Thanks, everyone, for joining us at the Vera Fireside Chat at the TD Cowen 44th Annual Healthcare Conference. I'm covering analyst Ritu Baral, and joining me from Vera is founder and CEO Marshall Fordyce. Marshall, thanks for joining us today, and thanks for the time. Let's start with highlights of your top-line 36-week phase II-B ORIGIN data from ERS last year and the more recent 72-week OLE data that you presented mid-January. Importantly, across both time points, you showed eGFR stability, actually statistically significant at 36 weeks, and continued stability reductions in proteinuria, hematuria, which we'll get to, Gd-IgA1 all the way through 72 weeks. So moving forward, you will be showing your 96-week data.
Just given that's sort of the next catalyst point that investors are looking at, what should our expectations for that 96-week data be on all of those, exactly what, exactly what we've spoken of the last few times: eGFR, proteinuria, hematuria, and Gd-IgA1?
Great. I can answer all of that, Ritu. Thanks so much for the opportunity to be here. Look, this is an incredibly exciting time. I think many investors know that in biotech, there really is a new and growing recognition of the unmet need in IgA nephropathy. This is an enormous unmet need with a large market opportunity. And the data that we shared last June, our 36-week data at the end of our randomized phase, and the data we just shared in January has really set a new standard for IgA nephropathy. What we've shown is that patients with IgA nephropathy who are at risk of having declining kidney function and end up on dialysis and transplant, which is a terrible outcome, an expensive outcome, we have now shown that over a year and a half on atacicept, they have the same GFR as when they started.
That's never been shown before in IgA nephropathy, and it really sets a new standard for new treatments for patients with IgA nephropathy. We can go into what exists now. Patients take ACE inhibitors and ARBs, so-called RAAS inhibition. Some patients take SGLT2 inhibitors. There are two drugs on the market that have really done a great job to unfold and open up the pathway for us. That's Tarpeyo and Filspari, two drugs that are not disease-modifying. One is a steroid, and one is an endothelin receptor antagonist. But both of those drugs that now have accelerated approval, the GFR still declines, even when you're on drug.
Even on the SGLT2s?
Even on SGLT2s. So ACE inhibitors, SGLT2s, you can see all of those curves over at least a two-year period. So the data already exists. We already know what happens to these patients with the disease. We already know what happens to these patients when they're on standard of care. And, we already know what happens to these patients when they're on the newly approved treatments. So, it was our hypothesis that if we had a drug that turned off that overactive B-cell compartment by dual targeting of BAFF and APRIL, and atacicept does that with the natural TACI receptor, this is a so-called fusion protein. There's a storied history of taking a fusion protein and using it as a therapeutic to soak up excess signal.
Multiple blockbusters have been built on this idea that you take that natural receptor, you don't alter it, you take it as it is and bind it to an inactivated Fc portion. When I looked at this molecule four years ago, the only data I saw was that it reduces the autoantigen, that inciting molecule.
The Gd-IgA1 .
Gd-IgA1, and it reduced it by 60%. And we thought, man, if that's what this molecule does, we think everything downstream is going to resolve. If you actually target the source and you reduce it that much. And, how do we know that 60%-65% would be enough? How do we know that 80% or 90% wasn't required? Well, there's published data showing that all of us have Gd-IgA1. What we know is that atacicept 150 is able to get all the Gd-IgA1 down to the normalized level. All of us have some residual level. So we don't actually think there's additional benefit by pushing it even further. And, what we now know is that Gd-IgA1 reduction of 65% is associated with resolution of glomerulonephritis. We got hematuria fully resolved in 80% of patients and improved in more of those patients.
We also showed a reduction in proteinuria, which is the validated surrogate endpoint for approval. What no one else has shown is that we've shown GFR stabilization. That's in a rigorously run randomized trial, a global trial, and that hasn't been shown by others with dual inhibition.
You expect that with your 96-week update?
Yeah, yeah. So here's the question.
Yeah.
So, maybe the GFR between baseline and a year and a half literally was zero.
Exactly.
Right? So what happens in normal patients, normal people, people without IgA nephropathy, you lose about 1 mL per minute per year. So, in the fourth quarter of this year, if it aligns with an academic conference, that would be great. And at two years, at 96 weeks, what we'd expect is if that patient had no disease, they'd have a -2 mL per minute per year change. So, success for us doesn't mean on the zero mark. It means error bars, including -2 mL per minute per surface area per year. So, we can be really clear about our expectations. And, if the error bars include -2 at two years, that means we've obliterated the disease. That means that GFR in patients on atacicept is the same as if they didn't have the disease.
That is very, very different from current standard care, current drugs on the market, and really whatever has been seen in nephrology.
How important is it to quantify, or is it even possible to quantify the complex? We were talking with Rob earlier today about the Gd-IgA1 IgG or IgA complex that then goes and sticks in your kidney and screws up the membrane. Do you need to quantify the downstream complex generation and deposition, or is that sort of a step in the disease pathology you can skip to ultimately get to a commercial drug?
We've already skipped it, and we're already well on our way in 2026 to commercialization. But, the technical question is a good one, which is, can a doctor in a clinic right now measure a Gd-IgA1 level? And, could they be even more specific and measure the immune complex level? The answer is no. And John Barratt's a really good source for this because he's got postdocs in his lab studying which, what is the, are all immune complexes the same between individuals? No. Is there a composition IgG, IgA in the same proportion every time? No. So, there are interesting scientific questions about immune complex, but we've already made the link. We've made the link to the most important thing, which is GFR slope, which predicts if someone's going to end up on dialysis. That matters to payers.
We have that data in hand right now, and we'll be the only program to have two-year data from phase II as opposed to any other B-cell modulator in the field.
You can extrapolate the delay to dialysis or delay to transplant with the data that you'll have in hand from two years?
100%. That's done in renal development all the time. Yeah. And, actually, I think our CMO, Rob Brenner, made this point before. There is a history of measuring what proportion of patients end, you know, end up with end-stage kidney disease, but they're starting at much lower GFR in the beginning. Thankfully, we're catching these patients in clinical trials at an average GFR of about 60. So, it would be a non-feasible trial to follow everyone out. In fact, I would argue it's not really ethical anymore to run a trial where you just follow someone on placebo over a long time and watch their GFR go to zero and put them on dialysis when you know you have a molecule that can stop that decline.
We literally get patients calling the company now, aware of our data, asking if they can get early access to someone who's outside the parameters of our entry criteria. It's an uncomfortable position because we have so much data supporting the disease modification hypothesis.
That would, I mean, if you have a stable eGFR, you're not talking time to delay of dialysis, you're talking prevention of dialysis.
100%.
That's a trial you could potentially design or like an endpoint you could eventually follow up after accelerated approval and...
Yeah, I think it would be challenging, feasibly, to run a trial like that, given the data we've shown. But that was exciting about Dr. John Barratt, as you know, one of the key opinion leaders in the field presented on, is it only certain patients with IgAN who will progress? And actually, he showed data that all patients with IgAN will eventually end up on dialysis in their lifetime. So, my father's 81. I just saw him this weekend here in Boston. I hope he's not on dialysis in the next 10 years. That would radically change his life. I'm sure people in this room are aware of what dialysis does to a patient. That argues the paradigm that Dr. Brenner started to talk about in terms of the implications of Vera's data and atacicept, which is, if you're diagnosed with IgAN, you just had a biopsy, you're already on an ACE inhibitor, what does the doctor put you on first? And, they should really put you on a drug that stops GFR decline, that saves nephrons over time. And, we think the data that we have supports that kind of communication with regulators, with payers, and really all stakeholders.
Well, they'll probably put, as Rob said, they'll put them on maybe an SGLT2 for good kidney housekeeping, for lack of a better word, but something more specific to...
Yeah, I would be more specific or two. Yeah, I mean, good housekeeping. There is an important area of renal medicine that Rob can speak to more clearly that I would just call treatment of chronic kidney disease, CKD treatment. And it includes an ACE or an ARB, SGLT2 inhibitors in non-diabetic kidney disease, and a subset of patients with IgAN showed some improvement in their downward slope of GFR. So, there is some data in a pretty different patient population supporting that mechanism. And, endothelin receptor antagonists, as we heard from Eric Dube, really have demonstrated a role in that mechanism to further delay dialysis. But look, the secret's out. All of the GFR slopes go down except when you target the source of the disease. And, that's like it's night and day versus what's come before.
Hematuria. I'd love to ask you how your hematuria data compares to others, but nobody else has generated any.
I agree.
I can't figure out why. But can you speak to what it means empirically by itself?
Yeah, I'm proud to talk about hematuria in Boston, the world of Boston medicine. Pathophysiology, how does the disease work? Elevated BAFF and APRIL levels overstimulate B-cells and plasma cells. You get this Gd-IgA1 immune complexes. Those are the inciting injuries. How does it cause injury? They circulate. They land in the kidney in the glomeruli, which are these fragile little filters, and they cause inflammation. When they're inflamed, that's inflammation of the glomeruli. That's glomerulonephritis. That's what this disease is. And this perfect filter starts to let out protein. That's why we get protein in the urine, which shouldn't be there, but we start to see it. We also see red blood cells.
Which does it let out first, the protein or the red blood cells?
I would say patients present with either. Patients present with hematuria, or they can present with proteinuria.
Is there sort of a differential between what drives proteinuria versus hematuria in terms of inflammation versus fibrosis? Does fibrosis preferentially drive one inflammation?
Yeah, as a technical point, glomerulonephritis is active inflammation, whereas if you have proteinuria, that could be fibrosis of a kidney downstream. But, in this disease, patients present with either/or, and we're able to show resolution of glomerulonephritis. And, as we show an update in the fourth quarter of this year, we hope to show continuation of what we showed at a year and a half. We really don't expect a massive difference because the data is already really setting a new standard in the field, given what we showed at 18 months.
ORIGIN 3 .
Yes.
Enrollment started in June. Top line is guided for first half 2025 and potential launch in 2026. How is that going? Enrollment sites, it's kind of a competitive environment. You've got Novartis, you've got Otsuka. How easy are you finding it to enroll patients?
I would say we're the leader. It's challenging for others when we have the only at-home self-administered drug in phase III, the only ones in the B-cell modulator space that has that mechanism that's with randomized control trials. That matters to physicians when they consent patients.
The at-home part?
The at-home part definitely matters. These are young patients on average in their 30s with active family lives and work lives. Everyone knows how painful it was to get your COVID vaccine and wait to kind of be observed for an hour or 10 minutes even. You want to move on with your life.
This is a weekly auto -injector?
We have a weekly and subcu injections given by the patient at home.
Does it need to be refrigerated for travel?
One does refrigerate it. It's a very long shelf life. So, we're in a very strong position from a commercial supply perspective. And, this is a really well-validated modality for commercial biologics. So enrollment's going really well. We started last year. And , I'm very proud to say the Vera team has been able to meet each of its timelines since we've been public about three years ago. So, when we set out a timeline, we've met it and we're on track to do so again this year. So, we should be announcing full enrollment of the phase III trial in the second half of this year. We can be more granular when we get there. And then, that would enable phase III results, the 9-month results in the first half of next year and BLA filing at the end of next year. That's years ahead of the next BAFF APRIL inhibitor.
It's on the basis of multinational randomized control trial data, which frankly, you must have if you're going to trust proteinuria or GFR results. You can show proteinuria and GFR results on any hand-selected people that you pick out of a crowd that you know you're going to give them your drug. It's very easy for that drug to be confounded. We learned that from a variety of predecessors in the IgAN space. So, I would be extremely cautious about interpreting other people's data when it's uncontrolled data without a control arm. So, when people talk about our competitive space, we do not really consider those who have not even initiated a control trial a competitor. We think that Novartis is already delayed a year. So, they went into phase III with zigakibart or BION-1301. They acquired it from Chinook. They had 30 patients of uncontrolled open-label data. It's been already reported they're going to delay a year out.
So they've said data, I think, in 2026, I believe.
Versus 2025, which is where they were tracking previously.
Yeah. Have they had to resize the study based on what they said?
We don't speak for Novartis. They can speak to that.
They don't answer my questions.
And then, the other competitor I would highlight is Otsuka. They have an anti-APRIL monoclonal antibody. We think fundamentally that's not as elegant an approach as using native TACI because native TACI binds both BAFF and APRIL. We know in medicine when you hit half of a mechanism, the other half can upregulate and escape. So, you have escape or resistance. We don't have enough data to really understand if that's going to happen yet. They did run a randomized trial. We appreciate that. But they did it with an IV infusion in the clinic. So, they're taking quite a leap from going from phase II to phase III. Phase III is now moving to subcu. We understand that that's subcu that's observed for an hour initially.
So, you have to go in every month and have your dose given subcu by a clinician, observe for an hour, and then you come back the next month. You have to have an observation for half an hour for the duration of the treatment. We're not talking about a limited...
Is there some sort of safety?
Again, we don't speak for that company, but I think it's important to recognize that that's what they're doing in phase III. It's going to be a leap to get from what you study in phase III to a very attractive commercial profile, which we've had since phase II. I think that's coming into focus. Most important for us is that investigators and patients understand that. They do. That's why we're enrolling well. More stakeholders will recognize that at-home self-administration is really going to unlock access for a paradigm-changing drug.
What should we expect from the top-line phase III data as far as UPCR and other secondary endpoints? I'm assuming we're going to get hematuria as well.
Yeah, yeah. I think a continuation of what we shared. So, I've been specific for two-year data, which we'll share in the fourth quarter this year. If we have eGFRs that include the - 2 mL per minute per year, our hypothesis continues, which is GFR is the same as the healthy population. That's a huge win for nephrology generally and IgAN patients specifically.
Can you hit stat sig again at 36 weeks, do you think? You got more paper.
This is open-label extension. So, we don't have a comparison arm through two years. So this is really following the RC3 cohort.
I meant 36 weeks for ORIGIN 3 versus what you showed at ORIGIN 2. Can you show that again?
Oh, in ORIGIN 3. Oh, are you asking either expectations for ORIGIN 3? So, expectations for ORIGIN 3, the primary endpoint is we're borrowing what's already been established, which is 9-month proteinuria reduction of about 30%.
Yep. Placebo- adjusted.
Placebo- adjusted. It has to be placebo -adjusted. We've seen in other programs, you can have a placebo effect of about 20%. So, you need placebo adjustment in randomized control trials and drug development. It's very well understood by global pharma. So, I think expectations are that we will replicate in phase III what we did in phase II. We think that chance is very likely given the design of our phase III is extremely similar to our phase II. To the upside, if we have a significant GFR separation at nine or 12 months, we will be aggressive in speaking with regulators about is it worth continuing a blinded trial where you have a group of patients in a phase III trial who are declining in GFR beyond nine months to a year?
Remember, we already showed at 72 weeks, patients on placebo went down for the first nine months on GFR, and then they were switched to TACI 150 and they stabilized. That's a vision for patients. Remember, these patient volunteers are incredibly brave and they join our trials. They deserve the best balance of safety and efficacy we can give them. And, the closer we get to filing, the more that'll get recognized, I think, by regulators.
So, let's move to commercial now. Nephrologists are very comfortable with ACEs and ARBs. Everybody's used SGLT2s for decades. What do you think the biggest challenge will be to moving these B-cell modulators into first line, first reach? Just given nephrologists are conservative, they're very comfortable with these other drugs. This is a completely or relatively new class. I mean, they're familiar with BAFF, but some of them are familiar with BAFF. What's going to be the biggest challenge? Is it the cost? Is it the needle? Is it the community setting inertia? How do you see this for IgAN?
You know, next for us is commercial. It's really fun to talk about nephrologists in Boston. I trained with Ravi Thadhani, who is head of the program at Mass General. Nephrologists, I think, are some of the smartest doctors out there. And they're driven by data. They're driven by data. And they're not fooled by open-label data. They are driven by GFR data. And that's what they use. That's the information they give to their patient. Your kidneys are doing fine. There's no change. Or, your kidneys are doing fine. They're still above 60. And eventually, if the GFR is dropping, they're paying attention. So, activating the providers and making sure that not just the top KOLs, but all of the nephrologists are aware that there is a drug out there that can arrest GFR decline. That's a medical affairs and commercial effort.
The Vera team is extremely experienced in that. Rob ran medical affairs at Amgen for multiple renal launches. That's what we're gearing up to do next is really making sure that our commercial planning and commercial prep includes broad distribution of the information that we've already generated. And, we think that data set's just going to mature and strengthen as we have longer-term phase II and then ultimately phase III data and a label that supports self-administration at home of 150 of atacicept that is backed up by a phase II study with two-year GFR data. I wouldn't want to launch a drug without two-year GFR data to nephrologists. They're smart. So you got to show them GFR data, show them GFR data from a well-designed trial. So these are all the day-to-day for the Vera team. It's exciting to be at this stage.
We've got a lot of interested parties given the strength of the data.
So, given the prevalence of the disease, well north of 100,000, probably 150,000 patients in the U.S., that doesn't really sound like a specialty launch. It sounds like a big specialty launch. Is that correct? Are those patient numbers correct? And then what sort of sales force would one need to field to catch all those community nephrologists who are seeing IgAN patients?
Yeah. Great question. So, I'd start with the sales force. So, we already know from the first-to-market in the field from Calliditas is Tarpeyo and from Travere is Filspari, roughly what a sales force is required to touch the number of just to contain this to the U.S., the number of known nephrologists in the U.S. So, we're not providing specific information about our planned commercial force, but I would say that those estimates aren't far off. The question then is, how broad is that effort? How serious is that effort? And we have plans to really make sure that we're very well prepared. And we optimize pricing and access and we ensure broad distribution of a disease-modifying therapy.
Optimize pricing? What does that mean? What is the price?
There's always a balance between price and access. We are going to optimize to make sure that we.
Is there a proxy, as you think of sensitivity analysis, a proxy in terms of disease? And obviously, pricing will depend on ultimate effect size. But if you're preventing dialysis, right, that's a pretty compelling value proposition. There aren't a lot of proxies to a 150,000 patient population where you prevent disease progression. But, I'm sure you've thought of a couple with price tags of.
Yeah. So...
Work with me here.
Yeah. I'm not going to give you a lot. But, I will say that in our business, we have this is one of the more interesting parts of biotech is you have all sorts of analogs that you can draw from. And in IgAN, we can draw from two drugs that have recently launched that are non-disease-modifying that have different-looking data sets. And they have prices. So, there's...
You should be thinking north of that.
Those are interesting analogs to look at. And then, there are other analogs that are outside of the disease area that are disease-modifying that we can also use. So, we would triangulate it. And, I wouldn't want to guide you to a stepping stone around price. But I mean, I think we can say generally that a disease-modifying therapy of this magnitude would support premium pricing.
Got it. And then as you think of potential lifecycle management additional indications, you talked about developing a once-monthly dose, which could be valuable and competitive. And you do have a phase III ready program for lupus nephritis. Given your cash levels right now, how do you think of once-monthly? How do you think of lupus nephritis?
Yeah. Great question. So, three important parts. We are in a good position right now. The first priority is to win an IgAN. Winning an IgAN means that we bring the pivotal trial to successful completion. We get this drug to market. That said, the data probably support exploring other IgAN patients who don't simply fit within our I&E criteria. The street should expect us to come back later on and describe how we might expand the addressable market for atacicept within IgAN on its own. So, that's thing one. Thing two is monthly dosing. We think that weekly dosing, self-administered at home, is an extremely attractive profile. We recognize in a variety of disease areas, there are some patients who want longer dosing intervals. We've modeled that. We see it's highly feasible.
We think it would be very feasible for us to bring a monthly dose to market well before others might. So, I think that's another component. And then third, thank you for saying so. Our strategy from the very beginning with atacicept started just with B-cells as a target for autoimmune disease. This wasn't all about IgAN in the beginning. It was, how come we still use steroids in immunology? It drives me nuts as a physician to know that we're still handing out steroids in a variety of autoimmune diseases like systemic lupus, lupus nephritis, Sjögren's.
I mean, as a physician, when I look across how many areas of medicine we still use a sledgehammer across the immune system with all of the known acute and chronic side effects that can be quantified by milligrams of prednisone, all from RA data that's over 20 years old, that's what motivates us at Vera. So, we've presented five disease indications in our pipeline that we think there's relatively near-term potential: systemic lupus, lupus nephritis, Sjögren's, myasthenia gravis, and primary MN. We think the amount of dose finding that we've done justifies late-stage development and really each of those therapies. So, the street should expect us to come back with more specific plans on how we plan to expand the opportunity.
Great. Well, we are at time, Marshall. Thank you so much for the insight. Looking forward to that 96th week update, potentially at ERA or ASN. Those are the two big meetings. And then first half 2025 pivotal data.
Great. Thanks so much for the opportunity too.
Thank you, Marshall.
Bye.