Good afternoon, welcome everyone to Kezar's webcast to discuss the result of the completed MISSION phase I-B clinical trial in systemic lupus erythematosus and lupus nephritis. I'm Celia Economides, the Senior Vice President of Strategy and External Affairs at Kezar. At this point in time, all participants are in a listen-only mode. A Q&A session will follow the formal presentation. If you would like to ask a question during the Q&A session, please use the raise your hand function on Zoom. This morning, we issued a press release detailing results from the MISSION phase I-B study, which were presented today in a poster session during the European Congress of Rheumatology. Both the press release and our poster presentation are available on our website at kezarlifesciences.com. During the course of this call, we will make forward-looking statements based on current expectations. These forward-looking statements are subject to a significant number of risks and uncertainties, and our actual results may differ materially from those described. We encourage you to review the risk factors in both our presentation and our most recent Form 10-Q that is filed with the U.S. Securities and Exchange Commission and available on our website. We will also make these slides available on our website following the call and as well as the recording of this webcast as well. With that, let me turn the call over to our Co-Founder and CEO, John Fowler. John? Wonderful. Thank you so much, Celia. Thank you, everybody, for dialing in today or Zooming in today, as the case may be, to catch up on the latest news with Kezar. We're very excited to be presenting the final chapter in the phase I-B portion of the MISSION study. I'm going to speak on today's call only for the first few minutes before handing over to our Chief Medical Officer, Noreen Henig, as well as one of our investigators, Dr. Samir Parikh. Joy, if you wouldn't mind advancing to the next slide. Celia did make this disclaimer very eloquently, we will be making forward-looking statements, that should come as no surprise. There's me with a full necktie on. Let's move on to the next slide, Joy. Great. From the Kezar team today, you've got myself, of course. I'm joined by Chris Kirk, who I'm sure many of you have met and spoken with before as my co-founder and Kezar's president and CSO, obviously involved with the six one six program from the very beginning. Dr. Noreen Henig is joining us today and will walk you through the majority of today's slides on the phase I-B results. From the final portion of the Kezar team joining us is Celia, who opened the call. I have to share the bittersweet news with you all that we're bidding farewell to Celia, who's been given the amazing opportunity to be a chief financial officer at a public biotech company in a non-competitive space. It's a really unique opportunity with a very sizable company. We're extremely happy for her and look forward to cheering her success in her future role and grateful for all the hard work she's brought to bear on Kezar's behalf over the last two years. That's not the only personnel news in Kezar land. We actually had a press release yesterday announcing the addition of a new director to our Dr. Micky Cleerman, who is a very experienced drug developer and clinician, trained rheumatologist with over 20 years of clinical practice before going into industry, had a pivotal role to play in the approval of Actemra and Janssen's Stelara. Also worked on Rituxan trials. Really phenomenal addition to the board as we look forward very apropos of this call into the next phase of development with KZR-616 and lupus nephritis and beyond. Next slide, please, Joy. I mentioned this earlier, but I'll kick things off. Noreen will ably walk you through the data, and then we're really grateful for Dr. Parikh to join us today. He is going to be able to speak to the burden of these severe illnesses of lupus and lupus nephritis, but also his direct experience working with KZR-616 in the phase I-B portion of this trial. I do believe, based on the number of slides we have to get through, there'll be a little bit of time left over at the end for Q&A, so definitely welcome your questions when we get to that point. Before we go into the handful of slides that I'll walk you through, it's really a highlight reel of slides that get me excited about the big picture of 616. I want to just take a moment to step back and celebrate what this means, the conclusion of the phase I-B portion of the study. We really feel that we achieved our objectives. Fundamentally, we answered the key questions we had posed around safety and tolerability. We know that we have a safe and well-tolerated drug. We know that we're hitting our target, the immunoproteasome, at multiple therapeutically relevant doses from 30 milligrams on up. We learned key things about how to effectively dose the drug. With this step-up dosing regimen using initial dose of 30 milligrams, we can really maximize the tolerability profile and increase the comfort level of patients taking the drug, and that was obviously a key learning. Perhaps most importantly, for many people who follow the proteasome inhibitor space, we fundamentally differentiate ourselves from bortezomib, carfilzomib, the dual proteasome inhibitors, by avoiding the systemic hematologic tox issues that are part and parcel of those drugs. Because of that, we don't think there'll be serum monitoring required for KZR-616. All this really sets it up as a drug that is really suitable for chronic administration, which is obviously critical when you're approaching late-stage development in autoimmune diseases like the ones we're looking at. In addition to the safety and tolerability profile, it's an efficacy profile that we were hoping to catch a glimmer of, and I feel like in an open-label phase I-B, that's what you hope to see the first signs of an active drug. We definitely feel like we checked all the boxes on that front as well. Noreen will walk you through that data. Again, rapid broad responses. Almost resembling steroids in terms of the rapidity and breadth of the response. We're seeing biomarkers improving, not just uPCR, but anti-double stranded DNA and complement levels when they were out of whack, but also composite scoring like CDAI, CLASI. Really the bright signposts for an active drug that we're so excited to, of course, get to the phase II data portion on in the latter part of this year and next year. Again, before I hand the baton to Noreen and Samir, I just want to walk through a couple of these slides. This one that Joy shared right here probably echoes a lot of what I just said about 616. My co-founder, Chris, likes to call 616 affectionately a very well-behaved drug. I think some of the bullet points here on this slide emphasize that statement, and particularly just that fourth check mark there on the right, I'd like to highlight as something that's come up over and over again over the last several months as we've navigated the later stages of this pandemic. The fact that we not only are avoiding off-target effects, but avoiding a deep immunosuppressive profile is a really big deal. I have a quick slide I'll share with you that seems to resonate in a major way with all the KOLs and investigators that we talk with. Joy, if you'll go to the next slide. If this was an animated slide, so if we hit the button a couple more times, we'll get a little bit of a pre-animation there. Exactly. The core of what makes 616 exciting is this mechanism of action, which is so uniquely broad. Whether it's the adaptive immune system or innate immune system, as it represents the T cells, B cells, and macrophages on the left side, the immunoproteasome is there, and it's the dominant form of proteasome. I just want to emphasize how special and differentiated this mechanism is from all the other blockbusters out there in the world of autoimmunity that are doing great things for patients, but no one would claim that treating these patients that the unmet need has been completely resolved. We're excited with this data and the data to come to further bolster the case that this is a uniquely broad-acting pleiotropic drug that when combined with the potential for limited humoral immunosuppression is really poised to be a game changer. That's a phraseology that you don't use lightly, but I've heard other KOLs use when asked about 616 over the past year. Joy, if you move to the next slide. I just have a couple of slides left here. It's really this mechanism of action background is what led to this slide, which many of you have seen in our corporate presentation in the past. I just felt it was worth reminding everybody on what has already been done with our compounds and with other proteasome inhibitors that demonstrates the broad potential across both large markets and orphan and unmet need markets. Obviously, we have to choose where we go. We've chosen, I think, wisely and boldly in treating patients with lupus and lupus nephritis, where there's both pre-clinical and clinical data with proteasome inhibitors that speaks to the potential efficacy profile for these patients who are much in need. The next slide that Joy will move to talks a little bit about the disease burden of lupus nephritis. I will not go through these points. I think Dr. Parikh will be much better poised to speak to this from his own experience. I know he has several slides to go through. There's no question that both lupus and lupus nephritis have massive amounts of unmet need, and we think it's going to be gratifying to see some of the recent approvals, particularly in the LN space. It's not the end of the storyline in that disease. I know that patients are still very much in need of new treatment options as well. The final slide, there we go. Thank you, Joy. Is something that we've been sharing recently, particularly with our investigators and KOLs, again, in the context of the COVID-19 pandemic, the idea that we can have a drug that allows patients to maintain normal vaccine responses is a really big deal. This has really increased the confidence interval in investigators and in patients to come onto the study and to be able to do so safely. This is just a long-standing Kezar slide that shows work that Chris and the team performed in monkeys, showing normal vaccine responses even after KLH immunization. Happy to talk about this and what this means and how really this will continue to differentiate KZR-616 and build upon the strong safety and tolerability profile that we've really laid a foundation for with this phase I-B portion of the study. Let's talk about the road ahead. I think this is the last slide, the next slide, Joy. As we look across the spectrum of the KZR-616 clinical program. In the middle portion here and downward, you can see that we're moving obviously into the phase II portion of MISSION and the phase II portion of PRESIDIO is ongoing. Both of these have either planned or ongoing open label extensions, which we think is a great opportunity for patients to get further benefit from the drug and also learn an incredible amount about chronic administration and safety and tolerability as well as efficacy. We get a lot of questions about where the trials are going, how they're doing, how the pandemic has affected the studies. Obviously, last year in the MISSION study and PRESIDIO, there were significant implications from the COVID-19 pandemic. Independent of that, we actually redesigned the MISSION phase II portion of the study to be both more enrollable and to reflect a more real-world scenario of patients, i.e., a scenario and world where they're not all entering an induction phase of treatment with the standard of care of high-dose corticosteroids plus MMF or cyclophosphamide. That's really the fundamental LN trial design that's been used by Voclosporin and by Benlysta, and it's been a successful designed, but we wanted to be able to, again, get a broader swath of patients and tease out what 616 might be doing in them in this phase II portion of the study. As a result, this newly designed, as of last year, MISSION phase II will look fundamentally different from those other trials in lupus nephritis because of the lack of that induction therapy backbone behind every one of the patients in the way in the study and the lack of a placebo arm here. As I mentioned, the COVID pandemic did cause delays, particularly in ex-U.S. countries, Latin America, Eastern Europe. The ability to review this amended protocol and get the sites initiated was delayed by many months. We've been working hard, and the team's done a phenomenal job making tremendous traction and getting screening back online in 2021 and enrollment. Since we have guided to and will be providing interim view of the data in the fourth quarter of this year, I felt with the team that it was important to provide additional guidance so you all could have a sense of what we would be able to provide in the fourth quarter of this year. Since early 2021, under this new protocol, we've been able to enroll patients, and as of June 1st, we've enrolled nine patients in the phase II portion of MISSION, which I think that's a statistic, even though we haven't been sharing enrollment updates, that was important to share this time so that there was clarity and understanding of what to expect in the fourth quarter of this year. The work is ongoing. We're continuing to work very hard with countries and sites across Latin America and in Eastern Europe to get additional sites online. We feel confident based on the progress and ongoing screening activity with our guidance for a top line on all 20 patients in the first half of next year, in the second quarter of next year, the later part of that first half of next year. In the spirit of updates on the PRESIDIO Study, that's a study that we launched in late 2019. It was open for a good period of time before the pandemic hit, and we were making good progress. We even enrolled our first patients before that pandemic hit. Similar to the MISSION Study, the COVID severely curtailed screening activity across the balance of 2020, and we revised our timelines accordingly, moving that top-line readout to the first half of 2022. I'm pleased to share that similar to the MISSION Study, that the screening activity has picked up significantly in the last several months. As of June 1st, we've enrolled 19 out of the 24 target patients in that study, which we're very pleased about. Roughly half of this enrollment has occurred since the start of 2021. Again, speaking to the particular headwinds of this pandemic for our studies, and I believe most, if not all, studies across the broader autoimmune landscape and beyond. As I've previously shared, our open-label extension is open with multiple patients enrolled into that open-label extension. The work continues, and we're excited to push to the finish and full enrollment. The being able to offer home visits across the United States for patients today has been critical to keeping this study moving forward during COVID-19. I'm really proud of our team's hustle, commitment, creativity to get this trial as well progressed as we have against the backdrop that we faced. I can reiterate our guidance for the first half of 2020 with a real focus on the second quarter of that timeframe for a top line readout there. Couldn't be more excited for the 616 development program overall and for what is to come in both the MISSION and PRESIDIO studies. This phase I-B update is a critical step along that journey. Let's dig into some of that data now. I'll look forward to any questions people have again. For now, let's hand the control over to Noreen and talk about the phase I-B results. Super. Thank you very much, John. I do have the pleasure of jumping in and sharing with you the results of the phase I-B portion of the MISSION Trial. It's a study that is designed in two parts, the phase I-B portion, which is finished enrollment, and here you are in our poster, we are sharing the complete results of this portion. As John mentioned, we are actively enrolling what we call the phase II, which is a small 20-person open label study of 616 added onto a patient's existing therapy without any induction. There's a lot of qualitative differences to some other phase II and especially phase III studies that you might be thinking to or referencing when looking at lupus nephritis studies. With that, I'm just going to set the stage for the MISSION I-B study. It was run in six cohorts. It was designed as a safety and tolerability study loaded with pharmacokinetics, pharmacodynamics, and some exploratory efficacy measurements. We evaluated six different cohorts, which are outlined here. We investigated doses of 45, 60, and 75 milligrams administered subcutaneously once weekly. In part of this, we also learned how to improve tolerability of the drug, and we also worked with the formulation of the drug. In the early cohorts, we evaluated a frozen formulation, which was then wholly switched to a lyophilized formulation by the end of the study. The key learnings, as John nicely summarized, include kind of a nice safety and tolerability profile, pharmacokinetics, and pharmacodynamics that are not only very interesting and significant and as predicted, but also completely the same as the healthy volunteer studies. Importantly, there's absolutely nothing about having an autoimmune disease that changed the responsiveness of the immunoproteasome to 616 as a therapeutic or anything that changes the pharmacokinetics. We also saw very positive early efficacy signals. For those of you who have been following the MISSION phase I-B study, you know that we've shared interim results of earlier cohorts, today there won't be any surprises. What we learned is at the highest dose cohort of 75 milligrams, that it just reinforces the same safety and tolerability profile. It strengthens our position that KZR-616 has the potential to be a meaningful immunomodulatory therapeutic in patients with lupus and lupus nephritis, and then also beyond for other immune-mediated disease. Let's go to the next slide. This slide is kind of the combined learnings of what we learned from our two healthy volunteer studies as well as this MISSION phase I-B data in patients with lupus. On the left-hand side is a summary of our safety and tolerability. KZR-616 was administered for 13 weeks, again, weekly administration. The majority of our treatment-emergent adverse events are considered injection site reactions. They're very manageable. They're often described as redness or pain and itchiness at the injection site, and they resolve usually within one day. Our safety concerns have overall been quite favorable without anything that is eye-catching and very specifically nothing that appears off target at this point in time. We also look for similarities between other immunosuppressives or compared to the dual proteasome inhibitors, and to date, we have not seen any safety concerns that are shared among these groups. On the right-hand side of the slide, we have pharmacokinetics and pharmacodynamics. As John Fowler mentioned, the half-life of KZR-616 is actually measured in hours, and it is highly selective for the immunoproteasome. The immunoproteasome is expressed exclusively in immune effector cells and then in tissues that are considered inflamed. Otherwise, it isn't normally expressed as a cellular component of normal tissue. What we found in the range of doses that we study is that KZR-616 is highly selective with inhibition targets of the immunoproteasome at greater than 80% with all doses studied, starting at 30 milligrams, but specifically 45, 60, and 75 milligrams weekly. Lastly, the middle panel kind of summarizes the efficacy and biomarkers that we have looked at. This is specific to the lupus patients, obviously. So we looked at seven parameters of lupus-specific disease activity, and there was improvement across all measured parameters. We saw rapid and sustained gene expression panel changes that were consistent with immunomodulatory effect rather than immunosuppressive effect, and we saw a reduction in key biomarkers of disease activity. One of the things that we will share with you today, and especially Dr. Parikh will dive into deeply, is a novel biomarker that is a very specific marker of kidney inflammation, and that we are able to measure in two of our patients in this one key portion of the study. Let's go to the next slide. This table is kind of a summary of all the safety and tolerability. You've seen a portion of this in previous sharing of our data. The key finding after the completion of cohort three and the ability to look across all the cohorts in totality is there really are no new observations. Injection site reactions continue to be the most common adverse event. Nausea is the second most common treatment-related adverse event, and it tends to wane with subsequent dosing. We've learned some strategies to coach physicians and patients to tolerating the dose administration better. We had four total serious adverse events. These all occurred in the earliest cohort. Again, we have shared these with you previously. Just as a reminder of the four serious adverse events, three of the four patients were rechallenged with KZR-616 and successfully completed the study. Let's go to the next slide, please. Now we're going to turn to the exploratory efficacy signal. In here you see the seven lupus-specific disease activity measurements listed. Overall, although obviously the sample size is low, we see improvement across the board. The three columns are baseline mean scores, the end of treatment at week 13, and then an end of observation period at week 25. Not only do we see a reduction in these scores across the board, but I think also very importantly, what we don't see is a significant rebound following removal or discontinuation of 616 in the observation period. Let's go to the next slide. This slide, we went ahead and summarized all of the biomarker changes that we've seen in the MISSION phase I-B study. First, we looked at whole blood RNA sequence data from the MISSION phase I-B patients. Again, overall, all of the inflammatory modules support downregulation of pro-inflammatory markers, but not over suppression. Again, an immunomodulatory footprint. The immune gene modules had higher expression in patients with lupus relative to healthy volunteers and are downregulated with KZR-616, again towards normal rather than to over-suppression. KZR-616 treatment upregulates erythrocyte gene modules which are suppressed in patients with lupus compared to healthy volunteers. It's well recognized that in states of chronic inflammation, there's often suppression of erythrocyte cell lines, and these seem to normalize over time. This was reflected in stable labs as well. Platelets and red blood cells remained stable after 13 weeks of treatment, so we were not seeing any new reduction in hematopoietic cell lines. Anti-double stranded DNA antibody titers reduced over time in the eight patients who entered the study with elevated levels at baseline. This was eight of eight patients had a reduction in this very specific anti-double stranded DNA autoantibody which is a known marker of lupus. We had reduced circulating plasma cells which were observed and likely account for the reduction in autoantibodies. This is in contrast to the idea of total suppression of all IVIG or all antibody levels. To that, we measured the total IgG levels and found that they were unchanged following treatment with KZR-616. Last but not least, complement levels can be suppressed in patients who have lupus. In active disease, you will see a lot more suppression. In these patients in the safety and tolerability study, the C3 normalized in five of 10 patients who entered the study with abnormal levels, and the C4 normalized in four of six patients who had depressed levels at study entry. Let's go the next slide. This is the beautiful heat map looking at the inflammatory modules. What you can see on the far left is essentially the abnormalities in the patients who have lupus compared to healthy volunteers. At week five and week 17, you begin to see a reversal of the color patterns consistent with normalization. We also are showing the heat map for the erythrocyte gene modules. The same idea that we are seeing normalization without any overt immune suppression. Probably the most new thing we're going to talk about today, and what we've shared on our poster at EULAR is a novel biomarker called urinary CD163. It's a protein that's primarily expressed by M2c macrophages but also likely other monocyte lines. Dr. Parikh is actually very skilled and has done a lot of work with this biomarker, so I'm going to actually turn over the virtual podium here to him to both teach you about urinary CD163 and then discuss the two patients in the MISSION phase I-B study who had elevated protein expressed in their urine measured as a uPCR. We've previously shown you reductions in uPCR, now we have the confirmatory biomarker data that Dr. Parikh will go through. With that, I hand it off to you. Good afternoon, everyone, thank you. It's a pleasure being here with everyone today. I'm very excited to share some of this data and then talk about some of the unmet needs in lupus and lupus nephritis as we go forward. First, let me highlight CD163 as Noreen Henig mentioned. A lot of the credit for this work goes to our collaborating colleague, Juan Mejía in Mexico, as well as our group here at The Ohio State University that have really done some really important and interesting work looking at CD163. CD163 is a cell surface marker that's seen on M2c macrophages, but also on monocytes and dendritic cells. It's known to be upregulated in the setting of inflammation. It was initially studied in other conditions like ANCA vasculitis. The idea was, since macrophages are thought to be heavily involved in the pathogenesis of lupus nephritis specifically, we wanted to study urine CD163 to see its expression in the urine at the time of flare, its specificity for lupus nephritis, and how it correlated with disease activity over time. The study that's referenced here really looked at multiple cohorts, one from Mexico City and one from Ohio State in Columbus. It was initially a cross-sectional cohort to look at CD163 in the urine at the time of flare compared against non-renal lupus, inactive lupus, as well as other glomerular diseases. I don't show the data here. It's certainly all there in the reference, urine CD163 was most highly expressed at lupus nephritis flare compared to the other glomerular diseases and compared to inactive lupus and non-renal lupus. Importantly, urinary excretion, but not plasma levels of urinary CD163 correlated highly with active inflammation in the glomerulus during lupus nephritis. Then I think probably the most interesting and relevant is the longitudinal analysis in two different cohorts that basically showed urine CD163 to rise prior to clinical flare and decrease over time in response. Actually, there was a threshold cutoff level of 370 at six months that predicted a one-year response. Finally, it really correlates strongly with activity index on a kidney biopsy. For those that don't know, activity index is a semi-quantitative score given by pathologists on what the active inflammation that's going on in the kidney at the time of flare. When they did repeat biopsies in patients and looked at urine CD163, it seemed to correlate strongly with the level of activity. A threshold score of 370 had a sensitivity and specificity of greater than 87% to predict response. Just to show, at least in those two cohorts, urine CD163 seemed to correlate strongly with disease activity. We can advance the slide. This is looking at actually a patient of ours that was enrolled in the phase I-B study with Class IV plus V lupus nephritis, had nephrotic range proteinuria, so proteinuria greater than 3.5 grams, and had been tried on multiple therapies. She has a long-standing history of lupus. She had been on multiple therapies, including mycophenolate, tacrolimus, mycophenolate mofetil, hydroxychloroquine, prednisone. Despite all of these therapies, she was just progressing through and was not responding. Her C3, C4 levels, her complement levels were low. Her proteinuria levels were obviously in the nephrotic range. She had active lupus nephritis and actually enrolled in the phase I-B portion of the study, really in part because she had limited options in terms of what else we could do to help get her disease under control. Just as a caveat, with this patient, and this was in the older formulation of the therapy, with her first injection, she actually had a very severe systemic inflammatory response that happened. After that response to the first injection, she actually asked us to continue to participate in the study because she felt later on in the week after she had recovered, that she was actually starting to feel better. She did have this two to four-week delay in getting restarted because as we were trying to tease all this out, this was at the very beginnings of the phase I-B study. Once she did restart, you can see here and what's shown in the figure in the blue is the CD163, and in the pink, you can see the urine protein-creatinine ratio. You can see her CD163 level was elevated at the time of flare and then comes down over time and correlates very well with the urine predates the proteinuria response. She had over a greater than 50% reduction in urine protein-creatinine ratio at week 17. Her double-stranded DNA titers had reduced by week 13. As I mentioned, her urine CD163 level preceded the reduction in urine PCR, and ultimately, she attained a clinical response. You can see the% changes in her anti-double stranded DNA and SLEDAI-2K, and her SLEDAI-2K changes in the table to the left. We can go to the next slide. This is another patient who actually had lupus nephritis. I think there was only two patients in the phase I-B that I think, and you can correct me if I'm wrong, that had lupus nephritis in the study, and this is the second patient of the two. This patient had a Class III lupus nephritis and was on baseline background therapy of mycophenolate, hydroxychloroquine, and prednisone. Also had nephrotic range proteinuria at the time of screening with 3.5 grams. This patient also, by week five, had a greater than 50% reduction in urine protein-to-creatinine ratio with improved symptom scores and a reduced anti-double stranded DNA titer at week five. You can see again the CD163 levels. Here's the proteinuria in pink. The CD163 levels decreased from the first injection on and remained low titer throughout the remainder of the study. Again, just showing just as another at least a non-invasive biomarker potentially we can use that correlates with disease activity and is showing that we're getting not just reduction in proteinuria that we're looking for, which is very important, but what seems to be suppression of intra-renal or glomerular inflammation, which is what we ultimately want to see. Leading to, hopefully, histologic inactivity, although we don't have any biopsies, that would be the suggestion from the decrease in the CD163 level in these two patients. Okay. This is looking at all patients experienced, basically the anti-double stranded DNA levels in patients who actually had an elevated level at the time of the study initiation, and I think there's eight patients here, and you can see that all of them had a significant or considerable reduction in anti-double-stranded DNA by week 13. That continued for the majority of these patients and by week 25, which was the observation period towards the end of the study. You can advance. I guess I can summarize this for the phase I-B, it seemed, checking all the boxes here of safety, tolerability, efficacy, and PK/PD dosing in the current trial, which I think was the goals of this therapy and certainly what we experienced with the three patients we had enrolled in the study. Okay. I guess for the remainder of the meeting, I'm going to touch on some of the unmet needs in lupus and lupus nephritis. You can advance the slide. What is lupus and lupus nephritis? Lupus is a systemic, multi-system autoimmune disease. It's basically the crème de la crème autoimmune disease, immune complex-mediated autoimmune disease. It can affect every organ in the body. The challenges with treating lupus is that it's quite heterogeneous, and we can't predict who's going to get what, frankly. When we try to target the treatment and try to predict outcomes and those types of things, we don't have the biomarkers available to help do that for the most part. It definitely impacts the ability to advance therapeutics, frankly. Overall, there's about 300,000 adults in the U.S. with lupus, and approximately 50% of those go on to develop lupus nephritis. Lupus nephritis, which is the hallmark kidney disease associated with lupus, carries the worst prognosis for patients with lupus. They have greater comorbidity, greater mortality, and the poorest outcomes. Lupus, in general, affects the young and predominantly female population of childbearing age, 9: 1 ratio of females compared to males. This is a younger population who for the most part oftentimes don't have any other illnesses, are perfectly fine until they're not fine. They come to presentation with multiple symptoms especially that are quite debilitating, fatigue, joint pains, rash. When the kidney's involved, as I mentioned, it's associated with the poorest outcomes. About 10%- 30% of patients who do develop lupus kidney disease or lupus nephritis progress to end-stage kidney failure within 15 years. Again, these are young patients, so within 15 years of diagnosis, they're still young patients. It's something that is a critical unmet need for us in trying to prevent this progression and preserve their overall health. Kidney involvement is associated with poor outcomes, as I mentioned. One of the most important influences of outcome is race and ethnicity. If you look at the two figures to the right, you can see who's at risk for developing lupus nephritis or lupus kidney disease. You can see by far it's those of Black patients and Latino patients are at much greater risk of developing lupus nephritis compared to Caucasian patients. In terms of progressing, having doubling in serum creatinine, end-stage kidney failure within three years of diagnosis, much greater risk in Black patients and Latino patients compared to Caucasian patients seen in these two trials, and that bears across the board. There's a lot of reasons for these disparities, but it's not just socioeconomic access to care. There is clearly differences in response to treatments as well, and those things are still being elucidated. There's a clear understanding that it's not just based on access to care and affordability of medicines, et cetera. You can advance the slide. Yeah, we talked about how lupus can cause a lot of debility, and these kind of data and facts just point to it. It can severely impact the patient's ability to work. An average annual lost economic productivity for a patient affected by lupus is $120,000 per year. It takes a considerable physical, mental, social, and emotional toll on patients. A lot of it's not quantifiable. I cannot tell you the number of times as a provider I say, "Oh, things are getting better," and the patient looks at me like I'm crazy. While our clinical data suggests that things are getting better, they don't feel any better. The fatigue and the joint pains and the weakness that goes along with this, as well as the considerable toxicity, as I'll mention with the current therapies that we use, are factors and challenges, the hurdles that we need to overcome to improve our patients' quality of life as well as improve their overall health. Some of the negative health factors, this was as reported by ICER or clinical and economic productivity group that looked at these factors. Patients tell you fatigue and joint and muscle pains and kidney disease are three of the most common reported factors that really are negative health factors for them. That leads to poor quality of life. As they get poor quality of life, the treatments that they're on don't seem to be helpful. Can you go back a slide? Reduced treatment adherence, that leads to disease progression. What about when we talk about economic burden? The average annual healthcare cost for a person with lupus is greater than $32,000 per year, that cost increases considerably in patients who have severe lupus and lupus nephritis. What accounts for that cost? Mostly inpatient admissions, outpatient visits are the largest drivers of cost, and I'm sure medications are a part of that. According to ICER, the negative treatment factors that patients report, side effects from the medicines, pill burden, which is considerable, and cost, as we mentioned. ED visits, hospitalization rates, inpatient length of stay, ambulatory care utilization are greater for patients with lupus nephritis compared to those with lupus without nephritis. As you can imagine, when the kidney is involved, there's a lot of other complications that can come along with it in addition to the more aggressive and intense immune therapy that they're on. Thank you. Advance. What are the goals of therapy for patients with lupus nephritis? Let's just take a step back and talk about treatment. When we treat patients who come to clinical attention with lupus nephritis, we're treating them initially with high-intensity immunosuppression. These are broad therapies. They're non-specific. They target the immune system broadly to help control the disease activity. That period is followed by a period of longer treatment with less intense immunosuppression to consolidate the response and help prevent flares. We do this with our goals to achieve a rapid response, prevent flares, with the idea at the same time trying to limit treatment toxicity. The whole point of all this is to improve quality of life and also to reduce morbidity and mortality. Can you advance one click? Ultimately, our goals, our long-term goals, is to preserve long-term health. When we talk about lupus nephritis, we're talking about long-term kidney health. When we talk about preserving long-term kidney health, what we really also mean is preserving long-term cardiovascular health. At every stage of chronic kidney damage that occurs or accrues, you have an exponentially increased risk for cardiovascular morbidity long term. It's really critical to actually treat the kidney early, prevent the chronic damage, as we look at globally of trying to preserve these patients' long-term health. Can you advance? What do we use to treat lupus? This is looking at lupus in general, and it's stratified here by mild disease, moderate disease, and severe disease. I'll qualify those statements as they're somewhat arbitrary in terms of how they're designated into these three buckets. You can think about the first-line therapies for mild disease. Anyone who walks in the door with a diagnosis of lupus, hydroxychloroquine is a mainstay immunomodulatory therapy that works well to help manage mild symptoms and is fairly well-tolerated. Corticosteroids, historically and to this day, are used routinely, often, and maybe overused for patients with lupus and lupus nephritis. They're used in mild, moderate, and severe disease at varying doses and often high doses to start. Other immunotherapies, broad immunotherapies that are used like methotrexate, azathioprine have been around for decades and used across the board in autoimmune diseases. Cyclosporine or calcineurin inhibitors are also used in moderate disease. mycophenolate mofetil, a medication used commonly for solid organ transplant, is a mainstay for treatment for lupus nephritis and severe lupus as well. Prior to mycophenolate mofetil, cyclophosphamide was the mainstay, an alkylating agent, broad immunosuppressant, basically used initially as a chemotherapeutic agent and then used for lupus and other autoimmune diseases as well. More recently, B cell depleting drugs like Benlysta or Belimumab have come online. There's more specifically targeted therapies addressing the B cells and depleting B cells in lupus is used for moderate lupus. In severe and refractory lupus and lupus nephritis, rituximab has been used. That is used based on more observational cohort data compared to randomized controlled data, which largely in those trials has been negative for rituximab. Still, in the observational cohorts in patients who do not progress through these standard care therapies, rituximab or anti-CD20 therapy has been used successfully to help control disease. Can you advance? What is the standard therapy for proliferative lupus nephritis? When I say proliferative lupus nephritis, I'm talking about Class III and Class IV lupus nephritis. These are the most aggressive forms of lupus nephritis or mixed lupus nephritis, that's III, IV plus V. Without getting into too much detail of the pathology, these are our most aggressive forms of lupus nephritis associated with the poorest outcomes. Okay. Our standard therapy historically has been utility of high-dose prednisone. This would be methylprednisolone IV at varying ranges from anywhere from 0.5 or 0.25 to one gram per day for three days, followed by oral prednisone up to one mg per kg per day, 0.5-1 mg per kg per day. That's tapered slowly over weeks. Unfortunately, the high-dose steroids stay on for quite a long time. If you look at the treatment algorithm, and this is just historically, it's been cyclophosphamide at three different regimens. Whether it's Euro-Lupus, which is a lower dose cyclophosphamide, which is more commonly used when it is used nowadays at 500 milligrams every two weeks for three months versus the older NIH regimens that had considerable cyclophosphamide exposure. We know what the side effects of cyclophosphamide are associated with cumulative exposure, really. Versus mycophenolate mofetil, which is not new, but certainly more recent, and ultimately has become more of the standard of care in addition to corticosteroids for treatment of lupus nephritis. When we use those therapies, the biggest question we have is how effective are they? You can advance by one click. If you look, and this is looking at the randomized control trial, the ALMS study, which is the hallmark study that compared NIH protocol cyclophosphamide and mycophenolate. It looked at overall outcomes, and this is response at six months. You can see the partial response was about 50% in both groups. The complete response is quite low, 8%-9%. If you go out to 12 months, that gets better, but not that much better. We're talking about 20%-30% complete remission rate at 12 months. This is not unique to the ALMS study or mycophenolate. This is across the board when we look at lupus nephritis trials, regardless of the regimens that we're using. If I highlight the most recent studies, this is looking at two drugs that were FDA approved recently, for treatment of lupus nephritis, the first two drugs. These are landmark trials, incredible to finally get drugs approved for lupus nephritis. I just want to hone in on one thing here. If you look at the voclosporin obinutuzumab, which was a phase II study that had positive results in lupus nephritis, an anti-CD20 drug, and Benlysta. Even with these positive trials, and there was clearly a difference, you're still seeing a good percentage of patients, over 50% of patients at 12 months, who have not attained a complete renal response. That in and of itself suggests that remains a large unmet need, and we have more work to do to treat our patients so that we can get to a level where 70%-80% of our patients are achieving the complete clinical response. If you could advance one slide. One of the questions then becomes, well, what about just overall response? Why complete response? This study here highlights it nicely. If we look at the difference between clinical response, type of clinical response, so really getting the proteinuria levels down, controlling disease clinically compared to partial and no response, you can see it makes a huge difference at 10 years. This graph just shows three different groups in patients with severe lupus nephritis and shows the number of patients that ended up in complete remission and whether they ended up on dialysis 10 years later. In the first graph, you see the patients who had a complete clinical response or remission, 92% of them were off dialysis or did not require dialysis 10 years later. They were still doing fine. What about partial response? Certainly better than no response, but you can see 57% of those patients ended up progressing to end-stage kidney failure requiring dialysis. Whereas if you didn't have any response, 87%. The point is that while having positive studies and new drugs is fantastic, we need to achieve a better complete clinical remission if we really want to move the needle in taking care of our patients with lupus nephritis and preserving our long-term kidney health. You can move forward one slide. Let's take a look at these immunosuppressants briefly. I'm not going to walk through all of them, but you can see the list, and many of these are well known, and their side effects are well known. From methotrexate to azathioprine, to mycophenolate, and cyclophosphamide, they are effective therapies. Certainly, they're broad immunosuppressants, but they do come with side effects, as you can see there. The one therapy I want to highlight is corticosteroids. With corticosteroids, these are the broad anti-inflammatory therapies that we all use for patients with autoimmune disease, in particular lupus nephritis. We use it in high doses routinely, although that is changing, that conversation is changing, and we are going towards less use of corticosteroids. The biggest issue, and patients say the same thing, initially, they're fantastic. They make you feel better. It's great. Long term, the side effects are quite frustrating, debilitating for both the provider and the patients. These side effects include fluid retention, weight gain, hyperglycemia, diabetes over the long term, hypertension, bone issues with osteoporosis, of course, infection risk, cardiotoxicity, and then other things that are really debilitating for patients and affects their quality of life, insomnia, mood changes, weight gain. All these things are really important, they really impact the patient's overall feeling towards treatment and what we're trying to achieve. The one thing I want to highlight here, especially when we're talking about kidney disease, is lupus nephritis and kidney disease are often silent. Patients don't know that their kidneys are injured a lot of the time, especially these patients. Why don't they know that? It's because early on, when there's heavy proteinuria and when there's proteinuria hematuria, oftentimes in these patients, their kidney function is not terribly abnormal. They may not have hypertension. Unless they have nephrotic range proteinuria, they may not even have that much swelling. They don't know, over time even. When they start to feel better, they feel like everything is getting better, and they still require these therapies. It's because we're telling them that, "Hey, you still have proteinuria, you still have blood in urine." If you're not feeling well and you don't like the therapies that you're on, logically, it does create an issue with drug adherence, medication adherence, and appropriately so, when you're feeling poorly and you're not understanding the results. Education is critically important. It just points to the fact that we need better therapies than corticosteroids to help treat our patients with lupus nephritis. On top of that, just better therapies, but with less side effects. To sum up here, and hopefully we have time for questions. There's currently no cure for lupus and lupus nephritis. In patients who develop lupus nephritis, within five years of proliferative lupus nephritis onset, about 5%-25% of patients will experience death due to renal disease. There are new medications that are FDA approved. Benlysta or Belimumab, their voclosporin received their FDA approval in 2020 and 2021. Even with the positive results, as I mentioned, there's more work to be done. We need to improve our response rates because they're still unacceptably low. The current standard of care therapies are associated with serious adverse events and side effects, as I mentioned. We want to maintain remission and limit the amount of toxicity. Induce remission, maintain remission, and limit toxicity. Those are our goals. In patients who have refractory disease, and many of them are roughly about fewer than 60% of patients with Class III to V lupus nephritis will achieve a complete response to induction therapy. Importantly, even when you do get a response, approximately 30% of patients will experience flare. We know that the more flares you experience, obviously the more chronic kidney damage accrues and the higher risk of progression of end-stage kidney failure. Again, I hope in this bit of time, I was able to impress upon the importance of, or at least describe the unmet needs and where we need to go with lupus nephritis therapy to help our patients get to a greater level of response and better quality of life. With that, I'll happily stop and we're happy to take questions. I'll pass it back to John. I'm sorry. Thanks so much, Samir. That was incredibly insightful and detailed and really powerful to hear those stats. I know we're getting towards the end of the half hour, so rather than try and wrap up with any comments there, I'll just open straight up to questions, see if we have people with specific questions we can help answer in the few remaining minutes. It looks like we have Philip Nadeau from Cowen ready to ask a question. Philip, I think your line is now unmuted. Great. Thanks, Celia. Just a couple questions from us. First on the new CD163 biomarker, Samir Parikh, could you maybe give us a little bit more information about what baseline levels are typical for LN patients? It looked like pretty divergent levels for the two patients that were shown. What magnitude of decline is clinically meaningful? Yeah. I think what I can point to is a study that was done and published in JASN with the two cohorts that we had in patients who had active disease. You're right, it can be divergent, and the levels individually may be different, a little bit of variability, and a lot of that might be related to the amount of inflammation that's present in the kidney at the time of biopsy or at the time of lupus nephritis. On average, we're seeing levels at the time of flare roughly above 1,000. I think the marker that really differentiates is being able to achieve that level below 370. That, at least in our data, in our study, looking longitudinally, if you see a reduction of CD163 to below 370, those patients went on to develop a complete clinical remission. Whereas if you didn't, those patients actually ended up being non-responders at the one-year mark. I hope that answers your question, but I want to qualify all this. This is not a clinical biomarker. This is not something that we use in clinical practice. It's not available for clinical practice. It does need to be validated in larger cohorts of patients, and we hope to do this in clinical trial settings like this one really to show that CD163 is a biomarker that can be used and really reflects histologic disease activity. In the data based on the JASN paper and the two cohorts, you can see on average, I think the levels were over 1,000 at the time of flare. That's perfect. Maybe just one question for management. In terms of the pre-medication that was studied in cohort two and three, I'm curious to get your conclusions on whether that pre-medication worked in reducing side effects. It seems pretty clear the step-up dosing and lyophilized formulation certainly did. What's your conclusion on whether pre-medication is necessary? Thanks for the question. This is Noreen. In general, we are not requiring pre-medication. We offer kind of suggestions that include, as you mentioned, non-sedating antihistamines, antiemetics, et cetera. Oral hydration actually is also a big one. From some investigator-level feedback, the oral hydration and an oral antiemetic has been helpful for patients who do experience nausea. The other ones is the benefit is less clear. That's very helpful. Thanks for taking our questions and congrats on the data. Thank you. Thanks, Phil. Okay, the next question is from Maury Raycroft at Jefferies. Maury, I believe you are unmuted. Great. Thanks, everyone. I had two quick questions. Maybe the first question is on just the total disease activity score that you are showing. The cumulative score is impressive and seems to have improved further with the cohort three data in there. Just wondering if you can talk about further potential use of the 75 mg dosing. Then also if you can comment on the two discontinuations in the 75 mg group as well. Yeah, super. Thanks for those observations. In the 75-milligram cohort, we did see levels of efficacy as well as PK and PD that was commensurate with the earlier cohorts. In general, we believe that the 75-milligram dose level was well-tolerated. It gives us a larger therapeutic window, we're also very content at this time to focus on the 45 and 60-milligram weekly doses that we're currently using in the PRESIDIO and the MISSION 2B study. With respect to the two discontinuations in cohort three. Those were a bit challenging. Ultimately, the two subjects were related, a mother-daughter pair, and there were issues related to participation in the study, as well as the fact that they each experienced somewhat different adverse events, but not one overwhelming one. I think the combination of the discomfort and some of the challenges of study participation, especially in the COVID era, led them to withdraw from participation. Got it. Okay. That's helpful. The other question was just on some of the data that you showed in the earlier slides. You mentioned that there was a reduction in plasma cells, which I think is an indicator of on-target activity. Just checking if you saw any reductions or differences in other lymphocyte types that you can comment on? Chris, do you want to jump in on this because you did those analyses? Yeah, sure. More happy to answer that question. The data, which actually came from the first two cohorts of data with 616, so cohorts one and two, and we are analyzing data for the remainder of the study now, indicates a significant reduction and long-lasting reduction in circulating plasma cells. A trend, though not statistically significant in central memory B cells as well, but no change in other lymphocyte compartments as measured by flow cytometric analysis. However, the gene expression data suggests changes both in the B cell compartment as well as T/NK and dendritic cell changes, and we'll be monitoring those by flow as well as by gene expression with the full data set over the coming year or so. Great. Thank you very much for taking my questions. Thanks, Maury. The next question is from Matt Phipps at William Blair. I believe you are now unmuted. Thanks for the presentation. Hopefully, you can hear me. One question I had on the enrollment of the MISSION trial. I appreciate you all providing an update for enrollment for that and PRESIDIO. Do you have any just comment to the rate of screen failures? You've enrolled nine, just how many you've screened, and if it's more of a screen failure issue or just kind of finding these patients to begin with? In the prior iterations of MISSION, the screen failure rates were very high, almost complete screen failure rates on previous iterations. Under this current amendment, it's really been the essential headwinds of the COVID pandemic, just finding the patients has been the big issue facing us over the last year. Thanks, John. I think maybe for Samir or Noreen, one of the biggest issues investors right now is just how to think about what a response rate would look like in a patient who's on stable therapy for at least eight weeks but still has proteinuria, and then you add on another treatment. I don't know if there's really much data to point to, but I guess if you had someone that was on, let's say, MMF, and hadn't responded by eight weeks, how likely do you think another 4- 12 months or 48 months that that patient could get to a complete remission by themselves without changing the regimen, I guess? Yeah, I guess I can try to address this. It's actually a really good question, and I think this is where the challenge is for a lot of lupus nephritis trials in general. Because there's several trial designs where we use this kind of window of enrollment and monitoring observation, and then they randomize after, say, three months of standard of care therapy into a treatment arm versus a placebo. I think the challenge there is, you're right. I think patients can respond to standard of care therapy over time, and we don't commonly see a complete clinical response in, for example, three months of therapy, right? I do think that a lot of patients, though, that maybe enrolled in this trial may have had background therapy for quite a while, frankly, because I think traditionally with lupus nephritis, when we talk about using standard of care, we give it to six months in many cases before we actually start to look at patients as being refractory, so to speak, to the standard of care therapy. I do think that there may be some of that where patients who are enrolled, say, after eight weeks of induction therapy could have continued to get better. I think part of that can be addressed by if they've had no movement in their proteinuria level at all prior to enrollment, and certainly less than 50% response. We do tend to see that within at least 12 weeks of therapy, that patients who are going to respond tend to start to have some movement in their proteinuria towards remission. Again, there's a good percentage of patients that don't respond to the standard therapy at all, and so having this potential add-on could prove helpful, certainly. Samir, can I just ask one follow-up to that? Would you expect CD163 based on the data you guys have, which I realize is not from a perspective to maybe move quicker, like if you maybe see CD163 drop by three months? Yeah. That's exactly right. I think that's the value in looking at CD163 in those two particular patients with lupus nephritis and, in a way, it really replicates the data we were seeing that was published in the JASN paper in 2020, where the CD163 not only went up prior to clinical flare, but also went down prior to proteinuria. We do expect to see that. If you're attenuating intrarenal inflammation, right? If that's the objective of all this, which it is, and proteinuria is our surrogate marker, which isn't a perfect marker, but if CD163 is reflective of macrophages and dendritic cells or monocytes, inflammatory monocytes in the kidney, and if you're attenuating the inflammation, I would expect to see the urine CD163 levels decrease before proteinuria levels do, because you have tissue healing that has to happen after that. It takes time. I think what we showed in these two patients actually reflects exactly what was published in the JASN paper, and yes, I would expect to see the urine CD163 levels to come down just like they did, prior to the proteinuria levels. Great. Thanks. All right. Thanks, Matt. Okay. Our last question that we have time for is from Yanan Zhu from Wells Fargo. Yanan, I think I just queued you to unmute your line. Okay. Can you hear me? Yes, we can. Yeah. Thanks for taking my questions. First, a question on CD163, for Dr. Parikh. I'm just wondering, are there CD163 data available for Voclosporin or Benlysta that we can potentially compare to when we have more? Yeah Hopefully from the phase II study of 616? Yeah, not yet. I think Voclosporin and Benlysta, and maybe it'll come in the future, I don't know, as they won't go back and decide what kind of exploratory studies they want to do. I can't speak to that. I can say that there is not urine CD163 data in those two large randomized control trials available. To be clear, the data on CD163 in lupus nephritis actually really was published just recently, within the past year. It wouldn't have been done when those trials were originated in the first place. They'd have to go back and measure them all post hoc. It's also not a marker that's used clinically yet, the data seems fairly, of all the biomarkers that have been tested in lupus nephritis, and we've been part of that conversation for years now. This has probably been the most exciting one that we've worked with, at least, in our ends here at Ohio State. Got it. Perhaps a follow-up question for Dr. Parikh. Regarding the efficacy and safety outlook for 616, Dr. Parikh, you emphasized that the unmet need is a greater complete response rate, currently for the treatment of lupus nephritis. I know we only have two patients of data, with that kind of renal manifestations in the current trial. Would you be able also to look at the lupus patients and, based on that data, and comparing it to perhaps Benlysta, and draw some conclusion as to whether 616 has the potential to demonstrate a greater complete response rate than Benlysta, for example? I think I can answer maybe to some extent. I don't know if I can answer fully. Let me first start by pointing to the lupus nephritis and what we talked about complete response rate. Yes, complete response is a goal, right? That's where we want to achieve, because we think those patients will do the best, right? They'll have less flares, they will have a better long-term outcome, et cetera. We also want to improve overall response. Of course, 50% overall response is not good enough either, right? We want to just be able to make everyone go through some form of response and increase that complete response rate. If we can get up to 70%, 80% complete response, that'd be fantastic. I will say, if you're trying to compare Benlysta and KZR-616, I think just in general, these are two very different products in terms of what they do. I think, when you look at the belimumab data and you look at belimumab's action, and B cell depletion in general, right? These are not anti-inflammatory therapies. They don't knock down or attenuate inflammation upfront. Their work is mostly done, this is not specific to lupus, this is true if you look at other diseases as well, and it applies from belimumab to rituximab, et cetera. Our experience, and this is not just us, this is in general, these drugs take a little bit of time to work. Their greatest benefit attribute, in my mind at least, is in prevention of relapse, and really kind of preventing flares once you're able to get the disease under control. Something like a KZR-616, if we're talking about induction therapy and trying to achieve an earlier clinical response and maybe limiting steroid use, this is where the excitement comes for me, with this type of product where it broadly addresses the inflammatory milieu that goes on in an autoimmune disease like lupus. It may suppress inflammation quickly. When we're talking about in the phase I-B, you're talking about 13-week responses. We never talk about 13-week responses in lupus nephritis. We're talking about 26 and 52 week, and even longer responses because we don't expect to see anything happen that fast, frankly. We just don't usually see it. I think it's important to make a little bit of distinction. It's hard to compare the two drugs, and I know that's what we try to do with all these drugs, but their mechanisms of actions are so different and where they may be best applied. I think this is the evolving story and discussion that we have amongst those who take care of patients with lupus nephritis is when should we be applying these therapies, right? From my perspective, I think, at least speaking to lupus nephritis, I think something like a KZR-616 has the potential to really help us upfront, attenuate the inflammation, reduce the steroid burden and side effects associated with steroids which are so considerable and may have benefit longer term too in preventing relapse. I don't know that yet, but I think that its mechanisms of action suggest that it'll have a more upfront role where something like a belimumab, I would expect that to have its role down the line, so to speak. I hope that answers your question at least for the lupus nephritis part. Then for lupus, I don't know that I can directly compare offhand the data from the belimumab trials and their response rates. Obviously, those are bigger trials, longer duration as well. I don't know that with this small study compared to that, I don't know that that would be an apples-to-apples comparison, so to speak. Got it. Thank you, Dr. Parikh. Thanks, Yanan. I think we're kind of out of time. Yeah, we're way past, but thank you. Appreciate it. I will hand it back over to John then for some closing remarks. Thanks, Celia. Thank you, everybody. I really appreciate those great questions. Samir, thank you so much for participating and lending your thoughts to this conversation. It's incredibly helpful, excellent context, and just really underscored a lot of what is getting us at Kezar most excited about this phase when we get it today and the broader potential for 616 as a possibly steroid, very rapid-acting very novel agent. We look forward to speaking with many of you on the call who didn't have a chance to get your questions in. We have a number of meetings over the next few days with some of you, and thanks again for tuning in today. Appreciate it.