Good afternoon and welcome to the Vera Therapeutics Investor Call and Webcast. At this time, all attendees are in a listen-only mode. A question-and-answer session will follow the formal presentation. Due to time constraints, we kindly ask that our analysts who have joined to ask a live question limit themselves to one question each. As a reminder, this call is being recorded, and a replay will be made available on the Vera website following the conclusion of the event. I'd now like to turn the call over to Marshall Fordyce, Founder and Chief Executive Officer of Vera Therapeutics. Please go ahead, Marshall. Thank you and welcome. I'm Dr. Marshall Fordyce, Founder and CEO of Vera, and on behalf of the entire Vera team, I'm thrilled today to share with you the interim results of the Phase III trial of atacicept for the treatment of adults with IgA nephropathy. I'm speaking to you from Houston, Texas, where the annual meeting of the American Society of Nephrology, or ASN, is hosting its Kidney Week. ASN is the largest association of nephrologists in the world. Our data were presented this morning by Dr. Richard Lafayette, Professor of Medicine and Nephrology at Stanford and Director of the Glomerular Disease Center, at this morning's opening plenary session with thousands in attendance and standing room only. These pivotal trial results were also published today in the New England Journal of Medicine. On this call, after my introductory remarks, you will hear from Dr. Richard Lafayette, who will take you through the data. Next, you'll hear from Matt Skelton, our Executive Vice President of Commercial, who will share with you some highlights of how we see the market landscape and the potential of atacicept to make a meaningful difference in the lives of patients with IgA and beyond. Then you will hear from our Chief Medical Officer, Dr. Robert Brenner, regarding Vera's expanding pipeline and broad potential in multiple large markets. Finally, there will be an opportunity for Q&A with this group, as well as Dr. Jonathan Barratt, who leads the Renal Research Group at the University of Leicester in the United Kingdom. Dr. Lafayette and Barratt co-chair the steering committee for Phase III origin study, and I'm extremely grateful to you both for your guidance and collaboration with Vera. Next slide, please. Before we get started, I want to remind you that my remarks contain forward-looking statements under the Safe Harbor Act, and as such, we present this disclaimer regarding at-risk statements. Next slide, please. Today marks an important milestone in Vera's history as we progress the development of atacicept, a potential first-in-class mechanism, dual-BAFF APRIL inhibitor to transform treatment of autoimmune diseases. Atacicept is foundational to driving Vera's bold growth trajectory. Vera's mission is to change the standard of care of patients with autoimmune disease from one based on steroids and the depletion of B cells to a more targeted modulation of the immune system and free patients from the burdens of their disease. Vera is poised for a potential commercial launch of atacicept in 2026 and to pursue development and additional indications in other autoimmune kidney diseases and beyond. Next slide, please. Vera has rapidly made progress towards its objectives in 2025 and is on track for our near-term catalyst in 2026. Following Phase III full enrollment and primary endpoint readout earlier this year, we're on track to file our BLA this quarter, enabling potential U.S. commercial launch in mid-2026. Our additional clinical trials of atacicept in the EXTEND trial and the PIONEER trial, in additional IgA cohorts and in other autoimmune kidney diseases, are enrolling well and will be sharing initial clinical trial results in the near future. Next slide. Vera today is in a strong position financially with pro forma cash of $497 million and 63.9 million shares outstanding. We also have access to an additional $425 million in non-dilutive capital through our Oxford facility, which we expect to be sufficient to fund through multiple catalysts, including approval and launch. Next slide, please. Atacicept's mechanism of dual-BAFF APRIL inhibition has broad therapeutic potential for certain autoimmune diseases, which are substantially driven by abnormal B cell function. Atacicept inhibits the two known cytokines circulating called BAFF and APRIL, which are both important for the survival and maturation of the B cell lineage. Elevation of both BAFF and APRIL are found in patients with IgA and lupus and other autoimmune diseases, and both play a role in disease pathophysiology, driving autoantibody production and damage to the body. Next slide, please. Patients with IgA currently face a very challenging path ahead. On average, people with IgA are young, 35 years old of age, and among those at high risk, rapid kidney function decline leads to end-stage kidney disease, or ESKD, before 50 years old. ESKD means your kidneys don't function, and you need dialysis or a kidney transplant, dramatically altering lives and those of patients' families. The severity of ESKD is often underestimated, and as seen here, mortality over five years from this diagnosis is similar to cancer. Through rigorous clinical science, we at Vera aim to demonstrate that the inhibition of immune complex formation in IgA through BAFF and APRIL inhibition offers the potential for these patients to avoid kidney failure over their lifetime. I'm proud to represent the Vera team and the progress we've made toward unlocking the pipeline and the product potential of atacicept. It's my great pleasure to share with you the results of our Phase III trial, and I'd like to introduce Dr. Richard Lafayette, who will take you through the data. Dr. Lafayette. Hi, good afternoon. It's a great pleasure to be with you. It was great to present the data this morning, and hopefully I can see my first slide to take you quickly through this presentation. That's just who I am. On the next slide, Marshall already gave you a beautiful background that IgA nephropathy is the most common primary glomerular disease throughout the world. Estimated incidence of about two and a half cases for every 100,000 individuals, but we feel that's underestimated given the need to diagnose by biopsy and that there's way too often very late presentations where patients go immediately into advanced chronic kidney disease care or dialysis. As already mentioned, this is a disease of young people in the prime of their lives, trying to start families and live their lives. Unfortunately, while this was previously thought to be a relatively benign diagnosis, people like Jonathan Barratt here and many other registries have really shown that patients are really facing a 50% risk of losing their kidney function or dying within 10 years or slightly longer at diagnosis. This has led the International Guideline Organization to suggest we get much more aggressive with these patients, really control their proteinuria, but most importantly, we need to try to achieve disease progression rates in terms of losing kidney function or estimated GFR at a rate of less than 1% or less than 1 mL per minute per year, which is similar to adults with healthy kidneys. Thus, there is still this great need for disease-modifying therapy that can truly stabilize kidney function in a safe, well-tolerated manner. Next slide. Again, as alluded to, we now have more and more evidence that IgA nephropathy itself is a B cell-mediated disease that causes kidney pathology. As you heard, these terms, BAFF and APRIL, are cytokines that have receptors on B cell, predominantly TACI, and can stimulate B cells to mature, to survive as plasma cells, and be long-lived producers of antibodies in an IgA nephropathy that leads to the production of galactose-deficient IgA1 and also to autoantibodies against that galactose-deficient IgA1, which together can form immune complexes. It is those immune complexes that we see in kidney biopsy within the kidney that are felt to drive the inflammation as a response to that immune activation in the kidney and lead to hematuria, proteinuria, and eventually scarring of the kidney such that they lose their function. Next slide. Thus, as introduced already, atacicept as a rationally designed fusion protein. Consisting of that TACI protein, which is very potent in binding both APRIL and BAFF with picomolar potency, can therefore stop this B cell activation and turn reducing galactose-deficient IgA1 and the autoantibodies and immune complex, reducing inflammation, reducing hematuria, proteinuria, and protecting the kidney from progressive injury and loss of function. This agent can be given at home in a 1 mL shot weekly in a well-tolerated fashion. Next slide. We have history with this agent through its development and in the Phase II study. As you likely know, three different doses of atacicept were compared to placebo in a 36-week randomized trial for patients at high-risk progression, adults with biopsy-proven IgA nephropathy who had more than 0.75 g per gram of proteinuria, GFR over 30, and well-controlled blood pressure on maximally tolerated RAS inhibitors. With the primary endpoint being the efficacy in terms of proteinuria reduction, all patients were offered rollover to atacicept at 150 mg each week at home for an additional 60 weeks. Next slide. As we would hope, our clinical desire for effective interventions in IgA nephropathy and the one now endorsed by the 2025 KDIGO guidelines suggests we really have a need to reduce immune complexes here assessed by galactose-deficient IgA1, that we would like to resolve the inflammation, perhaps assessed by glomerular hematuria. We need to reduce proteinuria as that's our most potent predictor of progressive kidney injury and, in turn, stabilize eGFR to progression rates similar to people without kidney disease. In the next slide, you of course know that in Phase IIb program, this was nicely achieved with a safe 2/3 reduction in galactose-deficient IgA1 with resolution of hematuria for those patients at baseline who had blood in the urine of nearly 80%. A reduction in proteinuria exceeding 52% through that 96-week period. And change of kidney function of less than 1 mL per minute per year at 0.6 mL per minute per year slope, again achieving similar rates of decline as would be seen in healthy patients and done without significant side effect burden compared to the placebo patients. Next slide. Phase III trial design went forward as a similar design to the Phase II study, same worldwide sites as a randomized global placebo-controlled trial, comparing placebo to that atacicept 150 mg subcutaneous weekly given at home and. Similar population of adults with biopsy-proven IgA nephropathy on stable RAS inhibitors and/or SGLT2 inhibitors as in the prior study. They had to have a urine protein greater than 1 gram or greater than 1 gram per gram and eGFR greater than 30, again with well-controlled blood pressure. The primary goal was to look at proteinuria change here at week 36. Next slide. 750 patients were screened to have 431 patients randomized. 428 of those were treated. This analysis includes 214 atacicept and 214 placebo patients for the safety analysis, but the pre-specified interim analysis occurred when there were 106 atacicept patients and 97 placebo patients reaching week 36, and there was wonderful retention, in fact better in the atacicept group than in placebo patients. Next slide. The demographics of these patients were very similar to Phase IIb study and similar to global trials of patients at high risk of progression with IgA nephropathy. These are young patients averaging 40 years, slight male predominance, slight Asian predominance, but excellent mix of racial background. eGFR showing that they've already suffered some decline in their kidney function, averaging 65 mL per minute, substantial proteinuria at baseline at around 1.8 g per gram, signaling a daily protein excretion well in excess of 2 g per day. These patients had relatively fresh disease diagnosed on average 2.5 years earlier than the study, but with a broad distribution. The main difference between the IIB study and ORIGIN III is that as per clinical practice, now more than half of the patients are co-treated with SGLT2 inhibitors along with their RAS inhibitors, while. Just a few years ago only 14% were. Next slide. Here you can see again the very substantial success in reducing proteinuria that was achieved with atacicept, where there is ongoing interval-by-interval reduction in proteinuria that has not yet plateaued, reaching 46% at 36 weeks. At that point, there was a 7% reduction among placebo patients. The modeled net difference between active treatment and placebo becomes 42%, again highly statistically significant and very clinically meaningful in predicting a benefit to kidney function. Next slide. Importantly, this benefit in reducing proteinuria was seen in all pre-specified subgroups. Whether you are older or younger, male, female, from Asia or otherwise, white or not white, have higher or lower proteinuria, higher or lower GFR, or whether or not you were treated with SGLT2 inhibitors, patients still enjoyed that 40%-50% reduction in proteinuria. Next slide. Again, biomarkers demonstrate that the galactose-deficient IgA1 was similarly reduced. Here we're seeing about a 68% reduction at 36 weeks with no change in placebo patients. Again, among patients with blood in the urine at baseline, there was an 80% resolution, 20x greater than what was seen in patients just on their background therapy. The eGFR is not disclosed for this data per regulatory recommendations. That's a difference that we don't have the confirmation that we had Phase IIb yet, but as you know, the study continues on awaiting its two-year GFR data. Next slide. Importantly, adverse events are generally balanced between atacicept and placebo patients. This is the full safety population. Now 428 patients, you can see overall adverse events are similar. In fact, the serious adverse events are numerically lower in patients who were assigned atacicept and received atacicept therapy. Drug discontinuation was also numerically lower in patients receiving atacicept. When we look at infections, infestations, there's really no difference in the overall number, and all the serious and severe infections occurred among placebo patients. There's no opportunistic infections, and any imbalance in adverse events is really attributable to differences in injection site reactions, which again are mild to moderate and did not cause patients to leave the study. No discontinuations. What was called hypersensitivity reactions actually was more common among placebo patients. Again, fortunately, there's no deaths in the study, and there was no hypogammaglobulinemia seen in this study to date. Next slide. In sum, again, IgA nephropathy is a B cell disorder causing kidney pathology. BAFF and APRIL are two key cytokines that drive B cells to make autoantibodies to lead to this pathology. Atacicept's been rationally designed as a native human TACI- Fc fusion protein to bind BAFF and APRIL and to modulate B cell effect, again with picomolar affinity, once-weekly dosing. Phase IIb study demonstrated reductions in galactose-deficient IgA1, hematuria, proteinuria, and wonderful stabilization of kidney function as measured by eGFR. Now we have the 36-week results Phase III, again showing numerically even better proteinuria reduction. Reduction in galactose-deficient IgA, resolution of hematuria, proteinuria reduction across all the subgroups of patients, and safety at least comparable to placebo without any evidence of serious severe opportunistic infections and without immunosuppression. Again, in setting up this intervention, this agent as a very viable option for long-term delivery to our patients who very much need therapy to stabilize their kidney function. Thank you very much. Thank you, Dr. Lafayette. Next slide, please. I'll note again that these results were also published online at the New England Journal of Medicine, and I appreciate Dr. Lafayette, your leadership and guidance. Next slide, please. I'd next like to introduce Matt Skelton, our Executive Vice President of Commercial here at Vera Therapeutics. Matt, thanks so much for your time. Thanks, Marshall. Hey, I'm pleased to update you on the progress we have made in Commercial and our view on the opportunity before us. I want to start off first with an update on some building out of the team. Vera's sales leadership team is hired. We attracted top talent. Leading the West region is the former national leader of Amgen's nephrology sales force, and leading the East is the former East region sales leader for Calliditas, a company in the IgA space. They have hired their sales management team, and soon we will build out the sales force, and they will be in territory well before our anticipated approval. Here is the opportunity before us. There is a large prevalent pool of 160,000 patients in the U.S., of which 90,000 are addressable. This is Phase III population. We are confident we can compete for a meaningful share in this population. As the data continues to emerge with atacicept, we hope to eventually expand into moderate and lower-risk patients. This is a market with lots of growth potential. Next slide. Here, these findings are from a third-party survey conducted with 100 nephrologists. We are very pleased to see the strong ranking for atacicept amongst other pipeline assets. I will focus you on the dark blue section of the graph. Here you see a clear preference for atacicept as the most desired pipeline product in IgA. With results presented at the plenary session this morning, this high-level anticipation will likely increase. Next slide. We've been conducting our own market research. The atacicept product profile is compelling to nephrologists. Phase IIb long-term eGFR data resonates the most, followed by the dual inhibition MOA and disease-modifying therapy. Another important attribute is the patient-friendly presentation. At-home administration with an auto injector and a low 1 mL injection volume led to over 90% patient retention in the trials. Next slide. To further the point. We are in good company with leading injectable biologics. A weekly self-administered low-volume injection with an auto injector is a very familiar presentation to patients and physicians. Next slide. Here's the existing market. Innovation in the IgA space is allowing for premium pricing. Fabhalta is a clear outlier, but remember, it was initially approved for PNH. The strength of our data and the promise of the long-term eGFR data Phase IIb gives us plenty of headroom when we consider pricing. Next slide. I'll conclude with this slide. The market and the product are attractive. It is a large and growing market with unmet need. Nephrologists are hungry for innovation. The payer mix is mostly commercial. Remember that patients are usually diagnosed in their 30s. We're excited about the atacicept profile. Nephrologists are excited about the profile. I'm confident we can gain significant market share with these results. I will now hand off to Dr. Brenner, Chief Medical Officer. Thank you, Matt. I want to begin echoing Marshall's comments from earlier, and I want to congratulate Dr. Lafayette and Jonathan for their leadership with Phase III program. For those people who were fortunate enough to be in the plenary session this morning, I think the energy in the room was palpable. In many ways, the meeting that's going on in Houston this week is an example of a transition point for clinical nephrology and for us to have greater optimism in the future therapeutic strategies that we'll be able to deploy for the patients that we collectively serve. As we think about where we're focused with atacicept, we have been absolutely focused. With Phase III program, the data readout this summer and into the fall. With the program that we began earlier this year called PIONEER, which is allowing us to expand into a really broad. Population of patients who suffer from IgA-mediated disease, but also to start looking at other forms of autoimmune kidney disease where autoantibodies are binding to not only circulating autoantigens like galactose-deficient IgA1, but they're also binding to glomerular antigens like nephrin and PLA2R. The program that we have designed and are executing that includes both ORIGIN, ORIGIN Extend, and PIONEER allows Vera to be in a leading position to study all comers with IgA-mediated disease, as well as patients who have other forms of autoimmune glomerular disease. That said, we also are very motivated to think about the long-term proposition of impacting other forms of autoimmune disease that exist outside of the discipline of kidney medicine. We have talked in the past about our focus on diseases that are cared for for patients who are cared for by rheumatologists, hematologists, neurologists, etc., where we think the long-term opportunity for B cell modulation to be transformative for patients is great. In the near term, our focus is on the IgA opportunity and in the adjacent indications that are defined by autoimmune glomerular disease. Next slide. A little bit more about the PIONEER study. This program got underway in the first half of the year, and it begins by looking at the reality that all of the trials that Dr. Lafayette and Dr. Barratt have been involved with have focused on a specific set of inclusion and exclusion criteria for patient enrollment. As we looked at the r elevance of the Phase II data that we read out a year ago, it gave Vera and our academic collaborators motivation to think about studying more of a broad footprint of IgA-mediated disease now and not waiting for years to elapse before we take on this daunting challenge of studying everybody. There are a number of cohorts of patients with IgA-mediated disease who would not be eligible for the ORIGIN program, but now have a home in the PIONEER study where we're able to evaluate the efficacy and the safety of the drug. Once we're in all of these sites studying patients with IgA-mediated disease, we can appreciate that the same clinicians, the same study coordinators, are caring for patients with other forms of autoimmune-mediated glomerular disease, namely patients with membranous nephropathy associated with anti-PLA2R antibodies and patients with both focal segmental glomerulosclerosis and minimal change disease who have antinephrin autoantibodies. Under the basket of one large umbrella, we're able to study all of these cohorts of patients in one singular program. Enrollment continues. There's been great enthusiasm globally for participation in this trial, and I'm thrilled with the progress that we're making, and we look forward to sharing results from this study as the data set matures. Next slide. Finally, a little bit about our pipeline. Clearly, our focus is on filing, gaining approval, and launching atacicept for patients with IgA-mediated disease, IgA nephropathy. In addition, now we're well underway to advancing our understanding of the impact of atacicept in patients with membranous nephropathy, FSGS, and minimal change disease where they have documented autoantibodies against glomerular antigens. We think in the future, there are other opportunities within the autoimmune glomerular disease space where atacicept offers the promise of being an important therapeutic advance. In addition, within the walls of Vera, we have MAU868, a monoclonal antibody against BK virus that has moved into Phase II clinical studies. Finally, at the beginning of this year, we announced the acquisition of VT109 through a transaction with Stanford University, which is an alternative form of an Fc fusion protein with a high binding affinity for both BAFF and APRIL, and could lend itself to a differentiated profile than what we've seen to date with other B cell modulators that are under development. In aggregate, we think that this integrated pipeline represents really strong opportunities for value creation in the months and years to come. With that, I will turn it back over to the moderator. Great, thank you. At this time, we'll be conducting a question-and-answer session with our speakers. Please hold for a brief moment while we pull for questions. Our first question comes from Anupam Rama at JPMorgan. Please go ahead, Anupam. Hey, guys. Thanks so much for taking the question, and congrats on a great session this morning. This morning at the oral plenary, we heard a lot about combination strategies. Given the safety profile of atacicept for both the company and the KOLs on the line, how do you think about combination strategies with the product going forward in IgA? Thanks so much. Dr. Brenner, why don't you begin, and then we'll ask Dr. Barrett to opine. Yeah. I think many patients, as they advance through their journey as a patient, come to be seen by a nephrologist after they've been recognized to have one or more of three things. They have blood in their urine, they have protein in their urine, or they have a reduced measure of their GFR or an elevated creatinine. Eventually, they'll make it to a nephrologist, and a decision will be made to bring them to the biopsy suite to make a tissue diagnosis. In advance of that, it's not uncommon for patients to start on either an ACE inhibitor or an angiotensin receptor antagonist, and in recent years, to even begin with concomitant SGLT2 inhibition. The specific prescription for IgA nephropathy would begin after a biopsy is returned and confirms that that's what they have. My view is that in the future, when a B cell modulator like atacicept is available, it would be the drug of choice to start treating patients who now have a tissue diagnosis that confirms the disease. There, in my mind, would not be a reason to discontinue an ACE or an ARB or an SGLT2 if it's already on board. My personal view is that over time, based on the data that we've seen to date and the data that we'll see after the trial is complete, I think there'll be less use of corticosteroids for this disease, and I think there'll be less use of complement inhibitors in this particular disease. That's my own view. It may not be the same view that others have, but that's really the way that I think the management of this disease is potentially poised to progress. Jon, do you want to share your thoughts? Yeah. I mean, as a nephrologist, all I'm interested in is preserving GFR and stopping my patient from developing kidney failure. If we replicate the data that was shown in Phase IIb and we return the rate of loss of kidney function to that seen in a healthy individual, why would I think of a combination therapy if I can achieve that? I can't do any better. I'm not going to get the kidney function better than it is because I can't grow new nephrons. I can preserve the nephrons they have. I think it's interesting what Rob said because I think the data that we've seen is already combination therapy in Phase III because the patients are on a RAS inhibitor, half of them are on SGLT2, and clearly half of them are on atacicept. That's already combination therapy. I would like to see a situation where we have an early diagnosis and we start atacicept, and we only come in with CKD treatment if we see a declining kidney function. Because Phase IIb data, where there were far fewer patients on SGLT2 inhibitor, they still were able to return their kidney function to the physiological state. There was no requirement to achieve that result with an SGLT2 inhibitor on board. For me, I think we will move to a situation, hopefully, where we have an earlier diagnosis and we treat the disease immediately with disease-modifying therapy, and we add additional therapies if we do not achieve our goal, which is to return loss of kidney function to the health of our patient. I think the requirement for combination therapies is going to be small if we see the results of the ORIGIN IIB replicated in Phase III. that's my hope for patients. Why would I want them to take five tablets when I can achieve what I want to achieve with one injection a week? Great. Thanks for the question, Anupam. Our next question comes from Pete Stavropoulos at Cantor Fitzgerald. Please go ahead, Pete. Hi, Marshall, Rob, and Sean. Congrats on the data and the publication as well. For Dr. Lafayette and Barratt, when you look at the benefit by subgroup and you sort of home in on the eGFR, greater than less than 60 mL per minute, and you see a much larger effect on proteinuria on those with greater kidney function at baseline, why would that be the case? What does that sort of suggest to you in terms of what patients benefit? Where would the atacicept fit in the treatment paradigm and in the backdrop of the updated KDIGO guidelines in terms of target proteinuria levels? Yeah. Thanks, I'll take first stab at that question. Again, when we do subgroup analyses, we're looking for similarity of effects. And when they're overlying error bars, we really reject the notion that there's a meaningful difference in the high GFR or low GFR group. Even though the dots may move slightly in different directions, as long as those little whiskers of sort of the range of effect are overriding each other and are way away from zero, we're pretty confident to say that there's not a meaningful difference in responsiveness among low or high GFR patients. Thus, I wouldn't really hazard speculating on why there might be a differential response because I really don't think it exists. Furthermore, this is formally tested statistically, and there really is no statistical difference between those two different lines. Yeah. I think what's most striking, as Richard says, is this effect is consistent across all pre-specified subgroups. There is no patient population that responds less well to atacicept based on age, sex, where they live, what race they are, what their baseline proteinuria, GFR is, or whether they're taking an SGLT2 inhibitor. It's very, very clear statistically. There is absolutely no evidence of a differential effect in different patient groups from the Phase III study. Okay. Just one quick follow-up. We always look at these biomarkers, and we're looking at kidney function stabilization. When you speak to the patients that you've treated, sort of how do they feel being on drug before and after? Any changes in physical ailments, mental health effects when they learn their kidney function is stabilized, and any feedback on administration? That's a really great question. I wish we had an adequate tool to assess quality of life in IgA nephropathy, but we do not have an adequate patient-reported outcome tool. We're working on it, but we do not have a validated, reliable way of assessing that in any of the clinical trials. It's absolutely something that's important to patients. It's important to us as clinicians. I wish we had a validated tool to test that, but unfortunately, we do not at the moment. What feedback do you get from the patients? Yeah. What I will just add to that, I think it would be nice to have a formal tool and really evaluate it. As an investigator taking care of these patients, of course, they are blinded, so I can't really know whether they are on or off therapy. Phase IIb data. Pardon me? On the Phase IIb? Yeah. I was an investigator there and do know what the patients were taking. Even there, it is sometimes hard to sort out who is having a good week otherwise, bad week otherwise. What we can say is that looking at the overall adverse event profile, willingness to continue on the study, the fact that there's, again, less discontinuations in the atacicept group means they're feeling at least as well as those taking the placebo patients. Just sort of viewing the patients, I don't see either elation, burst of amazing energy, or the reverse. I mean, Marshall has been at the patient events. The biggest challenge patients face is effects on their mental health, dealing with the uncertainty of what's going to happen to them. If we can show from the ORIGIN IIB, and it's replicated in the ORIGIN III, that we can stabilize your kidney function, that will deal with one of the major impacts on their quality of life, which is that uncertainty of whether they're going to develop kidney failure or not. Because we can take that out of the equation by stabilizing their kidney function. And that, if you talk to IgA nephropathy patients, and Richard and I talk to them a heck of a lot, is the major driver for what affects their day-to-day living. Thank you very much for taking my questions. Thanks for the questions, Pete. Our next question comes from Gavin Clark-Gartner at Evercore. Please go ahead, Gavin. Hey, thanks for taking the questions. Really great to see the positive reception to the data this morning at the conference. For doctors Lafayette and Barratt, I wanted to ask how you think about hypogammaglobulinemia. Do you think this is a harbinger for infections with extended treatment? What about hypogam that's clinically asymptomatic? How often do you measure IgG titers? For the Vera team, I believe there were zero cases of hypogam in Phase III. did you see any cases when looking longer term in Phase IIb? Thanks Turn it over to Vera first. First, we have not had cases of hypogammaglobulinemia so far in the program. Yeah. And given that, I think when we are dealing with a therapy that works with B cell modulation and part of parse, it is right up front that we know to expect about a 20%-30% reduction in IgG. We get a little bit anxious if there is significant hypogammaglobulinemia. Every week that goes by, every program that reports that this class does well without infections, that is the major issue. I think in a program where IgG is blinded, we didn't need to know it to safely manage our patients through it, that this is going to be really not a concern. Particularly in the atacicept program, where there's no significant hypogammaglobulinemia, I think that physicians and patients will enjoy being able to use this drug without needing to monitor IgG. Now, very clearly, patients who do get fevers, ill, acutely ill, will be looking at IgGs then. We'll be considering whether or not the drug needs to be put on hold. Right now, there's no indication that that's really a risk. Infections have not at all been associated with the change in IgG. I think the other thing which you need to realize is a 30% fall in IgG, if we actually looked at absolute levels of IgG. Patients don't fall out of the normal range for a healthy population. Their individual level has dropped. If you looked at their absolute level in the context of a healthy person, it is within the normal range. Perhaps that is a way we should think about presenting the data in the future rather than a percentage change, an absolute level with clear demarcation of where the normal ranges are. I think when we see those data, patients, even though their levels fall, they still remain within a normal range for the lab, which if I were to check, I would not even think twice about because it is normal for the population. As Richard said, it is something we need to think about. We need to bear in mind that practically it has not been an issue. That is very helpful. Thanks, guys. Thanks for the questions, Gavin. Our next question comes from Ritu Baral at Cowen. Please go ahead, Ritu. Ritu, you may be on mute. Sorry about that. I was on mute. Thanks for taking the question this afternoon. As I look at the biomarkers on Dr. Lafayette's slide as presented today. What's notable is that there's no degradation since Phase IIb. and as I look at the baselines, everything, maybe except for SGLT2 use, is pretty equal. Dr. Lafayette and Dr. Barratt, based on these biomarkers, is there any reason that the eGFR at nine months in ORIGIN III should be any different than the eGFR level? And it wasn't disclosed, but. Is anything about the SGLT2 or any other aspects of the baseline notable enough that. Investors shouldn't infer that the eGFR should look like the eGFR response Phase IIb? if I could squeeze one last check-off-the-box question in, Marshall, what's left before the NDA filing? Thanks. I think. The easy thing to say is no. There's no reason not to suspect the result will be identical, if not better, because it's slightly better resolution of hematuria, better reduction in proteinuria, and the SGLT2 inhibitor use certainly should not prevent the stabilization of the GFR. Yes, I'll just say no. There's no reason not to suspect that the data will be at least as good. For completeness, I completely agree. Yeah. I can say that the Vera team is very close to the filing of the BLA, and there really aren't any steps I would name today between us and that moment, and the filing is imminent. Thanks. Thanks for the questions, Ritu. Our next question comes from Paul Choi at Goldman Sachs. Please go ahead, Paul. Hi, everyone. Good afternoon and congratulations on the data and the standing room reception and the publication as well. My question for Dr. Barratt and Dr. Lafayette are, as you think about the magnitude of differences between SGLT2 naive and those on background therapy, can you maybe speak a little bit more to how you would contextualize the atacicept data today versus some of the combination data we've seen in terms of the competitive landscape? I guess for Marshall and team, I want to just ask and to clarify on the commercial prep. Are there any particular centers or as you think about the initial target population of physicians who could be prescribers, how should we sort of think about the ramp of penetration and timing there? Thank you very much. Great. Maybe we'll begin at a high level with your second question and go to your first question. Second question is, Vera is gearing up for U.S. commercial launch mid-2026. As Matt highlighted, some of the detail of that leadership is fully in place. This is a highly experienced and motivated group. We have strong opinions and depth of understanding of this potential market, and we're going to pursue it aggressively. This is not the moment where we're going to share thoughts on how we differentiate and how we think about that market. We will come back and have an analyst day at some point the first half of next year to provide a bit more color, but this is not the time we would do that. I think the SGLT2 story is a red herring. I don't think we need to be concerned. I actually don't think the SGLT2 inhibitors are necessary to return kidney function to the healthy state if you are taking atacicept. The fact of the matter is there are a number of reasons why you might be on an SGLT2 inhibitor. If that's all you've got available, you will use it. I would really warn against thinking that SGLT2 inhibitors will modify the effect of a true disease modifier in IgA nephropathy. Now, of course, if you have diabetes with cardiovascular disease, you absolutely must be on an SGLT2 inhibitor for cardiovascular protection. That's different to preservation of GFR, which quite clearly at the moment, from Phase IIb data, is not necessary to preserve kidney function if you are taking a true disease modifier like atacicept. People are on SGLT2s, as Rob said. We would never advocate stopping them, but we would equally be. I personally would not be advocating starting them if the goal of starting them is to preserve kidney function when I have a drug that is quite capable of doing that by itself. Yeah. I'll just take that to your remaining question, which is compared to the already approved drugs. I think when we present Phase III data and see this reduction in proteinuria, again, by itself, it predicts an improvement in the GFR progression rate. It's really astounding that both Phase IIb, and the expectation here is that it's going to be stable. I don't know if you saw the plenary session by Dr. Perkovich this morning, but he really took to task the IgA nephropathy development that while there is improvement, even with combination therapy of Tarpeyo plus sparsentan, you still would not expect normalization of GFR progression to healthy kidney function. This is really a new class, as John said, really true disease-modifying therapy, and it's likely to really be a first choice of educated clinicians. Excellent. Thank you for that clarification. Again, congrats to Marshall and the team. Thanks for the questions, Paul. Our next question comes from Rami Katkhuda at LifeSci Capital. Please go ahead, Rami. Hey, guys. Just wanted to pass along my congratulations as well for the presentation and publication. Thank you for taking my questions. I guess first, for doctors Barratt and Lafayette, there's historically been a discussion as to whether patients of Eastern Asian descent may have more severe disease and may react differentially, I guess, to BLyS APRIL inhibition. I guess, does the data today put that argument to bed? Then maybe secondly, for the Vera team, when should we expect data from the monthly atacicept dose range finding study, and what could that presentation ultimately look like? In terms of the patient population, if you look at the baseline characteristics, these are absolutely typical patient population that I see in my clinic every week. The sensitivity analyses that you've seen show that irrespective of their eGFR, their baseline proteinuria, race, region, sex, they respond as well to atacicept. For me, I think this population that we recruited is almost identical to the population of patients I look after in my clinic in the U.K. I'll let Richard comment on how representative this trial population are to the patients he looks after in the United States. Yeah. Again, I'm in Northern California, so we do have a very nice mix. In my practice, we have a slightly greater Hispanic population than is represented in this trial, but fortunately, there's enough patients that we can look and see later if they respond similarly. I suspect that they will. I just want to always be the academic. I think we still will feel that patients of Asian race are at higher risk and higher disease burden, but it's remarkable that these interventions still can have the same impact on those patients. Still, hopefully, when we get to the GFR data, we'll have the similar benefits on GFR progression. Okay. Rami, thanks for the question on the monthly program. Just to provide a little bit of background, earlier this year, Vera initiated a monthly dose range finding study looking at three different potential doses of atacicept administered subcutaneously on a monthly interval. Ideally, the way that we'll communicate about this is get to the point where we've been able to review enough of the data that the company's been able to determine what the appropriate monthly dose is, and then to provide guidance on what the path to getting that information into the prescribing information will look like with the regulatory authorities. I'd like to be able to do it all at once. If we're able to do that, we will. If we need to come forward and provide an interim update before I have all of that, we'll do that as well. I'm hoping to kind of wrap it all up and have one integrated disclosure. Makes sense. Thank you very much. Thanks for the questions, Rami. Our next question comes from Ryan Deschner at Raymond James. Please go ahead, Ryan. Hi there. Congratulations on the data and the publication. For the KOLs, how big of an impact would a positive readout for PIONEER in the lower proteinuria and lower eGFR IgA nephropathy patients have on prescriber decision-making once atacicept is on the market? When would you expect this impact to sort of occur? I have a follow-up. Thanks. You're a tiny bit garbled, but I think you're asking about how PIONEER can, first off, demonstrate benefits in a lower proteinuria group. I think our goals will be, again, short-term to read out proteinuria with full expectation that there will be similar proteinuria reduction. I think just that fact that there's similar proteinuria reduction together with safety in that group, as expected, would be enough to convince prescribers that that's a good way to go. As John has shown, those patients can still be of very, very substantial risk. Of course, beyond that, we will be gathering GFR data, looking at that in context, and really seeing if it's acting similar to the higher-risk patients. Let me make one comment, Ryan. I think one of the things that the attendees in the opening plenary session heard this morning, first from Vlado and then echoed indirectly by Rich, is the fact that I think we're in a period of transition in thinking about how we conceptualize patients and their overall risk of disease progression. Historically, in an era where the drugs that we had at our disposal were predominantly effective at reducing proteinuria, it made sense to categorize patients based on the amount of protein they had in the urine to think about when you would intervene and when you wouldn't. Now that we, for the first time, have drugs, at least in phase two over 96 weeks, have had a tremendous impact on GFR rate of loss, and current guidelines are calling for the achievement of a GFR rate of loss of less than 1 mL per minute per year to avoid lifetime risk of ESRD, I think we can start to pivot in thinking about what we prioritize when we're looking at when to intervene and when not. What that means is I can foresee a future where someone who has a very modest amount of proteinuria, but in the last two years has lost 10 mL per minute of GFR, that the prescribing nephrologist is going to be focused on their GFR rate of loss and will be thinking about proteinuria as a secondary component of their risk equation. Yeah. Just to echo that, the direction of travel is to treat as early as possible. As Vlado intimated, you can only treat patients that we have in our clinics. The next challenge that we are addressing is going out and finding these patients earlier because the average GFR for a new patient presenting to a nephrologist in the U.S. is between 40-50 mL per minute, which means by the time they present, they've lost half their nephrons, probably lost almost three-quarters. We can stabilize that kidney function, but we can never get it better. I'd much rather treat a patient with a GFR of 75 and know that I can treat those patients and they're going to keep that GFR. The direction of travel is earlier diagnosis and earlier treatment. I think if you look at what the FDA have done for full approvals, they do not stipulate proteinuria. They do not stipulate GFR. They say, "If you as a nephrologist believe that patient is at risk of progression, you should be thinking of you are allowed to use this treatment." That is very insightful by the FDA. As a community, we are informing what we believe the risk of progression is. That is only going to get lower, and we are going to want to treat people earlier. In a quick follow-up, can you remind us what the stratifications or which stratifications were employed in ORIGIN 3? I do not know whether Rob wants to answer that in terms of the clinical trial design. The GFR, proteinuria. Yeah. Region of sex, region. It is all in the manuscript. Great. Thanks for the questions, Ryan. Our next question comes from Farzin Haque at Jefferies. Please go ahead, Farzin. Congrats on the update, and thanks for taking my questions. Can you give us a sense of what proportion of the patients are getting to below certain UPCR thresholds, say below 1 gram, 0.7, or 0.5 mark at the 36 weeks? Sorry, I could not hear that. Would you mind repeating it? What proportion of the patients are getting the proteinuria below a certain threshold, like 1 g or 0.7 g or 0.5 g at the 36-week mark in the ORIGIN 3? It is a proportion of patients that hit a proteinuria less than 0.5 g in ORIGIN 2B. In 3, ORIGIN 3. Yeah. That data has not been subjected to that analysis yet. I think there'll have to be a discussion about whether and when we do it, but hopefully, we'll do it at some point, probably on the complete data set. It was not part of the predefined statistical assessment of the interim analysis. Got it. Maybe for, to find out, what is the current FDA feedback on the BLA filing package? How are they going to view this class of drugs differently versus the oral competitors, particularly given that it'll be under accelerated approval? Did you hear? Farzin, you're going to have to repeat the question more clearly. We can't hear what you're asking. For the BLA filing package, what is the feedback from the FDA? Are they viewing this class of drugs differently versus the oral competitors? We can't, at this point, share those conversations. I think we've been quite consistent in our public comments that. We have a strong relationship with the division of Cardiorenal. We're in close communication with them. They view these data sets in a similar way that we've been presenting them. They've been presented this morning. I think I'd just leave our comments at that at this stage. It's going to be really exciting to see the progress from this point on. Thank you. Thanks for the questions, Farzin. Our next question comes from Arthur He at H.C. Wainwright. Please go ahead, Arthur. Hey, Marshall and team. I just wanted to extend my congratulations. I think the atacicept has scored a drug profile every drug developer dreamed of. Maybe for Dr. Lafayette and Dr. Barratt. Given the strong efficacy in the subpopulation, what do you think about the agent just to remove the color of the UPCR at the beginning for the XR approval? Also It seemed like in the ORIGIN 3, the patient got a deeper and a faster response compared to the ORIGIN 2. Is there any thoughts around that? I think in terms of response, you can see data for Gd-IgA1, and you can see hematuria. We have not presented data of the granularity that we have for proteinuria yet, but that data will be coming. I think the thing that strikes me is very rarely do you see a Phase III trial replicate almost word for word and data point for data point the same thing you saw in Phase II. As Richard said, it is at least as good, if not better, for most parameters that we have looked at in a larger population, in a global population. That can only. Reinforce the value of targeting BAFF and APRIL in this disease and that this drug is truly disease-modifying. I think that's what I take. I would not look at the nuances yet until we have the full data set. What we have at the moment is as good, and I suggest better than what we saw in the Phase IIb. Yeah. I would echo that. Just because this is a point of discussion about whether or not patients have a demand for some drug in the interim before you see marked proteinuria reduction or hematuria reduction for active anti-inflammatory therapy. I think the Phase IIb results and these results would suggest that you can be patient without risking loss of kidney function. Of course, the GFR is the, if you have a, if your GFR has been lost at the same as a healthy person, how can you do better by an early anti-inflammatory intervention? Because your GFR is as good as if you were a healthy person. I think that is the proof of the pudding. That's why the GFR data from the Phase IIb over 90-plus weeks is so impressive and compelling. I just want to add my comments here. This is what we hope to deliver to the nephrology community and the patients that we serve. That's what we're doing here in Houston. One of the bedrocks of science is to have a control arm to make use of randomization and double-blinded. That's really the innovation in medicine that's transformed what we can offer patients. One is the gold standard design. There was consistency in design between Phase II and Phase III. The other bedrock of science is reproducibility. We are very proud to present that today in both presentation and manuscript form. Thanks, Marcia. If I may, maybe for Matt, I know it's kind of a little bit early. Could you give us more color of your strategy for early physician education and wellness campaign? Sure. We are actively out there now with a disease state education campaign. You can't walk around Houston and ASN here without seeing something about B-cell modulation. BAFF and APRIL as the right targets. The word is definitely out there, and I would say it is the buzz of Houston. We will strive when we get our sales force out there to continue that messaging around disease state and certainly have the market ready and educated about B-cell modulation before launch. Awesome. Thanks for taking my question, and congrats again. Thanks. Thanks for the questions, Arthur. Our next question comes from Dina Ramadane at Bank of America. Please go ahead, Dina. Dina, you may be on mute. Try pressing star six. Hi. Sorry. Can you hear me now? Yes, we can. Thank you so much. Thank you for taking the question and congrats on the presentation and the publication this morning. I guess a question for Dr. Lafayette or Dr. Barratt. I just wanted to maybe touch upon kind of the evolving drug pipeline and contextualizing atacicept's profile. And it kind of sounds like your view on atacicept is in line with Vera's market research that there's considerable excitement for atacicept over the other pipeline therapies. You talked a lot on this call already about your excitement. Can you maybe provide some. Additional color on why specifically there is excitement for atacicept over other agents, just kind of given that other agents have maybe kind of achieved a similar proteinuria or eGFR benefit in clinical trials. Is it really anchored by that two-year eGFR benefit from the Phase II or other aspects of the clinical profile we anticipate at launch? Just maybe a clarification question to your earlier point of proteinuria kind of being, I guess, secondary to eGFR. Is it kind of correct in thinking that if you have an agent like atacicept that's stabilizing eGFR, there's maybe kind of a lower unmet need in trying to get patients' proteinuria down to align with the new KDIGO guidelines past that 500 mg? Maybe that's why you foresee maybe no combo therapy in the future and that the Bafinapril will be getting to that first line in treatment option. Thank you very much. I think it's really simple. If you ask nephrologists what they want, they want a drug that safely and effectively stabilizes kidney function and prevents kidney failure. That's what we want. Therefore, if you look at the available data that has been published and peer-reviewed, the best quality data we have of a drug that stabilizes kidney function over the longest period of time is the ORIGIN Phase IIb data. If you ask me, if I know a patient's kidney function is stable, I really do not care what the proteinuria is because it's not translating to loss of eGFR. That's quite heretical in modern nephrology thinking. I think what we're seeing is we are going to have to reimagine the relationship between proteinuria and GFR dependent upon the drug that you are taking at the time. What I don't want to see is if I have a drug that stabilizes kidney function. The patient may have persistent proteinuria. I don't want patients filled up with antiproteinuric drugs they don't need that aren't adding value to kidney function protection. For me, we are going to, when we have the longer-term GFR data, if I'm able to stabilize kidney function, that is the thing I'm interested about with a drug that is safe and patients tolerate. Those are the major goals. That is what people will be looking at in the literature. At the moment, when you look at the data and the published data, the strongest and most compelling data is the ORIGIN 2B, that we can achieve this with a single agent. Thank you very much. Congrats again. Thanks for the question, Dina. Our next question comes from Sadia Rahman at Wells Fargo. Please go ahead, Saadia. Hi. Thanks for taking the question and congrats on the results. My question is on eGFR and the data that competitors are showing relative to your data. We do not have such long-term eGFR data from the competitor B-cell agents, but in the shorter-term data that we do have, we are seeing some increases in eGFR by like two or three millis per minute out to about one year. I just wanted to get your thoughts on that. Do you think those differences could represent true benefit, or could that. Rise be due to either variability in the data or even a transient benefit that comes with resolving inflammation? I think with atacicept, we also see some of that eGFR increase at earlier time points. Just wanted to get your thoughts on that. Thank you. I do not over-interpret minor increases in GFR. I think the key thing is a lack of loss of kidney function. Because at the end of the day, you cannot grow more nephrons. You have the nephrons you have when you start. We have drugs that have increased GFR detrimentally and have increased proteinuria because they cause hyperfiltration. We do not want to see that. We do not see that with this drug. The overwhelming message I would take from these data is in a p opulation treated with standard of care therapy, high-risk patients lose five to six mL of GFR per year, so 10% of their kidney function per year. The data from ORIGIN 2B completely negates that loss of kidney function and returns the loss of kidney function to the healthy population. I would not over-interpret minor increases in GFR. It is the fact that you are getting no loss that is the most important thing. That is what I aim for in my patients, not to increase GFR by any amount, but to maintain the GFR and prevent any further loss. Got it. Thank you. Can you just clarify whether an improvement in inflammation could lead to some early increase in eGFR? We do see that in a situation, say, for ANCA vasculitis, where someone could present with a rapidly progressive loss of kidney function, where the disease phenotype is very, very different. IgA nephropathy is not like that. And remember, GFR, certainly for the steroid therapies, eGFR is based on a serum creatinine. Creatinine comes from muscle. Changes in muscle metabolism due to steroids could alter serum creatinine and GFR. Again, I would not over-interpret this, and I certainly would not use it to compare one drug against another. The key thing here is the difference between loss of kidney function and maintenance of kidney function and return to the healthy population. Got it. Helpful. Thank you. Just to complete the answer, we know from the 1970s when micropuncture studies were done in models of Hayman's nephritis that the reduction in GFR in patients who had acute inflammation, the glomeruli, was due to loss of surface area. Theoretically, if you are able to have big impact acutely on the amount of inflammation in the glomerulus, you might be able to recover some of that. That would be the more mechanistic component of the answer. Yep. Thank you. Thanks for the question, Sadia. Our final question comes from Vamil Divan at Guggenheim. Please go ahead, Vamil. All right. Thanks for taking my question. Congrats also on the data and everything. Two questions that I could. One, just back on the regulatory side, Marshall, you mentioned the filing is imminent. I'm curious if you'd be willing to comment on whether you expect a priority review or not for this accelerated approval. Is that dependent in any way on getting permission in before, after the study is done and potentially getting approved later this month? On the commercial side, we now have a couple of comps to look at on the sort of IgA launches over the last few years. I'm just wondering how you think about atacicept's potential uptake initially relative to what we've seen from Tarpeyo and sparsentan. I think there's certainly going to be much more enthusiasm for the mechanism. Obviously, those products are already out there now, so they're capturing some of the eligible patients, especially some of the ones with maybe higher levels of proteinuria and obviously orals versus the injectable. Just I know maybe it's still a little bit early, and maybe there's more of a question for your commercial event in the first half of next year. Just your thoughts on how would you think about potential uptake initially relative to what we've seen so far. Thank you. Hey, Vamil, it's Rob. I'm not sure we got all of it, but let me see if I can answer two of the components that I think came through to us in the room. First, yes, our expectation is that we will be granted priority review given that we have breakthrough designation. Second, as it relates to do we think that the trajectory of the launch success for drugs that have come thus far with accelerated approval and IgA nephropathy are good forebearers of what we'll experience with atacicept? I think we would not look at any of the examples of drugs that have been launched thus far as a good direct readout of the performance that atacicept will have in the marketplace. I think we have higher expectations. Okay. Thank you. Thanks for the questions, Vamil. This concludes today's Q&A session. I'll now turn it back over to Marshall for closing remarks. Thanks, everybody, for joining. A huge congratulations to the Vera team and our important collaborators, Dr. Barratt and Dr. Lafayette, and all of the patient volunteers and study teams that made the data possible. Together, we strive to change the standard of care and improve outcomes for the patients we hope to serve. Thanks, everyone, for your attention. Let's close the call.