Vera Therapeutics, Inc. (VERA) Earnings Call Transcript & Summary

Good morning, and welcome to the Vera Therapeutics virtual investor event. [Operator Instructions] 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 your host, Marshall Fordyce, Founder and Chief Executive Officer of Vera Therapeutics. Please go ahead, Marshall.

Thank you, Tara. Good morning, and welcome to Vera's virtual investor event where we'll be discussing the long-term results from the ORIGIN Phase IIb study of atacicept in patients with IgA nephropathy or IgAN. These results were presented this past weekend at the American Society of Nephrology's Annual Medical Conference called Kidney Week. I'm Dr. Marshall Fordyce, Founder and CEO of Vera Therapeutics. This morning, I'm joined by Dr. Jonathan Barratt, Professor of the University of Leicester, an expert physician and researcher in the field of IgA nephropathy, who presented these trial results for the first time as a late-breaking oral presentation on Saturday. We're also joined by our Chief Medical Officer, Dr. Robert Brenner; and our Chief Financial Officer, Sean Grant. I'll provide a brief corporate overview. Dr. Barratt will discuss the ORIGIN Phase IIb long-term results and their significance and then we will open the call for questions for Dr. Barratt and management. Before we get started, I want to remind you that our remarks contain certain forward-looking statements under the Safe Harbor Act, and as such, we present this disclaimer regarding at-risk statements. Our mission is to transform the standard of care for patients with immunologic diseases, and the Vera team and all of our collaborators have made great progress towards a potential major advance in medicine. Our lead product candidate is atacicept, a potential best and first-in-class dual BAFF, APRIL next-generation B-cell modulator currently in Phase III for patients with IgA nephropathy, or IgAN, and with much broader potential to change how we treat a wide variety of autoimmune diseases. In IgA nephropathy, atacicept targets the source of the disease and our Phase II data show a reduction in immune complexes, resolution of glomerulonephritis, significant reduction in proteinuria, and most importantly, kidney function as measured by estimated GFR tracking with the normal population. These collective results suggest that chronic dosing with atacicept offers the potential promise of a functional cure. Atacicept is the only B-cell modulator in development for IgAN that has 2-year data from a Phase II trial, which, if approved, would enable a differentiated data set at commercial launch. Atacicept is the only investigational B-cell modulator in IgAN with at-home self-administration being studied in both Phase II and Phase III, which at 2 years has yielded a 90% retention rate. Since our last R&D Day in January, atacicept has been granted breakthrough designation by FDA and we have completed enrollment of the primary endpoint cohort in a Phase III trial putting us on track to read out our Phase III data in Q2 of next year with potential PDUFA in 2026. With a favorable clinical profile evolving in Phase II and Phase III, we believe atacicept has the potential to transform the treatment of multiple other autoimmune diseases beyond IgAN, different from steroids and different from B-cell or plasma cell ablation in which immunosuppression occurs. Atacicept's precise modulation of BAFF and APRIL appears to be amenable to chronic dosing over time, where a clinically meaningful reduction in autoantibodies is balanced by the retained ability to fight infection during treatment. Earlier this month, we shared an update on the expansion of our clinical programs for atacicept beyond the IgAN population in our pivotal trial and are exploring atacicept's clinical utility in a broader population of patients with autoimmune kidney diseases, where we project an opportunity to reach greater than 200,000 patients. Beyond kidney disease, the ability to deliver a safe and tolerable reduction of disease-causing autoantibodies may enable broader expansion into multiple indications in the rheumatology, hematology, neurology and metabolic fields. Vera is resourced for potential commercial launch in 2026. Regarding exclusivity, we expect biologics exclusivity protection through 2038 in the U.S., which represents 12 years from launch. And given the strength of our data set and our lead time to market and our near-term strategy to demonstrate leadership in IgAN patients and their physicians, Vera has already begun to execute on an IP strategy that may extend atacicept LOE beyond 2038 and the broad optionality that we've created. We've initiated work on a next-generation B-cell modulator with broad optionality for PK/PD exploration, dosing frequency, among other benefits, that may reset patent and IRA clocks. Vera is attracting fantastic talent, planning for success and has been actively scaling our organization for potential commercial launch in 2026. This is an exciting moment for patients as Vera leads a paradigm shift in how we treat autoimmune disease beginning with IgAN as atacicept's clinical data support its potential to target the source of several autoimmune diseases. Vera is in a strong financial position with $384 million in cash and has 54.8 million shares outstanding. Vera has created broad optionality to expand our clinical investigation of atacicept in IgAN, in non-IgAN kidney disease and in a broader autoimmune disease population. We shared our plans for 2 new studies earlier this month that expand atacicept beyond Phase III to the broader IgAN population where the prevalence in the U.S. is estimated to be 160,000 patients. You will -- you have also heard plans for our current clinical activities to expand into additional autoimmune kidney diseases beyond IgAN where we see a strong rationale. And in the future, we may share additional clinical activities to study atacicept in nonrenal autoimmune disease and further plans for additional molecules. There has multiple potential value-building catalysts in the near and midterm. Last month, we announced full enrollment of our Phase III primary endpoint cohort, which enables Phase III readout in Q2 of next year, BLA filing in the second half of next year and estimated commercial launch in 2026. With our expansion into 2 new clinical trials, we will be in a position to share additional clinical data from 2 new studies in 2025. Next, it's my pleasure to welcome Dr. Jonathan Barratt, Mayer Professor of Renal Medicine at the University of Leicester to present our 2-year results.

Thank you very much, Marshall. So I'm going to present the data that I presented to the ASN, and it's fair to say it generated a great deal of interest from my nephrology colleagues. So IgA nephropathy is an important cause of kidney failure, particularly in young adults. And we know that this disease is an immune complex-mediated disease with the formation in the circulation of IgA-containing immune complexes that deposit within the kidneys, where they promote inflammation, scarring, and ultimately, kidney failure. The immune complex is born because of an excess of Gd-IgA1, a particular form of IgA, and this immune complex formation is amplified by the presence in the circulation of IgA and IgG antibodies that recognize this Gd-IgA1. And therefore, it is an absolutely logical approach to fundamentally modify the disease by targeting the production of these pathogenic antibodies. And we know that BAFF and APRIL are critical in driving B-cell and plasma cell proliferation, survival and IgA class [indiscernible]. So targeted BAFF and APRIL signaling is a perfectly logical choice to fundamentally alter this disease at the source. And so what is atacicept? Atacicept leverages the natural biology, which is that one of the major receptors for BAFF and APRIL is the TACI Receptor and this binds BAFF and April with high affinity. And so atacicept combines this extracellular domain of the TACI Receptor fused to the Fc domain of an IgG1 molecule, providing a drug that is capable of binding and neutralizing the effect of BAFF and APRIL , thereby down regulating the proliferation and survival of pathogenic IgA-producing cells. The goal of this will reduce immune complex formation circulation, therefore, reduce the pressure the glomeruli are under in terms of new complex deposition and really stop the disease in its tracks. So this is the design of the ORIGIN Phase IIb trial. We've already pushed the [ first 36 ] data in Kidney International, that was the randomized placebo-controlled part of the trial, and you can see that here testing 3 doses of atacicept against placebo. What we're going to describe now is the 96-week data for all of those patients exposed to atacicept, and you can see for week 36 to week 96 all patients were offered the opportunity to take atacicept 150 milligrams weekly. And we're going to show you the impact of the treatment with the atacicept in this [indiscernible] . Just to remind you, this study recruited high-risk IgAN patients. They were adults. They have persistent proteinuria despite being on optimized renin-angiotensin-aldosterone system inhibition and SGLT2 inhibition were allowed. And roughly 1 in 4 patients was on an SGLT2 general baseline. I'm going to show you now some of the data that we have previously reported, but first, the baseline characteristic again, showing that this is a high-risk IgA population that is typical of those populations we see in Phase III clinical trials in terms of their age and gender distribution. Very reassuringly, we had a good split in race in terms of white and Asian, and that's really important when we understand the impact of race on disease prevalence and on disease severity. It's really important we understand how this drug is in Asian and non-Asian patients. You can see these patients already have established clinal disease with a GFR of 62 and significant proteinuria, so 1.8 grams per gram on a UPCR on the 24 [indiscernible], which equates to at least 2 grams per 24-hour proteinuria, so a high-risk population despite all of them being on RAAS inhibitor and 1 in 4 also being on an SGLT2 inhibitor. So you can see here the participants disposition. But I just want to take you through to those who are offered open-label extension, and you can see the vast majority of those offered took up the option and the vast majority of those who took up the option completed the 96-weak treatment. And I think that's really important. It shows the acceptability of a weekly subcutaneous injection that the patient delivers up through an auto-injector. And that's really important information to have when we think about how this drug is going to be taken up and used by patients when it's available to be prescribed. And so to remind you of the week 36 data, you can see here that treatment with atacicept if we're looking at the 150-milligram dose led to a significant and sustained reduction in the key pathogenic form of IgA, Gd-IgA1. You can see that, that reduction in Gd-IgA1 was matched by a reduction in proteinuria. And in those that have hematuria at baseline, a reduction in hematuria, really telling us that this reduction in Gd-IgA1 is translating to healthier glomeruli with less blood and protein in the urine, reflecting less disease activity. And of course, the fundamental thing we are most interested as nephrologists is [indiscernible]. And in that first 36-week period, we saw no change in GFR. So these are the data that we presented previously and these are now the long-term extension. And you can see that this drug clearly had exactly the same impact over the longer-term period. So we saw that reduction in Gd-IgA1 at 36 weeks. It was maintained out to 96 weeks. So no loss of efficacy with prolonged treatment, and that reduction in Gd-IgA1 was reflected by clear evidence of improved glomeruli health with lower proteinuria that was sustained and less hematuria. But the really important feature, which is the feature that got everyone excited at the ASN was what happened to GFR, reminding you this is a high-risk IgA nephropathy population. And what we see here that over the full 96 weeks of this study, the rate of loss of kidney function in an annualized was 0.6 ml per minute per year. And I just want to put this into the context of what we've seen in other clinical trials and what we see in healthy individuals. And so just to remind you, if you look at any of the published Phase III or even Phase II studies of what the rate of loss kidney functions is in a placebo-treated population on maximum supportive care, they lose on average 6 ml of GFR per year. If you look at what we achieved with atacicept over a 96-week period, we see the rate of loss of kidney function was 0.6 ml per minute, yes. And just to put this into context, it's estimated that after you reach 40 years of age, you lose on average -- a healthy individual with no kidney disease loses on average 1 ml per minute per year. So what you've seen is that we have transformed the relentless decline in kidney function we see in young people with IgAN nephropathy, the rate of loss of kidney function that the general population has who do not actually have a kidney disease, and this is something that is unprecedented and it's never been shown before. And again, just putting this into context from the RaDaR data that we published. If we work out what the rate of loss of kidney function needs to be to prevent kidney failure in the lifetime of our patients, you can see here where we need to get to. We need to get to less than 1 ml per minute per year if we're going to make any appreciable impact in the lifetime risk of kidney failure in our patients with IgA. And you can see what has been achieved with other agents that we currently think of in terms of treatment for IgA nephropathy, endothelin receptor antagonists, SGLT2 inhibitor, systemic steroids, other supportive therapy. None of them come close to achieving that target of less than 1 ml per minute per year. And this data for atacicept is the first time we have ever seen a treatment that comes close to what we want to achieve in terms of preventing kidney failure in the lifetime of our patients. So clearly, safety is critically important. And you can see the safety data here for the first double-blind period up to week 36. And then you can see the open-label extension for the following 60 weeks. And you can see here a very good safety profile. The drug was well tolerated. Remember, the vast majority, over 90% of patients, continue to take the drug through that additional 60 weeks showing its acceptability. There were few treatment emergent adverse events that led to study drug continuation. You can see here, one, in the placebo and one [ in all ] atacicept in that initial 36-week period; and two, in the open-label extension period. Really no signal here that cause concern about chronic usage of this drug. So in conclusion, participants treated with atacicept for 96 weeks demonstrated sustained and substantial reductions in the key pathogenic form of IgA, Gd-IgA1. This was reflected by reductions in hematuria and proteinuria reflecting the improvement in glomeruli health, and that was associated with long-term stabilization of GFR. The cumulative favorable safety protocol remains consistent with what we observed during the initial 36-week randomized part of the study. And the conversion, I think this is the most critical aspect that we have never seen before, the conversion of an eGFR profile in patients with IgA nephropathy from one of steady unrelenting decline to one similar to that of the general population without kidney disease through 96 weeks is a unique and compelling finding. And I have to say that -- this was a subject of many, many conversations I had at ASN after our presentation. But collectively, these data support the potential of B-cell modulation with the atacicept to modify the natural history of the disease and the potential to prevent kidney failure during the lifetime of patients with IgA nephropathy. So clearly, we need to acknowledge the entire team that has delivered this study. And as you can see, it is a global team of investigators, representing a good breadth of patients reflective of what has been recruited in the Phase III trial. And for more information, the manuscript for this data is now available on the JASN website as a simultaneous publication. So thanks very much for listening. I'll hand back to Marshall, but I'm happy to take any questions that you have.

Great. Thank you so much, Dr. Barratt. Just before we open up for questions, additional color on Kidney Week at ASN these past few days, a great opportunity to connect with the investigators of the ORIGIN trial to whom we're deeply grateful to deliver these results. And furthermore, we get a chance to engage with patients and the patient foundation, the IgAN foundation. And to remind those on the call, patients are diagnosed in their 30s. And a substantial portion of those patients progress to end-stage kidney disease before the age of 50. That is a diagnosis that has a 5-year mortality akin to colorectal or lung cancer. End-stage kidney disease is clearly a bad outcome for patients and it marks the beginning of life on dialysis. If you're lucky, you can access a transplant. And it dramatically increases both morbidity and mortality and cost to the health care system estimated to be an average of over $200,000 per patient per year. In the coming time, we plan to get atacicept to market as quickly as possible with these patients in mind. We're now on track to deliver Phase III top line results in the second quarter of 2025, BLA submission in the second half of 2025 and projected U.S. launch in 2026. As detailed earlier this month, we've initiated 2 new studies, ORIGIN Extend and PIONEER, and those data will begin to be shared in 2025 as well. With that, I'd like to open up the line for questions, operator, and questions can be directed to either our guests, Dr. Barratt; myself; Dr. Brenner, our Chief Medical Officer; or Sean Grant, our Chief Financial Officer. And I'm happy to open the line now, Tara, for questions.

Great. So our first question comes from Anupam Rama at JPM.

Congrats on the update. A quick question for Dr. Barratt. Dr. Barratt, from a patient perspective, how do you think about sort of a subcu weekly at-home administration as you have with atacicept versus sort of competitive in-clinic monthly approaches that may or may not require some amount of monitoring? Like how do you think about those 2 approaches from a patient perspective?

So I think we need to remember, as Marshall said, is a young patient with active, busy lives, with young families, careers. They want to be out having fun and they don't want to be tied to coming to hospital for rigid appointments. And so the ability to manage their own health with an injection that they can give at a time that suits them is going to be critical, I think, because it needs to map around their lives. And if they have the injection in the fridge and they give it themselves at a time that's convenient to them and doesn't impact on what they can get up to during the day or at the weekends, I think that's a really positive approach. And the bottom line is we see the acceptability of this approach because patients in the open-label extension, they could have left whenever they wanted, and they didn't. They stayed. And the over 90% patients continued through the whole period. If there was an issue, if there was some kind of systematic issue with the home administration, we would have seen it in the open-label extension. And I think the other thing to say is, of course, this was a global study, which shows the acceptability of this approach in all parts of the world in terms of North America, Europe and Asia. So I think that's really reassuring in terms of what we think the uptake will be from patients when this drug is finally able to be prescribed clinically.

So our next question comes from Ritu Baral at Cowen.

One for Dr. Barratt and one for the Vera team. Dr. Barratt, how do you see the impact of increasing SGLT2 inhibitor use going forward in the Phase IIIs, both on -- across the B-cell modulation landscape on the primary endpoint of UPCR as well as eGFR. And then I have a label marketing follow-up for Marshall and team.

So great question. In terms of just generally speaking about Phase III trials and not any particular trial in particular, patients aren't allowed in on an SGLT2 inhibitor. We do not want them starting an SGLT2 inhibitor once they have been randomized because that has an impact on the outcome, and we're working very hard to stop that from happening. But we know that if you're on a SGLT2 inhibitor, there'll be a slight reduction in proteinuria. But the eligibility criteria is such that we are taking people in with that degree of proteinuria on an SGLT2 inhibitor, potentially in RAAS inhibitor. And the rate of loss of kidney function is determined by the proteinuria level. So someone with 1 gram of proteinuria on a RAAS inhibitor will progress as fast as someone with 1 gram of proteinuria on a RAAS inhibitor and an SGLT2 inhibitor. But in a clinical trial sense, there will be less people available with 1 gram proteinuria if they're on an SGLT2 inhibitor because they'll have dropped and not become part of the inclusion criteria. What I think is very clear, certainly, in the draft KDIGO guidelines that we wrote is that CKD treatments are all well and good, absolutely fine, but they do not address the fundamental elements of this disease. And what we are going to see moving forward is the fundamental treatment you will give to someone with IgA nephropathy with an immune complex-mediated disease is a treatment to stop the production of immune complexes. So the first thing we're going to do is give them a therapy like atacicept to stop the production of pathogenic IgA. If they present with established CKD, we may need to layer in CKD treatments like RAAS and SGLT2, but they are not the fundamental treatment. The treatment is to treat the disease. And what I hope I've shown you with the data that [ has been presented ] to the ASN is exactly what this drug does. Remember, this is a combination trial. Atacicept was given on top of a RAAS inhibitor or [indiscernible] SGLT2 inhibitor. But the fundamental thing we are going to see is the first-line treatment for IgA will be a B-cell directed therapy.

Understood. And then my second question, actually, it's also for you as well as for the Vera team. But Marshall, insofar as your Phase II data showed statistically significant eGFR stabilization at 9 months and beyond compared to placebo, is there an opportunity for eGFR data to potentially be included upon an approved label based on the accelerated UPCR endpoint? Do you know what I mean? Like could you get approved with -- on UPCR, but with eGFR that you could detail -- eGFR data in the label that you could detail? And how much of a difference could that make upon first launch?

Ritu, good question. We, of course, can't make formal statements around labeling at this stage. On the other hand, these are formal data from a global randomized, controlled trial and one can expect that the publication just released over the weekend is out in the public domain currently and will make a difference with respect to physicians understanding the efficacy of this drug.

Our next question comes from Liisa Bayko at Evercore.

Congratulations on the data. First question is around eGFR. Can you give us a little more contextualization of the eGFR change? Like where did we start from in that new graph, which does include some of the crossover patients? And then where did we land at? And then if you could give the kind of confidence intervals around the minus 0.6, what are the upper and lower bounds of that at the end of the study? And then second question, could you give us a little more detail on safety with respect to infection risk?

Rob?

Yes. Thank you, Liisa. So in terms of GFR, the baseline eGFR in this study was in the low 60 ml per minute range. So these patients had already lost a good 40%, 45% of their endogenous kidney function at the time of enrollment in the study. Over the course of the trial, the eGFR slope, the annualized slope, was minus 0.6 ml per minute per year with a confidence interval of 0.5. So that means the range was from minus 0.1 to 1.1 ml per minute per year. In terms of infection, in the randomized period, we really saw a very little difference in the rate of infection between those patients randomized to receive atacicept versus those received placebo. Please recall that this program began during the era of COVID. And in that period of time, we saw no difference in the rate of COVID infection nor did we see a difference in the severity of COVID infection between placebo and atacicept-treated participants. We also know that patients who were treated with atacicept have been able to mount a robust response to vaccination. In the long-term open-label extension period, the overall infection rate was comparable to what we saw during the randomized period.

Our next question comes from Pete Stavropoulos at Cantor Fitzgerald.

Yes. Congratulations on the data. Great to see atacicept's effect on eGFR. A question for Dr. Barratt. In the published article, it states that -- I'm sorry, I'm going to read part of it, "The time course of reduction in hematuria and proteinuria suggests that atacicept compares favorably with the anti-inflammatory effects of corticosteroids and complement inhibitors. And that this effect is likely to be due to rapid decline in immune complexes along with possible direct effect on BAFF and APRIL stimulation on innate immune cells." Can you just touch on this a bit? How does ataci compare favorably to effects of steroids and then complement inhibitors? And a statement about BAFF and April stimulation of innate immune cells. Can you speculate on how not reducing BAFF could affect the innate arm of the immune system? And could this impact clinical outcomes?

Okay. So lots of questions, sir. So I think in terms of what we've seen with the reduction in hematuria and proteinuria, in particular, stability of GFR, we clearly have an impact on formation of circulating immune complexes. What I'm fascinated by is the effect that this drug may well have on BAFF and APRIL signaling within the kidney tissue itself, both within the glomeruli but also within the tubulointerstitium. And we know that there are receptors with BAFF and APRIL expressed on resident kidney cells, and there are B-cells and plasma cells within the kidney tissue itself that are likely to be driving inflammation and scarring, particularly in the tubulointerstitium. And so we have lots of preclinical data to support that. And when we talk about innate immune cells, what we're talking about here are predominantly monocyte macrophages, which are very much cells that promote inflammation and scarring. So there is a lot of interest in delving into these mechanisms in patients with IgA nephropathy. And I think we are scratching the surface of the many ways in which this type of approach can improve kidney function above and beyond the reduction of immune complexes. So you'll need to watch this space as we generate data from humans on the importance of these pathways. But I think they are undoubtedly important and are contributing to that stability in GFR, which is really unheard of. I think you need to remember if you think about systemic steroids, that you don't get the stability in GFR that we see with this approach. If you look at the testing data, you get a reduction in hematuria and proteinuria but it comes back the minute you stop it. And even if you -- even with the steroids, you see a decline in kidney function despite the massive doses that are used are the real issues with toxicity. In terms of complement inhibitors, we don't know the effect on GFR because we don't have any GFR data from the APPLAUSE study, we simply have proteinuria data. And the Phase II study was so short that it's very difficult to determine what the impact will be. I think the important thing with complement inhibition, however, is that it certainly does target one of the downstream effector pathways that are activated by immune complexes. But I gave a talk at the ASN this year talking about how immune complexes cause injury across different glomeruli diseases. And they do cause injury by more than just activating the complement system. So while you may stop complement activation, there are still other ways these immune complexes can cause glomeruli and tubulointerstitium injury. Therefore, I'm not expecting necessarily to see the same degree of kidney function protection if just target one aspect of the effector pathway that causes kidney damage. I think we need to think very much more upstream in terms of targeting those immune complexes before they even get to be formed and before they deposit in the kidney tissue.

Great. Just one additional question. The first question on the call, they basically asked about how having an auto-injector at home could impact and you talked a little bit about quality of life. But how about in terms of compliance? Is there a difference between patients from your clinical experience coming into the clinic in order to receive a drug versus at home?

To be honest -- yes.

And how can that impact clinical outcomes?

Yes. So in my practice, patients would vote with their feet. If I gave them a choice of a treatment they could get to at home or a treatment they have to come to the hospital for, I would have no one choose the one to come to the hospital. It's just -- we just don't do that in the U.K. All of these treatments are home administered by the patients across the whole rheumatological spectrum of anti-TNFs, et cetera, treatment of IBD, subcu therapies. Something as simple as erythropoietin, which we use in all our kidney patients when they get to progressive stages of CKD5 is home administered. That's what patients expect. And it's particularly what patients expect when they're young with active lives, child caring responsibilities, job responsibilities is they don't want to be tied down to appointments. And that was very clear during the pandemic. The pandemic opened the Pandora's box because patients suddenly realized they can have their health care managed without having to come to the hospital regularly. And when the pandemic finished, the young patients that I looked after with glomerular disease voted with their feet. They said, "Why should I come back? Why can I not manage this remotely because it's much more convenient for my lifestyle." So I think that is going to be a real -- the important aspect and it's going to be the expectation of these young, active people that they do not want to be tied to a hospital.

Great. And once again, congratulations on the data.