Good morning, and welcome to the Vera Therapeutics data call. At this time, all attendees are in a listen-only mode. A live question and answer session with our covering sell- side analysts will follow the formal presentations. As a reminder, this call is being recorded and a replay will be made available on the Vera Therapeutics website following the conclusion of the event. I'd now like to turn the call over to your host, Marshall Fordyce, founder and Chief Executive Officer of Vera Therapeutics. Please go ahead, Marshall. Good morning, welcome. I'm Dr. Marshall Fordyce, founder and CEO of Vera Therapeutics, where we're working to develop innovative new medicines and improve the standard of care for patients with immunologic diseases. Today, I'm very pleased to share the full week 36 results from the blinded phase of our ongoing multinational, randomized, placebo-controlled, double-blind phase II-B trial called ORIGIN. Before we get started, I want to remind you that this teleconference contains forward-looking statements under the Safe Harbor Act, and as such, we present this disclaimer regarding such at-risk statements. I will begin by providing some background on our lead clinical development program, which has just initiated our phase III pivotal trial, and summarize our recently disclosed week 36 results, which represent the full results of our phase II-B randomized phase. Next, I will ask Dr. Richard Lafayette to present the week 36 results in detail. He is the director of Stanford's Glomerular Disease Center and recognized as a world expert in IgA nephropathy, presented these results as a late-breaking clinical trial presentation at the ERA European Renal Association (ERA) Congress this past Saturday. I will describe our phase III pivotal trial, which was initiated this month, lay out key catalysts for the company in the next 18 months and beyond, open the line for questions. This is an exciting milestone for patients with IgAN, we're grateful to all our partners and stakeholders in this team effort to deliver these important results. Vera's clinical stage asset is called atacicept, a biologic molecule with a therapeutic potential in certain autoimmune diseases, in which modulating B cells and plasma cells could significantly improve disease. These include IgA nephropathy, lupus nephritis, systemic lupus, membranous nephropathy, systemic sclerosis, among others. We have advanced atacicept in the... For the development, for IgA nephropathy, a serious autoimmune disease of the kidneys, which causes kidney failure in young people. We're currently conducting a phase II-B study and reported the 36-week results this past Saturday. Based on our phase II data and input from the FDA, we initiated our phase III pivotal trial this month. We are now leveraging our global phase II study sites to initiate phase III enrollment. With approximately $197 million in cash equivalents, and marketable securities as of the end of the first quarter, and access to a $25 million credit facility, we're sufficiently funded through our IgAN phase III primary endpoint and project cash runway into 2026. IgAN presents a large unmet need and a potential multi-billion dollar market across the US, Europe, and Japan. There is emerging evidence in current clinical trials that targeting B cells, the source of the bad acting autoantibodies in IgAN, could be disease-modifying and substantially improve kidney function over time for these young patients. Vera's lead molecule in IgAN is atacicept, a biologic fusion protein that is delivered as a small volume, self-administered injection once per week. atacicept targets the source of IgAN by inhibiting the 2 circulating cytokines, BLyS or BAFF, and APRIL, which are both important for the survival and maturation of the B cell lineage. In preclinical models, atacicept's dual inhibition of BLyS and APRIL have been shown to be more potent than blocking BLyS alone or APRIL alone, which may translate into more robust and sustained B cell modulation versus other APRIL-only or BLyS-only approaches. Dual inhibition of both BLyS and APRIL, may be necessary for maximal and sustained clinical efficacy. Moreover, dual inhibition enables a lower dose and a simpler drug product for patient tolerability and convenience. While atacicept has been shown to reduce immune complexes and its precursors in a prior phase II-A trial, it was not known if atacicept also improved kidney function in IgAN patients with high risk of disease progression. atacicept targets the source of IgA nephropathy by inhibiting multiple upstream steps in disease. Blocking BLyS in APRIL inhibits the overstimulation of B cells and plasma cells, which has been shown to reduce the causative molecule, galactose-deficient IgA1, or Gd-IgA1. We have also shown that atacicept reduces IgG autoantibodies to Gd-IgA1, atacicept reduces immune complexes that form and cause downstream kidney injury. We designed the ORIGIN study to demonstrate whether atacicept's known effect on the upstream causes of IgAN translate into improved kidney function as measured by reduction in proteinuria and stability of estimated glomerular filtration rate, or eGFR. To demonstrate a clear treatment effect, we are running a multinational, randomized, double-blind, placebo-controlled trial, so that any factors that might influence the primary endpoint of proteinuria, called confounders, are well distributed between treatment and control arms. Without this design, a measured treatment effect on proteinuria may be influenced by a variety of factors that may make the result difficult to interpret or reproduce and make phase III success difficult to predict. Today, we report our results after 36 weeks or 9 months of treatment, which represent the full results from the blinded phase of this ongoing study. At week 36, we observed statistically and clinically significant reductions in proteinuria. The placebo-adjusted change in proteinuria, as evaluated by urine protein-creatinine ratio, or UPCR, at week 36 in the 150 milligram dose group, achieved statistical significance and showed a 43% mean reduction by the per protocol analysis and 35% by the intention to treat analysis. Looking at GFR, these high-risk patients receiving placebo had an expected decline in eGFR of 9% over 36 weeks. Patients receiving atacicept maintained stable eGFR with an absolute difference of 5.8 mLs per minute that was statistically significant. The 150 milligram dose showed a Gd-IgA1 reduction of 64% at 36 weeks. The safety profile of atacicept continued to be similar to placebo at the 36 week data cut. We've selected the 150 milligram dose to advance into a phase III trial and initiated that trial this month. With that, I'd like to introduce Dr. Richard Lafayette, who will present the results in detail. Dr. Lafayette is the director of Stanford's Glomerular Disease Center and recognized as a world expert in IgA nephropathy. This past Saturday at the ERA European Kidney Conference in Milan, Dr. Lafayette presented these week 36 results. Dr. Lafayette? Hey, it's great to be with everybody this morning. Thanks for having me. Again, this is a tremendous advance towards our goal of finding effective and safe, well-tolerated therapy for our patients with IgA nephropathy, who otherwise suffer progressive kidney dysfunction, ultimately needing renal replacement therapy in the forms of dialysis or transplantation. You've already heard the top-level data is extremely exciting. Let's get into the weeds just a little bit. As you can see, the ORIGIN trial is a multinational, randomized, placebo-controlled, double-blind, dose-ranging study, which evaluates atacicept versus placebo and has a total of 30 patients getting placebo with some experience here in atacicept at 25 milligrams, ranging up to 150 milligrams. The primary endpoint of this study was at 24 weeks to look at reduction of proteinuria, which was met. Today, we'll be focusing on the 36-week endpoints. As you know, this is a study of patients with IgA nephropathy, and to get in this study, these were adult patients who were unstable and optimized RAS inhibitors, the standard of care for at least 12 weeks before study entry. They could use SGLT2 inhibitors, and they had to have urine protein excretion of greater than 0.75 grams per day, and kidney function, above 30 mils per minute by eGFR. Again, the main endpoints we'll look at is the 36-week proteinuria endpoint by their urine protein-to-creatinine ratio. The GFR change is followed up to week 96, 'cause this is a randomized trial for 36 weeks, then patients can go to open label. Out to 96 weeks, we'll look at changes in the biomarker of disease galactose-deficient IgA1, and of course, look at safety. Again, just as a measuring stick, we know from prior experience that a 30% placebo-adjusted reduction in proteinuria is clinically meaningful. Proteinuria reduction is the hallmark of successful care in IgA nephropathy, and when you approach 30%, prior studies have all demonstrated that there's a substantial reduction in the progression of kidney disease, which relates to a reduction in hard endpoints of reaching end-stage kidney disease, the need for transplantation, substantial reduction of kidney function, or death. Again, a placebo-adjusted reduction of 30% could delay kidney failure by over 10 years, and the early change in proteinuria at week 36 is an approvable surrogate endpoint for the FDA, which is based on precedents set by other companies, where the proteinuria reduction has been in this range of 30%-35%. Of course, the eGFR slope at 2 years is the key confirmatory endpoint for full approval by the agency. In this study, 232 patients who would appear to have met the criteria were screened, but ultimately 116 were randomized and treated, as during screening some patients had slightly lower kidney function or slightly lower proteinuria than in pre-screening. That left 82 patients in the atacicept arms and 34 in the placebo arm. In the pre-specified approach to the study, there was a per-protocol analysis that was allowed, which excludes patients with protocol violations, which was identified by blinded third-party group, and this was mainly looking at patients who took medications that could have affected the endpoint of proteinuria change. Again, in the end, there were 80 patients evaluable in the atacicept arms and 31 placebo patients. As you can see here, this is a very typical high-risk IgA nephropathy population, marked by a young age at roughly 39 years, mostly men, approximately 60% of balanced race, with 44% of these patients Asian. There's a higher proportion throughout the world of this disease in Asian subjects. The eGFR was reduced at baseline to about 63 mils per minute throughout the groups. There was very substantial proteinuria at a average of 1.6 grams per gram. Again, there was already some use of SGLT2 inhibitors across the groups. As you can see in this slide, the goal at 36 weeks was readily met at the atacicept 150 milligram group, while the placebo patients saw a 5% increase in proteinuria. In the per-protocol analysis, there was a 40% reduction in the atacicept 150 milligrams for a net change of 43%. Indeed, in the intention to treat a group analysis, there was a net change of proteinuria of 35%, thus readily meeting that hallmark of at least a 30% reduction in proteinuria. Perhaps even more importantly, an early glimpse of changes of kidney function showed that patients treated with atacicept 150 milligrams enjoyed absolutely stable kidney function through 36 weeks, while the comparable patients in the placebo group, as you already heard in the top-line data, saw an expected reduction of 8.5% in kidney function. Again, for a net change of kidney function of 5.8 mils per minute, just in 9 months, a very substantial protection of renal kidney function just in this time. This is felt to be driven by the mechanism of action of drug, whereby you see dose-dependent reductions in serum immunoglobulins IgG, IgA, and IgM through week 36, and as predicted, the 150 mg dose has slightly greater reductions in these antibodies throughout this time course. Prior studies have shown that this reduction in IgA can be sustained safely for at least 2 years. Looking at the biomarker galactose-deficient IgA1, which again is thought to underlie the pathogenesis of this disease, there was a significant early and sustained reduction of galactose-deficient IgA1, which came towards its peak at week 12 and was sustained out to 36 weeks. In terms of safety, you can see the high-level safety here is very encouraging, with similar rates of treatment-emergent adverse events seen throughout the atacicept dosing arms as well as placebo. There were numerically slightly higher study drug-related adverse events, this was mainly due to some reactions to the injections, which were generally well-tolerated, with only one patient dropping out due to injection reactions. In terms of serious adverse events, they were actually numerically lower across the atacicept dosing groups than in placebo. It's important to note that there was no significant differences in infections across the groups either. In summary, atacicept was well-tolerated in patients with IgA nephropathy, no reported deaths, low rates of serious adverse events, and only one patient discontinuing due to an adverse event. Infections were balanced. There were no study drug-related serious adverse events at the 150 milligram dose that will be used in phase III. Again, no patient had study drug discontinuation due to low antibodies or hypogammaglobulinemia. I'll turn that back over to Marshall to discuss further. Thank you, Dr. Lafayette. Next, I'd like to provide an overview of our work to advance atacicept 150 milligrams into a pivotal phase III trial, announced initiation this month. We have had interaction with health authorities, including an FDA Type C meeting in Q4 of last year, as well as written feedback received earlier this year, enabling alignment on a phase III protocol to accelerate our phase III trial results in early June. We have now the ability to leverage the ORIGIN phase II worldwide sites into the initiation of ORIGIN 3, and there are important efficiencies gained with investigator familiarity with the phase II program, including dosing and administration by patients at home. We have a multi-part study design that streamlines these phase II-B sites for phase III. The data just reported by Dr. Lafayette provide UPCR and eGFR efficacy that met statistical significance and are clinically meaningful for atacicept at 150 milligrams at week 36, which we'll continue to share as we advance our phase III program. We now are advancing into phase III with the same subcutaneous formulation and dose as used in our phase II-B study, with a very similar design, but choosing to optimize certain features of study design and management. This includes observation of the ORIGIN subgroups. We've conducted subgroup analyses that have informed the phase III design to maximize our success with competitive positioning. We've tested the atacicept anticipated commercial formulation and setting at home sub-Q self-administration in patients with a wide spectrum of disease severity, geographically and racially diverse backgrounds, and incorporated the evolving standard of care of SGLT2 inhibitor use in our phase II multinational randomized trial. Turning to our phase III pivotal trial design, this will test atacicept once-weekly subcutaneous injection formulation. The study is very similar to the phase II, but we're evaluating a single dose, 150 milligrams versus placebo. This double-blind treatment will last for 104 weeks, approximately 2 years. The primary endpoint will be a week 36 assessment of proteinuria reduction, with an N of 200, and the secondary endpoint, an eGFR endpoint, a confirmatory endpoint, with a total N of 376 subjects. A fter 2 years, after which we'll have an open label extension until 156 weeks. Inclusion criteria for our phase III study are very similar to phase II, with a few exceptions. We will have again stable and optimized RAS inhibition for 12 weeks. We will allow the use of SGLT2 inhibitors, as we did in phase II. The threshold of proteinuria at entry instead of being 0.75, will be 1.0 or greater, and we'll allow an eGFR of 30 mLs per minute or greater, just as we did in phase II. Key secondary endpoints beyond eGFR will include, of course, safety, as we advance into a larger trial of 150 milligrams of atacicept. Our target commercial drug product profile is a self-administration of a small volume, 1 mL, via auto-injector at commercial launch. We believe this is the smallest volume among B-cell modifying drugs in development. We note that APRIL-only programs are advancing 2 or 4 mLs into phase III, and large subcutaneous injection volumes are associated with pain and may affect tolerability and adherence in commercial use and beyond. Turning to catalysts in the near term for Vera. After announcing these week 36 results of the weekend and initiating our phase III trial this month, we will present ongoing data from the ORIGIN phase II trial in the second half of this year, as well as the first half of 2024 and the second half of 2024, highlighting the open label extension portion of the eGFR data that you've seen today. We anticipate presenting top-line phase III results, the 9-month, the week 36 proteinuria reduction in phase III in the first half of 2025, enabling BLA submission in the second half of 2025, and a projected launch time of 2026. I'll remind you that Vera continues to hold worldwide exclusive rights to develop and commercialize atacicept in all regions. I'd like to open up the line for questions. I thank Dr. Lafayette for his presentation. Dr. Lafayette, our Chief Medical Officer, Dr. Lin, and myself will be available to respond. Tara, you can open the line for questions. Great. Thank you, Marshall. Our first question comes from Anupam Sharma, from JP Morgan. Please go ahead, Anupam. Hey, guys. Thanks so much for taking the question, and congrats on the data. Maybe one for the company and one for Dr. Lafayette. For the company, can you remind us of what the pivotal study is powered to show on proteinuria and eGFR? Based on kind of what you know from the sampling of and the N of competitor programs, any sense of how they're thinking about powering their studies? For Dr. Lafayette, as you think about the broader landscape, how do you think about differentiation within a class like B-cell modulation? Will it be proteinuria, eGFR, or another endpoint that will ultimately determine how you think about market share? Thanks so much. Great, thanks for the question, Anupam. At this time, we're not providing specific detail on our inputs for the power calculation in phase III, but I'm happy to provide a little bit of context. Power calculation is incredibly important to assess probability of success and being able to meet the goal of the phase III pivotal trial. It includes 4 elements: the predicted effect size, the standard deviation, the target power, and the alpha that's used in handling statistical alpha spend. It's a good position for us to have a week 36 intention to treat effect in phase II. That clearly gives us a good estimate of what how to power phase III. Standard deviation, alpha, and power are, I think, somewhat predictable. Those are the elements we've used, and the balance thereof, we're not sharing at this time. Dr. Lafayette, please go ahead and answer Anupam's question. Yeah, that's a fabulous question. Thank you. Obviously, what we want to deliver for our patients is a good deal of efficacy, safety, and tolerability within the B-cell targeting agents. It's very exciting to have that class of medications as we want to really have disease-modifying therapy. As you said, I think clinicians will mainly look first at proteinuria, then prioritize maintaining stable kidney function for as long as possible in this very chronic disease, and again, maintaining quality of life with good safety and tolerability of the medications. If there are multiple comparators that make it forward, showing efficacy and safety, one's gonna really look again at that tolerability, look to see if you can differentiate degrees of efficacy. Again, it'd be wonderful if we had further biomarkers or traditionally did follow-up biopsy, but we don't do that. We do anticipate that this class of drug can be used together with other medications, certainly, standard of care supportive therapy. Again, results like we've seen today are extremely exciting. We'd be very welcome for this to be proven and to already use that in our patients. In terms of differentiating different classes of medications and different medicines within a class, those will be the main issues. Thanks so much for taking our questions. Thanks for the questions, Anupam. Our next question comes from Ritu Baral from Cowen. Please go ahead, Ritu. Ritu, it looks like you might be on mute. Hello, can you hear me? Yes, we can. Okay. Sorry about that, guys, and apologies for the background noise. I'm still in Europe. A quick question on the eGFR of the placebo. Marshall, does that correspond to natural history as you understand it? Can you comment on whether you saw dose response on the eGFR from the 75 mg arm? I have a very quick follow-up for Dr. Lafayette. Sure. Thanks for the question. Yes, the decline in GFR in this study population is expected of about 8%, sorry, of about 11% over 9 months. You recall that in the phase II-A study, JANUS, of the atacicept, we did see about a 20% decline over 72 weeks. This is consistent with a similar study population that we've seen. We haven't shown other doses. They essentially superimpose, Ritu, so 75 milligrams as well stays on, and so we don't see dose separation on the GFR endpoint at this stage. Great. My follow-up question for Dr. Lafayette, also on eGFR. You mentioned that Marshall mentioned that the primary endpoint was eGFR slope at 2 years. Is there a threshold for clinical meaningfulness on this slope? I know there was a presentation, another late-breaker presentation that adjoined yours. Can we calculate right now, based on the eGFR slope, if atacicept is on track to meet this, or is there an acceleration of decline expected in the disease process? Thanks. Yeah, that's a great question. As you already mentioned, eGFR decline is certainly what we're trying to prevent and will translate into more time and hopefully sometimes approach lifetimes without the need for dialysis. That threshold for that very large experience in generalized chronic kidney disease and what's been seen in previously published IgA nephropathy studies, really sits for a very large population at just preserving 1 mil per minute per year. Clearly, this program is way ahead of that and looking at nearly 6 mils per minute in the first 9 months. Again, we don't really anticipate acceleration through the program. This is looking extremely promising. I've separately published patients where even first-year eGFR slope is very predictive of long-term outcomes. Again, in this small experience, this degree of eGFR separation is extremely exciting. It's a good predictor that a two-year study in similar patients would show a great effect that would, again, easily be considered very clinically meaningful and important for our patients. Very helpful. Thank you. Thank you for the questions, Ritu. Our next question comes from Rami Katkhuda from LifeSci Capital. Please go ahead, Rami. Hey, guys. Congrats on the update, thanks again for taking my questions. Two quick ones from me. I guess first, can you talk through the rationale for increasing the UPCR threshold at baseline for the phase II program versus phase II-B ORIGIN study? Yeah, Rami, thanks for the question. I will just simply say that the changes are a result of FDA feedback. Got it. I guess, have you seen, or do you expect to see a difference in eGFR slope in patients with higher versus lower baseline UPCR levels, similar to what we saw with some competitors in the space? Good question. You know, we believe that patients are at higher risk of disease progression as measured by GFR decline, and one would believe that the higher the proteinuria at baseline, the more rapid the progression. We believe what we're looking at here is approximately what we'd expect going into phase III. Got it. Thank you so much. Thanks for the questions, Rami. Our next question is from Liisa Bayko, from Evercore. Please go ahead, Liisa. Liisa, can you hear us? Yes. Can you hear me? Yes, we can. Go ahead. Okay, great. Thank you. I know you're gonna be showing eGFR data, over the course of 2023 and into 2024. Can you maybe just frame expectations for us? How should we think of eGFR going forward from here? Yeah, thanks for the question, Liisa. I think, first, important to recognize, I think, the strength of the study design, as we would see it as a gold standard for evaluating treatment effect. Now that we're ending the randomized blinded phase, there, you know, the potential for change is, you know, now no longer balanced. You know, we don't have the ability to compare to placebo. However, you know, open label extension of this population is, I think, gonna be quite informative, and we would expect that the eGFR is gonna continue to maintain close to baseline for these patients. That, I think, could be compelling results as we extend the time point from 9 months to 12 months, 18, 24. Those are gonna be intriguing data, and we hope will help us predict what will happen in phase III. Okay, great. Thanks. I know you didn't have any discontinuations, or stoppage of therapy due to hypogammaglobulinemia. I probably mangled that, sorry. Did you have any cases of that, and can you discuss that point a little bit? Yeah, thanks for the question. You know, it's important with a new treatment that is immunomodulatory, that you reduce antibodies or immune globulins enough to have a treatment effect, but not so much that you reduce immunoglobulin levels and make yourself vulnerable to infection and the like. That balance, which we would call therapeutic index or therapeutic window, is incredibly important as we advance a novel immune modulator into the clinic. We have not seen any patient interrupt or discontinue atacicept for immunoglobulin G levels that are below a protocol-defined threshold, which is 3 grams per liter. That threshold is really consistent across all trials and seen as the clinically relevant threshold. We have not seen that to date. Thank you. Okay, excellent. Then just final question from me. Marshall, if you were to be able to repeat these results and in fact, see a clinically and statistically relevant benefit on eGFR at the nine-month time point, when you're actually going to be collecting the surrogate endpoint, would you be able to file for full approval instead of accelerated approval? Thanks. Yeah, I would, I think that's a good question. Our, of course, our base case is to file for accelerated approval on the basis of UPCR. If we do see a substantial delta in GFR, that, of course, will be reviewed with health authorities, and we will take every action we can to bring this treatment to patients as soon as we can. Okay, great. Thanks a lot, and congratulations on the data. Thank you. Our next question comes from Maury Raycroft from Jefferies. Please go ahead, Maury. Hi, congrats on the update, and thanks for taking my questions. I was gonna ask about the UPCR reduction. It seems to be somewhat flat going from 24 to 36 weeks. I'm wondering if you can comment, at least qualitatively, on whether there are particular subgroups of patients where UPCR deepened and what you expect to be on 36 weeks? Yeah, thanks for the question, Maury. You know, yes, there certainly is a subset where we have a very substantial reduction in UPCR. We have, you know, certainly high responders and others where there's a substantially greater than 50% reduction in proteinuria. Important that in this study design to predict phase III, we've looked at the totality of patients that meet our entry criteria, and that's why we've designed the trial and shared the data in the form that we have. The real outcome in a study design like this is to look at the comparison to placebo. Placebo-adjusted delta is really what we focus on, and because proteinuria can be variable, and you want to look at how the treatment arm does versus placebo. If you look at the intention to treat at 24 weeks, with a 28% delta, and intention treated 36 weeks of a 35% delta, there's actually been a widening of that placebo-adjusted delta of 7%. Turning to per protocol, when you go from week 24 of a 34% delta to week 36 of a 43% delta, that's a 9% deepening of the placebo-adjusted proteinuria reduction. That's what we focus on in a study design like this. Makes sense. I wanted to ask you a question about the phase III. If you could just comment on how long patients have to be on stable SGLT2 prior to starting atacicept, and is it possible for treatment-naive patients to start the SGLT2 and atacicept at the same time? Great, great question. The answer to the second question is no. One of our key learnings from phase II is that in phase II, we allowed patients to initiate their SGLT2 inhibitor within 8 weeks of the screening visit, as opposed to 12 weeks. Based on our interpretation of our phase II data, we believe the 12-week lead-in period is going to be important as we move into phase III. A great question. That's one of our key learnings from phase II that we're applying in phase III. We think that's going to reduce the, you know, protocol violations that we saw in phase 2. Got it. Thanks for taking my questions. Yeah, good questions, Maury. Thanks. Thank you for the questions, Maury. Our next question comes from Ed Arce, from H.C. Wainwright & Co. Please go ahead, Ed. Ed, you might be on mute. Ed, can you hear us? Marshall, it looks like Sean or Ed is having difficulties, and that was our last question, so I'll turn it back to you. Okay. I'd like to thank you all for attending, and I want to share a particular thanks to Dr. Lafayette for his presentation at ERA in Milan on Saturday and for joining us at a very early hour for him this morning. Thank you all, we'll now close today's call.