Thank you. Excuse me. Thank you, everyone, for joining us today for the fireside chat for Vera Therapeutics at the 45th Annual TD Cowen Healthcare Conference. With us today from Vera, we have CEO Marshall Fordyce and CMO Rob Brenner. I'm covering analyst Ritu Baral, and thank you, gentlemen, for joining us this morning.
Thank you.
One key question that investors have right now is the timing of your phase III ORIGIN data of your APRIL/BLyS modulator, atacicept, in your phase III IgAN study. This is the ORIGIN 3, especially given the proximity to ERA, that very important European renal conference in the middle of the year, where competitor data may be. How should investors think about timing of this top line data and what will be included?
Yeah, I can tell you that this is one of the more exciting moments for Vera, and I think for the IgA nephropathy field, and even broader for autoimmune disease. Vera has taken a molecule through an exciting and transformative phase II trial, which we started to unveil last year with one and a half and two year data. We demonstrated GFR stability over a two year period. Now we have really an unlock to file our BLA and get this drug to patients. The primary endpoint for this phase III trial is nine month reduction of proteinuria. It's a regulatory unlock, UPCR, proteinuria, which is a regulatory unlock to then file our BLA in the 2nd half of the year. We've communicated publicly that we expect that data in the second quarter.
That does include the month of June, where the European kidney meeting called ERA, which is being held in Vienna, I think June 4th- 7th. We have some understanding that competitor data could be shown then. We haven't been more specific on our own timing, but we agree that that's an interesting moment for the field because positioning will be important. I would underscore that, you know, Vera is the only program to have two year GFR data in the IgAN space. We've shown that patients with IgA nephropathy on a biopsy who are on average 35 years old, those who are at high risk of disease progression is who we and others are examining in phase III, they lose 10% of their kidney function per year. They are desperately concerned about losing their kidney function and ending up on dialysis before the age of 50.
That's the high risk patient group. We showed that over two years of treatment with atacicept, those patients lose minus 0.6 mL per year, which is on par with normal kidney function. It's been called a functional cure. That's a first in the field.
Importantly, where does that rank? Where does the data that you've shown rank in comparison to the guidelines for target treatment?
Yeah, at or above. Rob is the nephrologist in the room, but maybe you could speak about the guidelines,
Before we even get to the draft guidelines, having a population of patients who have gone to a biopsy suite to have a diagnosis made of an underlying kidney condition, where historically they lose their rate of 5 to 8 mL per minute per year, for there to be a drug, a prescription that has the potential to change that. Now their GFR profile no longer looks like a population with diagnosed kidney disease. It looks like the GFR profile of the people in this room, healthy people who lose, you know, around age 40, about 1 mL per minute per year. That minus 0.6 is an overlay with what we see in the general population.
Based on that and based on thinking about how do we keep patients off dialysis, the draft KDIGO guidelines have called for achievement of GFR rate of loss of 1 mL per minute per year or less, which is exactly what is published in the Journal of the American Society of Nephrology from our phase II clinical program. Yeah.
How is conduct of ORIGIN 3 going? Discontinuations, compliance? I mean, there's always been prior studies, there's always been wobble around UPCR because of how the data is measured, collected, measured, et cetera. How has the demographic of the patients shaped up to be?
Yeah, the program is going phenomenally well. The ORIGIN program really is one that includes the phase II-B and the phase III study in one master protocol. It's as closely aligned a phase III experience following the completion of the phase II portion that I've ever been involved with. The inclusion criteria are virtually the same. As we've seen the evolution in enrollment, in general, the characteristics look superimposable from phase II to phase III. We've learned a lot as a sponsor and working with our research partners in terms of how to ensure that there is adherence to all the details of the protocol. I think that gives us a lot of confidence that as we project towards the data readout in Q2, we have very high expectations that the data will be comparable to what we've seen already.
Background SGLT2 use, that was an important differentiating feature of your phase II data in that your demographic was much more real world. How do you expect that use to evolve in the phase III? How could that impact top line?
Yeah, so in our phase II program, there was about 15% of participants who enrolled on stable doses of SGLT2 inhibitors, and they maintained that stable dosing throughout the program. What we learned from our competitor is that the numbers were much higher, closer to 50%. My expectation.
In their phase III.
In their phase III. My expectation, and we haven't completed enrollment, so I can't give you an exact number, but we'll also have a much higher number, probably in that range, if not larger, because our program's a little bit later than theirs. Over time, there's more and more SGLT2 inhibitor use. What does that mean for the readout of proteinuria that we'll have at 36 weeks? My view is it means very little. Why am I saying that? Because patients are coming in on stable doses of SGLT2s, just like they're coming in on stable doses of an ACE inhibitor or stable doses of an angiotensin receptor antagonist. Those drugs won't be changed in terms of dosing while they're in the program.
Therefore, if their baseline proteinuria is about 1.4 g per day, which is what it was in phase II, I expect it'll be very similar in phase III . The fact that they're not having adjustments in those concomitant medications means that we're going to get a really clear readout of the effect of the drug of atacicept versus placebo on proteinuria.
It's the adjustments. It's not so much that.
Exactly.
Okay. So what does that, where does that leave us as far as what expectations should be for the top line? Marshall, before the phase II data, you had always suggested that the threshold for provability was 30% placebo adjusted for FDA. Is that still where expectations should be for the nine month data? Because your own phase II data was actually slightly, well, a little more than slightly above that.
Yeah. Yeah, I would say, as Rob has mentioned, proteinuria at 36 weeks is a regulatory unlock for us. The bogey remains 30% placebo adjusted. Efficacy is really determined by eGFR. We know that proteinuria differences of 5%, 10%, or even more can exist between different mechanisms. The only mechanism, the only program that's demonstrated GFR stability is atacicept dual BAFF/APRIL inhibition over a two year period. To do this rank ordering of proteinuria of a 5% or 10% difference, we do not think is relevant to how certainly physicians and other stakeholders will be looking at the value of a drug.
Right, because they will be looking at, you know, if you have 34 and the competitor is 38, oh, that's better. That's actually not, that's not what our IgAN KOL suggested yesterday. Folks, that'll be part of the write-up for Monday. Nine month data top line, with an FDA focused very much on equipoise of the study at the two year point, what are we going to get at nine months? What will you see? What will FDA see to drive accelerated approval versus what investors will see at the nine month time point, secondary endpoint and otherwise?
Yeah, Rob, do you want to go?
Yeah, the FDA has been very clear with all sponsors that because we're using accelerated approval pathway that's predicated on an interim analysis of an ongoing study, they don't want to overcommunicate on the results of all of the endpoints at the time of the interim. Why? Because the more that we know about the full constellation of endpoints, the harder it is to keep people enrolled in a placebo controlled trial. The worst thing for the FDA is for us not to get a clear readout at the end of the two years. Therefore, there's clear guidance that for an interim analysis of an ongoing study, that we don't share endpoints like GFR from the nine month evaluation. I think the expectation should be we're going to learn about the proteinuria. We're going to hear that we intend to file.
That may be the magnitude of what is communicated.
And safety.
Safety, but until we present the data, right, we're not going to be able to say, you know, the full summary until we go through the complete analysis at the time that we file. We present the data in a public forum, as opposed to what will be in a press release.
We shouldn't expect hematuria data either?
I would say we're motivated to share as much data as we can without creating strife with the regulators. If we're able to do that, we will. I don't want to promise until we've had that conversation.
Is the FDA's concern about equipoise, does that extend to enrollment completion, or does it extend to last patient, last visit?
My expectation is we will complete enrollment probably prior to having data that we're going to share from the nine month.
So enrollment.
Yeah, through enrollment.
Essentially. It will be just like your competitor, probably a medical meeting.
Yeah, it would expect press release followed by sharing of the data in academic congress.
Got it. With more detail.
Correct.
With the detail.
Correct.
Okay. I'm sorry, when did you anticipate finishing the two year enrollment?
Soon.
Very soon. Okay. The deadlines for ERA have passed and the meeting after that would be the big major meeting after that is ASN later this year, isn't it?
Yes, it's Houston, Texas.
Oh, okay. Sorry. Commentary there. Anyway.
Ritu, you had asked about priority review. This is an important point. The only two programs that are approaching B-cell modulation that have breakthrough designation are Vera's program, atacicept, and Otsuka's program. The others do not. I think it is really important to see that breakthrough designation gives you a high probability of priority review. We will certainly be filed before a competitor would get full approval. That gives us very high confidence that priority review should be secured.
Designations in IgAN , is that a function of the quality of data generated? I mean by the fact that you guys have placebo controlled data, I believe Otsuka also had placebo controlled data before the phase III.
You're not picking up.
Sorry. Am I live now? Am I live now?
I'm live now. I accidentally turned my mic off, sorry. Why haven't we seen more breakthrough designation from competitors? Is it about the quality of the data and the placebo controlled nature of the data that you used in the breakthrough application or something else?
I mean, I can't comment on others, but I would just say that atacicept has the most robust data set and is first in secured breakthrough designation. You know, one has to show something different to secure breakthrough designation beyond that.
Can Vera launch atacicept by itself?
Yes.
What sort of commercial prep are you doing now and what sort of commercial force do you envision for approval?
Yeah, thanks for the question. This is important because I think appreciating the size of the IgA nephropathy market alone in the U.S. alone is an important component. Most estimates put this in the $6 billion-$10 billion range for U.S. only IgAN as a total opportunity. And consensus on the streets has atacicept in the single digit billion dollar range for a consensus estimate for peak sales. You know, IgA nephropathy is just under an orphan disease. So we're going to estimate somewhere in the 150,000 patient range, somewhere in the 10,000-12,000 nephrologists in the U.S. range. That is a very launchable approach for a company of our scale. We have fantastic commercial leadership that we brought in and have been preparing for commercial launch for some years now.
How many of those nephrologists would you need to target for this launch? I'm wondering like how much IgAN is managed in the community setting versus the center of excellence setting because I think that's going to be, there's labeling discussions we'll get to next or labeling aspects that might be important.
It's a good and logical question. We're not willing to share our nuanced view of how we're going to approach this market publicly yet, but we will come back to the street as we get closer to launch and share our broader.
Just from a market research perspective, is IgAN a center of excellence driven disease management profile, Rob, or is this something that most people just go to the community nephrologist?
Most practicing nephrologists are caring for patients who have IgA nephropathy. Our team is experienced both with biologic launches in populations of this size and in nephrology.
Your commercial team has hired currently.
We have clarity on what our target audience is. We're scaling to be able to compete and to win in the space.
Are you fully hired up, Marshall?
Are we fully hired up?
Hired up on the commercial side.
That's a growth area. I would say we're fully hired up, although it's always hard to say that. We're continuing to scale, but we're in very good shape. I would say we're early with respect to launch. I do think that there's a middle step that's often not well appreciated, which is clinical research doing the development work, KOL engagement presentations. Before you get to commercial, you need medical affairs. You need to have a very strong connection with nephrologists of all types. Under Rob's leadership, that has been built and is, I would say, a world-class team of nephrology med affairs. That's been a major part of our focus both last year and this year.
You know, if you think about our position, many companies that are launching a drug have to wait until their phase III readout before they talk about the strength of their data. Look what we have in phase II. We recognize that opportunity last year. We've scaled up. I think most people who went to ASN last year in San Diego would say that Vera showed up as the leader in IgA nephropathy. We're not hearing that from a few corners. That's really what the nephrology community is saying. Rob's team continues to build on that with the momentum this year. 2025 is an incredibly important year for us to communicate the potential value of atacicept in patients next year.
Let's go back to the label for a second. You have statistically significant placebo-controlled eGFR data from ORIGIN 2 that is published. But you believe that you can also get that data in the, or sorry, the indication in the label, is that correct? How should we think of how you can get eGFR claims in the label?
I would bookend it. And then Rob, I'd love to hear your thoughts on this. I'd bookend it and say, you know, we have precedent from the non-disease modifying agents that are out there today about what was in the label at accelerated approval and what became in the label in full approval. We've seen that with, you know, with both TARPEYO and FILSPARI. You know, the baseline pattern is that accelerated approval has a proteinuria threshold. There's no GFR data in the label until you achieve that endpoint in phase III with the confirmatory endpoint and you get a full approval. That's the baseline. Look at our data set. We have a very strong argument for a transformative patient benefit. We've got phase II data that stabilizes GFR for two years. We have discontinuation data to help understand risk benefit.
If 35 years old, you're at high risk of disease progression or you're losing 10% of your kidney function a year, if you start atacicept, that GFR stabilizes. If you stop it, it continues to go down. That's the discontinuation of ataci cept data we showed back in January. We got the safety database. There's a lot of data that goes into arguing that this patient benefit could argue for a different labeling cadence than what we've seen historically. That's how I'd kind of bookend each side. Rob, any further nuance of that, I'd welcome.
Yeah, I mean, when you're sitting on a data set that is transformative for patients who suffer from this disease, as a sponsor, you want to do everything in your power to enable patients to benefit from that drug as quickly as possible. It was a large effort to have a simultaneous oral presentation at ASN with the data and a concurrent publication in the Journal of the American Society of Nephrology to share that data with the community. Our team has been running with that data now. We want to be able to educate the community on what we've learned in an appropriate and responsible way.
As we project forward, we have every motivation to leave no stone unturned to try and enable our commercial enterprise to be able to message around the GFR results from the entirety of our program at the time that we launch the drug. We'll see how we go through that exercise with the agency, but that's our objective.
How important will that eGFR detail in the label resonate with community nephrologists versus KOLs? We've heard some conflicting things. We've heard one KOL basically say, "Oh no, he talked to," this actually wasn't his own opinion. This was earlier in the year. He's spoken to his community nephrologist friends and they don't really care about eGFR. They care about UPCR and understand what that means. However, yesterday on our panel, the IgAN specialist in the tertiary care basically said, "No, eGFR is where it's at for everybody, including KOLs who know how to interpret UPCR, but they'd rather not." If that's all they have, UPCR is fine. eGFR is ultimately where it's at. Where do, Rob, where do community nephrologists fall in importance between UPCR and eGFR?
Yeah, if you're a nephrologist anywhere, it's hard to imagine that any measure is more important to you than a measure of glomerular filtration rate. It's what we look at as we think about determining whether a patient should stay on preventative agents or is it time to initiate dialysis. We use GFR to figure out should we list them for a transplant or not. Proteinuria doesn't impact that directly the way GFR does. I think the feedback that you got at the panel yesterday is probably feedback that you can generalize across the community, whether we're talking about thought leaders or talking about community physicians. I think if they're presented with GFR results, that is going to be top of mind. The additional results in hematuria, proteinuria, et cetera, reductions in Gd-IgA1 are supportive of that. GFR is the main driver.
That's why for full approval, FDA has been looking at GFR.
Got it. We've got about seven and a half minutes left. I want to make sure that we talk about other programs. First, we have to make a stop at IP because of course we do. What's the strategy for atacicept beyond biological exclusivity? Is there going to be new IP around monthly?
Yeah, so I think, you know, this is a well-worn playbook in the biologics space where the process is the product. So composition of matter, of course, is the beginning. But when you talk about a monoclonal antibody or a fusion protein like atacicept, there are multiple opportunities to protect your position and innovate along that pathway. The answer is yes. I think the public has seen and will continue to see more filings for IP protection. There's also trade secrets and know-how that protects what we've built around the manufacturing process to make high yield, the ability to concentrate atacicept, the ability to formulate it. These are not simple things to do in the biologic space. We've seen competitors try to make versions of atacicept and can't concentrate it greater than 80 mg per ml, for example. That's a really key piece.
Right now, biologics exclusivity gets us 12 years beyond expected approval. 2038, many have seen that, you know, we've had public filings to get us into the early 2040s. We continue to innovate and move that forward. I would say, you know, that's wave one is what we're doing with atacicept self-administered weekly. There is a wave two and wave three that we've been talking about for a few months now. Wave two is ensuring that Vera generates an option for monthly dosing in case that element of convenience. Our view is that it's not the entirety of patient convenience. Certainly the convenience of an OZEMPIC-like format that we're taking to market next year is a good one. In order to make sure that we provide that option, we're doing a monthly dosing study.
Yes, there are abilities for us to protect that. That's wave two. We've announced that we're starting those trials this year. As we move on to longer than monthly dosing, that's why we brought in VT109, which we announced back in January. This is an unexpected novel fusion protein of BCMA and an FC fusion portion that binds BAFF and APRIL with high affinity with soluble binding.
Potential quarterly dosing, twice yearly dosing.
Correct. This is part of our long-term play to own the BAFF/ APRIL space, which we think is relevant to IgA nephropathy, which is already a multi-billion dollar opportunity, moving that into other autoantibody-driven kidney diseases that Rob talked about last October, membranous nephropathy, FSGS, minimal change disease. Just this weekend, we were exchanging emails about a new autoantibody in pediatric nephrotic syndrome that we think could be tractable with atacicept. That is what we shared at R&D day in October. You know, the next step for this to more than double the addressable market is to go into adjacent renal autoantibody-driven kidney disease. Beyond kidney disease, we see really the beginning of a transformation in how we treat autoimmune disease generally. This is a really important key about our insight at Vera when we brought in atacicept.
We have an idea that autoimmune patients, patients with autoimmune disease, which is about one in 10 Americans and one in 10 patients globally, are treated with, you know, relatively medieval tools. This is high-dose steroids, immunosuppressive therapy. Why is that important? If you look at what happened during COVID-19 with a high death rate from respiratory illness, if you were on high-dose steroids or you were on something like RITUXAN, a B-cell depleter, you had a high risk of dying of COVID or getting severe COVID.
Oh, so you had priority to get the vaccination when it first came out. Yeah.
You're still not seeing your grandkids, right? Like you're still not going to have a normal life. We think a thermostat approach to B-cell overactivation using BAFF/ APRIL with the right dose that's been carefully selected in a phase II program is a real unlock for these patients. We see a much larger opportunity than renal alone. That is at least a double-digit billion-dollar opportunity. This is really the larger vision. That underscores why we've done not only wave one, but wave two and wave three as we move into the BAFF/ APRIL space and lead it.
Let's just rewind to monthly, to the front of the pipeline expansion or the platform expansion. When are we going to get the next update on the monthly? Because I believe a phase I is ongoing right now.
Yeah.
Next update and what will it entail?
Yeah, we've said we're running the study this year. I think it depends on how that data come in. We haven't made a commitment on what will be showed when.
What is the regulatory path on the monthly? Do you think that this could be simple PK, PD around like PD around like Gd-IgA1 or maybe UPCR?
Yeah. The answer is it depends, Rob. You can get some more color there if you want.
Yeah. You know, part of it is going to be predicated on what the doses that we learn about. I think the endpoints that you're raising are the kinds of endpoints that we think about as we project the future program.
Yeah.
Got it. Now we've got the, sorry, let's go to the extended population study first. When are we getting first data and what sort of expansion, magnitude of expansion in IgAN does that address?
As Marshall said earlier, when we look at the numbers of patients who are eligible to participate in phase II and phase III trials by all the sponsors in this space, it represents maybe up to 50% of the total population. When we look at the data that we've published now and shows this transformative eGFR result, it raised the question in our minds and gave us the motivation and the conviction to invest more aggressively and say, "Why should someone who has a form of IgA-mediated disease not have the opportunity to benefit from a drug that has this kind of a profile?" Therefore, let's not wait until after we have the initial approval to start expanding the data generation and a broader footprint of the disease. Let's start now.
The pioneer program, this basket study that we announced in October, is our effort to do that and to go from studying a portion of the population with IgA-mediated disease to the totality of patients with IgA-mediated disease. Enrollment starts this year. Because it's an open-label basket study, we'll be able to look at the data on an ongoing basis. As soon as we're at a position where we have enough data to start telling a story, we will share it publicly. It's our intention to do that later this year.
Like, actually, we have no time, but I'll give you a minute. The PIONEER basket study of membranous nephropathy and FSGS, how is enrollment going and when could we get first data?
That program also starts this year. We hope that we'll have initial data readout later on in 2025.
What's the promise of APRIL/BLyS in these conditions?
In my mind, it's the same promise that we have started to realize in IgA nephropathy, which is really to transform the outcomes in patients with these diseases.
Yeah. Really important. BAFF/ APRIL inhibition is a transformative mechanism. We'll be first to market next year.
Great. With that, thank you everyone for joining us.
Excellent.