All right, let's go ahead and get started. Welcome everyone to the 42nd annual JP Morgan Healthcare Conference. My name's Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by my squad, Priyanka Grover, Lori Hall, Malcolm Kuno. Our next presenting company is Vera, and presenting on behalf of the company, we have CEO Marshall Fordyce. Marshall?
Great. Thanks, Anupam. Good afternoon, and welcome. I'm Dr. Marshall Fordyce. I'm the Founder and CEO of Vera Therapeutics. We're a clinical stage biotech company developing treatments for serious immunologic diseases. Our mission is to change standard of care for patients, and I'm thrilled to share our substantial progress with you today. Our lead clinical product candidate is atacicept, a first-in-class, next-generation B-cell modulator, currently in phase III for patients with IgA nephropathy or IgAN. IgAN is a serious progressive autoimmune disease that causes kidney failure in young patients. Today, I'll provide an overview of Vera, and then we'll focus on the phase IIb IgA nephropathy study results, highlighting key findings from the nine-month randomized period.
This year, we have the opportunity to share long-term data from this study at 1.5 and two years, respectively, in the coming quarters, setting apart the strength of our data set from other approaches in preparation for commercial launch anticipated in 2026. This is an exciting moment for patients with IgAN, as atacicept's clinical data support its ability to target the source of the disease and stop kidney function decline for the first time, offering a potentially transformative new treatment option for these young patients. Before we get started, I'll remind you, my remarks contain forward-looking statements under Safe Harbor, and as such, we'll present this disclaimer regarding at-risk statements. Atacicept is a biologic molecule with therapeutic potential in certain autoimmune diseases in which modulating B cells and plasma cells could significantly improve disease.
These include, of course, our first indication, IgA nephropathy, as well as lupus nephritis, systemic lupus, membranous nephropathy, and systemic sclerosis, among others. Based on positive phase II data and input from FDA, we advanced atacicept into a pivotal phase III trial in IgAN that is currently enrolling and on track to deliver results next year. Unlike other kidney diseases, IgAN is specifically caused by abnormal B cells. By targeting B cells, by targeting B cells, atacicept holds a unique promise of halting the decline of kidney function in these patients. Last year, we demonstrated for the first time in the field, that atacicept stopped kidney function decline through nine months of treatment. This year, we will share longer-term results and data that evaluate whether stabilization of GFR that was observed is durable through two years.
Our phase III trial is enrolling well, and we project primary endpoint readout next year, enabling atacicept to potentially be first to market among B-cell modulators in this exciting new class for IgAN patients. We're sufficiently funded through our IgAN phase III primary endpoint and project cash runway into 2026. This year, we will share the long-term kidney function results from phase IIb, starting with a 72-week result readout later this month in an event in New York on January 25th, and then at the end of the year, in the fourth quarter, 96-week results. We also expect to announce our full enrollment of our phase III primary endpoint cohort in the second half, enabling readout in the first half of 2025, an estimated commercial launch in 2026.
Beyond IgA nephropathy, atacicept has therapeutic potential in several other autoimmune diseases in which atacicept's demonstrated reduction of disease-causing autoantibodies could significantly improve disease. Based on atacicept's substantial clinical data, including substantial dose-finding and placebo-controlled clinical safety, Vera has a written agreement with FDA on the 150 mg dose and study design in three separate indications, including IgAN, lupus nephritis, and systemic lupus, enabling Vera to expand the atacicept opportunity to multiple autoimmune diseases. IgAN is a large unmet need, in which patients are diagnosed on average at 30 years old and progress to end-stage kidney disease before the age of 50, requiring dialysis and costing the healthcare system an average of $200,000 per patient per year, and very significant morbidity and mortality in the 5-10-year timeframe from the moment of ESKD diagnosis.
Considered an orphan disease in the U.S., with an estimated prevalence of 126,000 patients, and with a therapy that can truly modify the disease and delay the need dialysis for years, and even potentially decades, we estimate the commercial opportunity for novel IgAN therapeutics to be in the $6 billion-$10 billion range. The cause of this disease is dysfunctional B cells, and atacicept targets the source of IgA nephropathy by inhibiting multiple upstream steps in the disease. By blocking BAFF and APRIL, atacicept inhibits the overstimulation of B cells and plasma cells. Our data set is the first to demonstrate any agent that reduces the causative molecule, galactose-deficient IgA1, the antibodies that attach to Gd-IgA1, called autoantibodies, and also reduces the immune complexes that cause the downstream kidney injury.
By targeting B cells and reducing immune complexes, you would expect to see resolution of the downstream effects, and that is what our clinical results have demonstrated to date: reduction of immune complexes, resolution of nephritis as measured by hematuria or blood in the urine in the clinic, reduction of proteinuria, a sign of glomerular dysfunction associated with kidney function decline, and fourth, stabilization of kidney function, evidence of arresting disease progression. Halting kidney function decline, true stabilization of GFR, is completely novel in the IgAN field, and the implications for young patients facing dialysis are profound. With the data set already in hand and with confirmation in a phase III trial, we envision a new treatment paradigm in which atacicept is first-line therapy.
Atacicept's ability to stabilize kidney function is distinct from current standard of care with ACE inhibitors or ARBs, SGLT2 inhibitors, steroids in any form, endothelin receptor antagonists. No other mechanism has demonstrated this disease-modifying effect. Dual inhibition is really the most elegant approach to B-cell modification. Atacicept inhibits the two known circulating cytokines, BAFF and APRIL, which are both important for the survival and maturation of the B-cell lineage. This is well-known biology, both from academics and industry research. Elevations of both BAFF and APRIL are found in patients with IgAN, lupus, and other autoimmune diseases, and both play a key role in disease pathogenesis.
In preclinical models, dual inhibition of both BAFF and APRIL have been shown to be more potent than blocking BAFF alone or APRIL alone, which may translate into robust and more sustained B-cell modulation versus BAFF-only or APRIL-only approaches to B-cell modulation in certain autoimmune disease. Inhibiting both known signals is the most elegant approach and minimizes the possibility of signal escape, in which a compensatory increase of the uninhibited pathway reduces the potency or durability of the treatment effect. Dual inhibition also enables a low-dose, simple product. Vera has advanced into phase III, a dose of 150 mgs. It's unique in that it's self-administered by the patient at home, a low-volume, 1 mL, subcutaneous once per week. This is something patients often do with a novel biologic at home on a Saturday morning. It's easy to remember.
It's a biologic fusion protein that makes use of the true, unaltered TACI receptor. Unsurprisingly, atacicept has shown low nanomolar binding to both BAFF and to APRIL, and binding assays as expected from TACI, TACI's natural role in B-cell biology. We designed the phase IIb 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 GFR or eGFR. Proteinuria now, and I'll return to this, is a validated surrogate endpoint by FDA for accelerated approval for new drugs, and that's been demonstrated twice by Calliditas' Tarpeyo and Travere's Filspari. Our study was the gold standard and approach for evidence generation, as drug developers do. Multinational, randomized, placebo-controlled, double-blind, dose-ranging study to evaluate atacicept versus placebo and empowered to demonstrate a statistically significant difference in proteinuria.
Key inclusion criteria include basically adults at high risk of disease progression. They needed biopsy-proven IgAN, a minimum GFR of 30. They're on optimized RAS inhibition, with or without SGLT2 inhibitors, and they're still producing over 0.75 g of protein at screening. These are the patients we would expect to lose kidney function on average 4-8 mL/min/year. That means a 30-year-old is on dialysis by 50. The randomized phase lasts 36 weeks. We passed that threshold last year. The primary endpoint was 24 weeks, secondary endpoints at 36 weeks. We are studying open label extension of 150 mgs up to 96 weeks or two years. So this gives us the opportunity to look at long-term potency and durability, in data that we'll share, this year.
I want to note that a 30% placebo-adjusted reduction in proteinuria is known to be clinically meaningful in IgAN. This is the result of important regulatory and advocacy effort between American Society of Nephrology, Kidney Health Initiative with FDA in the form of a natural history study, where a 30% reduction in proteinuria is associated with a significant delay in end-stage kidney disease, even if it doesn't arrest end-stage kidney disease. Reduction of proteinuria at 36 weeks in a rigorously run Phase III trial has led to two accelerated approvals. Tarpeyo, with a placebo-adjusted delta of 31%, and Filspari, with a placebo-adjusted delta of 35%.
And some of you who are following the field will know that Tarpeyo also achieved full approval in the last month because of its two-year GFR primary endpoint, confirming the relationship between proteinuria reduction and GFR separation in this disease. This is not true across all kidney diseases. It's true for IgAN. For baseline characteristics, we're pleased that we enrolled the target population. Those are young people who are at high risk of disease progression. These are patients currently on optimized background regimen, allowing a clear assessment of treatment effect of atacicept versus placebo on top of the current standard of care. And you'll notice that about 14% of patients were on SGLT2 inhibitors across this study. Baseline characteristics reflect a relevant and diverse study population.
The mean age was 39 years old, 59% male, 44% Asian race, mean eGFR of 63 mL/min, mean UPCR of 1.6 g/g on a 24-hour urine protein collection, and these are characteristics that would worry any nephrologist. As the hypothesis is meant to do, the atacicept arms, in yellow, 25 mg, in light blue, 75 mg, and in dark blue, 150 mg, had a dose-dependent reduction of the galactose-deficient IgA1, which is the autoantigen that causes autoimmunity in IgA nephropathy patients. This is interesting in that those of you who follow the autoimmune space, there are few autoimmune diseases that have an identified autoantigen.
If you take the immune complexes in these patients and pull them apart, and you look at the epitope of the autoantibody, it's for the hinge region of galactosyl-deficient IgA1. That minimizes pathophysiology risk for drug development in this, in this space. How do we know at 150 mgs with a 64% reduction that that's enough? Why don't we need 90%? Why isn't 30% enough? We know from observational studies that those who have the highest levels of Gd-IgA1 have the worst renal outcomes. The inset on the left is an observational study of IgAN patients with varying levels of Gd-IgA1. The highest levels are in red, in group 4, and the lowest levels are in green, in group 1.
If you have group four, if you have high Gd-IgA1 levels, and you've got IgAN, you've got very reduced cumulative renal survival, which is what's on the Y-axis here. So the whole idea is, what if you had a drug that could move you from group four to group one? Would you see the survival curve of the green group one, where you do not have renal failure over a matter of not just years, but decades? On the right-hand side, you see actual data from our phase II study. Each row is an individual patient. On the left is placebo, and on the right is atacicept 150, about 33 patients. You can see by 36 weeks or nine months, almost all of those patients get to the green quartile, the lowest risk quartile.
That means that 64% Gd-IgA1 reduction is enough to achieve what's needed. We also saw dose-dependent reductions in immunoglobulin levels of IgG, IgA, and IgM, which are important, analog, looking towards autoantibody reduction. And also, we saw a reduction in hematuria. This is a clinical measure of active glomerulonephritis, which resolved in 80% of patients through the first nine months of treatment. At week 36, we observed a statistically and clinically significant reduction in proteinuria with a delta of 43%. That was stat sig. And in these high-risk patients receiving placebo, those receiving placebo had an unexpected decline in GFR of about 9% over 36 weeks.
What we observed was completely unexpected, and that in this disease, patients receiving atacicept maintained stable eGFR for the first time in the field, with an absolute difference of 5.8 mL/min at nine months. That was statistically significant. Such results, if durable, over one to two years, would represent a transformative new treatment for these patients. Importantly, the clinical safety profile of atacicept was similar to placebo. Atacicept was well-tolerated in IgAN patients. Infections were balanced between atacicept and placebo. All infections observed were mild or moderate, none were severe. Of note, 25% of patients got COVID during the trial. This was a trial of a B-cell modulator conducted in the time of global COVID
What we observed in a placebo-controlled trial was that, an even number between placebo and atacicept had tested positive. None were judged to be severe, and none led to hospitalization. So in summary, the Phase IIb ORIGIN study not only met its primary endpoint but builds a substantial data package supporting the disease-modifying potential of atacicept. A dual BAFF/APRIL inhibitor that targets the source of immune complex should improve all downstream consequences, resolve hematuria, reduce proteinuria, and, distinct from any other mechanism, halt kidney function decline. And that's what was demonstrated in the ORIGIN to study through nine months. Based on these positive results, we selected the 150 mg dose and initiated our Phase III trial last year. The design of the Phase III trial will be very similar to the Phase IIb trial, with slight optimization.
It will be a multinational, randomized, double-blind, placebo-controlled trial comparing atacicept 150 versus placebo, with a primary endpoint of proteinuria at nine months, which is now a validated surrogate endpoint for accelerated approval with FDA times two approved drugs, and a secondary endpoint of eGFR at two years. So what's distinct is that this is a blinded study through two years for the confirmatory GFR endpoint Atacicept's target commercial product profile is a self-administered, small volume auto-injector delivered subcutaneously at home once weekly. The commercial profile has been shown to be clinically acceptable and commercially successful for multiple blockbuster drugs in rare disease, in nephrology, and in autoimmune disease. The potential to explore longer dosing intervals, such as monthly, is certainly supported by Atacicept's pharmacokinetic profile and is part of a life cycle management opportunity.
In closing, we're excited this year to share longer-term kidney function results from the phase IIb study, starting with 72-week or year-and-a-half results that we'll plan to share later this month, and 96-week or two-year results in the fourth quarter of this year. Full enrollment of our phase III primary endpoint cohort is expected in the second half of the year, enabling phase III readout the first half of 2025, an estimated commercial launch in 2026. We're very excited about the strength of the phase II results, allowing us to advance this potentially transformative treatment to commercialization and aim to improve patients' lives. I want to thank you for your attention, for being here, and I'm happy to answer your questions. Thanks.
Thanks, Marshall. Many of you have probably heard me say this over the course of a day and a half, but there are three ways to ask a question, right? There's the old school way, raise your hand, I'll call on you. If you want to get fancy, you can put your question in the question portal, it'll show up on the iPad, and I will ask it anonymously on your behalf. Or there's, like, an intermediate strategy where you just email me, and I'll do the same thing. So, I will start, though, with questions. Marshall, so what's going to be the size and scope of the January update here in a couple of weeks? What would you focus us on?
Yeah. So remember, this is an open label extension data cut through 72 weeks, which is 1.5 years. This will be all patients who have made it through the 72-week data cut. So we've cut the data. So efficacy will be all patients through that specific time point. Safety data will reflect all data through the time we take a snapshot. So safety data will take even patients who get beyond the 72 weeks. So it's a comprehensive view of where we are in the phase II study at a given time point, and that's all patients through 1.5 years. As I've indicated here, we're interested in whether the GFR stabilization we saw at nine months will be lasting through 1.5 years.
That would be unprecedented in the field. We're interested in proteinuria as well. We saw a proteinuria reduction in the low 40% at 36 weeks. We think that that should be maintained as patients initiated atacicept should continue on. What's also interesting about this data set is that it's nine months of randomization plus nine months of open label. So patients who are on placebo, who had a GFR decline, are able to switch to 150, and so we can see if those patients continue to decline or do they start to see an effect of atacicept and stabilize their GFR? So that's an interesting view as well. And then from a proteinuria perspective, it's essentially like rerunning the study. We've got patients who were randomized to placebo for nine months.
They had no change in proteinuria within a 5% range at nine months. And then what happens when you switch them to open label atacicept 150 for nine months? So it's another snapshot at looking at how valid our proteinuria results are. That's the scope, and I think that's the, you know, that's incredibly informative to the field.
So, just to summarize, and you can correct me if I'm wrong, so, we could define a win scenario for, in a couple of weeks to be eGFR stability at 72 weeks for the patients who have been on for 72 weeks, stable proteinuria, and, ideally, the placebo patients who switch and have nine months of therapy to see something similar on proteinuria. Fair?
Yeah, that's fair.
Okay. And how's enrollment going in the phase III study? Where are you on site activation, enrollment dynamics, and I think the guidance is to be complete at the back half of the year, so.
Yeah. So, we took an efficient strategy from a multinational phase II trial to convert the protocol to become a phase III trial, and that was a regulatory strategy that the Vera team deployed and was successful in having a very rapid transition from phase II to phase III. So site activation has gone very easily with those sites that were with us in the phase II program. The phase III new sites are, of course, attracted by the data, by the ease of use, the self-administration, and so we're very pleased with site activation. Enrollment is on track. So, we continue to be able to guide to where we guided early last year.
Questions from the audience? We actually have a portal question. So how will Vera make decisions to launch phase II trials in potential additional indications?
Yeah, great question. I think, as I mentioned, atacicept is really a next-generation B-cell, modulating agent that, delivers dual BAFF/APRIL inhibition, we believe will be first to market. Our strategy has been to win in IgAN. We have a winning data set in phase II and a very fast path to market. We have the potential now, in agreement with FDA around study design and dose, to open up, additional phase III trials. So, there are multiple options on the table for, when and how we fund those trials. We're interested in, in bringing that out, and we're speaking to, you know, stakeholders about that.
In your prior comments, you talked about, you know, some phase III sites are pretty interested in the self-administration angle. Maybe you could expand on what your market research suggests about the importance of at-home self-administration with atacicept relative to other approaches.
Yeah. I'll go a little off script, Anupam, for fun, and say that, you know, my market research includes visiting IgAN patient families every summer at the IgAN Foundation Conference, which is held around the country. These are young people, on average, in their thirties. That's what you'll read in an epi report, but it's real. These are people who are starting their jobs and their families, and they do not want to go to a clinic once a month for an IV infusion or a complex sub-Q high-volume administration. So, that to me is pretty convincing. I think you'd see that bear out in, you know, looking at sub-Q administration, either in the clinic or by patients themselves throughout other diseases.
Each disease is unique, but this is the disease of young patients who want the freedom of self-administration.
Questions from the audience? Yep?
Is there a disease modification feature of the drug? Disease modification. In other words, it's chronic disease, so once you are on it, then you are on for life, I assume.
Yeah. Good question. If I could reframe your question around the possibility of remission and are we intending to continue to dose this chronically? This is intended to be dosed chronically. Unfortunately, in autoimmune disease, remission is relatively rare, and with this mechanism, these patients, for a variety of reasons, probably a genetic background of immune dysregulation. If you look at SNP studies, you'll find that patients who have IgAN have a highly, you know, an increased frequency of SNPs that are associated with immune dysregulation. So, we're not turning off the stimulation of their elevated BAFF/APRIL levels. We can simply use atacicept as a sink or a sponge to remove that excess stimulation.
But, it's a good question, unfortunately, not a cure, and requires chronic dosing. Yeah.
How do you see long-term differentiation playing out with atacicept relative to other B-cell modulators, either from a clinical perspective or a patient convenience perspective?
Yeah, great question. So, you know, within the IgA nephropathy development space, I think this is an exciting time for patients, and as I've tried to share today, B-cell modulating is really the most promising approach. We are the only BAFF/APRIL inhibitor in phase III. There are two APRIL-only approaches in phase III. Neither of them inhibit BAFF, and so there's this mechanistic view that in a dual inhibition approach, it's the most elegant way to stop the overstimulation of B cells, and you remove the possibility of biologic escape. If you inhibit APRIL, what happens to BAFF, and what are the consequences? So there's an important biologic view that I think is differentiating, and we need to see how that plays out in longer-term phase II data and certainly in phase III as well.
So one is the biologic piece, the other is the clinical data. Among that set of competitors, getting to the market, we are the only program that will have two-year GFR data at launch. You can imagine an APRIL-only program getting to a phase III readout with nine-month proteinuria data, but they will not have GFR data from their phase III study to share. That needs to remain blinded, and that's been the precedent set by FDA with both Tarpeyo and Filspari. So it really is a limit. We'd like to set atacicept up for success and have the most successful commercial launch, and that requires, you know, not just the clinical data, but also presentations and publications that convince providers, convince the conservative nephrologists, that we're actually changing the course of disease for their patients.
Two-year data is convincing. Nine-month data is not as convincing. So, I think that's really an important differentiation in the near term. The ability for the APRIL-only programs to become self-administered, I think, is to be seen. We already have that in hand. So those are some key differentiations that I would point to at this stage.
Questions from the audience?
Do you know the antigen of the the IgA, the the disease-causing IgA? Do you know what antigen it binds to?
Yes. Yeah. It's important to recognize that I think biomedical research has identified a galactose-deficient IgA1. We all make immunoglobulins or antibodies. This is IgA1, which is a dimerized IgA connected at the stalk, and the hinge region of that molecule is normally protected by sugars. And so for some reason, these patients make a higher proportion of IgA1 that lacks that sugar protection. It's called galactose-deficient IgA1, and that is the specific epitope of the autoantibodies. We can't say the same thing about lupus or MS or other autoimmune diseases, and that creates some of the challenges in that drug development space. It's a great question. It's really important to understand those two things about IgAN, is that, number one, it's a B-cell-driven disease.
This isn't diabetic nephropathy, this is not minimal change disease, it's not nephrotic syndrome. This is a glomerulonephritis that's driven by abnormal B cells, so the most logical intervention is to stop the B-cell overactivity. And the second is that we know what that autoantigen is. So it's a great question, and that's what got me excited about the molecule. We brought this in from Merck KGaA, and there was very early evidence that atacicept was the first and only molecule to reduce that autoantigen so significantly. And that insight, I think, has borne out now in a robust phase II clinical program. Thank you.
Additional questions from the audience?
How are you thinking about the OUS opportunity for atacicept? Are you-- is that something you're planning on retaining, or, or is that a potential business development opportunity?
Yeah, thanks for the question, Anupam. I mean, we, I would, didn't highlight this, but we do hold worldwide rights for all indications in all regions currently. And that retains, full, full optionality for us, at this time going forward. I would say in this environment, where there's significant global pharma interest in immunology and in renal, we're choosing to retain worldwide rights, as we continue to read out key results this year and prepare for approval in 2026.
Yeah, go ahead.
How do you compare yourself to Filspari? Obviously, that is a you know ease of dose, so-
Yeah, good, good question. Filspari is sparsentan. Sparsentan is a dual inhibitor of both angiotensin and endothelin, and neither of those targets do anything to the B cells. So it's downstream. It can relieve glomerular pressure and reduce proteinuria, and it was well demonstrated that they had a 35% delta in at nine months in proteinuria. But they were unable to demonstrate a clear separation in GFR. Now, I think that might have been a powering issue, and with a larger study, that may have been accomplished. But it did not arrest GFR decline. That's a really big difference. If you look at Filspari, and you can look at these curves of GFR decline, what's promising about Filspari is that you're delaying end-stage kidney disease by a matter of years, and that's very meaningful.
But we're talking about a therapy at a completely different level, where we are halting GFR decline, and these 30-year-olds are not thinking about end-stage kidney disease or dialysis before the age of 50. So that's the most important distinction. I agree, you know, oral dosing is certainly can be seen as convincingly easier than a subQ injection. But you know, if you've got a disease-modifying agent, patients are willing to do that, and we've heard that from patients themselves. I do think that one metric for that, which I hope you'll see when we share, is retention. You know, how many patients will stay on this treatment over 1.5 to two years? So Filspari was 11% dropout at nine months and about 14% at two years.
If we're retaining in the 85%-90% range, it's similar in terms of patient retention on that, on that treatment. Great question.
Any final questions? Okay. Thanks, Marshall.
Thanks for the opportunity. Thanks, everybody.
We'll see you tomorrow.
Okay.