Good afternoon, ladies and gentlemen, and welcome to the Eledon Pharmaceuticals Data Presentation conference call. At this time, all lines are in 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 Thursday, November 2, 2023. I would now like to turn the conference over to Paul Little. Please go ahead. Good afternoon, everyone, and thank you for joining Eledon's Phase 1b Data Update conference call. I'm joined on today's call by David-Alexandre Gros, Chief Executive Officer, Steve Perrin, our President and Chief Scientific Officer, and an outside guest, Dr. Jean Tchervenkov in kidney transplantation and one of the principal investigators in our Phase 1b trial. Earlier today, Eledon issued a press release detailing the updated results we presented at Kidney Week from our ongoing Phase 1b trial in kidney transplantation. You may access the release 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 remote 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 Eledon's CEO, Dr. David-Alexandre C. Gros. DA. Thank you, Paul, and thank you all for joining us today. I'm happy to be joined on this call by our President, CSO, Dr. Steve Perrin, as well by Dr. Jean Tchervenkov. Dr. Tchervenkov is a professor in the Department of Surgery in the Faculty of Medicine and Health Sciences in McGill University, and he is a renowned surgeon and expert in transplant surgery, as well as, like Paul just mentioned, one of the principal investigators in our ongoing Phase 1b trial. In terms of agenda for the call, I'll start by talking about Eledon's history in kidney transplantation and the current transplant market, after which I will turn over the discussion to Steve to review tegoprubart's biology before turning to Dr. Tchervenkov to talk about tacrolimus, calcineurin inhibitors, and the unmet need for newer immunosuppressive medicines in transplant. We will then return the call to Steve to discuss the data we presented today before ending the call with Q&A. The data we presented is particularly exciting in light of why we originally formed what is now Eledon in September 2020. At that time, while explaining the strategy for the new company, I said that our strategy would be to focus on areas where tegoprubart may provide a potentially life-saving treatment option, and that we would start with kidney transplant in particular, for five reasons. One, there is an important and immediate need to replace tacrolimus as the immunosuppressive backbone in transplant medicine. There are about 90,000 Americans on the kidney transplant waiting list, and while approximately 25,000 Americans undergo kidney transplant per year, another 5,000 die while waiting for a kidney. The average age of a transplant patient is only 50 years old, but the average functional life of a kidney is often only 10-12 years. So individuals will require return to dialysis, where the average five-year survival remains less than 50%, or if they are fortunate, they may receive one or more other transplants in order to live a regular lifespan, although that uses up kidneys that could otherwise go to first-time patients. The second reason was that a key reason for the shorter than desired life of transplanted kidneys is the current standard of care, tacrolimus, which is both directly toxic to the kidneys as well as indirectly toxic, since over time, it can cause both diabetes and hypertension, which are ironically, the two leading causes why Americans need a kidney transplant in the first place. Three, some of the best transplant data across preclinical models of transplantation has been seen using an anti-CD40 ligand. This is true in both allotransplantation, where the same species is used, as well as xenotransplantation, where an organ from one species is transplanted into another. Four, there is a clear regulatory path in transplantation with potential upside. Five, the potential market is large dollar-wise, but from a population perspective, it is compact in that it's more like a rare disease since there are relatively few patients concentrated across a limited number of transplant surgery centers.... As such, transplantation was an indication where a smaller biotech can execute and compete. Now, three years later, the rationale behind our strategy has been reinforced by both the market potential as well as our achievements to date. In terms of the market, the need for better transplant immunosuppression and the scale of the commercial opportunity continues, since the number of kidney transplants being performed is growing, as is the number of patients with end-stage renal disease that may ultimately need a transplant. To get a sense of the potential from a dollar perspective, one may look at Astellas, the company that originated tacrolimus. Tacrolimus was approved in 1994, and yet Astellas reported approximately $1.5 billion in revenues in their fiscal year 2022 from that now generic drug. Next, we published data evaluating tegoprubart in non-human primate models of both kidney and islet cell transplantation, and we published a meta-analysis demonstrating the advantages of using an anti-CD40 ligand in kidney transplantation. We have reported safety data from over 100 subjects on tegoprubart, with multiple subjects on treatment for over a year, including a patient with kidney transplant in our Phase 1b, who was out 380 days at the time of the data cut. We even have experience using tegoprubart in cardiac xenotransplantation, which is probably one of the toughest use cases. And finally, we are executing and have two clinical trials in kidney transplantation running in parallel, together with an open label extension study. These two trials include the single-arm Phase 1b, which we're discussing, and a Phase 2 study with a control arm, where we are evaluating the superiority of tegoprubart versus standard of care in terms of kidney function at 12 months, as measured by the estimated glomerular filtration rate, or eGFR. Today, we reported updated data from our ongoing Phase 1b trial evaluating tegoprubart for the prevention of rejection in patients undergoing kidney transplantation at the American Society of Nephrology Kidney Week in Philadelphia. These data are very encouraging in that they demonstrate that tegoprubart's safety in this indication was in line with or better than what would typically be seen with the standard of care, and that from the perspective of efficacy, measured in terms of kidney function, the eGFR outcomes that we saw were arguably unprecedented in a clinical trial. With that, let me turn over the call to Steve to walk through tegoprubart's mechanism of action and why we believe the MOA of an anti-CD40 ligand will be beneficial specifically in organ transplantation. Steve? Thank you, DA. The slide shown here shows a schematic or a cartoon, if you will, of CD40 ligand and its receptor, CD40. These are not new targets. These receptors were discovered and characterized initially back in the eighties as being cell surface receptors on immune cells. Initially, CD40 ligand was characterized as being expressed on activated T cells, and its receptor was being expressed on cells of the monocyte lineage, including B cells and other types of antigen-presenting cells. It became apparent biologically that the activation of this receptor pair occurs right downstream of foreign antigen presentation between MHC self surface receptors on antigen-presenting cells and the T cell receptor on T cells. When that activation of CD40 ligand CD40 occurs, it results in a potent inflammatory response with proliferation of both T cells and B cells that then can recognize those foreign antigens to fight infection. As antibodies that block the murine version of these receptors became available, it became apparent that if you block the activation of CD40 and CD40 ligand, it had profound effects on the ability to decrease multiple different types of autoimmune disease in rodents, including T-cell-mediated diseases like rheumatoid arthritis and multiple sclerosis, as well as more autoantibody-mediated autoimmune diseases like lupus nephritis and Sjögren's syndrome. In addition, in the murine models, we got the first hints that blocking this receptor pair was quite potent at preventing transplant rejection. Subsequently, as primatized antibodies were developed, antibodies that could be used in non-human primates, it became very apparent that blocking CD40, CD40 ligand access was the, probably the most potent way to prevent transplant rejection, and that statement holds true to today. The other thing that became apparent over that period of time is that blocking CD40 ligand appears to be more potent in those species compared to blocking the receptor. And that's because these are different targets with very different biologies. And we think that there's three major reasons why blocking the ligand has been more potent than blocking the receptor. The first is that the ligand that's expressed on activated T cells is only there for a short period of time after antigen presentation.... And then there's negative feedback loops that gets it off the cell surface to prevent the overactivation of immune responses. Contrastingly, CD40 receptor is constitutively on the cell surface. It's always on the surface of the cells in the monocyte lineage, and therefore, when you think about receptor occupancy and biodistribution of antibodies to these targets, there's going to be differences between trying to block the ligand versus blocking the receptor. The second component is that when you think about CD40 ligand activation, it actually activates costimulatory signaling on B cells and antigen-presenting cells, not only via interactions with CD40, but it binds to multiple other receptors on antigen-presenting cells that activates their functions, including, as an example, CD11 and the MAC complex, to inhibit the activation of CD8 positive cytotoxic T cells. So when you block the ligand, you're actually blocking multiple different costimulatory pathways. And then third and finally, probably the most intriguing that makes blocking CD40 ligand very unique is that when you block CD40 ligand on T cells, not only does it block their proliferation and expansion of cytotoxic CD4 positive cells, but it actually converts CD4 positive T cells into regulatory T cells, which creates a tolerogenic environment. And this is really what's important in the context of preventing transplant rejection. So that's a brief summary of why we have focused on the ligand therapeutically with tegoprubart and the history of why blocking the ligand has been more potent than blocking the receptor. Great. Thank you, Steve. Dr. Tchervenkov, I would now like to turn over the call to you, with a few questions, please. The first is, since this is, our first time, hosting you on an investor call, would you please introduce yourself, including your background and your practice? Thank you. Yes. So I'm a transplant surgeon, and I've been a transplant surgeon at McGill for 33 years. So I have the benefit of having seen the introduction of calcineurin inhibitors in my lifetime as a resident, when cyclosporine became the standard of care in transplantation back in 1983. And then I was a fellow in Cincinnati when tacrolimus became the standard of care in the late 1980s and was actually introduced in 1992 as I began my career at McGill. And I set up the liver transplant program here at McGill. And now, 33 years later, I've been waiting to replace the calcineurin inhibitors because we grew to love them and hate them at the same time because they were great the first year. They reduced rejection rates tremendously. I lived through the years when just about everybody had a rejection in the first six months to now not having that many people having rejection, but they invariably all get calcineurin toxicity. And then we see these patients return to dialysis a decade later. And once they return to dialysis, they often get reduced immunosuppression, because once they're on dialysis they don't need these medications, and they invariably develop antibodies, and they become extremely difficult to retransplant. And even though 30%+ of patients on dialysis are what we call sensitized, only 5% of these 30% eventually get retransplanted. So this is a devastating thing that we need to eliminate. Sure. Thank you. Maybe we could dive a little bit more into what you just spoke about. Perhaps, would you mind talking a little bit more about the origin and the evolution of the use of calcineurin inhibitors, including- Right. - which one is, is being primarily used today? So, you're quite correct. Calcineurin inhibitors started in the late 1970s. We didn't really know the mechanism, but we knew they were preventing rejection. So the first one was cyclosporine, and the next one was tacrolimus. So today we use tacrolimus because it's much more effective. Eventually, it turned out to be more effective at preventing rejection. So that's the one we use today. And there've been tweaks on it. There've been, like, twice a day down to once a day sort of formulations. But that's the main tacrolimus is the main calcineurin inhibitor. And they invariably prevent rejection by inhibiting T-cell activation, but it's not precise enough, and they have unwanted side effects, particularly kidney injury. I just transplanted a patient who was a liver recipient, and within two to three years of being on tacrolimus, his kidneys failed, and now he needs a kidney transplant. So that's a common, common occurrence, not just in transplantation of the kidney, but also in other organs where the kidneys fail due to tacrolimus. ... Are there any other areas of unmet need with regards to calcineurin inhibitors in terms of side effects that are seen from? Oh, yeah. Oh, yeah. For example, calcineurin inhibitors, particularly tacrolimus, are associated with a higher rate of type two diabetes. Type two diabetes is extremely problematic. Itself, it induces kidney injury and kidney inflammation, not to mention all the other side effects to the heart, to the vasculature, to the eyes, to the retina. And we often see the need for insulin and other drugs related to diabetes go up. High blood pressure is a little bit more difficult to control, so we need to increase the blood pressure medications as well on calcineurin inhibitors. Tremors, people always report to me, "Doc, I can't stop shaking." And sometimes GI side effects like increased diarrhea. Maybe I'm forgetting a few, but these are some of the main ones that we have to, you know, we have to deal with. So, if we could avoid them, you know, this would be tremendous, tremendous anyways. Yeah. Sure. You brought up your patients. Are patients overall happy to be on, on tacrolimus or? Well- How would a patient view it? Yeah. They're happy to have a kidney, and not be on dialysis. That's a fact. But in general, they report more headaches, they report more tremors. They often have, associated with the other medications, more diarrhea. So they don't see the creatinines, et cetera, but they're always worried when they're going up, the creatinines, and sometimes we need to do a biopsy, and that's another side effect of the drugs. So we need to do repeated biopsies 'cause we're not sure if the creatinine increase is due to toxicity or rejection or what. So we have these, you know, unmet needs right now that we would like to see calcineurins replaced, if possible. Maybe a last question, which is: How important is following kidney function for you, in patients after transplant? Well, the first year, it's quite frequent. We bring the patients quite frequently. And so, the one thing I gotta say, and I have quite a bit of knowledge in that area and we've published, is that you're quite correct. The creatinine or the renal function in the first 90 days and particularly in the first year really predicts the long-term outcome. We have some published data that if you have an excellent creatinine in the first 90 days, you keep that kidney for two decades, as opposed to somebody with reduced renal function. And there's older data from the early 2000s that if you have an excellent creatinine in the first year, your attrition curve down afterwards is much reduced. Having a good creatinine and a good renal function in the first year, the first few months, is crucial. Great. Thank you. Before turning over the call back to Steve, maybe I'll build on what you just said, and I'll spend a minute just talking about eGFR and kidney function, since that is one of our endpoints and one of our primary endpoints in the Phase 2. So, the estimated glomerular filtration rate, or eGFR, it measures the filtration of the kidney, in other words, how well the kidney is doing its job, how well it's functioning. And it is, as a result, the most common measure of kidney graft function. A normal eGFR is considered above 80, with kidney disease being considered at less than 60. Typically, end-stage renal disease is an eGFR of less than 15, and those are the groups of patients that will require dialysis or transplants, in order to have sufficient kidney function to live. From large retrospective studies conducted in transplant recipients taking calcineurin inhibitors, such as the data we're looking at on this slide, and this has been seen in prior clinical trials as well, we see that a median or an average 50th percentile eGFR generally falls around 50 or the low 50s during the first year post-transplant. As Dr. Tchervenkov just mentioned, a 12-month eGFR has been shown to be the most significant single predictive factor or with regards to future graft failure. And as eGFR values decrease, the risk of graft failure and actually of hospitalizations as well increases. One sees that on this slide, whereas the eGFR of transplanted patients decrease, there is an exponential increase in the risk of that transplanted kidney failing. Steve, I will now turn the call over to you to talk about our two studies, and the data that we presented today. Sure. Thank you, DA. So as DA mentioned previously, we have multiple kidney transplant programs running in parallel. We have a Phase 1b study that has been enrolling in Canada, the UK, and Australia. We announced our first patient enrolled last summer. This is a study that's going to enroll up to 12 participants undergoing de novo kidney transplant. It's a 52-week endpoint, open-label study, single arm. It has ATG for induction therapy, and plus for maintenance therapy, it has steroids, including a steroid taper, as well as MMF. And what we're doing in this study is we're replacing the CNIs that Dr. Tchervenkov and DA have spoken about, either tacrolimus or cyclosporine. We're replacing that with tegoprubart for maintenance therapy. So after induction therapy, patients will have steroids, tegoprubart, and MMF. The primary endpoint of the Phase 1 study is safety and tolerability, with secondary endpoints of graft function as measured by eGFR, as well as other typical endpoints, including participant and graft survival, biopsy, acute rejection, and other biomarkers of kidney injury and risk of rejection. The Phase 2 study, which we call the BESTOW study, is a 52-week head-to-head superiority study comparing tegoprubart to tacrolimus. It's 120 participants. It's going to be randomized one to one, so 60 per arm. That study will be enrolling in the U.S., in North America, as well as other countries in Europe, as well. Again, it's a 52-week study with ATG induction therapy, and then for maintenance therapy, will include steroids down to a steroid taper, as well as MMF. And then you're either randomized to the tacrolimus arm or the tegoprubart arm. The big difference here in the endpoints between the Phase 1b and the Phase 2 study is that the primary endpoint of the Phase 2 BESTOW study is actually graft function, eGFR. So this is a superiority study where we're going to compare kidney function at 52 weeks between the two arms. In addition to graft function, the other primary endpoint is safety and tolerability. And then we're also collecting data on the other endpoints that one would look forward to in subsequent clinical trials, including participant and graft survival, biopsy-proven acute rejection, biomarkers such as immune infiltrating to the graft, and then other types of side effects that's commonly seen, which we've discussed on the call, related to CNIs, including the incidence of new onset of diabetes, tremors, and other markers. In addition to these two studies, when a participant reaches 12 months, the 52-week endpoint in these two studies, they have the opportunity to roll over to a long-term extension study, a long phase, a long-term phase two study that they could roll over to after completing the 52-week endpoint. DA, can I have the next slide? So this is data from the Phase 1b study. We've enrolled, as you can see, 11 of the 12 patients in that cohort. You can see in the second column that the age and genders of the demographics of this cohort are pretty randomized between males and females. The average age is fairly typical for transplant, as you can see. We're enrolling both living and deceased donors in this study, and you can see the underlying cause of disease that has resulted in people's kidney failure is pretty diverse, and it's been discussed on the call to this point. The fourth column, the second to last column over, is the days post-transplant. So you can see we do have patients out past a year, as DA mentioned previously on the call. We have had two participants discontinue the study. The first participant discontinued at around 217 days. They were fairly far out on the study, as you can see. They had been unhappy with several side effects that's fairly common in transplant, including fatigue and alopecia. And although that's fairly common for all types of immunosuppressant protocols for standard of care to prevent transplant rejection, this participant decided to roll over onto tacrolimus' current standard of care. The other participant that discontinued the study was patient number three. They had a very early BK viremia in the study around day 28. The titers were fairly high, and the standard of care to reduce those titers is to reduce immunosuppression, which the investigator did by reducing MMF, and those titers fell very quickly. But when it came time for the next infusion of tegoprubart, because we're still very early on in the study, the investigator felt much more comfortable switching the patient over to TAC because they were more accustomed to understanding how to utilize TAC to manage BK viremia. So they rolled that person on day 54 over to the TAC. As you can see, the rest of the participants are still in the study, and we can talk some more about it in subsequent slides. So the next slide is showing the overall treatment emergent adverse events in the study. They're ordered by percentage of appearance. You can see most of the side effects thus far or emerging events have been GI related. They've been very low as far as their grades go, with, you know, very transient diarrhea as an example, that resolves itself very quickly. Obviously, we've talked a little bit on the call, but very commonly, drugs like MMF, one of their major side effects are GI effects, so this is not uncommon. The other one that has appeared that I've already mentioned is BK viremia. We've had three other participants in the study, besides that one, that stopped the study, show up with BK viremia. In those three patients, the titers were much lower. Investigators started treating and reducing immunosuppression with MMF much more quickly, and those titers have decreased, and those patients have been managed quite well, and they continue to be in the study. We did have one participant experience T-cell-mediated rejection with a Banff score 1A. The patient has been treated and still remains in the study and on tegoprubart. We had one patient that experienced a surgically related acute tubular necrosis on day zero. This was prior to administration of our study drug, which hasn't impacted kidney function, but the patient continues to be in the study and is still on tegoprubart. Importantly, there's been none of the side effects that we've talked about on the call that's typically associated with CNI exposures, including no cases of hypoglycemia, no new-onset diabetes, no appearance of tremor, and very importantly, no incidents of CMV infections to this point. DA, can I have the next slide? So this is a summary of the mean eGFR values for these 11 participants that have been in the study so far. The number of participants at any given time is on the bottom, as you can see, next to the N. You can see, much like other studies, and even standard of care in the first 30 days, eGFR climbs very, very quickly post-transplant. We're at an eGFR of 60 by day 30. That has continued to climb out to day 90, where the mean eGFR is around 70 and continues to be 70 or greater thereafter for this population. As already been mentioned on the call, if you were to visualize what a typical CNI tacrolimus population would look like, DA showed it a couple of slides ago. Although kidney function increases quite quickly in the first 30 days, it tends to plateau much sooner than what you see here with the mean eGFRs for tacrolimus for tegoprubart. The mean eGFRs for TAC tend to stop in the low 50s, so we're seeing about a 20-point delta between the eGFRs that we're seeing in our study of tegoprubart compared to what patient populations would typically see on TAC. One person has reached 12 months, as I showed you in the demographics table, and has rolled over to the long-term extension study. And at day 374, that patient's eGFR was a 91, which is incredibly healthy. Actually, most healthy adults have eGFR somewhere in the high 80s or 90s. So a quite exciting result to have somebody roll over into the long-term extension with that high of an eGFR. So in conclusion, so far in the study, in the Phase 1b study, 11 participants have shown that tegoprubart can successfully prevent kidney transplant rejection. And so far, tegoprubart, much like we've seen in other patient populations, has been safe and well tolerated. The aggregated mean eGFR is above 70 at time points after day 90, showing that tegoprubart potentially can better protect organ function compared to CNIs and compared to what's used in current standard of care. And we'll continue to report upcoming data from the Phase 1b study at scientific conferences in 2024. Thank you, DA. Thank you, Steve. To conclude, preliminary data from our Phase 1b trial indicate that tegoprubart was safe and well-tolerated, with the potential to provide superior graft function compared to the current standard of care. We are highly encouraged by these results, which reflect our continued conviction and commitment to the transplant community as we seek to provide a new treatment alternative to standard of care that has barely changed in almost three decades. At the beginning of this year, we increased our focus as a company on kidney transplantation. Since then, we've reported safety and efficacy results from 11 participants now in our ongoing Phase 1b trial, and we initiated an open-label extension study to generate key long-term insights. We also initiated our Phase 2 BESTOW trial this summer and are making good progress in site activation and enrollment as we seek to further differentiate tegoprubart from the standard of care tacrolimus. tegoprubart was also used to prevent rejection in a patient who received a cardiac xenograft. Finally, we have multiple transplant preclinical studies underway in non-human primates, including kidney and cardiac xeno, as well as liver allograft. In conclusion, Eledon continues to build momentum and to deliver in the transplant space with the goal of bringing tegoprubart to transplant patients in pursuit of our mission of One Transplant for Life. With that, I will now ask the operator to begin our Q&A session, please. Operator? Thank you. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press star followed by one on your touch-tone phone. You will hear a three-tone prompt acknowledging your request, and your questions will be pulled in the order they are received. Should you wish to decline from the polling process, please press star followed by two. If you are using a speakerphone, please lift the handset before pressing any keys. Your first question comes from Pete Stavropoulos with Cantor Fitzgerald. Please go ahead. Hi, DA and team. Congratulations on the data at ASN. Nice to see the data maturing and observing tegoprubart's activity, you know, in kidney transplant. And thank you for taking my questions. So, first one I have is, you know, one subject completed one year of treatment. You know, can you provide some detail, you know, as to their eGFR measurement, you know, right after transplant, you know, through the one-year marker, sort of how it evolved? And for Dr. Tchervenkov, I hope I pronounced that right, you know, if I'm reading the slides right, the patient out past the year received a kidney from a deceased donor. Are there differences in terms of mean eGFR post-transplant, you know, from a deceased donor versus a live donor? How does this patient's eGFR performance, you know, sort of shape your perspective on tegoprubart's potential efficacy? Thank you for the question, Pete. So maybe I'll turn your first question around, how that first transplant patient performed to Steve. Steve, do you recall what the initial or the original eGFRs were for that person? So I don't know it off the top of my head. However, I can tell you that all of these patients had very low eGFRs prior to transplant, you know, teens, twenties, for the most part. I don't know what this person had off the top of my head. Yeah. I recall our first three participants, of which this is one, had a mean eGFR at 10 at the time of transplant. So it was ±10. Okay. And we reported in March, when we reported on those three patients, I believe that this patient was in the high 70s, maybe low 80s, in that range. So the patient has continued to do well, and right now, at a 91 eGFR at a year, as Steve mentioned, has continued to show a little bit of improvement since that time. And maybe Dr. Tchervenkov, I'll turn over the question to you, in terms of what this 91 eGFR means from your perspective, and is that perspective different, considering that this is a deceased donor as opposed to a living donor? Well, thank you. This eGFR in one year is exceptional. It's not just great; it's exceptional. We don't see deceased donors perform that well. Living donors, yes, because they almost all have immediate graft function, and we prefer living donors because of that. Their half-lives, which is a measure of how long the kidneys are, will last, is very good, and it approaches 18 or so years. Deceased donors, on the other hand, in some databases, is only eight to nine years. In our own database, it's around 12 years, but it's definitely lower than living donors. So you had a question about that particular patient. And so that particular patient, the second patient that's at one year, it's my patient, had basically within a month creatinine clearance, as you said, Steve, around 75, 80, but that continued to improve, and currently it's 91. And I've never seen a creatinine clearance for that particular patient age, with one kidney being superior to what she could expect had she had her own two kidneys in good health. At 77, most... The average creatinine clearance is around 70, 75, certainly not 91. So this is really, for a transplant surgeon, wow, it's amazing. Great. Thank you, Dr. Tchervenkov. Yeah, thank you for that. You know, very helpful. Another question that I have, you know, if you can just provide a little bit of color around the one case of T-cell-mediated rejection. You know, how was it treated, and is that patient still on tegoprubart? Sure. Steve? So we really haven't gone into individual patient details on treatment. It was, the patient was treated with current standard of care for T-cell-mediated rejection, and yes, they do continue to be in the study. Okay. And if I can, one last question. You know, the BESTOW study, you know, you're gonna be evaluating if there's a difference between the rate of new-onset diabetes, you know, after transplant, in the Tego arm versus CNI arm. So for, again, for Dr. Tchervenkov, you know, can you just help me understand why there may be a difference in the new-onset diabetes, you know, after transplant, in the Tego versus CNI arm? You know, what's the mechanism that drives that new-onset diabetes? ... Well, we're not sure. But the tacrolimus induces new onset diabetes, several papers in the literature, and it's in the order of about 20%-30%. And it's often associated with obesity. And what it does to obesity, our patients on tacrolimus tend to gain weight. Is that the mechanism? Is it some inflammation? Diabetes is an inflammatory disease, and maybe tacrolimus' mode of action, which targets type one immunity, but is not very good about type three immunity, which Tego is much better at. Maybe that is potentially the effect it may have. I don't want to speculate too much, but this is something that's well recognized in our transplant community, that that tacrolimus is associated with an increased de novo type two diabetes. And type two diabetes is a major indication for kidney disease and kidney transplantation. These are one of the most common group of patients in North America and around the world that require kidney replacement. All right. Thank you very much. Thank you. Thanks for taking my questions. Thanks, Pete. Your next question comes from Thomas Smith with Leerink Partners. Please go ahead. Hey, guys. Good afternoon. Thanks for taking the questions, and let me add my congrats on the updated data. Just one question for Dr. Tchervenkov, and thank you, Doc, for sharing your perspective and your experiences here in the field. I was just wondering if I could ask you to comment at a high level on your perspective on the totality of the initial data set here for tegoprubart, and how the experience of the first 11 patients compares versus, you know, your expectations and versus your experience with CNIs historically. , I don't know about the other seven patients, but the ones we have taken on here at my institution- I think, so just to be clear, Dr. Tchervenkov, so this is all based on the data we presented today. I see. Okay. So we haven't expressed individual patients, right? Yeah. All right. So we're not going to go into details of individual patients, but my impression looking at the data is that this is really a very, very outstanding data for the initial introduction of this new novel clinical anti-rejection maintenance immunosuppression. And it's better than what I have seen in my last 30 years experience in terms of creatinine, in terms of kidney function, and the risk of rejection is at par, if not better, than what I would expect with calcineurin inhibitors. Thank you. Got it. That's, that's helpful. And if I could just ask a follow-up question for the company here. I was wondering if you could just elaborate, maybe provide some additional details on where you are with the BESTOW study with respect to site activation, and if you could maybe comment on how the early enrollment's going relative to your expectations. Sure. Thank you. Thanks, Tom. So we're not providing a direct update in terms of number of sites activated or patients enrolled at this time. We are, as you know, we're looking to finish enrollment in the Phase 2 BESTOW study at the end of next year, so at the end of 2024. And so far, our experiences opening sites and recruiting patients is, it continues to be aligned with that goal. If we go back to the beginning of the year, we had guided that we would do a number of things. We were going to look to raise financing for the company. We then said that we would look to open up our first sites in the Phase 2 BESTOW study in June specifically and that we would bring in our first patients into that study over the summer. And so far we were able to execute and meet all of those milestones. So we're feeling good. We think that this data should be helpful in helping get researchers and potentially patients interested and on board in participating in the Phase 2 BESTOW. And so far we continue to expect to be able to hit the milestones that we're looking to hit and complete enrollment at the end of next year. Got it. That makes sense. All right. Thanks for taking the questions, and congrats on the progress. Thank you, Tom. Thank you. The next question comes from Robert LeBoyer with Noble Capital Markets. Please go ahead. First, let me congratulate you on the data, and my question has to do with this patient who had the mild T-cell-mediated rejection. There was a mention of the Banff score of 1A, and that it was treated, the patient remains in the study. But could you just elaborate a little bit on- ... what the Banff score of 1A really means in terms of severity, the treatment, the inflammation, and the extent of the rejection that was seen? Sure. So we're not going to go into specific individual patient data, but if you'd like, I'm happy to ask Dr. Tchervenkov in general what a Banff score of 1A means. Sure, that would be great. Yeah. Sure, Doc. So, again, these are mild to moderate rejections that are easily treatable with medications that we have on board for the last 25, 30 years. And so, this is what we use, and we were able to treat it quite effectively. Yeah. Okay. Now, is a score of 1A something that's treated for a week, a month, or, you know, just elaborate a little bit on the extent? It's under one week, and it quickly reversed. Yes. It's not something that... They usually respond in the majority of cases, the vast majority of cases, to the current anti-rejection medications we have, and this one responded quite effectively, yes. Okay, great. Thank you very much. Thank you, Robert. Your next question comes from Matt Kaplan with Ladenburg. Please go ahead. Hey, guys. Thanks for taking my questions and nice update to the data. I guess we've spoken about the efficacy or what you're seeing so far in this Phase 1b. I guess maybe for Dr. Tchervenkov, maybe could you comment on, I guess, the totality of the data with respect to the safety profile that we're seeing so far now that some patients are out for quite a long time on the drug and the AEs that you're seeing and how this compares with tacrolimus, and what you typically see in patients on the drug this long? Sure. So Dr. Tchervenkov, looking at the totality of the data that are posted today, you know, how would you- Well, these are- compare that to Yeah, these are common side effects. I mean, you know, we need to, in a study, report any side effects, or adverse events, whether they're due to the medication or not. It's related to being undergoing surgery, transplantation. We see these patients quite often, quite frequently, and we ask them through a standard questionnaire, anything to report. And so these are commonly seen after transplantation in terms of the some of the side effects, we saw the sort of. I don't have the actual presentation in front of me anymore, but we see quite a bit of these, you know, these reported side effects. So that's nothing unusual for me. Thank you. Okay. That's helpful. And then, second question, in terms of the Phase 2b study, what you're looking for superiority as the primary endpoint in terms of eGFR. What level of difference would we like to see between the two arms? And what are you powered to show there with this, with the size of the study? Sure. So, Matt, we are 80% powered to show a 9% difference between the two arms. Okay, great. That's helpful. Great. Again, congrats on the updated results. Great. Thank you. Thanks, Matt. Thank you. Your next question comes from Rami Katkhuda with Life Sci Capital. Please go ahead. Hey, guys. Congrats on the update, and thanks for taking my questions as well. Just a quick one from me, but can you touch upon the four cases of BK viremia? Are doses of tegoprubart lowered in these cases as well, or is it just MMF? And is it purely physician discretion whether to discontinue treatment with tegoprubart? Sure. Thanks, Rami. Let me turn it over to Steve. Hi, Rami. I'm sorry, I apologize. I actually missed a little bit of your question. You faded out there for a second on my phone. I'm in a hotel room. All good. I guess I was asking about the four cases of BK viremia. Are doses of tegoprubart lowered as well, or is it only MMF? And then the second part of that, is it purely physician discretion whether to discontinue treatment with tegoprubart? Yes, it's up to the PI. I mean, that's an easy one. Investigators have a lot of experience in this patient population in treating things, and they're very well adept at seeing BK viremia and how to respond to that. The first thing that we've done, which is standard practice, has been to reduce MMF dosing, which is a very common way to reduce BK viremia, and that's been quite effective thus far in our population. We don't play with the doses of Tego. As far as I think you specifically said, do you lower the dose? We don't play with the dose of Tego. That's a standard. The protocol does allow an investigator to skip a dose if they choose to, and that's acceptable as part of the protocol. But for the most part, that has not occurred, and these patients continue to be on tegoprubart in the study. Got it. That makes sense. And then I guess with regards to kind of the kinetics of eGFR benefit and stabilization, it seems like treatment with tacrolimus, patients kind of have their eGFR peak relatively early, whereas with Tego, you see a continued benefit over time. I mean, it's still early, but is there any kind of indication as to where, at what time period does the benefit with Tego kind of hit, if that makes sense? I think right now, the N is small, so we're, and when we only have one patient that's gone out to a year, so it's just difficult to know where things are going to land. But overall, the takeaway, you know, in our opinion, is that we're very happy with these eGFRs, and whether it's, they're a 70, let alone an 80 or a 90 in one year, these are quite high. But it's probably too early to predict whether everybody will look the same and how things can evolve. Steve, do you, maybe I'll turn it over to you to see if you have some more thoughts. Yeah. I agree with everything D.A. said. I mean, this is very exciting and very encouraging data. Dr. Tchervenkov said that himself. The data was very well received at ASN this morning, because the eGFR data was, is quite compelling. But it's early days, and we only have one patient that's actually gone out a year. Now, if you fast-forward back, I mean, we've made an incredible amount of progress this year. You know, a year ago, we had submitted data to the Singapore conference, and we only had three patients of data, and none of them had gone out even close to that far. So, the company continues to make great progress, and we're obviously very excited about where we are today. Got it. Congrats again. Thank you, Rami. Thank you. The next question comes from Pete Stavropoulos with Cantor Fitzgerald. Please go ahead. Yeah, just, one additional question, I guess for Paul or, or D.A. You know, can you just remind us, remind us about the, the financing, agreement you entered into earlier this year, and, you know, what would trigger the next tranche and, sort of expected timeline? Thanks. Sure. I'll turn that over to Paul. Sure. As you know, we received $35 million upfront, and then there was an additional $105 million that will come under two triggers. Both of those are clinical milestone triggers. The first $47 million when the 10th patient is enrolled in a Phase 1, this trial, which we hit, and when the 12th patient is enrolled in the BESTOW trial. There's also share price and volume trading triggers as well for that, but it's, the clinical milestones are clearly set on these two trials, and then the second funding of $58 million is set on the 78th patient is enrolled in BESTOW. And so again, as D.A. has mentioned, our intent, our goal is to complete enrollment on the BESTOW trial at the end of 2024. All right. Thank you. Thank you. Thank you. Ladies and gentlemen, as a reminder, should you have a question, please press star followed by the one. Your next question comes from Vernon Bernardino with H.C. Wainwright. Please go ahead. Hi, thanks for taking my question, and congrats on the results. I'm sorry that if I don't remember this, but is there an interim look, such as a look at 90 days built into the BESTOW trial? And if so, if you have results, for example, at 90 days, that show that you have an eGFR of 70 or better, as compared to what you usually see in such patients of 50, is there a rule that would actually stop the trial early? Thank you. Thank you, Vernon. There is no interim look, currently built into our Phase 2 study. Right now, our plan is to run the study and then flip over that card and see how well patients have done. In the meanwhile, though, we have the opportunity to use our Phase 1b in order to generate data and to report it out. Currently, that first cohort is 12 patients, but in the future, we might be able to add additional cohorts as well, which can help generate data both for the field as well as, obviously, for investors. Okay. Thank you. That's my only question. Thank you. There are no further questions at this time. Please proceed. Thank you, operator, for your assistance, and thank you all again for joining us on today's call. Operator, you may end the call. Have a great night. Thank you. Ladies and gentlemen, as a reminder, should you have a question... I'm sorry. Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines.