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

Yes. 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 to $10 billion range for U.S.-only IgAN as a total opportunity. And consensus on The Street has atacicept in the single-digit billion dollar range for a consensus estimate for peak sales. 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 to 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 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.

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 broad view...

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 nephrologists?

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...

Yes. So we have clarity on what our target audience is and 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. And 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. And 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. And that's been a major part of our focus, both last year and this year. So 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. So we recognize that opportunity last year. We've scaled up. And 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, and we're not hearing that from a few corners. That's really what the nephrology community is saying. And 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.

So let's go back to the label for a second. You have placebo -- 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 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 was -- what became in the label in full approval. We've seen that with both TARPEYO and FILSPARI. So 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 confirmatory endpoint and you get a full approval. So 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 2 years. We have discontinuation data to help understand risk benefit. If you're 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. So that's the discontinuation of ataci data we showed back in January. We've 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. But Rob, any further nuance of that, I'd welcome.

Yes. 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 concomitant -- or concurrent publication in the Journal of American Society Nephrology to share that data with the community. Our team has been running with that data now, and we want to be able to educate the community on what we've learned in an appropriate and responsible way. And 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? And 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. But eGFR is ultimately where it's at. So where do -- Rob, where do community nephrologists fall in importance between UPCR and eGFR?

Yes. 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. So I think the feedback that you got at the panel yesterday is probably a feedback that you can generalize across the community, whether you'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, reduction in Gd-IgA1 are supportive of that, but GFR is the main driver. And that's why for full approval, FDA has been looking at GFR.

Got it. We've got about 7.5 minutes left. I want to make sure that we talk about other programs. But first, we have to make a stop at IP because, of course, we do. What's the strategy for atacicept beyond biological exclusivity? And is there going to be new IP around monthly?

Yes. So I think 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. So the answer is yes. I think the public will -- 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 biologics space. We've seen competitors try to make versions of atacicept and you can't concentrate greater than 80 mg per ml, for example. So that's a really key piece. So right now, biologics exclusivity gets us to 12 years beyond expected approval, so 2038. Many have seen that we've had public filings that get us into the early 2040s, and we continue to innovate and move that forward. And then I would say that's Wave 1 is what we're doing with ataci self-administered weekly. There is a Wave 2 and Wave 3 that we've been talking about for a few months now. Wave 2 is ensuring that Vera generates an option for monthly dosing in case that element of convenience. So our view is that it's not the entirety of patient convenience. And certainly, the convenience of an Ozempic-like format that we're taking to market next year is a good one. But in order to make sure that we provide that option, we're doing a monthly dosing study. And yes, there are abilities for us to protect that. That's Wave 2, and we've announced that we're starting those trials this year. And then as we move on to longer than monthly dosing, that's why we brought in VT-109, 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, so [indiscernible] binding.

So potential quarterly dosing, twice yearly dosing?

So this is part of our long-term play to own the BAFF/APRIL space, which we think is relevant to IgAN, which is already a multibillion-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 e-mails about a new autoantibody in pediatric nephrotic syndrome that we think could be tractable with atacicept. So that's what we shared at R&D Day in October. The next step for this to more than double the addressable market is to go into adjacent renal autoantibody-driven kidney disease. And then beyond kidney disease, we see really the beginning of a transformation in how we treat autoimmune disease generally. And 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 1 in 10 Americans and 1 in 10 patients globally are treated with relatively medieval tools. This is high-dose steroids, immunosuppressive therapy. And 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 high risk of dying of COVID or getting severe COVID.

Oh, you had priority to get the vaccination when it first came out, yes.

But you're still not [ senior granted ], right? Like you're still not going to have a normal life. And we think a thermostat approach to B-cell over-activation using BAFF/APRIL with the right dose that's been carefully selected in the Phase II program is a real unlock for these patients, and we see a much larger opportunity than renal alone and that is at least a double-digit billion dollar opportunity. So these are -- this is really the larger vision and that underscores why we've done not only Wave 1, but Wave 2 and Wave 3 as we move into the BAFF/APRIL space and lead it.

So 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 the Phase I is ongoing right now.

Yes.

Next update and what will it entail?

Yes. We've said we're running a study this year and 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?

Answer is it depends. Rob, you can give some more color there, if you want.

Yes. Part of it is going to be predicated on what the doses that we learn about. But I think the endpoints that you're raising are the kinds of endpoints that we think about as we project the future program.

Yes.

Got it. And 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?

So 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 the 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 in a broader footprint of the disease. Let's start now. And 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. And because it's an open-label basket study, we'll be able to look at the data in an ongoing basis. And as soon as we're in a position where we have enough data to start telling a story, we will share it publicly and it's our intention to do that later this year.

And then we have -- 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?

So that program also starts this year, and 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.

Really important. BAFF/APRIL inhibition is transformative mechanism, we'll be first to market next year.

Great. With that, thank you, everyone, for joining us.

Excellent.