Ready? Yeah. So, welcome to the Cantor, Global Healthcare Conference. I'm Pete Stavropoulos, a biotech analyst with Cantor.
With us, we have, Vera Therapeutics, a company I cover, and I'm pleased to introduce, Marshall Fordyce and CEO, and, Robert Brenner, CMO. Welcome.
Thanks so much, Pete. Great to be here.
Let's start off with a brief intro for for those that don't know who you are. What's number?
I'm Marshall Fordyce. I'm the founder and CEO of Verra Therapeutics based in San Francisco. We are I've been a public biotech company now for about four years. Made great progress with our lead product candidate called Atacicept, which is an immune modulator for B cell driven diseases. We've recently read out our phase three trial in a major unmet medical need called IgA nephropathy, and we are now planning to file for a BLA at fourth quarter this year.
So very shortly, we'll file our package and expect to be on the market mid next year. So really exciting time and have been building the commercial profile of the company in the recent years.
And I'm Rob Brenner, I'm Chief Medical Officer. I've been with the company for coming up on two years. It's been an amazing journey. I'm a nephrologist by training and I think the kidney community is appreciating that we're on the precipice of a new era in our ability to manage patients with IgA nephropathy and other forms of autoimmune kidney disease.
It's a super exciting time both for patients, for providers, and certainly for all the employees of Era.
Yeah. So, you know, when I was doing due diligence in the IGAN space, I remember in, it was probably around November 2023, I had spoken to a KOL, a nephrologist, but not an IGAN KOL, but looking at acute kidney injury. And I had asked him about your thirty six week data and, you know, his perspective on IGAN. And he was a little bit dismissive at that time, meaning like, you know, IGAN, you know, kick the ball down the road and not that big of a deal. And and and then you had your seventy two week data in January.
And then I spoke to him again in March after that, and he had a completely different perspective and a different tune. And he was impressed by your eGFR data, seventy two weeks. And so, you know, first, you know, the exact what is the burden of disease? You know? And is it something that you just kick down the road?
That's number one. And then number two, are the more, let's say, a community based nephrologist becoming more and more aware of iGAN and and your drug?
I'd love to start and then Rob, as the nephrologist on the stage, talk about this. But, this is a large unmet need. I'm a physician By background, in The United States alone, there are one hundred and sixty thousand patients with biopsy proven IGAN, of which at least half have high risk of disease progression. This is a significant unmet need.
Diagnosis on average is delayed, but it happens currently at the age of 35 years old. We now have seen, Pete, in our data and others' data that if you're on placebo with that profile, you're on dialysis before the age of 50. So this is an urgent unmet need, and we're the first and only to show that on a TACCEPT over two years, you can stop kidney function declines measured by GFR, and that data set is not just understood by KOLs, it's understood in the field. Last week I was in Florida talking to nephrologists who were not normally on stages, and they're very aware of our Phase II data. So, that's an exciting moment for us. Rob, any other thoughts on the GFR data?
Yeah, it's in the history of drug development in kidney disease, we've never been in a situation where we have a population of patients who actually had a kidney biopsy and have been found to have a specific kidney disease where we've been able to intervene with an agent that changes the course of the progression of their kidney function from one that has them on pace, to Marshall's point of maybe needing dialysis in a decade, to one where they could potentially live the remainder of their life without the need for a transplant or to go on dialysis. It's never happened before. And now we're on the verge of being able to provide a drug or a new class of drugs, are able to do that for patients, starting with IgA nephropathy. And I think it's the magnitude of the evolution in a data package that is now sitting in front of clinicians that they've never seen before that does create this opportunity.
So, you know, you just mentioned 160,000 patients in The US, you know, but when you look at different companies and, you know, you look at the academic literature, you know, when I go to academic literature, it's about a 112, where I put it. But I also see, Novartis had about a 185,000 patients in The US, and Otsuka published a paper, I think late last year, showing about 200,000. And so, what's your perspective on that? Are you being conservative or?
We're generally conservative. We do think that this disease is underdiagnosed. So, you know, somewhere in the middle is 160,000 feet, and as you can do pretty simple math with current pricing, that's, you know, a 10 to $20,000,000,000 market. So, it's a very large opportunity commercially, but more importantly, we're focused on identifying those patients beyond just those who currently have biopsy, but also pushing out. When you bring a transformative new therapy to patients, diagnosis tends to increase because there's a reason to diagnose and you can do something about the disease.
I've seen it in prior work in infectious disease. We think that's the situation again here. Okay.
So, you know, touching on entacacept, it's designed to address the disease from immunological standpoint. Can you just walk us through the therapeutic hypothesis, which you've proven with your phase two and phase three data? And that we'll get into in a moment. And from a mechanistic point, why the drug has disease modifying properties while not compromising safety. Sure.
Bob, do want to take it?
Yeah. So what is IgA nephropathy? It's a B cell disorder with kidney pathology. So this is a disease that has a its hallmark is a formation of an immune complex. There's an autoantigen which is recognized by an autoantibody.
Those immune complexes circulate. They deposit in the kidney where they drive inflammation, fibrosis, nephron loss, and kidney failure. But we know that both components of the immune complex originate in the B cell. So the B cell is the cell that we want to intervene against. How might we do that?
It turns out that there are two cytokines that act as the energy source for B cells that are fueling the production of immunoglobulins. A tachycept is an example of a rationally designed biologic agent. It has an extracellular binding domain for both of those two cytokines. One is called BAF, one is called APRIL, and it's got picomolar binding affinity for both of them. It's a soluble receptor that we can administer to patients.
They can administer themselves once weekly at home using an auto injector, low volume and we can reduce the amount of BAF in April. And when we do that, we reduce the expression of antibodies, we reduce the generation of the immune complex, we reduce the inflammatory burden in the kidney, we lower proteinuria, a marker of disease, and we can stabilize GFR. So, that's the mechanism of the drug and those are the key readouts that we've seen through the phase two and now into the phase three program.
Yeah. The hypothesis that we've proven out is target the source of the disease and see everything downstream actually resolve in terms of inflammation, proteinuria, and GFR. And that's that's been very exciting to see.
Yes. So, you know, you have shared multiple data sets. And, you know, key for me is that there's consistency there. Alright?
Phase two to phase three. In fact, you know, you didn't see a degradation of signal. It actually increased. So the first thing to touch on is, the patient population that you enrolled. A, were there any differences, and also when you compare to other studies, such as SIBI?
Yes. So first, internal consistency within the Atacicept program from Phase II to Phase III. In the Phase II and Phase III programs, we enrolled patients who had same age, they were about 40 years old. They had the same amount of, kidney function remaining, about a GFR of what we call 60 mls per minute, which means they've lost 40% of their endogenous kidney function at the time they enrolled. They had the same vintage from the time that they were diagnosed with the disease of a couple of years.
They had the same amount of protein in their urine. They had the same ethnic background and we know that IgA nephropathy is overexpressed in patients of Asian descent, so that was accounted for. The one difference in the VERA program between Phase II and Phase III was the amount, the number of patients who were receiving SGLT2 inhibitors on top of an ACE inhibitor or an angiotensin receptor antagonist. In Phase II, it was fifteen percent. In Phase III, it was fifty percent.
What was super interesting is that the presence absence of an SGLT2 inhibitor had zero impact on the results that we've observed in the clinical program.
Okay. When you do look at the data, Phase II to Phase III, your Phase III was in line with the protocol versus the ITT. And so, you know, just walk us through, you know, how you accomplished that. And when it comes to safety outcomes, particularly infections, what were the observations in phase three?
Yeah. I the phase two program, studied three different doses of TACCEPT versus placebo. There were 30 odd participants in each cohort, and the proteinuria reduction was robust, well north of what the FDA is looking for, which is a thirty percent reduction compared to placebo. In the Phase III program, in two zero three participants randomized to placebo or the commercial dose, will which be one hundred and fifty milligrams administered as a one ml volume, once a week by patients at home. We saw a forty six percent reduction in proteinuria, in the active group and overall a forty two percent placebo adjusted reduction, well north of the FDA thirty percent threshold.
Those results are as impressive, if not more impressive than what we saw in Phase II. I think it has to do with the sample size, I think it has to do with the effectiveness of our ability to have people follow the protocol as it's written and not deviate. So I think it's a very good representation of the magnitude of effect that patients will see commercially once the drug is approved.
Alright. And, you know, at ASM last year, you did present, ninety six week data, from your your phase two. And, you know, can you just discuss those data and, you know, what gives you confidence that you're actually gonna replicate it in phase three?
Yeah. Great question. The most important thing that we measure in patients with kidney disease is a measure of their function. What we use is something called glomerular filtration rate or GFR. When people are young and healthy, they've got a GFR of about 100 mls per minute.
And when patients need kidney replacement to stay alive with either a transplant or dialysis, they have about 15 mls per minute or less, so only 10 or 15% of their endogenous kidney function. People, once they reach the age of about 40, lose about one mlmin per year just as part of the normal aging process. So unfortunately, looking around the room, that's what all of us are experiencing today. The ninety six week data that we showed was this long term experience of patients receiving Atacucept at home. They entered with a GFR of about 60, so they're already about 40% reduced from completely normal, but they've got a biopsy proven kidney disease, and they're losing about six mls per minute per year, even when they're on an ACE inhibitor and an SGLT2 inhibitor, you know, maybe even an ERA or steroid.
So that means they're losing 10% of their remaining kidney function a year, and to Marshall's point, they are on a track to needing dialysis or a transplant within a decade. What we showed is that over the ninety six weeks, over two years, they had a GFR slope of minus 0.6 mils per minute. That means at that rate, if they're 40 years old, they're going to live the rest of their life without needing dialysis or a transplant. That's how transformative the dataset was and is unprecedented, as I said earlier, in the history of kidney drug development. What do I think for phase three?
Well, we've seen the GFR data for the interim analysis at thirty six weeks. We haven't disclosed it publicly because the FDA has asked us not to. The FDA has seen the results. I will tell you the only reason we're not disclosing the results as now is because the FDA has asked us to. There'd be no other reason for us not to disclose it.
And my expectation is that the GFR results from the Phase III program, when it completes, will look very comparable to what we saw in Phase II.
Excellent. And so you are going to show some data at ASN? I'm assuming you are. You know, what should we expect to see and what should we be looking out for there?
Yeah. In in my view, there are four parameters that we look at to provide evidence for true disease modification in IgA nephropathy. First, we look for a reduction in sort of the burden of immune complex. We can measure the autoantigen. It's a form of IgA called Galactose Deficient IgA1.
We can measure that and we showed in Phase II that there was a two thirds reduction in the GDiJ-one. So I would hope that we'll be able to disclose the GDiJ-one result at ASM. Next, we look at the burden of inflammation in the kidney in people who have IgA nephropathy, and there's an easy way to do that. We can use a point of care device. We can use a urine dipstick for hematuria, for blood in the urine.
And in the Phase II program, we showed that there was an eighty percent reduction in hematuria in patients who had blood in their urine at baseline. To me, clear evidence that we're having an anti inflammatory effect and it begins early when you start using the drug. Then we can measure proteinuria, which is the surrogate endpoint that the FDA uses to grant accelerated approval. And as I said, the threshold is a 30% or larger reduction compared to placebo. And then the fourth component is the GFR.
And so we've shown for the Phase II the quartet of findings that all are improved, that indicate true disease modification. We'll show as much of that quartet as we can at ASN, but still to align with FDA expectations of what we disclose.
Okay. You know, after you did announce the phase three data for UPCR competitor program from Otsuka, they also presented at ERA their phase that that are in else?
Yeah, I think as much as we would like these trials to be identical and superimposition of one another, they're not. There are some meaningful differences in this study. The high level take is that the results from a tachyceptor incredibly encouraging. And I think the superficial results from Otsuka's program are also very encouraging. I think until we get to the point where we have final results that make it into a label, make it into a peer reviewed publication.
There may be some movement a little bit with each of the datasets. But Verra is incredibly confident that the results that we've demonstrated both in Phase II and Phase III reflect a new era for future management of this disease, and the future has never looked brighter for patients with IgA nephropathy.
Some movement, in data sets. What do you mean by that?
If you look at the precedent in this space for data disclosure followed by publication and approval labels, there's not a one to one concordance of what the preliminary release data look like compared to what's presented. And so my expectation is what we saw in Vienna may not reflect what is actually written in a label or in a peer reviewed manuscript. That's my only point.
Okay. So you do have extend. It's the open label extension for for Origin. Just give us a sense if you can, if not quantitatively, but qualitatively how the rollover is going.
It's going great. We've been enrolling that program since the end of last year. It is an opportunity for any participant in our clinical program who's completed a study to have an opportunity to receive a Tacicept in an extension program until it's approved in the region in which they reside. We feel that we have an obligation to do that for patients. It's also provided an opportunity for us to have some real world experience with our auto injector, which we're going to have when we launch.
So that's been a nice opportunity. Enrollment is going great. Programs moving forward.
I might also highlight what we shared last year, which is when treatment with a tachycept is interrupted, the disease comes back, and we measure that by the recurrence of the immune complexes and a continued decline in GFR. So this data set's gonna be pretty interesting to show not just the continued chronic dosing, but what happens after interruption and reinitiation of the drug. Incredibly important for physicians to see what is the risk benefit profile of taking this drug and what what an interruption might mean.
Alright. So, you are re enrolling patients from the phase 2b, you know, that had that drug holiday.
Yeah.
What's the enthusiasm to come back?
Been high. Very high. Yeah. Yeah.
Alright. And, you know, are any of the patients enrolled in Xtend? You know, you did mention it either being with the auto injector. And so, is this the majority or is this
It's not the majority, but it's a it's a cohort of the program where we have the ability to provide them with auto injector, and it's been a smooth transition.
Have you gotten any feedback in terms of, the use of the auto injector from patients or physicians who are treating those patients?
I think it's been an advantage for patients to have this device to use at home the way that other auto injector biologics are used. A low volume one ml once a week self administered, algorithm is about as successful an approach we've had for any biologic drug in the history of our planet. So we're really confident as we look forward to the future world where we're providing this commercially for patients.
All right. So I guess the next major step, for the program is the BLA filing, and, followed by an approval. Do things sort of remain on track for 4Q? And, are there any gating factors? And is there any reason why we should, not expect priority review?
Yeah. Things are going great. You know, we we locked our database at the May. Team has had their head down, focused on executing. We're in the final stages.
There are no major gating activities before we submit. Feel really good about the quality of the application and really grateful for the hard work of all of my colleagues back at Verra who it's been a summer of Verra for a lot of us, and that's what it should be because patients are waiting and every day counts. So we're really close. And fourth quarter is coming pretty soon.
Is there any reason you should not expect a priority review? Did you mention it?
We're planning for it.
No. All right. So, you know, how are you thinking about the label? You know, I've had some discussions on whether or not, the agency will use a filsparine tarpeo, accelerated approval label, as sort of precedence. So restricted to one point five grams per gram.
Patients restricted to patients who have one point five grams per gram. Do you expect that to be the case? Or, you know, do you think the agency is actually going to take into account all the data that's been generated to date, including safety and, you know, also taking into account the mechanism of action?
Yeah. I think the agency is going to look at the data for Atacicept with fresh eyes. What may be viewed as regulatory precedent within the IGAN space that's tethered to other mechanisms with other datasets, I don't think may be a great predictor of what's going to happen, for VERA and for ATACYCEPT. The quality of the narrative and the dialogue that we have with FDA is really high. I've been doing this for a long time.
I have a lot of respect for our review division. We have a great relationship with them. The conversations have been extremely collaborative and productive, and I'm cautiously optimistic that, we'll be in a position to have a very competitive label out of the shoe.
Right. Looking forward to that. You know, so what are some
of the ongoing early efforts, commercialization efforts? You know, it looks like you have experienced leadership in place, you know, including the medical affairs commercialization. You know, how are you thinking about this, and, what are some of the ongoing activities, to prepare for?
I I can tell you that, we've been preparing commercially for a good long time. We're focused on The US launch. There are roughly 8,000 nephrologists in The United States. We've got sales leadership now in place after phase three readout. We have cited the structure in terms of the team, and we've been really engaged with the nephrology community for a very long time.
So early early feedback is that, Vera and the Atacucept data are very well understood, by the nephrology community. We have great awareness, and I think that should be expected for a company, that is entirely focused on its first launch, and can can credibly say that, we're committed to the nephrology community and bringing new patients new new therapies to patients. So it's been a it's been a major focus for us. We're thrilled by the talent that's attracted to the opportunity that we've been building.
I I don't know if I missed it or while you were discussing it, but you're also, I think, know, sort of in touch with the patient community.
Yeah. I mean, we've been doing this for a long time. I I've been going to the IGAN Foundation, meeting every year. We've been, deeply engaged with them and, was there in Chicago over the summer. So, you know, the pioneer study, Pete, that you've been tracking with us to to go beyond our phase three protocol and say, what are the other IGAM patients who could benefit from Atacicept?
You know, part of the cohorts in in PIONEER come directly from my conversations So we've been deeply engaged with this this community and, you know, this is this is how you transform medicine is to stay super focused on patients. And and I think, you know, in every area of medicine, there are advocates at varying forms, and I think the IGAN Foundation and the advocacy community around this this disease has been, gaining momentum. It's been, you know, an incredible effort to see, really poised to change medicine in the way that, doctor Brenner has seen and and, and been a part of.
Excellent. So, you know, I guess one thing, that investors do wanna see is, if it's feasible to do a monthly dosing. And so I do know that you have a study that's ongoing. I believe it was initiated back in May. Are there any updates on this program? And, or when can we expect some updates?
Yeah. We, shared last October that we plan to do a dose range finding study to identify a preferred dose for monthly. That study is up and running, it's enrolling. And as soon as we feel like we've identified what the right dose is, we'll be able to come back to the market and talk about what the cadence will be to get that information in the label. It's a little early to do that and I don't want to show too much of my hand to our competitors because it's such a dynamic space.
With that, I would also remind folks that in January, we announced the acquisition of VT-one hundred nine. We did a license from Stanford. This is a novel fusion protein that we think has the potential for a very differentiated product profile. And so when I think about how we're going to play in this space for decades, how we're going to win, part of it is with the tachycept and part of it is to harness the potential in VT-one hundred nine and to use those in an integrated way to have a dominant position for an extended period of time.
Yeah. So I think both of those programs are exploring longer dosing interval, I think it's an interesting thing to focus on when first you begin with, does the drug work well? Does it have a transformative outcome for patients? That's efficacy. Then you've got safety, which looks similar to placebo in both phase two and phase three, and then the patient experience, and we'll be on track to be the first and only mechanism of action on the market next year with an at home self administered small volume auto injector.
That's a phenomenal profile between does it work, is it safe, and does it is it a convenient thing to take? It's a few seconds once a week. We've had 90% retention over two years with that profile, and that's a that's great position for us to be in.
Yes. Okay. I guess so. We have two minutes left. Just quickly touch on, you know, pipeline interproduct potential and, PIONEER, where are you with that study?
Yeah. I I let me speak to this just briefly. From an overall perspective, we are focused on the nephrology community, and that's why we're pursuing IgAN first. PIONEER captures additional IgAN populations. We're moving into membranous nephropathy as well as other autoantibody driven glomerular diseases like FSGS and MCD.
So conceptually, think about Vera as focused on the patient population and the physicians who serve them. We think that's the highest value in terms of what we build in terms of near term value. But without a question, there are rheumatologic, neurologic, dermatologic indications for a BAF April inhibitor that has this type of profile. But maybe an update on progress in PIONEER.
Yeah. Actively enrolling, enormous appetite for the program, and it's super exciting. I love the fact that after our Phase II data, really leaned in, dedicated resource to looking at kind of all comers with IgA nephropathy, not just those individuals who meet Phase II, Phase III entry criteria. That hasn't been done before. Think we'll address many questions when we get to commercialization and how phenomenal it is to think about using this drug in patients with other forms of autoimmune mediated kidney disease.
We're really kind of leading, with the community and and thinking about what future management's gonna look like, and and let's go get some data.
Alright. You know, and I assume you're you're leveraging the sites, same same physicians, treating, for audience?
Yeah. A lot of synergy, a lot of, from a you know, how are we managing our capital, being good stewards of that capital. It's a very efficient program.
Last question, if we're sitting here a year from now, what would you like to say that you accomplished?
Transforming medicine. We've got to have a have a new drug on market. We expect to see this very well received and start to open up the pipeline in a year. So it's a very exciting position for us.
All right. Well, thank you very much for participating in our conference and the fireside chat. And looking forward to BLA filing and approval.
Thank you. Thank you, Pete. So Good.