant that they don't get. In other words, an increase in iBOX score for 0.4, if it translates truly over five years to 5% improvement in survival, could allow 1,500 more kidneys per year to make it out and thus reduce the number of people dying waiting for a kidney by about 30%. That would be remarkable. Of course, here, even more remarkable would be the impact since doing so would impact two people. It would impact the person that I just mentioned who would have otherwise not received a kidney and now would receive a kidney. It would also impact the individual that received the kidney initially since they would have an organ that would survive longer. It would decrease the chance of all of the morbidity, mortality, and of course, costs associated with needing a repeat kidney either sooner or potentially in their life. We are very excited by this data. We are very excited by where we are today with tegoprubart. We very much look forward to completing our ongoing phase II BESTOW study and being able to present that data later on this year when we expect to do so in the fourth quarter. With that, operator, I will open up the call for questions. Thank you gentlemen, we'll now begin the question- and- answer session. Should you have a question, please press the Star followed by the one on your touchtone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press the Star followed by the two. If you are using a speakerphone, please lift the handset before pressing any keys. One moment, please, for your first question. Your first question comes from Thomas Smith from Leerink Partners. Please go ahead. Hey, guys. Good afternoon. Thanks for taking the questions and congrats on the data here. Just on the anti-thymocyte globulin dosing and induction, could you just expand a little bit on some of the potential underdosing in cohort one? It looks like it was associated with some of these rejection events. Could you just remind us of the dosing regimen that's being used in BESTOW? Sure. The history here, as Elie mentioned, it's DA. Tom, thank you for the question. We initially, the regulators asked us to start with labeled dosing of ATG and then the higher dose of tego that we had used in our animal studies. Over time, as we generated safety and efficacy data, they allowed us to go and explore a lower dose of induction, which is what we did. After that, as we continued again to generate more data, they allowed us to go and explore a lower dose of tegoprubart itself. What you're seeing here is over time how we are experimenting with tego in order to learn how to best use it. Let me, Elie, turn it over to you to talk about BESTOW. Sorry. Excuse me. In BESTOW, we are recommending 4.5 mg per kg. I think we need the data to see what was the compliance and what is the distribution of the dosing. Overall, the ATG we believe is an important part of our immunosuppression regimen. As you may know, the most vulnerable period as far as rejection development is the first few weeks, up to three months post-transplantation. That's where the idea with ATG is to give another level of protection. I think 4.5 mg probably is a reasonable dose to achieve this goal. Got it. That makes sense. One more thing to notice, as you saw, and I think it's going to be important here as we think about rejections. The first point is around rejections and just how important rejections are in terms of long-term outcomes. As you saw, their rejections are poorly predictive of long-term outcomes. The other thing is rejections may not be the same. There may be one can make an assumption that a rejection on tego might be the same as a rejection on CNIs. At least with a small N, it appears that we're seeing something that's different. The patients that experienced the rejection episodes and were kept on tegoprubart rebounded immediately. As you saw, they actually do on average better than your average patient that did not experience a rejection. They have full recovery of their kidney function. While patients that get exposed to CNIs after having a rejection episode seem to then get hit by the direct and indirect nephrotoxic effects of those CNIs and hence not recover as well or not recover. It has been, although again, small N, but it's very striking to see just how disparate the 12-month outcomes were in those patients between the ones that remained on tegoprubart or the ones that were switched over to CNIs. Yeah. If I may add another thing, I think it's pretty remarkable that here it was a small number of patients, but three out of six rejections, the investigator with the patient decided to stay on tegoprubart to treat the rejection and stay on tegoprubart. You know this is an investigational drug. This is a phase I study. It shows confidence in the drug based on what they see and what they hear. The matter of the fact that this patient who stayed on tegoprubart, as DA mentioned, did much better than the one who switched to tacrolimus. As you know, in a study like this for investigators, the first instinct is to, when you have a rejection, to go to tacrolimus, to go away from the investigational drug. Staying on the investigational drug to treat the rejection, I think, was very important. It gives us a lot of information about how tegoprubart is behaving. I think I hope that the BESTOW study, the allowed phase II study, will prove this point again. Got it. That's really helpful. On the abbreviated iBOX data here, I think the data set here looks really strong. Could you just help put that data set into context and how those data shape your expectations for the BESTOW readout, what you're expecting for tegoprubart versus tacrolimus in that study? Let me turn that over to Steve. Yeah. I mean, this was encouraging data, Tom. It's a great question, by the way. Obviously, iBOX has not been utilized in the context of a clinical trial at this point. This was abbreviated iBOX, not full iBOX, because we're not collecting a mandatory 12-month biopsy in the phase I study. You saw from the historical data and the validation data that iBOX is a very good predictor of long-term five-year graft survival with one-year data. I think we're demonstrating that here. eGFR is the biggest driver of both abbreviated and full iBOX, and our eGFRs, as you saw, are quite good in our study. We're hoping that that will obviously translate over to BESTOW. Co-stimulatory blockade as a whole has tended to have better eGFRs than CNIs. We've seen that in the belatacept, not only clinical studies, but long-term follow-up. Even in clinical use today, bela tends to have better eGFRs than CNIs. Putting all of that together, the mechanism of action of tegoprubart is to block germinal center formation, so we think we'll have a better effect on DSA, which is another major component of both abbreviated and full iBOX. We'd be hoping to replicate this data in BESTOW. We'll see in the fall after we do database lock. Got it. That's super helpful. Just one last question, if I could. I know last week we saw some advancement on the regulatory front for iBOX. It seems like we could get an FDA decision in April of next year. What's your current thinking on the likelihood of acceptance as a surrogate and how are you thinking about potentially incorporating this into a registration program? Thanks so much. Sure. We're hopeful and we believe that this will be approved as an endpoint. Obviously, the TTC is having discussions with the agency directly, and those are completely independent from us. We too are going to approach the FDA, and we'll do so in an independent manner in order to talk about our phase III plans as well as what we'd like to use as an endpoint. What's nice here is the two discussions are going to have overlap so that we may be able to get feedback from the agency about in the same broader timeframe as the TTC, which should allow us to be in a position to launch the phase III as planned later on in the year next year. Thank you. Your next question comes from Pete Stavropoulos from Cantor Fitzgerald. Please go ahead. Yeah. Hi, DA, Steven, Elie. Congratulations on the presentation and data. Nice to see the eGFR and iBOX data. First question I have is, you know, could you just provide a little bit of color on the 10 mg per kg cohort? The last two data points, you know, at days 217 and 259, are sort of hovering close to the historical tac line of about 53 mg for eGFR. You know, I know I understand that it's only two patients, but, you know, did those patients have a higher eGFR at early in time points and decline, or, you know, was the eGFR on the lower end to begin with? I know it's still early data for those receiving 10 mg per kg. From this data through PKPD modeling, you know, data from other programs, you know, where you evaluate the tegoprubart, is there a possibility to go lower, or do you think dose exploration is sufficient at this point? Sure. I'll take a quick step. Thank you, Pete, for your question. I'll turn it over to Steve. In terms of your question, first, I'll start with the second question about the use of 10 mg per kg. That is why we're looking at this lower dose, and we're using our p hase Ib to do some dose exploration to see if it might make sense. Now that we have more data, in the future we may potentially expand to that dose level as well. In terms of how the patients, the distribution, as I think Steve mentioned earlier, and I'll turn the microphone over to him, that's really just based primarily on which patients were enrolled when. We had some patients that were some of the lower performing patients early this time instead of some higher ones last time. This is not because we're seeing a decline in performance over time. Steve, let me turn it over to you. Yeah. I'll try to add color. Pete, great questions on both of those points. As far as the dose of reducing dose to 10 mg per kg, this is typical dose finding as a common thing that we do in drug development, as you know, especially in phase I studies. 10 mg per kg dosing was supported by preclinical data going back to even the original anti-CD40 ligand studies in the 1990s. Based on the data that we have today, we're pretty confident that our 20 mg per kg dose was doing a good job at protecting organs over time, and we've seen that kind of play through. Increasing the dose doesn't make a lot of rational sense, but testing a lower dose certainly did, which is why we went down to 10 mg. I think your next question is, would you go even lower? Based on the preclinical data, I think the answer there is no. There was a very steep decline in graft survival in non-human primates when one went down to 5 mg per kg. Just given the precious nature of organs and whatnot, I think this would probably be the least comfortable dose that we would want to explore at this point. To DA's point, as far as your other question, this is exactly the opposite side of the coin on what we saw last year. Last year, people were excited asking us if we thought the increase in eGFR for a couple of patients way out the end was meaningful, and we guided that no. We thought that that would end up coalescing to the mean. I think we're seeing the opposite side of that coin here. Our first couple of patients at 10 mg per kg really never had great kidney function out of the gate, and they've been kind of flat since. As you get further out, they're really driving reduction in the mean eGFR out past 150 days. All right. Thank you for that color. Another question. For the phase II study, is there a protocol in place, or what is the guidance you provided to the investigators on how to deal with acute rejection? Is it at a specified threshold, meaning a greater rejection that an investigator would pull a patient from the study or switch them to tacrolimus? I'm also trying to understand how decision-making is conducted in Phase II since transplanters or institutes may have their own treatment algorithms. Same question for infections like DCAC. Elie, let me turn that over to you. Rejection in this study and also in BESTOW, the treatment of rejection is based on standard of care of each center. Most of the centers treat rejection the same. The first treatment is a high level of push of IV steroids. If there is no real response as far as creatinine going down, then they make a decision in combination with what the biopsy shows to give one cycle of anti-thymocyte globulin. These two treatments usually resolve, make the cellular rejection resolve, and the patient keeps going. We had a lot of discussion in phase I and in the phase II with investigators to encourage them, and they understand that, as I mentioned before, there is no reason to move patients immediately into the tacrolimus arm or to go away from tegoprubart. Treat the patients, keep the patient on the drug. This is the only way we can learn long-term what's going to happen. That's what we guided the centers in also in BESTOW, and we need to wait and see the result of the BESTOW. There was another question? The second question was around infection and how infection. Okay. In infection, you know, we also work closely with the site. Our recommendation for them in this study and the BESTOW study is whenever you solve uremia, even in a low level, start to decrease the dosing of MPA and respond to that aggressively. If you start with 25% of MPA dose, if the uremia starts to resolve, that's okay. If not, go to 50% and so on and so forth. By this approach, I think we were able to, and that's maybe what we see here, to control the infection and remain in uremia and never translate, except one case in BK, translate to an end-stage organ disease, which is the one that we're really concerned about. I think in BESTOW and in this study, the same guidance. We are going to look at in BESTOW to the changes in dosing of MPA as related to the rejection and other parameters. When we have the data, we can draw some conclusions as far as what we're doing, what we're going to do in the future. This is reducing the rate of MMF or MPA, which is the same thing that's done to treat infections today with tacrolimus. Essentially, this is the same approach that's being used by transplant physicians today. Yeah. I think the most important thing about that question, Pete, is that there's actually detailed instructions in the protocol to guide investigators on how to treat BK. All right. Thanks. Just one last question. I know there was one case of delayed graft function. Could you just talk a little bit about how this compares to tacrolimus and anything about the donor kidney that may have caused this, live versus deceased or the quality of the kidney or cold ischemia time? I mean, the delayed graft function for us is a big win. We've had one case lasted only 72 hours as opposed to delayed graft function that could last, you know, weeks. Typically, you see that in tacrolimus in the 8%- 10% range. Delayed graft function is not only associated with poorer long-term outcomes, it's also associated with increased costs since these patients, until they get their graft function, need to continue to get dialysis. Elie, let me turn it over to you. Delayed graft function is part of the kidney transplantation. Sometimes I'm saying, you know, what do you expect when you clamp the blood vessels at the donor, take this kidney and put it in high ice for 20 hours or 24 hours, then go back and reperfuse it? You expect the kidney to start immediately to work. If it happened, most of the time it happened, it's a miracle, right? The fact that we have from time to time grafts that are not functioning well from the beginning, it's mainly donor fractures, donor issues, or harvesting and preservation issues. Most of the kidneys are, as DA mentioned, you know, you put them on dialysis for one, two, three days, four days, it's resolved, and then the patient going on with some, probably in some more severe cases, effect on long-term survival. We will see delayed graft function from time to time, especially, you know, if you start to use donors that are more high risk. There's a lot of people now using DCDs, cardiac death donors, and this can lead to increased rate of DGF, but this is part of doing kidney transplantation. We are very happy with our rate of delayed graft function to date. This is a big win versus standard of care. All right. Thank you very much for taking our questions, and congrats once again. Thank you. Thank you. Your next question comes from Vamil Divan from Guggenheim Securities. Please go ahead. Hi, guys. This is Edward on for Vamil from Guggenheim. Congrats on the data, the strong eGFR results. I guess maybe two questions for me. Maybe one starting on the safety. It does look like there may be a bit of a dose response on the opportunistic infections in cohort one versus cohort two. I guess what's your perspective on that? Do you think this could be sort of the CD40 ligand mechanism or tegoprubart driven? There's obviously other things like ATG that's changing between the two doses. Kind of your thoughts around that and on the severity of the viremia? If you can share any color on that. I know there was one nephropathy. I don't think the patient lost the kidney, if I remember correctly from the slides. The second question was just on baseline characteristics. Thinking about the phase II, should we expect sort of similar sort of donor versus deceased and HLA mismatch in the phase II study? Are you putting anything in place to ensure sort of balance between the two arms in BESTOW for these baseline characteristics? Thank you. Great. Thanks, Edward. You asked two questions. The first one was about infection rates at the various doses, and the second one was around baseline characteristics. When it comes to infection rate, obviously, one of the reasons why we wanted to look at 10 mg per kg as opposed to 20 mg was to see if that would improve outcomes. That's both from an efficacy as well as from a safety perspective. From a safety perspective, that would include infection rates. The potential to reduce the dose of ATG upfront, as well as to ultimately reduce the dose of tego, might help overall with infections. That said, if you look at the 20 mg arm today, our infection rate is within the range of what you typically see. There are some important things to highlight. One is our infections to date have all been controllable. We spoke about how some immunosuppression may be reduced in order to gain back control over the infections, and that has worked. Also, not all infections are equal. One can have severe infections, one can have sepsis, as an example. Across our patients to date, as an example, we haven't seen any sepsis. You asked about organ graft loss in the phase Ib. We have not had any cases of graft loss. The infections were all able to be controlled. As we look forward to the phase II data, I think we all expect that we're going to see not only infection, we're also going to see graft loss. We may see patient death. Those are normal things that are happening because kidney transplant patients are very, very sick. One would expect, the same way as with standard of care, that they would need to face the full panoply of side effects of adverse events that occur after organ transplantation. What's going to be important, of course, is to compare how patients are doing on tegoprubart to how patients are doing on standard of care. In terms of the baseline characteristics, the biggest likely change between the two is going to be around the percentage of deceased donors versus living donors. In our phase Ib, it's not surprising that we had more living donors. That was just primarily due to how easy it is for a handful of sites to recruit patients. It's much easier to recruit a living donor where that patient can be consented in the office than to recruit a deceased donor where that organ might come in in the middle of the night and one has to talk to the patient about consent before the surgery, at the same time as they're being prepped for an organ that they might have been waiting years for. In the phase II study, we were asked by the FDA, and so it's what we've done. The early subjects all received deceased donor kidneys. The FDA asked us to first enroll deceased donors, and after we demonstrated safety and efficacy with those deceased donors, we were able to get the green light to begin to enroll living donors. The reason for that was the FDA's perspective that a living donor kidney could impact, if something were to go wrong, two individuals, both the recipients as well as the donors. That said, if we go back and look at the baseline characteristics of our phase Ib, while we have more living donors, these are not, they don't appear to be close family members. As you saw, these are tough kidneys. These are the three most common criteria that we look at to see how hard or how risky a kidney transplant will be: deceased donor age, the donor age, recipient age, and of course, HLA mismatch. Here, on average, our patients are slightly older, get kidneys from patients that are slightly older, and have an HLA mismatch that is above what you typically see. Typically, HLA mismatches are about four, while most of our subjects in the phase Ib are at either five or six, so a perfect mismatch. Importantly, we've excluded perfect matches, so we have none of those. Great. Thank you. Thank you. Your next question comes from Rami Katkhuda from LifeSci. Please go ahead. Hey, guys. Congrats on the update and thanks for taking my questions as well. I know you touched upon this briefly, but can you kind of remind us on the rates of acute rejections and opportunistic infections that are commonly seen with tacrolimus on a quantitative basis and how the tegoprubart data ultimately compares? Secondly, have you had the chance to look more so on a patient-by-patient basis to see if there's any key characteristics that drive better tegoprubart response at the end of the day? Thank you. The first question I think you asked was around, you know, what typically is seen in tacrolimus. Normally, in the first year today, tacrolimus sees rates of rejection of about 10%. From our perspective, you know, rejection today can be treated. The big question is, what's the impact of that rejection? Does that rejection lead to a negative impact on the kidney or not? As you saw, the rejections that we saw in subjects that continued on tego, there doesn't appear to be a negative impact of those rejections. I'm not saying it was a good thing that they occurred, but the eGFRs are so high, right, about 40% higher than what one might expect to see on tacrolimus on average, that it shows that those patients were able to come back. We have one of our, there was a physician that gave us that had an interesting statement about he doesn't lose patients to rejection. What he loses is patients to our tacrolimus side effects, including the vascular effects, which lead to heart attacks and strokes. Did you have a second part to the question, Rami? Yeah. Just around opportunistic infections as well, what does that rate look like for tac historically? It goes up to about 30%. Very similar. Got it. The second question was about any key characteristics that seem to influence a better tegoprubart response, and if you guys have looked at a patient-by-patient basis perspective. Steve, Elie. No. At this point in time, first of all, it's a small data set at this point. It's hard to tease out what might be a patient characteristic or, if you want to use a fancy word, reidentify a biomarker that could help identify patients that might respond to tegoprubart. This data set is pretty small, so nothing blatantly comes out of that. As we lock down the database and collect the study data, those will be things that we'll be looking at. Got it. Thank you, guys. Thank you. Thank you. Your next question comes from Yi Chen from H.C. Wainwright. Please go ahead. Hi. Thank you for taking my question. Between cohort one and cohort two, the dose of ATG is different. How do we know the observed differences in efficacy or safety solely come from the different dose of tego? It's a great question. If you recall, the way that the cohort one ATG was guided was doses up to 6 mg. We saw a complete range from 3 mg- 6mg, including doses around 4.5 mg. We just felt as we reduced the dose of tego and with the data that we had in hand from the first cohort, that we'd be optimistic to say a 4.5 mg dose would kind of thread that needle, if you will, between infections and rejection. That's why we guided towards a mandatory dose of 4.5 mg. In cohort one. Those patients are doing well. We're seeing patients that are at half the dose of tegoprubart and, as you saw, have kidneys that are protected. Even with the lower dose of tego as well as the lower dose of ATG versus the initial patients that we had in cohort one. Okay. How did the doctor determine which, after a patient's experiencing rejection, how did the doctor determine which patient remained on tegoprubart, which patient switched to tacrolimus? There is no specific criteria to make this decision. As I said, the first instinct in a study like that is the investigator and the patient get a little bit, you know, concerned, and they want to go to something that they know and they have confidence in. It's a question of education, of getting experience. As we move forward, we see that physicians get more confident in tegoprubart, understand the patient can be treated on tegoprubart for rejection, respond very well to the treatment, and can continue. It's a question of clinical judgment and of decision-making and how comfortable the physician and the patient are with continuing. We've seen that. If you go back to where we were a year ago, the first subject that had a rejection, as well as the first subject that had an infection, those subjects, the physicians elected to withdraw them from the study. As you can see now, subsequently, people got more experience, got comfortable with the drug, and so elected to keep their patients off drug. Okay. Ultimately, this is really the PI's call. PIs can choose. It's completely their call as to how they want to treat their patients. Does the data on slide 12 suggest that patients are better off having at least one rejection and then stay on tegoprubart? No, I don't think you can. There was actually a discussion at the WTC on exactly that point. There is a hypothesis one sees something similar with belatacept, and there are some hypotheses out there that suggest that these early rejections that can be controlled might help patients in the long term. That saud, I think today the end is obviously small and it's early days for us. What's good is that, you know, we have now demonstrated that rejections can be controlled and that patients have a chance of doing very well post-rejection. Okay, thank you. Thank you. Thank you. Your next question comes from Robert LeBoyer from Noble Capital Markets. Please go ahead. Congratulations on the data. I had a question for you on the abbreviated iBOX score, and you mentioned the 4.11 score as 96% predictive of five-year outcome and graft survival versus 2.98%, a score of - 2.98 for the CNIs. Is there a predictive value for the CNIs at five years that would be used for comparison? The CNI comparison is the average five-year survival for CNIs today, which is, I believe, in the 80%, somewhere in there. All right. Is there any way? That 96% is actually the lower, is associated with the 3.7 number, the - 3.7 number. The - 4.1 number would be higher than that. Okay. Is there any way to project the abbreviated iBOX score at five years to longer terms, say 10 years or 12 years? Let me turn that over to Steven, Robert. Yeah, the original publications actually did guide that the one-year data from both abbreviated and full iBOX was predictive at three, five, seven years. I don't believe they went out beyond that. To my knowledge, I don't think they went out to 10. I think the furthest the algorithm went out to during validation was seven. Okay, great. Thank you very much. Thank you. Your next question comes from Julian Harrison from BTIG. Please go ahead. Hi, thank you for taking my questions and congrats on this comprehensive update. It was nice to see the favorable comparisons to calcineurin inhibitors on the abbreviated iBOX score. I'm wondering if you're able to share the median and range of iBOX changes for tegoprubart in this study. I'm also curious if the iBOX results had any significant interactions, either from dose of anti-thymocyte globulin received or number of HLA mismatches. Thank you. Thank you for that question. Let me turn that over to Steve. Yeah, we haven't looked at the individual patient iBOX scores at this point for the parameters that you're discussing. I go back to this as really exciting preliminary iBOX data, but with a really small N. I don't think you'd be able to even tease out anything that would really correlate at this point in time. We really need to get to data lockdown and look at our BESTOW data in that regard. Thank you. Thank you. Your next question comes from Albert Lowe from Craig-Hallum, please go ahead. Hi, thanks for taking my question. Maybe for the first one, I was wondering about the cases of hypertension and actually more particularly hyperglycemia. Can you just give us a little more color on some of these AEs that were recorded? On the phase I? Thank you. I mean, we're not. One of the things that you see in tacrolimus is a delta both in terms of hyperglycemia and post-transplant new-onset diabetes, as well as an increase in hypertension. Here, when it comes to hypertension, we've had as much hypo as hypertension. We're not seeing increases in hypertension. We have had some cases of hyperglycemia, but we have had no cases of post-transplant new-onset diabetes. Our patients, remember, our patients are also on steroids. Seeing some hyperglycemia is not unexpected. We're not seeing the levels of hyperglycemia and, of course, the post-transplant diabetes that you typically see with calcineurin inhibitors. Okay. All right. Got it. I just wanted to, I know you kind of described this, but just maybe to clarify, for the doses of ATG that were used, were these, was it just a protocol that determined that, or were there any other, I guess, patient-specific determinants? Can you also, I guess, clarify or maybe break out where all the cohorts that these rejection episodes occurred in? All of the rejection episodes were in the first cohort. The dose of ATG that the physicians can use is up to them. They choose the dose they want to use. What stuck out here, as Eliezer mentioned, was that these were quite high HLA mismatch patients. They go low to very low. Anything less than a three is considered a very low dose of ATG, and we had two subjects there. It is a bit surprising, but all of that is in the physician's discretion. What was nice and important, of course, was that once the rejection was detected, the patients on tegoprubart could be treated right away, and those kidneys bounced back and continued to perform where they were as if there hadn't been a rejection. Okay. You said BESTOW would be using 4.5 mg/kg of anti-thymocyte globulin. I guess that's similarly, it's not a fixed dose. It's up to the physician, it would be up to that dose. Is that correct? It's the suggested dose, but ultimately, physicians have. It's up to the physicians. Okay. I see. All right. Thank you for taking my question. Thank you. Your next question comes Yuan Zhi from B. Riley. Please go ahead. Thank you for taking my questions. Just one, can you maybe phrase this question differently? Can you clarify the median ATG used during induction in cohort one and cohort two? Thank you. Cohort two is easy because everybody's getting 4.5 mg. I don't believe, I don't have the calculation in front of me, but it would be the mean of the six that are on the slide. That should be pretty easy to calculate. 4.5 mg, yeah. 4.5 mg on two, but in cohort one, you just have to count. Oh, no, those would be the ones with the rejection. I don't believe. Do you know what the mean? No. We don't have it in front of us. We'll get back to you. We can get that for you. Thank you. Thank you. There are no further questions at this time. I will now turn the call over to Dr. David-Alexandre Gros for closing remarks. Please go ahead. Thank you very much for joining us today. As I opened up the call by saying, we continue to be very happy and excited by how tegoprubart continues to perform. We now look forward to completing BESTOW and to reporting out that data, hopefully, later this year. Wishing everyone a great evening. Bye. Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.