Alr ighty. Let's go ahead and get started. Welcome to the afternoon session of the Tuesday 41st Annual JP Morgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JP Morgan. I'm joined by Malcolm Kuno and Priyanka Grover from the team. Our first presenting company of the afternoon is Vera, and presenting on the behalf of the company, we have CEO Marshall Fordyce. Marshall? Thanks so much, Anupam. Good afternoon and welcome everyone. I'm Dr. Marshall Fordyce. I'm the Founder and CEO of Vera Therapeutics. Today I'm really pleased to share a company update with a particular focus on the top line results from our ongoing multinational randomized placebo-controlled phase II-B trial called ORIGIN, that we announced last week. These data are positive, both statistically significant as well as clinically meaningful, and they compare very favorably with competition. Moreover, the results enable us to refine our design, carefully with the information from the quality of the study and move rapidly into phase III. Before we get started, I'll remind you that I'll be making forward-looking statements under the Safe Harbor Act, and as such, we present this disclaimer regarding at-risk statements. Overall, our vision is to change standard of care with an initial focus on autoimmune kidney disease. Our lead clinical stage asset is atacicept, a potentially disease-modifying agent with well-characterized clinical safety and a mechanism that targets B cells and plasma cells that are the source of this autoimmune disease. We have a further pipeline in a drug potential, as evidenced by our first two indications. First, the phase II-B program that I'll focus on today is in IgA nephropathy or IgAN, and we have clinical data in-hand that show best in disease potential, which I'll spend time on today with our positive readout from just last week. We also have initiated a phase III program in lupus nephritis, another autoimmune disease affecting the kidney. That was enabled by positive FDA feedback upon review of our significant clinical data from prior work on atacicept in systemic lupus and an integrated safety analysis of over 1,400 patients at the doses being explored. We have a second clinical stage asset called MAU868, an anti-BK virus monoclonal antibody, which is a potential first-in-class agent targeting high unmet medical need condition, called BK virus-associated nephropathy, which is a cause of kidney graft loss. We have encouraging proof of concept data that I won't focus on today, which shows a clear antiviral response for the first time in patients on standard of care in a placebo-controlled trial. We have a strong financial profile with $134 million in cash and sufficient to fund operations to 2Q of 2024. That cash runway estimates ongoing funding all three programs, which we would expect to advance into phase III per our projections by the end of this calendar year. We believe our current market cap does not reflect the value we've created, and we're exploring a refined cash runway focusing on our IgA nephropathy clinical program only, which is driving value today. We're funded to operate through several near-term drivers of value, particularly in IgAN, and here we summarize the potential value creation events over the next 18 months. The next of which is highlighted in blue, which is our 36-week results from the ongoing phase II-B IgAN trial in Q2. We've observed deepening trends in proteinuria after 24 weeks, we believe that 36-week results will be meaningful and enable a better comparison to competition as we continue to mature our dataset and others continue to mature theirs. Additional data beyond the 36-week time point from phase II-B IgAN study will be shared in 2023 and 2024, which will be informative regarding atacicept's proteinuria reductions and effect on glomerular filtration rate or GFR over time for up to two years. There is emerging evidence in current clinical trials that targeting B cells, the source of pathogenic autoantibodies in IgAN, could be disease-modifying and substantially improve kidney function over time for these young patients who are on average diagnosed at the age of 30 years old. Vera's lead molecule in IgAN is called atacicept. It's a fusion protein that's self-administered as an injection subcutaneously once per week. Atacicept targets the source of IgAN by inhibiting the two known circulating cytokines, BLyS, also called BAFF, and APRIL, which are both important for the survival and maturation of the B-cell lineage. In an earlier randomized controlled trial, atacicept substantially reduced the causative molecule of this disease called galactose-deficient IgA1 or Gd-IgA1. We've also shown in 2022 that atacicept reduces IgG autoantibodies to Gd-IgA1, and atacicept also reduces immune complexes that form and cause the downstream kidney injury. This is the only dataset in the IgAN field targeting each of these hypotheses and showing randomized controlled trial evidence of impacting the source of the disease at three upstage hits. We designed the ORIGIN trial, which I'll present shortly, to demonstrate whether atacicept's known effect on the upstream causes of IgAN translate into improved kidney function as measured by a reduction in proteinuria and stability of estimated glomerular filtration rate or GFR. The best evidence to demonstrate a clear treatment effect is to run a multinational double-blind, placebo-controlled randomized trial so that any factors that might influence the primary endpoint called confounders are well-distributed between treatment and the control arms. Last week, we reported positive results after 24 weeks of treatment. I'll highlight that our results include all randomized patients through 24 weeks of treatment, which is a first for the B-cell modulating class. We've only seen partial data sets and different study designs up until our data release last week. As a summary of the results, this clinical trial was positive, meeting the primary endpoint of statistically significant reduction in proteinuria between the combined 150 mg and 75 mg doses versus placebo. Moreover, statistical significance was also achieved for the 150 mg dose alone, showing a 33% reduction from baseline at 24 weeks. We observed a trend toward further reduction beyond 24 weeks in the subset of patients who've gone on to the week 36 time point with available data, which includes approximately 1/3 of patients enrolled. Patients on atacicept had stable renal function as measured by GFR over 24 weeks, and the 150 mg dose showed a Gd-IgA1 reduction of 60% at 24 weeks. The safety profile for atacicept in these otherwise rather healthy patients was similar to placebo, giving us good confidence going forward into phase III at the 150 mg dose, which is what is planned in the near term. To focus on the study design, which is a major strength of this program, this was designed as a multinational randomized placebo-controlled trial, powered to detect a 28% difference between the pooled 75 mg and 150 mg doses versus placebo. You can see that patients were randomized to one of four arms, placebo, atacicept 25 mg, 75 mg, and 150 mg respectively. You'll notice the 25 mg dose, the lowest dose, we enrolled half of the population, so a target of 15 enrolled. That was simply to have additional dose information as we understood the dose range in effect with these parameters in IgAN patients for the first time at this size. The primary endpoint was reduction in proteinuria at 24 weeks. We have a secondary endpoint at 36 weeks. We have a blinded phase all the way through 36 weeks, also called nine months. Then we'll have an open label extension where all patients will be offered a transfer to atacicept 150 mg, and we'll follow those patients for a total of 96 weeks. We will have ongoing data cuts beyond the 36-week endpoint. Inclusion criteria you would find quite similar across the field. These are adults who have biopsy-proven IgAN and are at high risk of disease progression. This is really the target for initial approval and the only population for which a drug is approved in this space. Patients are on stable and optimized RAS inhibition, so an ACE inhibitor or an angiotensin receptor blocker. They needed to have, despite that treatment, at least 0.75 g of protein or more per day, which is standard now for those who are at high risk of disease progression. We enrolled a GFR of over 30. A 30% reduction in proteinuria is known to be clinically meaningful in IgAN patients. A 30% reduction in a natural history study of IgAN patients collected by Kidney Health Initiative as well as FDA and published is associated with an improvement in renal function in IgAN as measured by the slope of GFR. Reduction of 30% could delay end-stage renal disease by over 10 years. That's the evidence that led to the first drug approval in this disease called TARPEYO, which showed an 18% proteinuria reduction from baseline at week 24, the time point we're looking at today. A 34% reduction from baseline at week 36 with a calculated delta of less than 30%. I believe it was in the 27% range. Setting the precedent for accelerated approval in IgAN on the basis of proteinuria reduction and then full approval on the basis of following GFR over one and two years. The next PDUFA date is for Travere's sparsentan, which showed a 35% delta active controlled adjusted reduction in proteinuria at week 36. Just briefly, the ORIGIN study was a multinational trial, enrollment was not over-represented in any single country. This is a diverse global randomized controlled trial. For disposition of 232 subjects screened, there were 116 randomized and treated patients. Safety results include all patients through 24 weeks and beyond, at the December time cut. For this analysis of efficacy, it's important to note that we are reporting the intention-to-treat or ITT population, which reflects data from all randomized patients regardless of protocol violations that may have had an impact on proteinuria. This is a better reflection of real world use, and is the most rigorous test of efficacy used by FDA, and is essentially the same approach taken by the approved drug TARPEYO in phase II and provided the right initial presentation of the most rigorous test. Discontinuations were similar between atacicept and placebo. On atacicept, one patient discontinued in order to have an elective surgery, another due to an adverse event of injection site reaction, and on placebo, one patient discontinued in order to initiate a prohibited medication for a concomitant disease. For baseline characteristics, overall, the study enrolled patients who were at high risk of disease progression and were on a current optimized background regimen, allowing a clear assessment of atacicept's treatment effect on top of the current and emerging standard of care. The average age was 39. It was 59% male, 44% Asian race, an average GFR of 63 mls per minute, and an average UPCR of 1.6 g/ day. Patients were on optimized ACE or ARB. In addition, if a subject was also on a stable SGLT2 inhibitor without change for at least eight weeks, that patient was allowed to enroll, and that comprised of about 14% of this study population at this analysis. The primary endpoint analysis was performed on all randomized patients and assessed. Not shown here, the pooled 75/150 mg dose achieved stat sig versus placebo with a p-value of 0.037 in the all atacicept group versus placebo with a p-value of 0.026. Shown here is the statistical significance that was also achieved with the individual dose, 150 mg, that we're carrying forward into phase III with 33% mean reduction in proteinuria versus baseline. You can see the calculated delta is 28%. Just to remind you, these are geometric means, so a simple arithmetic subtraction is not the appropriate way to assess the delta. This is a calculated delta between active and placebo. We also looked at patients who reached the 36-week time point, roughly a third, and we saw trends towards deepening proteinuria beyond this 24-week time point. The exploratory endpoint analysis of GFR showed stability really in all atacicept arms. A positive 3 ml/ min increase at 24 weeks for active versus no decline for placebo. This is an early time point at which to assess separation between active and placebo because these patients take up to two years to have roughly a 20% decline in GFR if on placebo with patients characterized this way. We had robust reductions in Gd-IgA1 through week 24 of about 60% for the 150 mg arm, and dose-dependent reductions in serum IgG, IgA, and IgM levels. Importantly, IgA reduction of about 59%, which is comparable to the only other reported IgA and Gd-IgA1 reductions in the field, which is BION-1301. Similar reductions in IgA and Gd-IgA1 between our 150 mg dose and what's been reported with a 600 mg sub Q dose from an open label study for BION-1301. Importantly, dose-dependent, s orry, from a safety perspective, these immunoglobulin reductions were well above the lower limit of normal. No patient had a study drug discontinuation, interruption, or a sustained IgG of less than 3 g/L through week 24, which is seen as the safety threshold at which you might pause a B-cell modulating therapy. We did not see any pause or interruption. Safety results indicated that atacicept was well-tolerated and generally balanced with placebo. Study drug-related adverse events were higher for atacicept versus placebo, and the majority of those were injection site reactions. As I've already mentioned, just one led to study drug discontinuation. That patient discontinued after three injections due to injection site reactions. The patient also had a positive hepatitis B DNA test that was normal without treatment at a retest and had normal liver function tests throughout. It was not a concern for hepatitis B, but there was a positive test. Serious treatment-emergent adverse events were observed in 2% of patients in all atacicept arms and 9% of patients in the placebo arm. The results demonstrate a safety profile in IgAN patients that's comparable to placebo and builds upon the prior integrated analysis of atacicept in randomized double-blind placebo-controlled trials in over 1,500 patients across all indications to date. We did look at infections as we were focused on B-cell function, and all infections in the trial were mild or moderate. There were no severe infections. Rates on atacicept were comparable to those on placebo. We did run this trial in the time of COVID-19, and it was interesting to see about 25% of patients got COVID-19 during the trial. As we looked at those cases, only none were judged as severe, and one led to a brief hospitalization that was followed by a quick recovery. For a safety summary, atacicept was well-tolerated, no reported deaths, a low rate of serious adverse events overall. One patient discontinued for an injection site reaction. Infections were balanced. There were no serious events, adverse events on the 150 mg group. No patient had a study drug discontinuation or interruption due to hypogammaglobulinemia or low IgG levels. In the last few minutes, I just wanna point out these data in context. This is of critical importance for our description of these important and robust data to the street. We're reporting for the first time positive results from a multinational randomized placebo-controlled trial for a dual BLyS/APRIL inhibitor in IgAN patients, and they compare very favorably to other available results. TARPEYO, which also conducted its analysis in randomized patients, showed approximately 18% reduction from baseline at 24 weeks. As we look to the next program that we anticipate potential approval, we have not yet seen 24-week numbers, so we can't compare. As we turn to the third program, Otsuka's sibeprenlimab, this is now in the same mechanism field as we are. It's a B-cell modulator and anti-APRIL agent, and we have the benefit of an interim analysis that was presented in November, looking at sibeprenlimab. That study was a global, randomized controlled trial with slightly higher proportion of patients from Asia. They studied IV infusions once monthly and presented their data as combined dosing, so didn't break out the data in the presentation. On the basis of that data, have decided to go forward with a subcutaneous formulation of 400 mg subQ, which we understand to be a one injection of 2 mL/ dose. They have not reported 24-week data. Their week 36 report of a reduction in proteinuria showed pooled IV doses at 43%. That was not the full data set, so they've enrolled 155 subjects. This is an interim analysis of 72 subjects with proteinuria data and further detail on that subset and how it's different from the total set is not yet described publicly. We have not seen numbers on its impact on IgA or Gd-IgA1, and we haven't seen placebo comparison for safety data. As we turn just to the B-cell modulating class, we think it's important to focus on our approach of dual APRIL BLyS inhibition advancing into phase III this year, along with two other programs, the anti-APRIL programs I've mentioned, both Otsuka's sibeprenlimab and Chinook's BION-1301. I think it's important to point out that Vera's data is really the first, we believe, that's been reported with SGLT inhibitor use, SGLT2 inhibitor use in an RCT. We haven't seen some of the baseline characteristics that would be helpful to compare between what we've reported and some of these programs. Finally, I think it's important to point out that the anti-APRIL program, BION-1301, has shown a case series. It's an open label study of reporting up to 24 patients so far at the week 24 time point. What we've seen is an impressive, roughly 50% reduction in proteinuria at that time point. We see essentially the same IgA reduction between our program and their dose that they've explored for IgA and galactose-deficient IgA1, but we see quite a disconnect in terms of proteinuria reduction. I think it's important to focus in our view that that really is driven by a study design. When you run an open label study with observed doses in the clinic, they did it on a every other week basis. One has control of confounding factors and knows which patients are on your drug because there are no placebo patients. This is a very important difference in terms of study design that could lead to the disconnect in proteinuria reductions that we've seen in our global randomized controlled trial versus this open label study. Uh, we believe that dual inhibition of APRIL and BLyS may confer important potency advantages, uh, which is evidenced in the dosing, uh, profile, uh, that all of us are now advancing into phase III. Atacicept is the only B-cell agent at less than 200 mg and delivered as a single ML, making subcutaneous injection small volume and simple, uh, in our, uh, target commercial profile. Uh, we will soon be pointing out, uh, that, uh, week 36 data will be shared in Q2. Uh, and additionally, we'll have, uh, ongoing, uh, uh, data readouts from the open label extension, uh, further into 2023 and into 2024. We did have an FDA meeting in Q4 of 2022, uh, discussing preliminary alignment around a phase III study design to enable rapid study start. That's why we chose the primary endpoint of week 24, was to speed, uh, development. The final trial design is of course, pending final FDA concurrence. We have the ability to leverage our existing worldwide sites. Importantly, we have a dose with clear dose response along multiple metrics that met statistical significance in this study at an early time point. With that, I know I went a little bit over time, Anupam, but thanks for the extra time. I'll thank you for your attention and provide a chance for questions now. Yeah. Thanks, Marshall. Just want to remind folks that there are three ways to ask a question. You can send a question through the digital portal, and I will get it here. You can email me, or you can go old school and raise your hand and ask a question. All are welcome. We actually have a bunch of email questions and portal questions, so maybe we can work through those. The first one is, there seems to be a disconnect between what you're hearing from KOLs, like on your conference call, and how the street reacted to the data. Do you believe that you've enrolled a sicker population than your competitors? Put the SGLT2 inhibitor enrollment and those patients in there into context. How can you basically message this to KOLs so that they can be champions of the drug? Yeah. I think there's an opportunity, as we continue to share analyses with KOLs. I think there's an important balance between what we share publicly and what informs our phase III program. Importantly, in drug development, we learn from phase II to inform and improve probability of success into phase III. That disconnect between kinda market dislocation and what we felt was positively received by KOLs, I think it needs to be shown with additional analyses what could account for this difference in proteinuria response that we have shown in a global randomized controlled trial versus the others of different design. I think really the field should be combining their thinking about how why this might be the case. I would continue to put forward that a global randomized controlled trial where we gave prefilled syringes to people to take home and self-administer is a very good test of what we'll study in phase III and beyond. We think that's an important standard that will help us know what was going to happen in phase III. Another email question here is, based on your understanding of the data today, what do you think BLyS is adding to the clinical benefit of atacicept? Yeah. I think it's hard to say. But maybe the best way to look at it is, you know, at 150 mg subQ once a week, our atacicept with dual APRIL BLyS can achieve the same IgA reduction as two separate anti-APRIL monoclonal antibodies that require several hundred mgs to get the same reliable PD effect. So I think that's the key. It's potency. It doesn't surprise us. We've seen this both in understanding the biology of APRIL and BLyS. If you take a mouse model, inhibit APRIL and BLyS, you get more potency than inhibiting APRIL alone or BLyS alone. So to us, it's becoming self-evident that, you know, the dosing going into phase III represents that difference in potency. Another question that we've gotten in the portal here is, do you think KOLs distinguish between a 30% reduction in proteinuria or a 37% reduction in proteinuria? You've crossed that threshold of 30% that you talked about in your presentation. What is the delta where a change in proteinuria all of a sudden becomes clinically meaningful? I think I would go back to first, this is really important when you open up a new field in medicine, that there's a potential to have a surrogate endpoint. We in IgAN are at an incredibly privileged position to put forward a nine-month proteinuria reductions and have the hope that you could get an accelerated approval. That was really put forward by academics and regulators to show that a 30% reduction in proteinuria at nine months leads to at least a 10-year delay in end-stage renal disease. That's a quantifiable clinical benefit that is meaningful to patients, providers, and even payers within renal autoimmune disease. That's a pretty meaningful number. Now we know that an approved drug, TARPEYO is the only one approved, had a delta of 27% from placebo. I think we need to be really thoughtful about what number is the bar. The bar really is set by the only approved drug, which was over a 30% reduction from baseline, and they achieved under a 30% delta from placebo, but that led to an approval. We'll continue to see this play out with other agents in the field, but that's the bar. We've been very consistent about that being our target. Raising the bar to 40% or 50%, I think, doesn't have a sound scientific basis behind it. You've committed to running a phase III, in IgAN. One of the questions is, you know, you didn't have perhaps the magnitude of dose response that you were looking for. Mm. You know, what gives you the comfort to move forward given you didn't see this? Yeah. I wanna address that. Importantly, if you look at the only approved drug, TARPEYO, in their phase II study, they ran a global randomized control trial that was well powered. They studied placebo in two doses, 8 mg and 16 mg of what's now TARPEYO. They also didn't see a dose response by proteinuria, and that's inherent in proteinuria. There's wide variability, and I think the field is starting to appreciate that. Expecting a clear dose response in a phase II-B study in a global randomized controlled trial of this kind was never our target. What we did see was a very clear dose response for IgA and Gd-IgA1. Admittedly, Gd-IgA1 is less of a separation from between 75 mg and 150 mg. In, you know, in this disease, we're using the totality of the evidence. There are additional analyses that we've looked at that give us more confidence on 150 mg. Questions from the audience? Marshall, what are your hopes for the 36-week data? Maybe can you address how in your study you had more Asians in the treatment arm, given that Asians are known to have a more severe form of the disease and more quickly progress? Hopes for week 36 data and then looking at potential imbalances in baseline characteristics. Hopes for week 36 data, you know, I wanna be clear, we've already met the bar in phase II with a statistical significance result and over a 30% reduction really by three ways of looking at efficacy for proteinuria. We've met the bar. You know, my hopes are that we'll continue to see ongoing reductions in proteinuria over time, and that would continue to validate the disease-modifying mechanism of atacicept in the way that we have imagined that by targeting Gd-IgA1 autoantibodies immune complex, you're essentially stopping injury to the kidney. And if you're doing that, We'd love to see improving kinetics of proteinuria reduction over time. We haven't seen that yet in a randomized control trial, the B-cell modulator. We hope to be the first to show it and happy to be transparent where we can. The question about imbalances, you know, we, of course, are doing lots of subgroup analyses to fully understand the data. I hope the Street will understand, we're not sharing all of those 'cause this is important proprietary and competitive information that enables our success in phase III. Questions from the audience? Another question that has come in, which is why is there such a big confidence interval delta on Gd-IgA1, while maybe some of your competitors, even in the smaller patient population, have a little bit less noise on that endpoint? Sure. Good question. Two key biomarkers or, what you might call a PD marker, is the drug having the effect on the body, and can you measure it consistently? IgA is better than Gd-IgA1. If you went to your doctor right now, you could get an IgA drawn. It's a CLIA-certified common lab. Gd-IgA1 is the pathogenic molecule in this disease. It's not commonly tested in the clinic. To our knowledge, there are two labs in the world that do this. We work with one. There could be intra-lab, differences, but I do think those confidence intervals might reflect, just a difference in the development of the assay. We do have data from our prior phase II-A study conducted by Merck KGaA that has confidence intervals that give us really clear dose separation between 25 mg and 75 mg. We are interested to see ongoing data between 75 mg and 150 mg, and if the separation we are starting to see continues to deepen. Maybe just switching gears just a tad. We didn't talk about it as much in this presentation, but for MAU868, what are the potential advantages or disadvantages of a monoclonal antibody approach versus a T-cell approach? What are the gating factors to starting phase II-B or III, which I think you've guided for this year? Yeah. Yeah. Great. MAU868, it's a neutralizing antibody against BK virus. I'm an infectious disease doctor by background and did my drug development work in HIV, where we have nice solid endpoints, like this, which is one of our attractions. MAU868, and a BK virus is a important cause of losing your kidney transplant, and that's a terrible outcome for the patient, the family, and the entire system. It's an expensive way to end someone's freedom from dialysis. BK virus has been a large unmet need for a long time. We showed for the first time in a randomized control trial an antiviral effect of over a log with MAU868 versus placebo. We have shared phase II data. We're now discussing with all stakeholders what the next step in development would be. We've publicly commented that could be further phase II exploration or it could be a phase III trial. We're not being specific until we have alignment with FDA. We don't have it yet. We hope to provide an update later this year. That's really the gating piece. You know, there is a cell therapy that is targeting transplant-associated viruses that's in development. We're interested in seeing how that plays out as well. We'll be looking at efficacy. You can imagine if you have similar efficacy between a monoclonal antibody and a cell therapy, there may be a simplicity advantage of just going with the monoclonal. Questions from the audience? Okay. Marshall, thanks so much for the presentation. Great. Thank you, Anupam.