Good morning, welcome to the Calliditas Therapeutics webcast. At this time, all attendees are in a listen- only mode. A question and answer session will follow the formal presentations. As a reminder, this call is being recorded and a replay will be made available on the Calliditas website following the conclusion of the event. I'd now like to turn the call over to Renée Aguiar-Lucander, Chief Executive Officer of Calliditas Therapeutics. Please go ahead, Renée. Thank you. Welcome to this conference call regarding the top line data readout from our phase III study, NefIgArd. This is obviously great news for patients living with IgA nephropathy to be able to say that we see a persistent effect on eGFR or the underlying kidney function even after 15 months off drug, which we feel is fantastic, and we're truly very happy to be able to share this data with you today, which also just happens to be a couple of days after the World Kidney Day, which is very appropriate. With me today on the call is our CMO Richard Philipson and Professor Jonathan Barratt from Leicester University. Andrew Udell, President, North America, our CFO Fredrik Johansson, are also going to be available for the Q&A portion. Before we go into the actual presentation, however, I would like to draw your attention to the disclaimer page, related to forward-looking statements, and refer you to the company's reports and other filings, including those which contain risk factors and other relevant information. In terms of some of the kind of takeaways that we're going to cover in this presentation, it is with great pleasure that I can report that the long-term follow-up portion of our phase III study successfully met its endpoint of eGFR, with highly statistically significant. As you will see from Richard's presentation shortly, in terms of additional support, also 2-year eGFR slope analysis were highly statistically significant, with estimates well above those which can be derived from relevant meta-analysis to predict clinically meaningful treatment effects. The beneficial eGFR effect was observed across the entire study population, irrespective of UPCR baseline, and we believe that the dataset supports a regulatory filing for full approval for the study population. UPCR was shown to be durable over the entire 15 months of follow-up without medication, and despite this very long period off drug, the treatment benefit persisted, and at 24 months, the treatment arm showed only half of the kidney function loss experienced by the placebo group. I want to point out, however, that this is headline data. We have not had the opportunity to fully analyze the dataset, and there is additional work which is required before we're in a position to provide details, which we plan to do in further publications and at conferences. Just a brief reminder of the actual study design before I hand over to Richard. Obviously the entire study included just over 360 patients in total. It was an oral daily treatment for 9 months, followed by 15 months with no drug being administered. In terms of base inclusion criteria, patients came in with a biopsy-proven IgA over 1 g of proteinuria and an eGFR between 35 mils and 90 mils per minute. Patients were required to have well-controlled blood pressure of 140 over 90 or less to enter into the study to ensure that there wasn't any confounding effects on proteinuria reduction related to higher levels of blood pressure. No immunosuppressive drugs were permitted during the study, and changes to antihypertensive medications were discouraged. No other medications were encouraged during the time of the trial. With this, I'm going to hand over to Richard, who's going to take us through some of the data. Thank you, Renée. I'll begin by presenting a brief summary of the disposition, demographics, and baseline characteristics of the study population in the NefIgArd phase III trial. In total, 395 patients were randomized into the study. This includes an additional 29 Chinese patients required for local Chinese regulatory purposes only. The safety analysis set of 389 patients includes all randomized patients who received at least one dose of study medication. The full analysis set, comprising 364 patients, is the dataset used for all efficacy analyses performed for the global study. It's noteworthy that only just over 10% of patients withdrew from the study at any time, indicating a good rate of retention of patients in the study, and early discontinuations were broadly similar in the Nefecon and placebo treatment groups. Moving on to demographics. Overall, the enrolled patient population is clearly representative of the intended primary IgA nephropathy population. Disease characteristics describe a clinically relmilsevant high-risk IgAN population. Treatment groups were balanced with regards to baseline characteristics, and of note, blood pressure was well controlled at study entry. There has been an increase in the proportion of Asian patients in the study population since the release of data from Part A, reflective of the active recruitment of patients in China. To summarize the efficacy results. The primary endpoint of Part B of the study was a time-weighted average of eGFR observed at each time point over 2 years. The primary endpoint was met, over 2 years, eGFR was on average 5.05 mils per minute higher with Nefecon compared to placebo, a result that was highly statistically significant. On average, over 2 years, the loss of eGFR was 2.47 mils per minute for Nefecon versus 7.52 mils per minute for placebo. Several different supportive analyses of eGFR total 2-year slope were performed. These were all statistically significant, with improvements in slope estimated to fall in the range of approximately 1.8 mils - 3 mils per minute per year. The differences in 2-year total slope observed between Nefecon and placebo considered clinically relevant since all of the estimates are well in excess of the difference per year required to predict clinically meaningful treatment effects on the composite endpoint of end-stage renal disease, eGFR less than 15 mils per minute, or sustained doubling of serum creatinine, as published by Inker et al. in 2019. When we look at the eGFR outcomes in placebo-treated patients, at 9 months, there was a decline in eGFR of approximately 8%, corresponding to a loss of approximately 4.6 mils per minute, which increased to a decline of 21.5% or loss of 12 mils per minute by 24 months. In contrast, in patients treated with Nefecon, eGFR was essentially stable compared to baseline at 9 months, and by 24 months, there had been a decline in eGFR of 11%, corresponding to a loss of approximately 6 mils per minute. In summary, 9 months of dosing with Nefecon in 364 patients resulted in 50% less loss of kidney function compared to placebo at 24 months. Turning to proteinuria, we have seen a cumulative improvement in proteinuria in patients treated with Nefecon versus placebo during the 9-month treatment period, which continued to improve at 12 months. At month 24, proteinuria levels in patients who received Nefecon were still at a reduced level, similar to that observed at the 9-month time point. In summary, the Part B primary endpoint of eGFR AUC over a 2-year period was met, showing statistical significance of Nefecon compared to placebo. Supportive analyses of 2-year eGFR total slope was statistically significant and clinically relevant, showing a magnitude ranging from approximately 1.8 mils-3 mils per minute per year, with all estimates of eGFR slope well in excess of the threshold required to predict clinically meaningful treatment effects. Treatment benefit on eGFR was apparent across baseline UPCR subgroups, and reductions in UPCR and UACR achieved during treatment were durable. Sustained proteinuria effects and long-lasting treatment benefit, even after 15 months of observation following treatment discontinuation, support a disease-modifying effect. Now turning briefly to safety. Overall, we saw a pattern of adverse events in the safety analysis set for Part B that was similar to the Part A analysis and which has previously been described in our publication in Kidney International and which is also described in product information. The most frequently occurring adverse events occurring in 5% or more Nefecon-treated patients with a frequency 2% or higher than placebo, in difference were peripheral edema, hypertension, muscle spasms, acne, upper respiratory tract infection, face edema, weight increase, dyspepsia, arthralgia, and white cell count increase. Overall, Nefecon was generally well-tolerated with an adverse event profile similar to that seen in Part A. The most commonly reported treatment-emergent adverse events observed with an increased frequency compared to placebo were peripheral edema, hypertension, muscle spasms, and acne. The majority of treatment-emergent adverse events were mild or moderate in severity, and adverse events led to discontinuation of study drug in fewer than 10% of Nefecon-treated patients. I'd now like to ask Professor Jonathan Barratt to now make some comments with respect to the results that have just been described. Thanks very much, Richard. I'll just check that you can hear me. Yes, we can hear you. That's great. Well, thank you for allowing me to comment. I mean, I think these results are really a game changer in terms of our understanding of IgA nephropathy. What we've seen with the data is we can truly modify this disease with a short course of a gut-directed steroid that leads to sustained proteinuria reduction over a full 24 months, which I think is really outstanding, with only nine months of treatment, showing that for the further 15 months, we are still getting suppression of disease activity. Most exciting, of course, is that that is translating through to sustained protection of and reduction in the rate of loss of kidney function in these patients. I think collectively, what this data is really showing is that we're able to modify the underlying disease process here and which results in sustained impact on rate of loss of kidney function and with a drug that is well-tolerated from the data that you've just presented, with very few treatment discontinuations, side effects that we already have known about, but really are adverse events that we are very able to inform our patients about, but are not leading to patients not being able to take this treatment. I think for me, the key thing here is a nine-month treatment has a significant long-lasting effect over the two years of the study. Of course, we don't know what happens after 2 years, but the exciting thing is to think that this may well be extended beyond that. We have 2-year data to talk about today. That's my first impressions of the data, and I'm happy if you want me to comment on anything else or answer any questions. Thank you, Jonathan. With that, I think we'll hand over to the moderator, to take any questions. Great. Thank you, Renée. At this time, we will be conducting a question and answer session with our speakers. Please hold while we poll for questions. Our first question comes from Maury Raycroft from Jefferies. Please go ahead, Maury. Hi. Thanks for doing this call and much congrats on the data update. I was gonna start with just a question around proteinuria. You mentioned that in the context of baseline UPCR greater than or less than 1.5 g subgroups, you noted you're seeing benefit across the entire population. What are your expectations for the label in respect to proteinuria? Maybe if the company can talk about the eGFR data and next steps with updating the label with the supplemental NDA. Sure. I guess that our expectations were obviously that for the actual trial and for this regulatory submission, the endpoint obviously is eGFR. My expectation would be actually that the label would reflect eGFR primarily rather than proteinuria. In terms of obviously we did see, kind of, you know, consistent and persistent proteinuria reduction across the entire population. We also obviously saw the same thing with regards to eGFR. Our intention really is to file for full approval based on the phase III population. I think our target there is, hopefully we can file around July, is our target to file with the FDA. Obviously depending on what the review period is, we should have a response from the FDA sometime in the first half of 2024. Got it. As follow-up, Dr. Barratt also talked about disease modification. Could that present some claim around disease modification? Could that go into the label as well? I think it's very difficult to comment on what the FDA, you know, how the FDA will look at this and what they will say. My experience with the FDA is that they probably will be quite conservative around using that kinda language. I guess we'll have to just wait and see until we engage with the FDA on that. Got it. Maybe just one other question, if you can contextualize the 5 mil delta on eGFR, and, how should the treatment duration be in the commercial setting in light of that? I guess, how does that change your view around the 9-month course versus something longer than that? I mean, I think that it might be a little bit difficult to already now start thinking about how the data will guide treatment decisions. I guess I will hand over to Dr. Barratt to see if you may have any comments on that. You're on mute. Oh, sorry. Yeah. Hi, can you hear me? Yeah, we can hear you now. Yeah. Myself and other nephrologists from around the world are very keen to get our hands on this data, as you can imagine. We want to use this data to understand about frequency of treatment. It's very early. As Renée has said, this is top-line data. We haven't got an answers for that yet, that is clearly a question we want to look at in terms of the clear disease-modifying effect I think this treatment has, and can we gain more by repeated administrations. We have the open-label extension study happening at the moment, which will be generating data. I think it's too soon to say, but it is a question that we as nephrologists are asking. We'll work with Calliditas to come up with, some thoughts on how we think this should be structured going forward. Great. Okay, congrats again, and I'll hop back in the queue. Thank you. Thanks. [audio distortion] from Citi. Please go ahead, Ygal. Hold on. Can you hear me now? Yeah. Okay, great. Can you just clarify something on the eGFR slopes? You said -6 at 24 months for Nefecon, -12 for placebo. Okay. You also said delta was -1.8 to -3 per year. I'm just a little confused on the math, 'cause I would have thought the delta would have been -3 per year. Is there some kind of, like, very large variability with the error bars. Just can you help me understand how it's -8 to -3 per year when you have a 6 delta for the 2, you know, at 2 years? Yeah. Well, there are a number of different methods that can be used for slope analysis. We've applied several different methods in the slope analysis. They provide an estimate that ranges between 1.8 mils-3 mils per minute per year. Actually, that does then correspond to that difference we've seen at 2 years, where we see a 6 mils per minute difference over 2 years. Okay. I guess I was just thinking more on the lower end of the range. The 1.8 would not connect with the delta of 6. You know what I mean? Okay. I guess there might be some variability with it. I guess it all depends on the kind of statistical approach that's used, and that's actually. There are a variety of different ways you can do it. That's kind of, just for completeness and transparency, we provided all of those different ways of doing it. There's a range of looking at different kind of supportive, statistical analysis. Have you guys actually seen the slopes yet or you just have seen the numbers? When would we see the actual graphs of the slopes? I think that what we'll do obviously is we are going to have to kind of look at the data more in detail and do more analysis. I think that it'll probably most likely be part of kind of our plans in terms of releasing additional information at conferences and in publications. I can't give you an exact time, but it'll be part of kind of disclosure or information. Okay. I had a question for Dr. Barratt. I would be curious on your thoughts, Dr. Barratt, as to how you would compare and contrast what we've seen now for Nefecon with this 2-year data with what was seen in the TESTING trial for methylprednisolone, as I'm sure you're familiar with. How would you compare these two studies? I think we need to think very carefully about these studies. What I think is really exciting for me is the pattern of proteinuria change that we see with this drug is completely different to the pattern of proteinuria change we see with this high-dose systemic steroids. Telling me that we are doing something fundamentally different in terms of the disease pathogenesis. To see that the proteinuria is still at 30% lower at 2 years, despite only having a 9-month treatment, suggests to me that we are doing something fundamental to the production of the abnormal IgA. I think the TESTING study, you give a very high dose, you have multiple tolerability issues. We know this is associated with significant toxicity for patients, which we just haven't seen in terms of the data that Richard has presented to you. I think there is an efficacy issue that is telling us this is doing something fundamentally different, in my view, to the underlying disease compared to a large systemic anti-inflammatory dose of steroids. We also have the safety efficacy aspect in terms of tolerability. Remembering that the dose of steroids used in the TESTING equate to between 30 mg-40 mg of oral prednisone, which we know from many, many studies patients find very difficult to tolerate. I think, you know, as more data comes out, as Renée has said, we will be looking very closely at the differences we see, and we're already seeing very significant differences in terms of patterns of response with this therapeutic approach compared to large doses of systemic steroids. I think there's more to become from this. I think from the data that I've seen, and again, it's early days, we're seeing fundamental differences in the pattern of response. Okay. Thank you very much. Yes. Thank you for the question, Ygal. Our next question comes from Dan Akschuti from Pareto Securities. Please go ahead, Dan. Can you hear me now? Dan? Yes. Perfect. Thank you for taking my questions, and congrats to the whole Calliditas team on this major milestone. Most of the questions were already answered, but maybe one question to Professor Barratt, which was partially taken up already. How would you see currently the treatment course for a patient over 3 years, let's say? Where do you see the potential of that second drug that has now been conditionally or accelerated, approved based on biomarker data? Where do you look at those currently two available drugs with quite different profiles and data? Thank you. I guess the retreatment discussion we've already had, I think we are going to be looking very closely at how we use this drug over the longer term, remembering our patients are diagnosed in their thirties and have a lifetime ahead of them where we need to control this disease. We've always thought that a large number of patients are going to need a second or third course. We need to look at the data to better understand what those criteria might be for retreatment and where we look at where we gain extra benefit. The open-label extension study that is currently ongoing is going to give us some really useful information about that. I can't give you an answer because I just haven't seen the data to give you a sensible answer on that. I know we will be looking at that in close detail. In terms of where this therapy fits in in the context of other therapies. I think that we've got a really clear indication here of a safe and effective therapy, but we can always think about where we might gain advantage with other therapies. I think combination therapies are things nephrologists are going to look very carefully at. We clearly need to ensure that we gain on efficacy while not increasing safety signals. Mode of action is gonna be critical to make sure that we don't compound any effects in terms of certainly immune modulation or infection risk. The good news is we saw no real infectious signal here with the NefIgArd trial, unlike the TESTING study where there were significant infections leading to death. I think we this is an open, but we are at the very beginning of a journey, and we are going to be asking those questions in terms of combination therapies, the right combinations for the right patients. We've never had that opportunity before in managing IgA nephropathy because we quite frankly have had no drugs. I think we will be looking at all opportunities, and I'm sure Calliditas and every other company will be looking at as many opportunities as possible to improve the lives of patients with kidney disease and to prevent kidney failure in the lifetime of patients with IgA nephropathy. That must be our focus, and we now have a drug with 2-year eGFR data, the first data we've ever had, showing a really beneficial effect of a treatment that potentially is disease modifying. We need to work on that. I can't give any complete answers. Of course, we need the full 2-year data for any other drug to make sure we understand both its efficacy and its safety so that we know how we combine these drugs going forward, if that's what we choose to do. Okay. Thank you. A follow-up to that. You just mentioned, yeah, you currently there is no such data from any other drugs. You would kind of hold off on other drugs as until they have such data as Nefecon has or? Well, I can only speak that, we only have one approved drug in the U.K., and in Europe at the moment. As new drugs become available, we will be starting to think about how we might combine them in the right type of patient. That is something, you know, the sparsentan was only approved two weeks ago. It's very early. We really are just starting to think how we might start combining therapies. What we need to know is we need to have the confidence around safety and efficacy, and that's where the 2-year data come in. We have the most confidence around safety and efficacy with Nefecon at the moment, and therefore that's the drug that really has set the benchmark, in my view, for where we go next. Okay. Thank you very much. One last question to the company. Do you have any indication or data on patients that are going back on drug after 9 months already, like after a certain pause? Do you have anything related to that? Thank you. Obviously in terms of, kind of in terms of our commercial drug in the U.S., you know, it's a little bit early probably at this point in time to know kind of whether people are going back on drug. I mean, what we have seen, obviously is that, you know, for some patients, the physician's choice is to keep them on drug after the 9 months. I think it's probably a little bit early for us to have any of that data in terms of retreatment at this point in time if we haven't been in the market long enough to actually have any of that data. Okay. Thank you. That was it. Congratulations again. Bye. Thank you. Thank you for the questions, Dan. Our next question comes from Annabel Samimy from Stifel. Please go ahead, Annabel. Hi. Can you hear me? Yeah. Okay. Hello? Okay. Great. Thank you. Yes, we can hear you. Just a question for Dr. Barratt. You just mentioned that this is a different proteinuria change than systemic steroid. Would you say that the proteinuria change that you're seeing here might also be different than the new ERA class, such as sparsentan? Obviously, we know what the mechanism is here. You're addressing the source of the disease here. Do you have any thoughts on how predictive proteinuria is for other drugs in this space? A good question. We haven't seen any data for sparsentan. There's been a press release. There have been no scientific public presentations, no publications, and therefore it's really impossible to comment on the pattern of proteinuria change we see with an endothelin receptor antagonist because the data is just not in the public domain at the moment. It's really difficult to comment. I think the fundamental mechanisms are very different in terms of sparsentan having a predominantly hemodynamic effect, whereas Nefecon is impacting on the fundamentals of the disease and ultimately reducing immune complex deposition within the kidneys is our theory. I would love to have the pro patterns of proteinuria up next to one another to try and understand how these are potentially working in different ways and what the patterns might mean clinically. Of course, proteinuria is a surrogate. What we're ultimately interested in is GFR protection, and that's what we need to see in terms of any drug to ensure that the proteinuria reduction we're seeing is acting as a true surrogate of future kidney function protection. I think we've got that now with Nefecon, and we need to wait to see that with other drugs and other mechanisms of action. I think the challenge really is because of the way that the approval process, accelerated approval process is working, data is at a premium in terms of what is in the public domain, and we need to wait for that to come out before we can give any sensible comments. Okay, great. Maybe other questions for the company. I know that this is top line. Will you be breaking out eGFR benefit based on severity, similar to what you recently showed us on the fourth quarter call, where patients with greater than 1.5 UPCR had significantly better eGFR? Is there any sense as how you're gonna break up the data to sort of illustrate who gets the most benefit here? I guess that is part of what we're gonna have to do kind of going forward, and an additional analysis will certainly be conducted. I think that obviously what we have seen is actually that the, you know, the treatment benefit is very consistent across the study population. I'm not sure what, you know, what we will find or if we will find any kind of particular benefit in different subgroups. That is certainly something that, you know, is a little bit further down the line when we've had a chance to look more properly at the data set. Okay, great. If I could just ask a couple other questions related to financials. You know, when you laid out your guidance for 2023, did your guidance already assume this positive outcome? Then just a follow-up to that, do you have any sense how this might facilitate reimbursement? Have payers been also waiting for this data to, let's just say, facilitate the process? I know your coverage is strong, but just to facilitate the process for the nephrologists. Thank you. I guess in terms of the payers, I'll give a quick, and maybe Andy wants to comment on that. My view is really kind of that, you know, this, I mean, this can only improve any kind of situation with payers, but I wouldn't say that payers have been waiting for this data. Certainly we're going to, you know, be in conversation with them. Andy, maybe you want to cover this. Yeah. I mean, as you pointed out, Annabel, I mean, we have currently over 90% of U.S. lives covered for TARPEYO. However, we continue to have dialogue with payers, and obviously this data further supports the value of TARPEYO, its health and economic benefits, and it's gonna be shared with payers at the appropriate time in order to support, the appropriate, management of our product. We're very excited, but it could only improve, I would say, from this data. Okay. Yeah. Go ahead. And are they- No, just on the guidance. Sorry, did you have a follow-up question for Andy? Yeah. Well, just on the guidance that you provided for 2023, did your guidance already assume this positive outcome? I think obviously in terms of the guidance, you know, we were certainly, you know, assuming that we would get, you know, I would call it kinda reasonable data out of this, out of the trial. I think we have, you know, very good data, I guess we're positively surprised in terms of where we've ended up. I mean, at this point in time, we're not, you know, we're certainly not going to re-guide or change our guidance. I think realistically, you know, this type of data obviously cannot be used in promotion and that's highly regulated, as you know. I think it'll still be... It'll be you know, a while before this information and data gets kind of into conferences and publications and where nephrologists really can take, you know, kinda partake of it properly. My assumption is that the full effect will kinda be more medium term than near term. Obviously there will be, in my assumption, kind of, you know, clearly some positive, you know, impact near term from the fact that nephrologists are gonna be aware of the fact that there is this, you know, long-term effect. Okay. Great. Thank you very much. Yeah. Thank you for the questions, Annabel. Our next question comes from Ingrid Gafanhão from Bryan, Garnier. Please go ahead, Ingrid. Hi, good afternoon. Thank you for taking my questions, and congrats on the data. I have two questions, if I may. Let me start. Over the call, you mentioned a couple of times the open-label study. I was wondering if you can provide us with some update on what is the status of that open-label study, and when do you think or when you're planning to share some more data on that? Yeah, sure. I mean, the, the study is ongoing. We continue to enroll patients into the study. The number of patients who are now eligible to get into that study, that's clearly low, as most patients now have completed the pivotal study. There's only a few patients coming out of that who can get into the open-label extension. We expect therefore that study to complete in terms of the last patient completing the study in the first half of 2024. Great. As a reminder, all of these patients that are being enrolled, they are getting a new course of therapy, right? Yeah, that's right. Okay. all patients who go into the open-label extension will receive treatment with Nefecon. Clear. Thank you. If I may have a second question for Dr. Barratt. I was hoping, can you maybe contextualize the eGFR data for us a little bit more on how you look at it? Calliditas has presented like the data on the total slope. We also have some point data for what happens to eGFR at 12 months. In your practice, in your daily life, how do you look at eGFR yourself, and what does it mean in terms of clinical benefit for patients? Yeah. Thanks. clearly the thing that matters to patients, and therefore matters to me, is the risk of kidney failure ending up needing a kidney transplant or needing dialysis, and that is determined by how quickly your kidney function deteriorates. That's what we're looking at here in terms of the data that Richard presented, that over the 2-year period, the placebo patients, lost 12 mils of GFR. If you think about someone starting off with a GFR of 60 mils, it's gonna take 5 years, and they will have 0 mils, and before then they will need to have dialysis. If you slow that rate of progression, you are delaying the time to which the average patient is going to need to start dialysis. Every year is precious to these 30 -year-old to 40-year-olds who are living with kidney disease. We've worked out using real world data, and we've presented this data on multiple occasions, and we will rework the data. Now we actually have this data in front of us that if you're able to reduce proteinuria by 30%, that you can delay the time to dialysis for the average IgA patient by a decade. What we can do now is look at the assumptions we made in those calculations related to the data we have from the phase III, which I don't think are far off, in fact may even be better than the assumptions we made in the original calculation. What we're talking about here is a really meaningful impact on the risk of kidney failure and the time to dialysis or transplantation for most patients with IgA nephropathy. That is what patients are asking us for. That's what we as nephrologists want to achieve. This, you cannot underestimate how important these data are for patients in terms of what it means for their quality of life, for how they live their life in terms of their ability to work, their ability to enjoy time with their family. It is exactly what patients have been asking for for the last 30 years, 40 years. Really is, you know, groundbreaking data here in terms of what this means for patients. That was very clear. Thank You very much. Thanks for the questions, Ingrid. Our next question comes from Rami Katkhuda from LifeSci Capital. Please go ahead, Rami. Hey, guys. Wanted to pass my congratulations on the update as well. Two quick ones for me. First, can you provide any more context about how the eGFR slopes kinda changed after the 12-month period? Do you expect eGFR for the Nefecon arm to kind of start to fall at a similar rate to placebo, or is there potential for it to be slightly more accelerated? I think at this point in time, you know, we really haven't kind of, you know, had the opportunity to really kinda review the data set completely. That type of information we will share as kinda we get to conferences and publications, et cetera. I guess, is there any proof from prior studies or is this kinda too novel and we have to wait for the data? I think we do have to wait for the data. I don't think that there are any other studies really that we can rely on. I think it's... If, if you're going to do that, I think you need you know, lots and lots of different studies and then kinda try to draw some kinda general conclusions. I don't think we're in that situation, I think it is very much waiting for the data here. Makes sense. Then can you remind us when the KDIGO guidelines are updated and whether this data can be included or whether you need to wait for full approval? My understanding, and maybe Dr. Barratt has better information on this, actually my understanding is that there are plans at least to update the KDIGO guidelines for this year, before the end of this year. I don't know if Dr. Barratt has better information on that. Yeah, hi. I'll be leading that revision. You may or may not have seen, but the lupus KDIGO guidelines are now out for public consultation. It was always agreed that lupus and vasculitis would go first. Clearly there's a limited capacity within KDIGO to do this. We are next, but we haven't got a definitive timeline. I think we will have revised guidelines out for public consultation at some point in 2023. We haven't started the process yet. There is every opportunity that this data could be included in those. As I say, we haven't got a start date yet. Makes sense. Thank you guys for taking my questions. van Voorthuizen from Kempen. Please go ahead, Suzanne. Hi, team. Congrats on the data, and thanks for taking my question. I just have a follow-up, regarding your TARPEO guidance for the coming year. Very helpful, the color that you already gave on what assumptions on the data were underlying in there. I'm wondering if you can elaborate on what factors we should think about regarding potential upside or downside to reaching that guidance. What could be sources of potential positive surprises, and where do you see potential risk for, reaching your sales numbers? I guess I'll hand over to Andy, but I guess my core kind of view really is that this is very much driven by, you know, physicians having experience with the drug, right? You have positive success stories from patients. You have peer-to-peer recommendations. Physicians are clear about how the drug works, et cetera. We're just about getting to that point, obviously, because we've now been in the market for, you know, a sufficient period of time. I don't know, Andy, if you have any comments on that. No, I'd echo that. I mean, I think there's a lot of things that we continue to focus on and add promotionally, and with our expanded field force. I think as Renée alluded to, we're getting to the point now that physicians are getting more and more experience with the product, and this just further, these kind of things, this data further gives us confidence in the consistency in the product and how it's performed. New data, certainly, this data we only could see as a huge positive. As Dr. Barratt said, things like game changer and groundbreaking data and what it means for patients. Hopefully that's echoed and that is gonna be well received. Got it. Can you elaborate on what you see currently as the key barriers to further adoption? Currently I think, you know, we're not seeing a lot of barriers to adoption. We're seeing physicians that are trying to find the right patients in their practice that meet criteria that they feel are appropriate for this. It just takes time. There's habits, there's a lot of things. We were the first real specialty product that a lot of these nephrologists have been exposed to, so there's some adoption period that takes, and this is normal. I don't think that there's been a lot of barriers per se. Okay. Got it. Thanks a lot. Thank you for the question, Suzanne. This concludes our question and answer session today. I'll now turn it back over to Renée for closing remarks. Thank you very much. First of all, I wanna thank Professor Barratt for taking time to actually be part of this call. It's greatly appreciated. It's always so insightful to have a practicing nephrologist with a completely kind of different view, obviously, on this than many of the people on the call. Thank you very, very much for taking the time to comment on this. I think it's very insightful and very helpful. Thank you for all of you who listened to this, and we look forward to sharing additional data as we continue to work through the data set. Thank you again.