Good afternoon and welcome everyone to Qsar's webcast to discuss the results of the completed MISSION Phase 1b clinical trial in systemic lupus erythematosus and lupus nephritis. I'm Celia Economides, the Senior Vice President of Strategy and External Affairs at QSAR. At this point in time, all participants are in a listen only mode. A Q and A session will follow the formal presentation. If you would like to ask a question during the Q and A session, please use the raise your hand function on Zoom.
This morning, we issued a press release detailing results from the MISSION Phase 1b 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 Both the press release and our poster presentation are available on our website at kedarlivesciences.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 on 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 a 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. And thank you everybody for dialing in today or Zooming in today as the case may be to catch up on the latest news with Keyzone. We're very excited to be presenting the final chapter in the Phase 1b 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 Henning as well as one of our investigators, Doctor.
Samir Parikh. So Joy, if you wouldn't mind advancing to the next slide. Celia did make this disclaimer very eloquently, so we will be making forward looking statements. So that should come as no surprise. And there's me with a full necktie on.
Let's move on to the next slide, Joy. Great. From the Keyzars 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 Keyzars' President and CSO and obviously involved with the 616 program from the very, very beginning. Doctor.
Nordorian Henning is joining us today and will walk you through the majority of today's slides on the Phase 1b results. And from the final portion of the key to our team joining us is Celia, who opened the call. And I have to share the bittersweet news with you all that we're bidding a 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, but it's a really unique opportunity with a very sizable company. We're extremely happy for her and look forward to sharing her success in her future role and grateful for all the hard work she's brought to bear on Kizar's behalf over the last 2 years. It's not the only personnel news in Kizar land.
We actually had a press release yesterday announcing the addition of a new director to our doctors, Doctor. Mickey Clearman, 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 in giant cell arthritis, 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 KZR616 and lupus nephritis and beyond. So next slide please, Joy. And then I mentioned this earlier, but I'll kick things off.
Noem will ably walk you through the data and then we're really grateful that for Doctor. Creek to join us today. He is going to be able to speak to the burden of these severe illnesses of lupus and lupus defrost, but also his direct experience working with KZR616 in the Phase 1b portion of this trial. I do believe based on the number of slides we had to get through that there will be a little bit of time left over at the end for Q and A. So definitely welcome your questions when we get to that point.
And 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 kind of celebrate what this means, the conclusion of the Phase 1b 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 immunoprolosome at multiple therapeutically relevant doses from 30 milligrams on up. We learned key things about how to effectively dose the drug. So 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 learn. 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.
And because of that, we don't think there'll be serum monitoring required for KZR616 and 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. So in addition to the safety and tolerability profile, it's an efficacy profile that we were hoping to catch a glimmers of. And I feel like in a open label Phase 1b, that's what you hope to see the first signs of an active drug. And we definitely feel like we checked all the boxes on that front as well. And Lalin will walk you through that data.
But again rapid broad responses almost resembling steroids in terms of the rapidity and breadth of the response. And we're seeing biomarkers improving not just uPCR, but any double stranded DNA complement levels when they were out of whack, but also composite scoring like SLEETI, CLAZ. So really the bright signposts for an active drug that we're so excited to of course get to the Phase 2 data portion on in the later part of this year and next year. So again, before I hand the baton to Nouri and Samir, I just want to walk through a couple of these slides and this one that Joy has shared right here is 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 emphasized that statement and particularly just that 4th check mark there on the right, I'd like to highlight as having 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. And I've had 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. So Joe, if you'll go to the next slide, What and this is animated slides, if you hit the button a couple more times, we'll get a little bit of a pretty animation there exactly. Again, the core of what makes 616 exciting is this mechanism of action, which is so uniquely broad.
And whether it's the adaptive immune system or innate immune system as it represented on the T cells, B cells and macrophages on the left side, the immunoproteosome is there and it's the dominant form of proteasome. And we really 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's treating these patients that the unmet need has been completely resolved. So we're excited to 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 hormonal 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 K-six 16 over the past year. Joy, if you move to the next slide, I just have a couple of slides left here.
And 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 and we've chosen, I think, wisely and boldly in treating patients with lupus and lupus nephritis where there's both preclinical 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 slide we'll move to talks a little bit about the disease burden of lupus and lupus rest. I will not go through these points.
I think Doctor. Pareek will be much better poised to speak to this from his own experience. I know he has several slides to go through, but there's no question that both lupus and lupus nephritis have massive amounts of unmet need and we've been extremely gratified to see some of the recent approvals, particularly in the LN space, but it's not the end of the storyline in that disease. And I know that patients are still very much in need of new treatment options as well. The final slide or 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-nineteen pandemic, the idea that we can have a drug that allows patients to maintain normal vaccine responses is a really big deal. And this has really increased the confidence interval in investigators and in patients to come on to the study and to be able to do so safely. This is just a longstanding CECLAR slide that shows work that Chris and the team performed in monkeys showing normal vaccine responses even after KLH immunization. So happy to talk about this and what this means and how really this will continue to differentiate 616 and build upon the strong safety and tolerability profile that we've really laid a foundation for this Phase 1b portion of the study.
So 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 616 clinical program. In the middle portion here and downward, you can see that we're moving up 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 has to learn an incredible amount about chronic administration and safety and tolerability as well as efficacy. So we get a lot of questions about where the trials are going, how they're going, how the pandemic has affected the studies.
Obviously, last year in the MISSION study and Perseus said there were significant implications from the COVID-nineteen pandemic. We independent of that, we actually redesigned the mission Phase 2 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 Baclosporin and by Benlis. And it's been a successful design, 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 2 portion of the study.
As a result, this newly designed as of last year MISSION Phase 2 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 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 has 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 Q4 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 Q4 of this year. And since early 2021 under this new protocol, we've been able to enroll patients. And as of June 1st, we've enrolled 9 patients in the Phase 2 portion of MISSION, which I think will be that's a statistic even though we haven't been sharing enrollment updates, it was important to share this time so that there was clarity and understanding what to expect in the Q4 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.
And we feel confident based on the progress and ongoing screening activity with our guidance for a top line on all twenty patients in the first half of next year, in the second quarter of next year, so later part of that first half of next year. And in the spirit of updates on the PRECIDIO study, that's a study that we launched in late 2019. So it was open for a good period of time before the pandemic hit and we were making good progress. We had enrolled our first patients before that pandemic hit. But 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 into the first half of twenty twenty two.
I'm pleased to share that similar to the mission study that the screening activity has picked up significantly in the last several months. And as of June 1, we've enrolled 19 out of the 24 target patients in that study, which we're very pleased about. And roughly half of this enrollment has occurred since the start of 2021. So it's 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 and with multiple patients enrolled into that open label extension and the work continues.
We're excited to push to finish in full enrollment and being able to offer home visits across the United States for patient stays been critical keeping this study moving forward during COVID. I'm really proud of our team's household
commitment
and creativity to get this trial as well progressed as we have against the backdrop that we faced. Again, I can reiterate our guidance for the first half twenty twenty with a real focus on the second quarter of that timeframe for a top line readout there. So couldn't be more excited for the 616 development program overall and for what is to come in both the MISSION and PERSIDIO studies. This Phase 1b update is a critical step along that journey. And let's dig into some of that data now.
I'll look forward to any questions people have at the end, but for now let's hand the control over to Noreen and talk about the Phase 1b results.
Super. Thank you very much, John. I do have the pleasure of jumping in and sharing with you the results of the Phase Ib portion of the MISSION trial. It's a study that is designed in 2 parts, the Phase Ib portion, which is finished enrollment and here at EULAR in our poster, we are sharing kind of the complete results of this portion. And then as John mentioned, we are actively enrolling what we call the Phase 2, which is a small 20 person open label study of 616 added on to patients' existing therapy without any induction.
So 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. So with that, I'm just going to set the stage for the MISSION 1b study. It was run-in 6 cohorts. It was designed as a safety and tolerability study loaded with pharmacokinetics, pharmacodynamics and some exploratory efficacy measurements. We evaluated 6 different cohorts, which are outlined here.
We investigated doses of 45, 60 and 75 milligrams administered subcutaneously once weekly. And in part of this, we also learned how to improve tolerability of the drug and we also worked with the formulation of the drug. So in the early cohorts, we evaluated a frozen formulation, which was then wholly switched to a lyophilized formulation by the end
of the
study. So 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. So importantly, there's absolutely nothing about having an autoimmune disease that changed the responsiveness of the immunoproteosome to 616 as a therapeutic or anything that changes the pharmacokinetics. And we also saw very, very positive early efficacy signals. So for those of you who have been following the MISSION-1b study, you know that we've shared interim results of earlier cohorts.
And today, there won't be any surprises. What we learned is that the highest dose cohort of 75 milligrams that would just reinforces the same safety and tolerability profile. It strengthens our position that KZR616 has a potential to be a meaningful immunomodulatory therapeutic in patients with lupus and lupus nephritis and then also beyond for other immune mediated disease. So let's go to the next slide. So this slide is kind of the combined learnings of what we learned from our 2 healthy volunteer studies as well as this MISSION Phase 1b data in patients with lupus.
So on the left hand side is a summary of our safety and tolerability. KZR616 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.
And 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 immunosuppressants 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. So as John mentioned, the half life of KZR616 is actually measured in hours and it is highly, highly selective for the immunoproteosome.
The immunoproteosome is expressed exclusively in immune effector cells and then in tissues that are considered inflamed. But otherwise, it doesn't is it normally expressed as a cellular component of normal tissue. And what we found in the range of doses that we studied is that KZR616 is highly selective with inhibition targets of the immunoproteosome at greater than 80% with all doses studied, starting at 30 milligrams, but specifically 45, 60 and 75 milligrams weekly. And then 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 7 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. And one of the things that we will share with you today and especially Doctor. Pareek 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 2 of our patients in this one key portion of the study.
So let's go to the next slide. So 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. And so the key finding after the the completion of Cohort 3 and the ability to look across all the cohorts in totality is there really are no new observations. Ejection site reactions continue to be the most common adverse event.
Nausea is the 2nd most common treatment related adverse event and it tends to wane with subsequent dosing and we've learned some strategies to coach physicians and patients to tolerating the dose administration better. We had 4 total serious adverse events. These all occurred in the earliest cohort. So again, we have shared these with you previously. And just as a reminder of the 4 serious adverse events, 3 of the 4 patients were re challenged with KZR616 and successfully completed the study.
So let's go to the next slide, please. So now, we're going to turn to the exploratory efficacy signal. And in here, you see the 7 lupus specific disease activity measurements listed. And overall, although obviously the sample size is low, we see improvement across the board. The board.
And the 3 columns are kind of baseline, mean scores, the end of treatment at week 13 and then an end of observation period at week 25. And not only do we see 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. So this slide, we went ahead and summarized all of the biomarker changes that we've seen in the MISSION-1b study. So first, we looked at whole blood RNA sequence data from the MISSION Phase 1b patients.
And again, overall, all of the inflammatory modules support down regulation of pro inflammatory markers, but not over suppression. So again, an immunomodulatory footprint. The immune gene modules had higher expression in patients with lupus relative to healthy volunteers and are down regulated with KZR616, again towards normal rather than to oversuppression. KZR616 treatment up regulates erythrocyte gene modules, which are suppressed in patients with lupus compared to healthy volunteers. So 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.
And 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 8 patients who entered the study with elevated levels at baseline. So this was 8 of 8 patients had a reduction in this very specific auto antibody, which is a known marker of lupus.
We had reduced circulating plasma cells, which were observed and likely account for the reduction in autoantibodies. And this is in contrast to the idea of kind of total suppression of all IVIG or all antibody levels. And to that, we kind of measured the total IgG levels and found that they were unchanged following treatment with KZR 616. And then last but not least, complement levels can be suppressed in patients who have lupus. And in active disease, you will see a lot more in these patients in the safety and tolerability study, the C3 normalized in 5 of 10 patients who entered the study with abnormal levels and the C4 normalized in 4 of 6 patients who had depressed levels at steady entry.
So let's go to the next slide. So this is the beautiful heat map of the looking at the inflammatory modules. And what you can see on the far left is essentially the abnormalities in the patients who have lupus compared to healthy volunteers. And then at week 5 week 17, you begin to see reversal of the color patterns kind of consistent with normalization. And then we also are showing the heat map for the erythrocyte gene modules.
And again, this same idea that we are seeing normalization without any overt immune
suppression.
And so now 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. And Doctor. Parikh is actually very skilled and has done a lot of work with this biomarker. And so I'm going to actually turn over the kind of virtual podium here to him to both teach you about urinary CD163 and then discuss the 2 patients in the MISSION 1b study who had elevated protein expressed in their urine measured as a UPCR.
We've previously shown new reductions in UPCR and now we kind of have the confirmatory biomarker data that Doctor. Preak will go through. So with that, I hand it off to you.
Good afternoon, everyone, and thank you for it's a pleasure being here with everyone today. And I'm very excited to kind of share some of this data and then talk about some of the unmet needs in lupus and lupus nephritis as we go forward. But first, let me highlight CD163 as Noreen had mentioned. And a lot of the credit for this work goes to our collaborating colleague Juan Milla in Mexico as well as our group here at OSU that have really done some really important and interesting work looking at CD163. So CD163 is a cell surface marker that's seen on M2 macrophages, but also on monocytes and dendritic cells.
It's known to be up regulated in the setting of inflammation. It was initially studied in other conditions like echo vasculitis. And so the idea was since macrophages are thought to be involved in the pathogenesis of heavily involved in the pathogenesis of lupus nephritis, but 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. And so the study that's referenced here really looked at multiple cohorts, one from Mexico City and one from Ohio State in Columbus. And it was initially a cross sectional cohort to look at CD163 in the urine at the time of flare compared against nonrenal lupus, inactive lupus as well as other glomerular diseases.
And I don't show the data here, it's certainly all there in the reference, but 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 lumerulus during lupus nephritis. And then I think probably the most interesting and relevant is the longitudinal analysis in 2 different cohorts that basically showed urine CD163 to be to rise prior to clinical flare and decrease over time in response. And actually there was a threshold cutoff level of 370 at 6 months that predicted a 1 year response. Finally, it really correlates strongly with activity index on the kidney biopsy.
For those that don't know, activity index is a kind of a semi quantitative score given by pathologists on what the active inflammation that's going on in the kidney at the time of flare. And when they did repeat biopsies in patients and looked at urine CD163, it seemed accordingly strongly with the level of activity. And that threshold score of 370, I had a sensitivity and specificity of greater than 87% to predict response. So just to kind of show at least in those two cohorts, urine CD163 seemed accordingly strongly with disease activity. We can advance the slide.
So this is looking at actually a patient of ours that was enrolled in the Phase 1b study with Class 4 plus 5 lupus nephritis at nephrotic range proteinuria, so proteinuria greater than 3.5 grams. It had been tried on multiple therapies. She has a long standing history of lupus. She had been on multiple therapies, including mycophenolate, tacolimus, leflunomide, hydroxychloroquine, prednisone. And despite all of these therapies, she was just progressing through and was not responding.
Her C3, C4 levels or complement levels were low. Her proteinary levels were obviously in the nephrotic range. She had active lupus nephritis and actually enrolled in the Phase 1b portion of the study, really in part because she had limited options in terms of what else we could do to kind of help get her disease in control. And just as a caveat, with this patient and this was in the older formulation of the therapy, she had a very with her first injection, she actually had a very severe systemic inflammatory response that happened. And 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.
Anyhow, so she did have this 2 to 4 week delay in getting restarted because as we were trying to tease all this out, this was at the very beginnings of the Phase 1b study. But once you did restart, you can see here and what's shown in the figure is in the blue is the CD163 and in the pink you can see the urine protein creatinine ratio. You can see your CD163 level is elevated at the time of flare and then comes down over time and correlates very strong very well with the and 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.
And as I mentioned, her urine CD163 level preceded the reduction in your BCR and ultimately she attained a clinical response. And you can kind of see the percent changes in her double stranded DNA and CDX2K changes in the table to the left. We can go to the next slide. So this is another patient who actually had lupus nephritis. I think there was only 2 patients in the Phase 1b, I think Nerine can correct me if I'm wrong, that had lupus nephritis in the study and this is the 2nd patient of the 2.
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. And this patient also by week 5 had a greater than 50 percent reduction in your protein creatinine ratio with improved symptoms scores and reduced double stranded DNA titer in week 5. And you can see again the CD163 levels here is a proteinuria and THINK and 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 intrarenal or glomerular inflammation, which is what we ultimately want to see.
So leading to hopefully histologic inactivity, although we don't have repeat biopsies that would be the suggestion from the decrease in the CD163 level in these two patients. So this is looking at all patients experience basically the anti double stranded DNA levels and patients who actually had an elevated level at the time of the study initiation. And I think there's 8 patients here and you can see that all of them had a significant or considerable reduction in anti double stranded DNA by week 13. And then that continued for the majority of these patients and by week 25, which was the observation period towards the end of the study. So I guess I can summarize this for the Phase 1b.
It seemed checking all the boxes here of safety, tolerability, efficacy and PKPD dosing in the current trial, which I think was the goals of this therapy and certainly what we experienced with the 3 patients we had enrolled in the study. Okay. So 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. So what is lupus and lupus nephritis?
So lupus is a systemic, multi system autoimmune disease. It's basically the creme de la creme autoimmune disease, immune complex, median autoimmune disease. It can affect every organ in the body. And the challenges with treating lupus is that it's quite heterogeneous and we can't predict who's going to get what, frankly. And so when we try to target 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.
And it definitely impacts the ability to advance therapeutics frankly. So overall, there's about 300,000 adults in the U. S. With lupus and approximately 50% of those go on to develop lupus nephritis. And 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. So lupus in general affects the young and predominantly female population of childbearing age, 9:one ratio of females compared to males. So this is a younger population who for the most part don't have any other, oftentimes don't have any other illnesses are perfectly fine until they're not fine And they come to presentation with multiple symptoms, especially that are quite debilitating, fatigue, joint pains, rash. When the kidney is involved, as I mentioned, that's associated with the course outcomes, about 10% to 30% of patients who do develop lupus kidney disease or lupus nephritis, progressed end stage kidney failure within 15 years. Again, these are young patients.
So within 15 years of diagnosis, they're still young patients. And it's something that is a critical and unmet need for us in trying to prevent this progression and preserve their overall health. Kidney involvement is associated with course outcomes as I mentioned. And one of the most important influences of outcome is race and ethnicity. So 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.
And 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. And then in terms of progressing, having doubling the serum creatinine end stage kidney failure within 3 years of diagnosis, much greater risk in black patients and Latino patients compared to Caucasian patients seen in these two trials and that there's across the board. And 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 treatment as well and those things are still being elucidated, but there's a clear understanding that it's not just based on access to care and affordability of medicines, etcetera. Can you advance the slide?
So we talked about how lupus can cause a lot of debility and this just kind of these kind of data and facts just kind of point to it. So it can severely impact the patient's ability to work. So an average annual loss 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. And 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. Because while our clinical data suggests that things are getting better, they don't feel any better. And the fatigue and the joint pains and the weakness that goes along with this, as well as the considerable toxicity, as I mentioned, with the current therapies that we use are factors and challenges that hurdles that we need to overcome to kind of improve our patients' quality of life as well as improve their overall health. So some of the negative health factors, this was as reported by ICER or political and economic productivity group that looked at these factors. And patients tell you fatigue and joint and muscle pains and kidney disease are 3 of the most common reported factors that really are negative health factors for them.
And that leads to poor quality of life. And as they get poor quality of life, the treatments that they're on don't seem to be helpful. So you see less, sorry, can you go back to slide, reduced treatment adherence and then that leads to disease progression. What about when we talk about economic burden? So the average annual healthcare costs for a person with lupus is greater than $32,000 per year and that cost increases considerably in patients who have severe lupus and lupus nephritis.
What accounts for that cost is mostly inpatient admissions, outpatient visits are the largest drivers of costs and I'm sure medications are a part of that. And 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, Vince.
So what are the goals of therapy for patients with lupus nephritis? So let's just take a step back and talk about treatment. So when we treat patients who come to attention, 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.
And then that period is followed by a period of longer treatment with less intense immunosuppression to consolidate the response and help prevent flares. And 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 rheumatoidality. Can you advance one click? But 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. Because at every stage of chronic kidney damage that occurs or accrues, you have an exponentially increased risk for cardiovascular morbidity long term. So it's really critical to actually treat the kidney early, prevent the chronic damage as we look at globally is trying to prevent, preserve these patients' long term health. Can you advance?
So what do we use to treat lupus? So this is looking at lupus in general and it's a stratified here by mild disease, moderate disease and severe disease. And I'll qualify those statements as they're somewhat arbitrary in terms of how they're designated into these 3 buckets. But 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 kind of help manage mild symptoms and can be fairly well tolerated.
Corticosteroids historically and to this day are used routinely often and maybe overused for patients with lupus and lupus nephritis and they're used in mild and moderate and severe disease at varying doses and often high doses to start. Other immunotherapies, broad immunotherapies that are used like meflotrexate and azathioprine have been around for decades and used across the board in autoimmune diseases, cyclosporin or calcineurin inhibitors are also used in moderate disease. Mycophenolate mofetil, medication used commonly for a solid organ transplant is a mainstay for treatment for lupus nephritis and severe lupus as well. And prior to mycophenolate mofetilaciclophosphamide 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. And then more recently, B cell depleting drugs like Benlysta or belimumab have come online more specifically targeted therapies, addressing the B cells and depleting B cells in lupus is used for moderate lupus and in severe and refractory lupus and lupus nephritis rituximab has been used.
And that is used based on more observational cohort data compared to randomized controlled data, which largely in those trials has been negative for rituximab. But still, in the observational cohorts and patients who did not progress through the standard of care therapies, rituximab or anti CD20 therapy has been used successfully to help control disease. So 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.
So that's 3, 4 plus 5. Without getting into too much detail of the pathology, these are our most aggressive forms of lupus nephritis associated with the poorest outcomes. Okay. So our standard therapy historically has been utility of a high dose prednisone. This would be a methylprednisolone IV at varying ranges from anywhere from 0.5 or 0.25 to 1 gram per day for 3 days, followed by oral prednisone, 1 mg per kg up to 1 mg per kg per day, 0.5 mg per kg per day.
And that's tapered slowly over weeks. And unfortunately, the high dose steroids stay on for quite a long time. And then if you look at the treatment algorithm and this is just historically, it's been cyclophosphamide at 3 different regimens, whether it's urolupus, which is the lower dose cyclophosphate, which is more commonly used when it is used nowadays at 500 milligrams every 2 weeks for 3 months versus the older NIH regimens that had considerable cyclophosphamide exposure. And we know the side effects with cyclophosphamide are associated with cumulative exposure really. And then versus mycophamilamolpatel, 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.
But when we use those therapies, the biggest question we have is how effective are they? And, you can advance by one click. And if you look, and this is looking at the randomized controlled trial, the ALM study, which is the hallmark study that compared NIH protocol cyclophosphamideamycophenolate and looked at overall outcomes and this is response at 6 months. You can see the partial response was about 50% in both groups. The complete response was quite low, 8% and 9%.
And if you go out to 12 months that gets better, but not that much better. We're talking about 20% to 30 percent complete remission rate at 12 months. And this is not unique to the ALM study or microphenolate. This is across the board when we look at lupus nephritis trials regardless of the regimens that we're using. And if I highlight the most recent studies, so this is looking at 2 drugs that were FDA approved recently, for treatment of lupus nephritis, the first two drugs.
And these are landmark trials, incredible that they finally get drugs approved for lupus nephritis. But I just want to hone in on one thing here. So if you look at the voclosporin obenituzumab, which was a Phase 2 study that had positive results in lupus nephritis and anti CD20 trial study drug in the Namista, 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. And 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% to 80% of our patients are achieving the complete clinical response. If you can advance one slide.
So one of the questions then becomes, well, what about just overall response? Why complete response? And this study here highlights it nicely. So 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. So this graph just shows 3 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.
So 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. So they were still doing fine. What about partial response? So certainly better than no response, but you can see 57% of those patients ended up requiring the progressing 10 stage kidney failure requiring dialysis. Whereas if you didn't have any response, 87%.
So 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, really want to move the needle in taking care of our patients with lupus nephritis and preserving our long term kidney health. And we can move to the 4th slide. So let's take a look at these immunosuppressants briefly and 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 and Mycophenolate and cyclophosphamide, they are effective therapies, certainly they're broad immunosuppressants, but they do come with side effects as you can see there. But the one therapy I want to highlight is corticosteroids.
So with corticosteroids, these are the broad anti inflammatory therapies that we all use for patients with autoimmune disease, in particular lupus, lupus nephritis. We use it in high doses routinely, although that is changing, that conversation is changing and we are going towards more less use of corticosteroids. But the biggest issue and patients say the same thing. Initially, they're fantastic. They make you feel better.
It's great. But long term, the side effects are quite frustrating, debilitating for both the provider and the patients. And these side effects include fluid retention, weight gain, hyperglycemia, diabetes over the long term, the 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 and they really impact the patient's overall feeling towards treatment and what we're trying to achieve. And the one thing I want to highlight here, especially when we're talking about kidney disease is lupus nephritis and kidney disease is often silent. Like patients don't know that their kidneys are injured a lot of the time, especially these patients.
And 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. And unless they have nephrotic range proteinuria, they may not even have that much swelling. So they don't know, over time even and then they start to feel better.
They feel like everything is getting better and they still require these therapies and it's because we're telling them that, hey, you still have protein urine, you still have blood urine. So if you're not feeling well and you don't like the therapies that you're on, it does make logically, it does make an issue create an issue with drug adherence, medication adherence and appropriately so. And when you're not seeing when you're feeling poorly and you're not understanding the results. And so education, education, education is critically important, but it just points to the fact that we need better therapies and corticosteroids to kind of help treat our patients with lupus nephritis. And on top of that, just better therapies, but with less side effects.
So to sum up here and hopefully we have time for questions. There's currently no cure for lupus and lupus nephritis. So in patients who develop lupus nephritis within 5 years of proliferative lupus nephritis onset, about 5% to 25% of patients will experience death due to renal disease. There are new medications that are FDA approved. Benlysta or belimumab and voclosporin received their FDA approval in 2020 2021.
But even with the positive results, as I mentioned, we need 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.
And in patients who have refractory disease and many of them, roughly about fewer than 60% of patients with class III to V lupus nephritis will achieve a complete response to induction therapy. And importantly, even when you do get a response, approximately 30% of patients will experience flare. And 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. So 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. So with that, I'll happily stop and we're happy to take questions.
And I'll pass it back to John, I'm sorry.
Thanks so much, Sameer. That was incredibly insightful and detailed and really powerful to hear those stats. And I know we're getting towards the end of the half hour. So rather than try and wrap up with any comments here, I'll just open it straight up to questions, see if we have people specific questions we can help answer in the few remaining minutes.
Yes, it looks like we have Phil Nadeau from Cowen ready to ask the question. Phil, I think your line is now unmuted.
Great. Thanks, Julia. Just a couple of questions from us. First on the new CD163 biomarker, Doctor. Perry, could you maybe give us a little bit more information about what baseline levels are typical for LN patients?
It looked like some pretty divergent levels for the 2 patients that we're showing. And what magnitude of decline is clinically meaningful?
Yes. So I think what I can point to is a study that was done and published in Jason with the 2 cohorts that we had in patients who had active disease. And you're right, it can be divergent in 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, right, or at the time of lupus arthritis. But on average, we're seeing levels at the time of flare roughly above 1,000. And I think the marker that really differentiates is being able to achieve that level below 370.
So that at least in our data and 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 1 year mark. So I hope that kind of answers your question. But I want to qualify all this, right? So 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 1 is a biomarker that can be used and is specific can be used and really reflects histologic disease activity. But in the data based on the adjacent paper in the two cohorts, you can see on average, I think the levels were over 1,000 at the time of flare.
That's perfect. And then maybe just one question for management. In terms of the pre medication that was studied in Cohort 23, 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 Maureen. In general, we are not requiring premedication. We offer kind of suggestions that include, as you mentioned, non sedating antihistamines, antiemetics, etcetera. And oral hydration actually is also a big one.
And kind of from some investigator level feedback, the oral hydration and an oral antiemetic has been helpful for patients who do experience nausea. And the other ones is that the benefit is less clear.
That's very helpful. Thanks for taking our questions and congrats on the data.
Thank you.
Thanks, Phil.
Okay. So 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're showing. The cumulative score is impressive and seems to have improved further with the Cohort 3 data in there.
Just wondering if you can talk about further potential use of the 75 mg dosing? And then also if you can comment on the 2 discontinuations in the 75 mg group as well?
Yes, super. Thanks for those observations. So in the 75 milligram cohort, we did see levels of efficacy as well as PK and PD that was commensurate with the earlier cohorts. And so in general, we believe that the 75 milligram dose level was well tolerated. It gives us a larger therapeutic window, but we're also very content at this time to focus on the 45 60 milligram weekly doses that we're currently using in the Presidio and the Mission 2b study.
With respect to the 2 discontinuations in Cohort 3, those were a bit challenging. Ultimately, it was the 2 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. But I think the combination of the discomfort and some of the challenges of steady participation, especially in the COVID era, led them to withdraw from participation.
Got it. Okay. That's helpful. And 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?
So Chris, you want to jump in on this because you did those analyses?
Yes, sure. More happy to answer that question. The data which actually came from the first two cohorts of data with 616, so cohorts 12, and we are analyzing data for the remainder of the study now indicates a significant reduction in 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 suggest changes both in the B cell compartment as well as TNK 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.
Hi, guys. 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 PRECEDIO.
Just wondering if you've had can you give any just comment to the rate of screen failures? So you've enrolled 9, just how many have screened and if it's more of a screen failure issue or just kind of finding these pages to begin with?
In the prior iterations of Mission, the screen failure rates were very, very high, almost complete screen failure rates on previous durations. In this current and under this current amendment, it's really been the essential headwinds of the COVID pandemic and just finding the patients has been the big issue facing us over the last year.
Thanks, John. I think maybe for Sameer or Maureen, 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 8 weeks, but still has proteinuria and then you add on another treatment. So I don't know if there's really much data to point to, but I guess if you had someone that was on, say, MMF and hadn't responded by 8 weeks, how likely do you think another, I guess, 4 to 12 months or 4 to 8 months that patient could get to a complete remission by themselves without changing the regimen, I guess?
Yes. I mean, I guess I can try to address this. So 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 is where is the right because there's several trial designs where we use this kind of window of enrollment and monitoring observation and then they randomize after say 3 months of standard of care therapy into a treatment arm versus a placebo. And 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, 3 months of therapy, right?
I do think that a lot of patients so that may be 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 6 months in many cases before we actually start to look at patients as being refractory, so to speak, to the standard of care therapy. So but I do think that there could be some there may be some of that where patients who are enrolled, say, after 8 weeks of induction therapy could have continued to get better. But I think part of that can be addressed by they've had no movement in their proteinary level at all prior to enrollment and certainly less than 50% response, because 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. But again, there's a good percentage of patients that don't respond to any the standard therapy at all. And so having this potential add on could prove helpful certainly.
Mary, 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 a totally perspective, to maybe move quicker, like if you maybe see CD163 drop by 3 months, that's a
Yes, Yes. So that's exactly right. So I think that's the value in looking at CD163 in those two particular patients with lupus nephritis and kind of in a way it really replicates the data we were seeing that was published in the Jason paper in 2020, where the CD163 not only went up prior to clinical flare, but also went down prior to proteinuria. And so it can we do expect to see that. So if you're attenuating intrarenal inflammation, right, so 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 to decrease before proteinuria levels do because you have tissue healing that has to happen after that. And it takes time. So I think that what we showed in these two patients actually reflects exactly what was published in the JASON 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.
Thanks, Matt. Okay. So our last question that we have time for is from Yanan Zhu from Wells Fargo. So Yanan, I think I just queued you to unmute your line.
Okay. Can you hear me?
Yes, we can.
Yes. Thanks for taking my questions. So first, a question on CE163 for Doctor. Parikh. So I'm just wondering, are there CD163 data available for voclosporin or Banvista that we can potentially compare to when we have more data hopefully from the Phase 2 study of 616?
Yes, not yet. I think voclosporin and Benlysta and maybe it will 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 don't want I can't speak for that. But I can't say that they did there is not urine CD163 data in those 2 large randomized controlled trials available. And to be clear, the data on CD163 in lupus nephritis actually really was published just recently within the past year.
So it wouldn't have been done when those trials were originated in the 1st place. So it would have to be go they'd have to go back and measure them all post hoc. And then but it's also not a it's not a marker that's used clinically yet, but the data seems fairly of all the biomarkers that's been tested in lupusoparibis, 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 hands here at Ohio State.
Got it. And perhaps a follow-up question for Doctor. Parikh regarding the efficacy and safety outlook for 616. Doctor. Parikh emphasized that the unmet need is a greater complete response rate currently for the treatment of lupus nephritis.
I know we don't we only have 2 patients of data with that kind of renal manifestations in the current trial. But 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 whether as to whether 616 has the potential to demonstrate a greater complete response rate than BANLYSTA for example?
So 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 when we talk about complete response rate, I want to make it, 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, etcetera. We also want to improve overall response, of course, 50% overall response is not good enough either, right? So we want to just be able to make everyone go to 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 KZR1616, I think just in general, these are 2 very different products in terms of what they do.
I think when you look at the belimumab data and you look at the bolutumab'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 and this is not specific to lupus. This is true if you look at other diseases as well and it applies from the belimumab to rituximab, etcetera. Our experience, and this is not just us, this is in general, these drugs take a little bit of time to work and 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 kind of get the disease under control, whereas something like a KZR616, 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 and potentially and may suppress inflammation quickly.
When we're talking about in the Phase 1b, we'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 is because that's kind of we don't expect to see anything happen that fast, frankly, we just don't usually see it. And so I think it's important to kind of make a little bit of a distinction. It's hard to compare the 2 drugs and I know that's what we try to do with all of these drugs, but their mechanisms of actions are so different and where they may be best supplied.
And 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? And from my perspective, I think at least speaking to lupus nephritis, I think something like a KZR616 has a 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 will have a more upfront role or something like a belimumab, I would expect that to have its role down the line, so to speak. I hope that kind of answers your question, at least for the lupus arthritis part. And 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. So, 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, Doctor. Farik.
Thank you, Yanan.
Oh, I
think we're kind of out of time, Yanan. We're way past, but thank you. Appreciate it. So I will just I will hand it back over to John then for some closing remarks.
Thanks, Celia. Thank you, Maria. I really appreciate those great questions. And Sameer, thank you so much for participating and lending your thoughts. This conversation is incredibly helpful, excellent context and just really underscored a lot of what is getting us that T's are most excited about this phase when we did it say on the broader potential for 616 as possibly still very rapid acting very novel agent.
So 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.