All right. Good evening, everyone, and thank you for joining us today for Chinook's event on data presented at ASN Kidney Week 2022. At this time, all participants on the phone line are in listen-only mode. Following our prepared remarks, we will hold a brief question and answer session. If you're in this room and would like to ask a question, please come up to the microphone at the front of the room. If anyone on the phone would like to ask a question, please press star followed by the number one on your telephone keypad. As a reminder, the audio from today's event is being recorded. Before we start, I would like to remind you that today's event, which is intended for the investment community, will include forward-looking statements based on current expectations. Such statements represent management's judgment and intention as of today and involve assumptions, risks, and uncertainties. Chinook undertakes no obligation to update or revise any forward-looking statements. Please refer to Chinook's filings with the SEC, which are available from the SEC or on the Chinook website for information concerning the risk factors that could affect the company. Joining me today are Eric Dobmeier, President and CEO of Chinook, Andrew King, Chief Scientific Officer of Chinook, Charlotte Jones-Burton, Senior Vice President of Product Development and Strategy, Dr. Sreedhar Mandayam, Professor of Nephrology at the University of Texas MD Anderson Cancer Center and Baylor College of Medicine. Finally, Dr. Laura Kooienga, practicing nephrologist and Director of Research at Colorado Kidney Care, is joining us by phone. Eric Bjerkholt, Chief Financial Officer of Chinook, will be joining us for the Q&A portion of this call. I'll now hand it over to Eric. Thanks, Noopur, and welcome everybody. This is actually the first in-person IR event Chinook has ever done in our whole history. We've been a public company for two years, so it's great to see you all in person instead of just a face on the Zoom screen. Welcome. We're excited to be here to talk about our ASN data. We had nine presentations at the conference, which I think underscores how committed we are to kidney disease, and we're really thrilled to especially be talking about atrasentan and BION-1301 for patients with IgA nephropathy. We had some really fantastic data on both programs here at the conference. IgAN is a huge unmet medical need, as you probably all know. There are very few therapeutic options to reduce proteinuria and delay progression to kidney failure in IgAN. We're thrilled to have two promising drugs in this space that we're developing right now. Before I go through the agenda, I do wanna talk a little bit about the ALIGN trial. We're now in a position to narrow our guidance for when we'll have the top-line proteinuria readout, which we expect to be in the third quarter of next year. I'm really proud of our team that we enrolled this trial on, you know, on timely basis during a global pandemic, and really looking forward to reporting data in less than a year now. We're getting close to having a readout from ALIGN, which is exciting. Moving on to the agenda. We're gonna start with Dr. Sreedhar Mandayam presenting the data from atrasentan and BION-1301. It's the AFFINITY IgAN cohort data that we had a poster on yesterday, and it's the BION-1301 phase I-II data that we had a poster on this morning. After that, we're going to have Dr. Laura Kooienga on the phone to talk about her experience treating patients with BION-1301. She's our highest enroller in the trial. She's actually put nine patients on the trial, so she's got a lot of experience with the drug in IgAN. Andrew King will talk about several of our preclinical posters, both on CHK-336, our first internally discovered program for kidney stone disease, as well as some of the work we're doing in our research programs and our approach in collaboration with Evotec. Charlotte Jones-Burton will talk about our status and plans for atrasentan and 1301 development programs, so an update on where we are with both and our plans to take 1301 into phase III next year. Then I'll have some closing remarks, and we'll take any Q&A. With that, I'm gonna turn it over to Dr. Mandayam. Thank you. Thanks, Eric. I'm gonna present the atrasentan IgA nephropathy, the interim results from the AFFINITY study. A lot of this data has been previously discussed at ERA-EDTA, we'll quickly go through this and then get to the important stuff. These are my disclosures. As everybody probably knows in this room, IgA nephropathy is an important problem, primary GN with a pretty significant incidence. About 30%-50% actually progress to end-stage kidney disease. Proteinuria is definitely associated with risk of progression, and any treatment that reduces proteinuria has been known to improve clinical outcomes in patients with IgA nephropathy. The endothelin system has been identified as an important contributor for progression, and elevated expression of ET1 predicts progression of IgA in patients. Also activation of the endothelin receptor is known to cause damage to the mesangial cells, inflammation, and fibrosis. We also know that proteinuria patients with IgA nephropathy have elevated levels of ET-1 and endothelin receptor activation. This seems like a good target to go after in patients with IgA. AFFINITY is a global phase II open-label basket study. The intent was to assess the efficacy and safety of atrasentan in patients that have proteinuria glomerular diseases. There are four diseases that are being investigated, IgA nephropathy, FSGS, Alport, and diabetic kidney disease. We're gonna spend some time talking about the IgA cohort. The IgA nephropathy cohort received a dose of 0.75 mg daily for 52 weeks, followed by a four week follow-up. In order to be eligible, you had to have biopsy-proven IgAN. You need to be on maximally, or at least optimally dosed, maximally tolerated RAS inhibitor therapy for over 12 weeks prior to screening. You had to have significant proteinuria despite being on maximal therapy, which is defined as either 0.5-1 gram per gram of urine protein creatinine ratio and an eGFR of greater than 30. Endpoints were at week 12, change in urine PCR, and we were also looking at adverse events and incidence seriousness and severity. This is the IgAN cohort. These are 20 patients with biopsy-proven IgA nephropathy. As I said, 100% of them had to be on maximally tolerated RAS. It's important to note that about 70% of the patients are greater than 1 gram per day proteinuria despite being on maximal RAS therapy. Patients were on a mean duration of about 45 weeks of treatment when the data cutoff happened in October. Safety and tolerability, very well tolerated. There were no treatment-related severe AEs to date. There was one subject that had to withdraw from the study because he developed treatment-emergent headache, which the investigator didn't seem to think was related to the compound. Otherwise, as you can see, there were no significant AEs or SAEs that led to any discontinuation. An important point to consider in the ERAs, there was no increase in mean body weight, no elevation in BNP, and no change in eGFR in patients that were on the drug. This is the proteinuria reduction is certainly impressive. You could see that by 6 weeks, all 20 patients had a 38.1% reduction in urine protein-to-creatinine ratio that persisted and improved by 12 weeks to 48%, and now we have the updated 24-week data that shows that it was a greater than 54% reduction in proteinuria in the 19 patients that were on the study drug. This is just splitting it in deciles. The histogram clearly shows that at the 12-week mark, 75% patients achieved a greater than 40% reduction, and at the 24-week mark, of the 19, close to 80% of patients achieved a 40% reduction in proteinuria. In summary, in the 20 patients with IgA nephropathy, 70% of our patients that had a baseline protein greater than 1 gram, treatment with atrasentan resulted in meaningful reductions in proteinuria at week six that persisted at week 24. There were no changes in blood pressure or eGFR, suggesting the proteinuria reduction is not mediated by any hemodynamic effects. Well-tolerated, no treatment-related SAEs, and more importantly, no change in BNP or body weight, so fluid retention was minimal, if at all. As stated below, clinically meaningful proteinuria reductions are definitely seen in patients with IgA that had risk of proteinuria or risk of progression because they had residual proteinuria while they were on standard treatment. I'm gonna move on to BION-1301, which is the more exciting molecule for me. This... We all know IgA nephropathy, but the APRIL pathway is something that is new in the nephrology universe. It's a TNF superfamily cytokine. It drives IgA class switching. It's also known to drive survival of plasma cells that secrete IgA. We have evidence that patients with IgAN that have higher APRIL levels tend to have higher galactose-deficient IgA1 and tend to have greater proteinuria and lower eGFR. There's also some in vitro data that says APRIL increases the secretion of galactose-deficient IgA1 from lymphocytes in patients with IgA nephropathy. We're sort of going through a disease-modifying mechanism with the BION program. Monoclonal antibody binds and blocks APRIL, so therefore we're directly targeting the pathogenesis of IgA and interfering at the hit one in the multi-hit hypothesis. It has been previously shown to be well-tolerated and resulted in good depletion in galactose-deficient IgA1 and proteinuria reductions at week 12. The phase I bioavailability showed very good correlation between IV and subcutaneous data, and we'll show more data about that. This is the study design of the ongoing study. There are two cohorts. Cohort one is where patients start with 450 milligrams Q 2 weeks IV, and then they switch to 600 milligrams Q 2 weeks sub-Q at the 24-week mark, and all patients are followed for two years, so 104 weeks. There's a cohort two that has 30 patients, where everybody starts in the de novo sub-Q 600 milligrams Q 2 weeks and then are followed up for 104 weeks. Both cohorts have an optional one year treatment extension. The objectives are obviously safety and tolerability and also prelim data on proteinuria in patients with IgA nephropathy. It is both a proof of concept and a proof of mechanism study, and we're trying to explore dose schedule and compare IV and subcutaneous administration. In order to participate in the cohorts, you need to have IgA nephropathy diagnosed with a biopsy in the past 10 years. You need to have proteinuria as defined as urine protein excretion greater than 0.5 grams, and you need to have an eGFR greater than 30, and all patients have to be stable on an optimized dose of a RAS inhibitor for at least 3 months prior to entering the cohorts. The baseline characteristics are, as you can see, the. I guess the main differences in cohort two has a little more diversity, a lot more Asians, some African American subjects. The ethnicity is about the same. Patients had about three years since biopsy. eGFR is comparable between the two groups, and as you can note, there was 1 gram mean proteinuria, about greater than a gram at least in the cohort two, and all patients had to be maximized on a optimal dose of RAS inhibitor. 24 patients have been enrolled so far in cohort two, and the mean treatment duration for the cohort two is at 17 weeks as we speak. I also want to mention that in cohort one, at the 24-week mark, the IV group gets switched to sub-Q, and all patients now have been switched to sub-Q and have been followed for about 40 weeks in cohort one. Pretty good data for close to a year. Safety, this is very important. It's very well-tolerated. There have not been any deaths, SAEs or any AEs leading to discontinuation of drug. Infections in patients that had IgA nephropathy were graded as one or two in severity, and only 1 infection, which was graded as grade 1 by the investigator, was considered to be treatment-related. Injection site reactions have all been graded as one or two in severity. IgG levels that fell below study-defined threshold of 3 g/L occurred in only one patient in cohort 1 that led to a protocol-mandated withholding of study drug. There was no baseline IgG level to enter into any of the cohorts, so we're not entirely sure what their baseline IgG was, but the drop that led one person to discontinue. They have not had any infections as far as we know. You see the table of all the AEs and treatment-related AEs. Pharmacokinetics, so we were comparing the sub-Q and the IV dose, and you can see that the inter-individual variability between IV and sub-Q is very small. Trough concentrations after the 600 milligrams sub-Q two weeks is consistent with trough concentrations on the 450 IV Q two weeks. Very importantly, no anti-drug antibodies have been observed in any of these patients with IgAN to date. There's proof of concept here, the mechanism that it works. You can see a rapid and sustained decline in IgA levels. By the sixth week, by 6-8 week, you can see a 40% decline, and that decline in IgA level persists all the way to the 100th week. On the right side, you see the decline in the pathogenic galactose-deficient IgA1. Again, it decreases quite rapidly, and you can see both cohorts, one and two, have very parallel, very similar graphs on the reduction in galactose-deficient IgA1 that is accomplished by this drug. We also see reductions in IgM and to a lower extent, reductions in IgG, which is really reassuring. Again, both cohorts have very similar IgG and IgM reduction patterns. One of the primary outcomes is the change in proteinuria. We see reduction in proteinuria that starts by 12 weeks at about 30% in the IV group and 28% of the sub-Q group, and improves all the way down to 53% in the IV group, and continues to improve at 67% and then 71% reduction in proteinuria at 100 weeks in the sub-Q group. The cohort two had a mean reduction of 53% at the 24-week mark that we have data in cohort two. Both the IV and the sub-Q groups seem to show a dramatic and sustained reduction in proteinuria at 52, 74, and 100 weeks with the data we have. In conclusion, rapid, durable reductions occur in IgA and in galactose-deficient IgA, which is the pathogenic variant that drives the hit one that is responsible for the pathogenesis of IgA nephropathy. Some reductions in IgM, but a much lower reduction in IgG. Very well-tolerated, no SAEs, no treatment-related AEs that led to cessation. Definitely, clinically meaningful reductions in proteinuria have been seen in patients that had high-risk disease despite being on maximal ACE and ARB therapy. So far well-tolerated and seems to be doing well. I'm gonna hand it off to Dr. Kooienga. We're actually having some audio issues right now, so we're gonna just move to Andrew in the research lab. Thanks, Noopur. We provided an update on the preclinical profile of CHK-336 on a poster presentation today. This is our internally discovered oral small molecule liver-targeted LDHA inhibitor that blocks the final step in hepatic oxalate synthesis that we're developing for the treatment of both genetic primary hyperoxalurias as well as secondary hyperoxalurias associated with increased endogenous oxalate production resulting in kidney stone formation. We used X-ray crystallography to drive structure-based drug design that led to the discovery of CHK-336, which is a potent sub-nanomolar inhibitor of LDHA in biochemical enzyme assays across species. It is also a potent inhibitor of LDHA in primary hepatocytes across species as well. CHK-336 was engineered with a liver-targeted distribution profile that results in high concentrations of CHK-336 in the liver to inhibit LDHA and block oxalate production, which is associated with low systemic, plasma exposures of CHK-336. On the right panel of this slide, CHK-336 was able to decrease the conversion of a stable 13C-glycolate tracer to 13C-oxalate in vivo in a rat in a dose-dependent manner, demonstrating in vivo target engagement of the ability of CHK-336 to block hepatic oxalate production. In a mouse model of PH1 which we generated, CHK-336 decreased urinary oxalate excretion at low once-daily oral doses, resulting in urinary oxalate concentrations that were driven back largely to within the normal range observed in healthy wild-type mice, which is important to not only reduce the risk of end-stage kidney disease, but reduce the risk of recurrent stone events that can occur if urinary oxalate remains above the normal reference range. On the right-hand panel, we observe that CHK-336 produces urinary oxalate reductions in this mouse model of PH1 that are at least comparable to those achieved by varying doses of injectable siRNA targeting GO, with a much more rapid onset of action with a small molecule inhibitor relative to the siRNA. In a mouse model of PH2 and elevated levels of urinary oxalate, CHK-336 significantly reduced urinary oxalate excretion compared to control, demonstrating the potential for broad applicability of CHK-336 by targeting the final pathway in hepatic oxalate production. CHK-336 is currently being studied in a phase I healthy volunteer, single and multiple ascending dose study to establish safety, tolerability, and pharmacokinetics. We're also incorporating administration of the stable isotope 13C-glycolate to these healthy volunteers to demonstrate or determine the ability of CHK-336 to block the conversion of 13C-glycolate to 13C-oxalate and demonstrate proof of mechanism in humans that CHK-336 can block hepatic oxalate production, as well as helping define dose ranges to move forward into proof of concept studies in both genetic and secondary forms of hyperoxaluria. We plan to provide an update on the data from the study in the first half of next year. We also presented data from single-cell RNA sequencing of the kidney from a mouse model of IgAN in collaboration with the University of Michigan and Juntendo University. This study generated a high-resolution single-cell data set to characterize the kidney-specific transcriptional networks that drive IgAN and also assess the impact of pharmacological intervention with ACE inhibitor or atrasentan on these disease-driving transcriptional pathways. We identified 26 distinct clusters of cells from the IgAN mouse kidney, highlighting the cellular complexity of the kidney and providing great coverage of both the glomerular and tubular interstitial compartments. Infiltrating immune cells were the most increased cell type in the kidney of the IgAN model, although the gene expression of these immune cells was largely unchanged from control mice. Failed repair proximal tubule epithelial cells were identified as the most expanded kidney-specific cell type in the mouse model of IgAN and were the cell type with the most differentially expressed genes compared to control. Ligand receptor interaction analysis suggests that these failed repair proximal tubule cells are a key source of cytokines and chemokines, leading to immune cell recruitment and fibroblast activation, resulting in tubular interstitial inflammation and fibrosis, essential driver of eGFR decline in IgAN. Atrasentan significantly reversed the pathogenic gene expression changes in failed repair proximal tubule epithelial cells that were induced in the IgAN model, including reversal of pro-inflammatory TNF-alpha signaling. However, ACE inhibition had minimal impact on IgAN-induced gene expression changes in failed repair PTECs and rather primarily induced new gene expression changes unrelated to disease pathogenesis, most prominently in vascular smooth muscle cells, demonstrating very distinct mechanisms of action of these two agents. We also gave an oral presentation earlier this evening on our integrated multi-omics approach to IgA nephropathy characterization in the NURTuRE CKD patient cohort in collaboration with Evotec. The aim of this work is to use multi-omics approaches to the characterization of IgAN in the NURTuRE cohort, integrating clinical, histological, transcriptomic, and serum proteomic data to provide deeper insights into patient stratification and disease pathogenesis. Serum proteomic analysis from the NURTuRE IgAN cohort identified serum proteins which have a significant association with kidney function decline in IgA nephropathy patients. Of interest, increased serum endothelin-1 concentration had a strong and significant association with decreasing eGFR. Serum APRIL also had a strong and significant association with reduced GFR and increased proteinuria. However, serum levels of the TNF superfamily member BLyS were not associated with eGFR in this analysis. Finally, we also generated an atrasentan transcriptional response signature from the failed repair proximal tubules in the single-cell analysis we did in the IgAN mouse model treated with atrasentan that I just described. We scored these IgAN patient kidney biopsies for this transcriptional signature. The atrasentan signature score from kidney biopsies was correlated with kidney function and proteinuria in the IgAN cohort and was also associated with tubular atrophy and interstitial fibrosis histologically in the NURTuRE IgAN cohort of patients. We are using this work to define non-invasive biomarker strategies to be applied in our ongoing clinical trials for atrasentan to demonstrate the mechanism of action of atrasentan on these key pathways that drive IgAN pathogenesis. Dr. Kooienga's back on. I'd love to hand it over to Dr. Kooienga. Next slide. I'm a practicing nephrologist at Colorado Kidney Care, where I'm the director of our clinical research division. Our practice is comprised of 30 nephrologists and 12 nurse practitioners. Collectively, we see over 10,000 non-dialysis and non-transplant chronic kidney disease patients in a year and complete approximately 22,000 CKD patient visits per year. We currently are treating between 400-450 patients with IgA nephropathy. The IgAN patients we typically enroll in clinical trials are primarily from patients within our private practice. They're referred to me from their primary nephrologist. Typically because they've continued to have progression of their kidney disease despite adjusting their diet, their lifestyle, and being on maximally tolerated doses of ACE inhibitors or ARBs. My partners in the practice are actively engaged in research and have had a great experience outcome with their patients, and therefore continue to refer them to our clinical trials. I'll spend a few minutes reviewing my clinical experience with patients with IgAN. I've enrolled in cohorts 1 and 2 in an ongoing phase I and phase II study here. Do you want to go to Charlotte's section and come back to it? Yeah. Let's move on to your section, Charlotte, and we'll come back to this. Okay. Great. For slide 28. I'll start there. My computer cut out. I currently have four patients in Cohort 1 who have been on the study for 56-76 weeks. On this slide, you can see that their demographics and baseline characteristics for my four patients. Their median age is 47.5 years. All are male, all are White, and all live in Colorado. We have one patient in Cohort 1 who travels 231 miles to come to our office for his study visits. The median time from biopsy was 2.4 years, and the median systolic and diastolic blood pressures were 128 and 84.5 millimeters of mercury, respectively. The median eGFR at baseline was 70, and the median 24-hour urine protein excretion at baseline was 1 gram per day, with a range between 0.7 and 3.5 grams per day. I also have six patients in cohort two who have been on study for up to 34 weeks. The demographic and baseline characteristics of my six patients enrolled in cohort two are similar to my patients in cohort one. Their median age is 37 years. Five of the six are male, four are White, two are Asian, and all live in Colorado. The median time from biopsy was 4.1 years, and the median systolic blood pressure was 128.5, and diastolic blood pressure 84.5. The median eGFR at baseline was 58.5, and the median 24-hour urine protein excretion at baseline was 1.5 grams per day, with the range being between 0.8 and 5.1 grams per day. Our experience with BION-1301 phase I + II study has been phenomenal. All of my patients in the study have tolerated the treatment extremely well with absolutely zero complaints. Most of our patients tell us that they're feeling better, and none have ever told us that they're feeling worse. Without getting into individual patient data, I can say that all nine of my patients enrolled in the study have had clinically meaningful reductions in proteinuria as of their most recent visit. The subcutaneous injections of BION-1301 in general have been well-tolerated by my patients. The patients I enrolled in cohort 1 had no issues transitioning from IV to sub-Q delivery. None of my patients enrolled in the study have had any complaints about the dosing frequency or subcutaneous injections. My patients' concerns have usually been centered around what will happen to them when the trial ends, and if the trial ends and they can't get the medicine, if they'll potentially have to go on to dialysis and/or need a kidney transplant in the future. In closing, my patients in this study have had a great experience. They're highly motivated, engaged, committed. These patients are all young. They all work and participation in a clinical trial requires a large time commitment from them. They graph their proteinuria. They text us to see if their labs are back. They bring their spouses and family with them to all their office visits. With new potential treatment options like BION-1301, this has been a game changer for them. They are happy, they're thankful, and they're hopeful for the health of their future. I'm excited that they are doing better and so happy to be a part. I'd like to hand it over to I believe it's Charlotte now. Yes. Thank you for that report. I'll now give an update on our clinical programs, beginning with atrasentan first. Our ALIGN trial is currently enrolling. Just to remind you, this is a global double-blind placebo-controlled study. We are enrolling approximately 320 patients in a one-to-one fashion to atrasentan or placebo. Patients have to have had a biopsy-proven diagnosis in order to be in this trial and be on a stable RAS inhibitor. Proteinuria levels have to be greater than 1 gram and eGFR greater than 30. The primary endpoint is proteinuria at 6 months, and the secondary endpoint is eGFR at 2.5 years. We have opened an additional stratum to enroll up to 64 patients who are on a stable dose of an SGLT2 inhibitor for at least 12 weeks. We are on target to report top-line proteinuria data in Q3 of 2023. Also, in the atrasentan clinical program, we have two other studies that I'll provide an update on. Our AFFINITY study is our phase II open-label trial. Our IgAN cohort has completed, but we continue to enroll patients into the other cohorts. As we reported in May, we've added an additional FSGS cohort so that we can study an increased dose of atrasentan. In the first half of 2023, we will begin a new phase II study looking at atrasentan in combination with SGLT2 inhibitors in IgAN patients. The purpose of this study will be to provide additional safety and efficacy data on this combination. This data will support the exploratory analysis from the ALIGN strata that I spoke about. Our goal is that this data will also support future use, but it is not required for approval. Now I'll move to our BION-1301 program and provide an update. The Cohort 1, which has been spoken about this evening, has completed enrollment, but we continue to enroll in Cohort 2, which is our de novo sub-Q cohort. The strong data that we've presented gives us reason to continue to believe that BION-1301 demonstrates disease-modifying potential, and we're planning to move forward. We're currently aligning with global health authorities, conducting site and country feasibility so that we can initiate a pivotal trial in 2023. The proposed trial design for that pivotal trial is listed on this slide. It will be a global double-blind placebo-controlled trial. We will randomize patients in a 1:1 fashion to either receive BION-1301 sub-Q Q2 weeks or placebo. Thank you. Patients will need to have biopsy-proven IgAN, be on a stable dose of a RAS inhibitor, have proteinuria of greater than 1 gram a day, and eGFR of greater than 30. The primary endpoint will be proteinuria at three months, and the secondary endpoint will be eGFR at two years. I'll now hand it back to Eric for closing remarks. Thanks, everybody. I think you've heard why we're excited about both these programs. When we started developing atrasentan and BION-1301, we were hoping for 25%-30% proteinuria reductions on top of RAS inhibition, and what we're seeing is 50%-60% with atrasentan and up to 70% with BION-1301. We're just really thrilled with the data that we're seeing, and we wanna move quickly to get these drugs through clinical trials so that we can help patients who desperately need better therapies. In terms of catalysts upcoming, as Charlotte mentioned, we're gonna start the combination trial, the phase II combined with SGLT2 inhibitors in IgAN next year. We'll also be reporting the top-line ALIGN data in Q3 for atrasentan, and we'll have data from some of the other cohorts in the AFFINITY trial to present next year as well. With BION-1301, we'll continue to present data from the ongoing phase I-II trial, so additional follow-up from Cohort One, and then we'll be completing enrollment, hopefully soon in Cohort Two, and then we'll be moving forward with reporting data at additional time points from Cohort Two as well. In parallel with that, we're doing all the work that Charlotte described to get the phase III going as soon as we can next year. Regulatory interactions are underway, and there's a lot going on to get that trial started quickly. With CHK-336, we'll have the healthy volunteer phase I data, and that'll be both safety and target engagement data in the first half of next year, and then we're gonna move towards initiation of phase II proof-of-concept trials in both primary hyperoxaluria and idiopathic hyperoxaluria. We're gonna move to those trials as soon as we can. The exact timing is gonna be dependent on when we finish the phase I and some of the startup work. We're gonna hopefully get one of them started by the end of the year, but it might slip into 2024. We'll see. Just a lot going on at the company. There's also a bunch of work happening in the research group that we're not talking about yet for competitive reasons. Hopefully, we'll be able to update you on some of that work next year as well. Our goal is to build the leading kidney disease company. We think we've already made substantial progress towards that, and we don't intend to slow down anytime soon. It's great to be here with you, and we're happy to take questions. I think we have microphones out there in the audience. Yeah. Thanks, Eric. At this point, we'll open the floor for questions. Please walk up to the microphone to ask a question. If you're on the phone line and would like to ask a question, please press star followed by the number one on your telephone keypad. We'll take questions from the room before taking questions from the phone line. Hey, Laura. Hello. I guess I'll have two questions. First, with the BION-1301 phase III, could you talk a little about powering assumptions at the nine month time point, and how might placebo rates change? Thank you. BION-1301 phase III, how might placebo rates change over the next few years as we're seeing more adoption of things like SGLT2 inhibitors and maybe newer agents on the market? Then maybe a philosophical question. Do you envision the regulatory bar changing in IgAN? I guess curious how long you see the accelerated approval pathway remaining. Thanks. Charlotte, do you wanna take that? Yeah. I'll start. As I mentioned, we are actively designing the phase III trial, and we're in conversations with health authorities. We haven't disclosed our powering assumptions. Obviously, our sample size is determined by some assumptions that can be made around treatment effect, variability, drop-in, and those are things in which we would like to get a agreement on prior to disclosing that information. We will, at a later date, provide those details. In terms of your question about endpoints. I personally think that proteinuria is gonna be a full approval endpoint someday once there's enough data showing that strong correlation between proteinuria and eGFR. It's gonna take some time to get there, but I do think we're moving in that direction in IgAN. You know, in other glomerular diseases, it's still uncertain. I mean, eGFR certainly plays a role in FSGS. There's some novel endpoints that are being explored by, for example, Vertex with their APOL1 program. I think the FDA's been very forward-looking with this and really does wanna. Because unless we have surrogate endpoints, it's very difficult to develop drugs in rare severe kidney disease because you can't do these large, long, hard kidney outcome trials. I think we're gonna see a lot of evolution about that over the next coming years as we have more data. 'Cause what the FDA wants is correlation to show the surrogate translates into clinical benefit over the long run. Andrew, do you have any other thoughts on that? No, no, I agree. Maybe just the other part of your question, Laura, around placebo responses. I don't think they'll be significantly impacted even though there's new additional agents. Typically, if one is initiated following randomization, that patient will then be censored after that. So you won't get an additional placebo response. You will need to consider in your powering assumptions how many patients may be lost to censoring because of a drop-in of the new agents. Cool. Thanks for taking my questions. I guess as a follow-up to Laura's question on BION-1301 and Andrew's comments. You know, with the nine-month endpoint for the BION-1301 phase III trial, if you don't expect placebo effects to maybe increase with different treatments over time, why not do a six-month primary endpoint for that trial? Then also on powering assumptions for atrasentan's phase III, you know, how, if at all, is the SGLT2 cohort impacting your powering assumptions? Is it big enough to impact that? Just any thoughts there would be helpful. Thanks. Yeah. Do you wanna start? I. Yeah. Charlotte, do you mind? Why don't I start? I'll take the question in terms of the SGLT2 stratum and the Atrasentan, and then you can speak a little bit about BION-1301 and why we chose nine months. Sounds good. Great. As I talked about, we have included an additional stratum of patients who are on SGLT2 inhibitors in the ALIGN study. There will be up to 64 patients. This will be an exploratory analysis. It will not be included in our primary or secondary endpoint, so we don't believe that it will impact the assumptions that have been made, and there's no risk in including them here. Regarding the time point for the primary endpoint for the BION phase III, we think 9 months gives us the optimal opportunity to see the largest treatment effect to support that primary endpoint and an accelerated approval. The magnitude of the treatment effect on proteinuria is important for the FDA's review under that accelerated approval pathway. The onset of action of BION is a little slower than with atrasentan, requiring neutralization of APRIL, depletion of Gd-IgA1, and prevention of pathogenic immune complex formation. In the dataset that Dr. Mandayam just presented, we see continued reduction in proteinuria from the 6-1 2 month time point. We unfortunately don't have a nine month time point, but we wanna maximize treatment effect, and we feel that nine months gives us the best opportunity to support that. Great. Ed Arce from H.C. Wainwright & Co. Thank you. A few for me. Firstly, with BION-1301, I wanted to ask if you could give us a little more detail around I believe there was the one patient that dropped off due to the IgG levels dropping below threshold. A little clarity there would be helpful. And also, you know, given this is a disease-modifying, immune-related target, and you're seeing continued reductions consistently out to 100 weeks, now 71%, do you think this can continue? How do you think about potential plateau? And a couple more, if I may. On NURTuRE CKD cohort, the omics study that you're doing, I'm wondering The BLyS signature was not associated in that analysis. I'm wondering if you can talk about what that might suggest. Maybe we should hit those three ones. We're gonna forget them. Yeah. That's it. We'll start. We'll let you ask more if you want. Charlotte, why don't you take the first one? There was one patient in the current BION-1301 study who had a low IgG, and based upon the protocol definition, hit the critical point for us to withhold study drugs. That one patient came into the study with a low baseline IgG and then was continued to be treated, hit the point around six months ago in terms of the critical point defined by the protocol. At that time we did stop study drug. We have continued to follow that patient very closely. What we're really concerned about with low IgG is obviously severe recurrent infections. Happy to report that patient has not had any infections, and we have continued to follow their levels. The patient has nadired. The past two levels of IgG are starting to increase, and we continue to monitor that patient. I think your second question was about, you know, do we expect to see continued benefit added over time? I mean, 70% is a lot of reduction and, you know, even normal proteinuria levels are, you know, in the kidney. We don't know. It does seem, you know, when you look at small numbers of patients, but 70% kinda seems where we're kind of plateauing out, which depending on where you started, gets a lot of people into a really good range of proteinuria. We'll keep following that, but I think there is a limit to how much proteinuria reduction you can get. We're depleting APRIL and, you know, IgA and galactose-deficient IgA in a really robust way. We probably are maximizing it at some point when you get out to 1-2 years, is our assumption. Then the third question is for Andrew, I think. The third question, we did not see an association between serum BLyS concentrations or eGFR or proteinuria in the NURTuRE cohort. That's consistent with other published reports in other IgAN cohorts failing to show an increase in BLyS expression. In contrast, we, like others, have seen a strong association between APRIL and clinical endpoints in IgA nephropathy, in addition to genetic signals from GWAS studies supporting the pathogenic role of APRIL in IgAN. This is really consistent with supporting our hypothesis that selective targeted neutralization of APRIL is the optimal approach rather than dual APRIL BLyS inhibition because of the lack of evidence that BLyS really plays a key pathogenic driving role and the potential for broader immunosuppression when you neutralize both TNF cytokines. Jingming Chen from Evercore. Hi, thank you for taking my question. I have two of them. The first one is, how should we think about influence of ethnicity and baseline proteinuria on the magnitude of response? And my second question is, what's your latest thoughts on doing some future work to lower dosing frequency or decrease the injection volume? Maybe I'll ask Dr. Mandayam and Charlotte to comment on the first question about ethnicity and baseline proteinuria levels. Do you have any thoughts on that? No. Actually, it's a very interesting thought, ethnicity and baseline proteinuria as a predictor of reductions and improvement. I don't know of any data that would support the difference in baseline proteinuria by ethnicity or response. In general, we notice that certain racial groups and ethnic groups have higher adverse responses to having IgA nephropathy or CKD, but I don't think. Charlotte, do you know? No, I'm not. Do you know of? We do know that baseline proteinuria doesn't impact response. Do you wanna say- To atrasentan. Yeah. To atrasentan. That is at least in diabetic kidney disease, where we have over 5,000 patients with a broad range of proteinuria from about half a gram to 5 grams. We see a consistent% reduction from baseline irrespective of what that baseline is. It's a small data set in AFFINITY, but we haven't seen an association with baseline proteinuria and response there either. With atrasentan we also have the luxury in DKD of a lot of experience globally, and didn't see a significant difference between proteinuria reductions in different patient populations with a detailed analysis done between Japanese DKD patients and North Americans with no difference there. For atrasentan, we have data to suggest that it doesn't have a significant impact. For BION-1301, it's obviously earlier days. We do have a broad range of baseline proteinuria in the ongoing BION-1301 study from just over 0.5 gram to over 6.5 grams, which is extremely high for an IgAN patient. Again, haven't seen that association, but again, a very small data set. Cohort two did enroll patients from South Korea, and we're seeing very similar responses in cohort two as cohort one. There's still a lot to be learned around BION-1301 as a novel mechanism of action. I'm sorry, I've forgotten the second question that you asked. Oh, sure. What's your latest thought on doing some future work- Oh. Yeah, lowering dosing. Yeah. -frequency or, injection volume? Yeah. We've decided for phase III to put our best foot forward. We understand the 600 mg sub-Q dose every 2 weeks really well. We really like the data, so we've decided to optimize for safety and efficacy in phase III. There may be ways to have a less intensive dose and schedule for sort of maintenance, once patients have the effect that we're seeing, maybe there's a way to back off on frequency of dose or dosing holidays. That's something that we're gonna explore in parallel with phase III. We will have patients rolling off the phase I-II onto an open-label extension, so we have some opportunities to look into what happens when patients come off drug, while we're doing that. That's our plan as of now. In terms of, you know, the format for the phase III is gonna be prefilled syringes, and it's a formulation of 150 mg per mL. So it's two injections of 300 mg each currently. There are ways to look at, you know, auto-injectors or other technologies that we could do as a lifecycle management exercise. But from what we found from market research as well as talking to our clinicians, you know, two sub-Q injections every two weeks is not something that's been a barrier to them coming on trial. And we don't hear in the market research that it's one of the top differentiators. They really focus on safety, efficacy, and then the convenience of dosing is further down the list. Ultimately, with pre-filled syringes, we should be able to have the patients give themselves the injections at home rather than coming into the physician. Matt Phipps from William Blair. We just wanted to make this feel like a real medical presentation, making us walk up to a mic. I don't suppose Laura's still available. She is. Oh. She's on the line. Dr. Kooienga. Is she? Dr. Kooienga. Maybe. Yes, I can hear you. Oh, hey, great. Thanks. You mentioned that a lot of your patients say they are feeling better. Can you characterize that just broadly, what symptoms are improving? Anything you can give on that? Yeah. You know, we actually try to ask them to figure out what they're feeling better, and I think that they just in general feel better and have better energy. I also think psychologically for a lot of these young patients, when they see that their protein is getting better, and some of my patients' protein is down into the normal range, it makes them feel better and more hopeful that they're not gonna die from their kidney disease. Great. Okay. Just one comment in terms of, you know, like, the injections. I don't think any of them. Like, some of them have said, like, "You can give me 10 injections, you know, like, if it continues to work and help them." They're very easy to give and, you know, not associated with discomfort. So I don't think that that's been a barrier for any of our patients that we see. There were a couple, this is a general question, a couple of low grade, you know, injection site reactions. Is there any temporal nature to those? Are those in some of the first injections? Is it just sporadic? Is there anything additional you can give? Charlotte, do you wanna take that one? Yeah. The number of injection site reactions in subjects have been fairly low. We've had 8 subjects overall experience it. In totality, we've given about 375 doses, and we've had 14 injection site reactions. Most have been mild in nature. We have had one that was a grade two, which was erythema. Overall, really, that's the characterization that we ask to be reported with ISR. It's a good formulation. We've been really happy with you know. It's not too viscous. You know, it's been well-tolerated. Great. Lastly, I know on the BION-1301 poster, it said the sub-Q APRIL data had not been evaluated. I assume that's for cohort two. Have you been able to look at free APRIL in some of the cohort one switching patients yet? Just curious if it is staying at that very low level. Andrew, hey. Yeah. We don't have that data yet, Matt. They're to be measured. We will plan to report that, probably at a future medical conference. All right. Great. Thanks. The thing we're encouraged by, though, is the biomarker responses maintain, which is a key driver of efficacy and suggests likely similar to APRIL neutralization. That's what we would expect for it to be similar, given all the rest of the data's similar. But it's just was an assay that we need to, optimize. Justin. Great. Thanks. Justin Kim from Oppenheimer. Maybe just for the clinicians in the room. You know, there's a number of different MOA that are being investigated to treat IgAN. As you think about having more options sort of in your toolkit to treat these patients, do you think the goals of treatment will change that, you know, because you can reach different bars of efficacy that you may be looking to treat, you know, more patients, less patients, use more options and combinations. You know, can you just provide some thoughts on how you think about, you know, how you practice and how you treat patients changing over the next couple of years? Do you want Laura to try or you more than happy to? I can start and then. Yes. I think this is a fantastic time for our patients with IgA nephropathy. There will very soon be most patients on probably two or three tiers of baseline treatment. I think in addition to ACE and ARBs, ERAs will probably be on all of our patients and an SGLT2 inhibitor. That will probably be, like, first line, everybody gets these three modalities to go with. Depending on how much proteinuria they have, depending on the slope of eGFR, depending on any other adverse risk characteristics, maybe things we discover in our cohorts, people will start doing biological therapies or immunomodulatory therapies. I think that there will be two distinct groups of treatment strategies clinicians will pursue, and most of our patients will be on a combination of ACE, ERA, SGLT2 standard. Depending on how they respond, depending on when we find them, we'll decide about the rest. Dr. Kooienga, did you wanna add anything? No. I would agree with that, assessment. Okay, great. Any other questions in the room? Ed, yeah. Ed Arce. We didn't get to your fourth question. Just a quick follow-up. Kind of related to another question before. Do we understand the differential impacts of race and ethnicity on IgA disease severity and progression? Specifically, with either of your two compounds, do you, are you seeing any differential responses? Thank you. Charlotte, do you wanna start with that? Yeah. We do know that in Asian populations treatments have been different. Usually, when you look in the Asian region, these patients are diagnosed sooner. It's likely because they are screening for it in countries, Asian countries. The treatment is different and can include things like tonsillectomy. I think we understand that there are differences in Asian populations, and that's the population where we really know most information from. We're not seeing any differences in the datasets that we currently have, though. I will just say that it could be because there is underdiagnosis in some of the other populations, and we don't have other populations enrolled. That is something of interest, for us to try to make sure that in our studies, we're getting a good representation, of populations throughout the globe. That's something that we're actively working on. Andrew, anything else to add? No, I think you covered it really well. Laura. Laura Chico from Wedbush. I'll be quick with this one. You mentioned underdiagnosis, and that's a theme that we've heard a lot, I think, this week at ASN. Was there anything that presented at the meeting this week with respect to biomarkers or diagnosis? Any tools out there that you would highlight that can kind of accelerate diagnoses or anything that you're watching for? Do you see anything? Unfortunately for IgA nephropathy, it's still biopsy required. I don't think we're close really to a non-invasive surrogate for definitive diagnosis. The work like we're describing in these cohorts, like NURTuRE, hopefully ultimately will help categorize patients better non-invasively than the current need for biopsy. Great. We're gonna move to the phone line, Will Sargisian from SVB Securities. Hi, all. Congrats on the data here. It looks like cohorts 1 and 2 of the BION-1301 study enrolled patients with GFRs in the 70-75 ml range, which seems a bit high, whereas the AFFINITY trial enrolled patients around the 45 ml range. We also noticed that the time from biopsy was much less than the BION-1301 trial at 2-3 years versus four years in AFFINITY. Is this because patients in BION-1301 trial had higher risk features? If so, does this pattern make sense for potential uptake in the marketplace? What do these representative segments look like in terms of prevalence according to your market research? Okay, so there's a number of questions in that. Andrew or Charlotte, do you wanna talk about the cutoffs and the average baseline characteristics for eGFR? Yeah. Maybe I'll start and just give some distinctions in terms of both studies. I think the biggest study distinction between the Atrasentan studies is that we don't have a criteria in terms of time from diagnosis or time from when the biopsy was. Whereas in the BION-1301 phase I-II trial, the biopsy had to be within 10 years. We are seeing that, as you've mentioned, time from biopsy is lower in the BION-1301 phase I/2, and that's likely a combination of, number one, mechanism of action, where this is a immunomodulatory agent. Clinicians are going to want to see some inflammation or inflammation in terms of the patient's biopsy as well as then the self-selection that comes with that. I think that's why we're seeing differences because of mechanism of action, number one. Number two, the study protocol requires for BION-1301 that it's a time from biopsy of 10 years. Andrew, anything to add there? I think this could be a great question for Dr. Mandayam. Mm-hmm Dr. Kooienga because they've got choices in clinical trials when they enroll their patients. In general, the IgA nephropathy universe has opened up, so a lot more people are getting biopsied, and a lot of our patients are aware of the fact that they have IgA, and proteinuria is a risk factor, and they're willing to enroll to clinical trials. I think this is just part of the landscape that has changed in IgA. It is good that we are enrolling people earlier rather than waiting for GFRs to drop into the 30s and 40s to try to do things for them. I think this is a positive sign that we're able to get people on biologic therapies at higher GFRs, especially if they have the risk markers of higher proteinuria when they have higher GFRs. Dr. Kooienga, do you have anything to add to that? I would say for our site, just because there are clinical trials for IgA, that our patients are often referred like from the hospital when they first get their biopsy. The time from their biopsy might be only, you know, six months or however long it takes them to get stabilized on RAS inhibition. I think the other part of your question was market size. Great. Yeah. That's you know, eGFR is really a function of time. When did you catch the patient and diagnose them? Whereas proteinuria is really, you know, the driver of how quickly patients are gonna progress. When you think about the market, about 40%-45% of the patients, and according to our market research, have proteinuria over a gram per day, and another 20%-25% are between half a gram and a gram. Roughly two-thirds of patients could use better therapies in addition to RAS inhibition. What their eGFRs are is just really a function of how long have they had the disease and how much kidney damage have they suffered. And Yeah. Great. Next we have Great. That's all. Thanks, Will. Next, we have Antonia Borovina from Bloom Burton. Hi there. Can you hear me okay? Yes. Okay, great. I'm just wondering if you have any thoughts on the differential efficacy that you're seeing between BION-1301 and Otsuka's similar anti-APRIL antibody, given the fact that they have a shared mechanism. I believe those drugs are binding to the same epitope. Just wondering if you have any theories on that. Yeah, it's a little hard to comment on their data set from the poster. You know, first of all, it looks like they're validating that APRIL inhibition is important in this disease. Their median proteinuria reduction at or mean at nine months was 43%. It's good data. What we can't comment on. It was a pooled doses, so we don't know if there was a dose response. We also haven't seen any biomarker data yet. It's a very different patient population. They enrolled this trial in different countries than we did. It's really hard to compare the two drugs. All I can really say is it validates APRIL inhibition and we really like our data, and we're gonna need to wait. I think they're gonna have more data at WCN. We're gonna need to wait to see that. Okay, fair enough. I have another question for the KOLs. Just wondering, I know that it's early days, but where in the treatment algorithm would you slot a drug like BION-1301? Is it a drug that you think could benefit, you know, all stages of IgAN, or is it primarily something that you would use in early stages of disease? If it is something you'd use earlier stages of disease, what proportion of the target patients would actually be diagnosed through biopsy at that stage? Maybe we'll start with Dr. Kooienga first, this time. Dr. Kooienga, are you there? Yes, I was just trying to remember her first question that you wanted me to answer. Oh. Where in the treatment algorithm, would you slot a drug like BION-1301? You know, I think that's part of the question that needs to be answered. It seems like this treatment could be used at all stages of the disease because it's part of the pathology and contributes to the progression. Dr. Mandayam. Yeah. I think this is a philosophical question more than how much data we have. I think that if you have a disease-modifying therapy that can intervene on the pathogenesis of the underlying disease, you should treat early. If we wait till they develop significant proteinuria or decline in eGFR, it may be too late. I think that as the data is read out, as the phase III results come in for all of these drugs, I think that they will be very early on treatments, especially if we can validate some good biomarkers for risk progression. Thank you. Great. We have a couple questions from Charles Duncan at Cantor, who's not here, so I'll just read them. When you look at the baseline characteristics of the patients in the AFFINITY trial for atrasentan and the enrollment criteria for the ALIGN study, how similar are those patient populations? What are your thoughts on the read-through from AFFINITY to the ALIGN study? Yeah. I mean, they're very similar patient populations aside from the starting proteinuria levels, a bit lower in AFFINITY. It's about 1.2 grams per day versus we expect ALIGN to be closer to two. Maybe 1.8 is what the PROTECT trial's atrasentan was. They'll be a little bit higher proteinuria, but otherwise very similar. We have not yet seen a difference in percentage reduction across starting baseline proteinuria levels. We do think it's a representative patient population. The company is in a unique position of having two drugs in development, for IgA nephropathy with distinct mechanisms of action. I'm wondering what your perspectives are for combining the two, and do you have any plans in the short term or long term to conduct such a study? I would love to combine our two drugs together. As far as we know, there's never been a novel-novel combination. They're smiling in the back 'cause they've heard me say this before. There's never been a novel-novel combination in kidney disease that I'm aware of. You know, it's definitely something we think could be great because the mechanisms of action are very complementary. We don't think they'd have overlapping toxicity. With BION-1301, we could hit one, and with atrasentan, we could hit four. We'll probably do this after atrasentan's approved because the combination's not on critical path for getting either drug approved. It's something that we'll probably do once atrasentan's on the market, and then as we're moving towards getting BION-1301 approved, I think that combo data would be useful then. Great. Thanks, Eric. Any other questions on the phone or from the audience in the room? Great. Oh, one more. Oh. Yeah. I'm just curious. You mentioned, like, I think, above 150 mg per ml, the solution would be viscous. What does that really mean, why it matters? I mean, each antibody is a little different. It's just harder to get the concentrations above, you know, 150. Andrew, you can comment more specifically on that. Yeah. Based on the normal solubility of a monoclonal antibody, you typically target to get above 100 milligrams per ml. That's a well-performed antibody. Up to 150 is a encouraging formulation, but you don't wanna push it too hard to change viscosity, so the experience for injection will be different. We're pretty comfortable with where we are with a well-behaved formulation. All right. Thanks everybody, in particular Dr. Mandayam and Dr. Kooienga, for joining us this evening. I encourage everyone to view our website for more information, including the slides that were developed to complement this discussion this evening. We look forward to keeping you updated on our progress in the coming months. This event was recorded and will be available shortly for replay in the investors section of Chinook's website. This concludes our event. Have a good night. Thanks, everybody.