All right, let's go ahead and get started. Welcome, everyone, to the JPMorgan Healthcare Conference. My name's Anupam Rama. I'm one of the Senior Biotech Analysts here at JPMorgan. I'm joined by my squad: Malcolm Kuno, Priyanka Grover, [Ruhi Phiny] . Our next presenting company is Vera Therapeutics, and presenting on behalf of the company is CEO Marshall Fordyce. Marshall.
Thanks so much, Anupam Rama. Good afternoon and welcome. I'm Marshall Fordyce, the founder and CEO of Vera Therapeutics, and on behalf of the entire Vera team, I'm really pleased to present you an update here at the opening of 2025. Vera's mission is to lead a paradigm shift in the treatment of patients with autoimmune disease, from a standard of care based on steroids and B-cell depletion to a more targeted modulation of the immune system and free patients from the burdens of their disease. I'm thrilled to share with you today our substantial progress towards that end. Before we get started, I want to remind you that my remarks contain forward-looking statements under the Safe Harbor Act, and as such, we present this disclaimer regarding at-risk statements.
Our lead product candidate is Atacicept, a potential first and best-in-class dual BAFF/APRIL B-cell modulator, currently in phase III pivotal trial for patients with IgA nephropathy or IgAN, and with much broader potential to change how we treat a wide variety of autoimmune diseases. IgAN is a serious progressive autoimmune disease that affects young people and causes rapid loss of kidney function and ultimately kidney failure, requiring dialysis or kidney transplant, a life-altering and cost-intensive outcome. Atacicept is the first and only molecule in development to demonstrate in a global placebo-controlled randomized trial that over two years, patients taking Atacicept have kidney function similar to healthy individuals without a biopsy-proven kidney disease. eGFR normalization over two years suggests that chronic dosing with Atacicept might achieve a functional cure for these patients.
Last year, Atacicept was granted breakthrough designation by FDA, and our two-year results were published last quarter, simultaneously with the late-breaking presentation at the American Society of Nephrology Kidney Week. Atacicept is the only investigational drug being studied in both phase II and phase III as an at-home self-administration, 1 cc subcutaneously once weekly, and over two years, 90% of patients were retained on that regimen. B-cell modulation represents a treatment paradigm shift for autoimmune diseases, and dual BAFF/APRIL inhibition has non-clinical and early clinical validation in a wide variety of autoimmune conditions, and today, I'll highlight Vera's near-term clinical development plans beyond IgAN. This year, we're focused on our phase III primary readout, which reads out next quarter, preparing for a BLA filing in the second half of this year, commercial launch in 2026, as well as the expansion of our pipeline. Atacicept has best-in-class potential for IgAN.
Among a variety of approaches and development for treatment of IgAN, dual inhibition of BAFF and APRIL with Atacicept has established a high bar for safety and efficacy over a two-year period. Of the four B-cell modulators in phase III, Atacicept is anticipated to be first to market among the two BAFF/APRIL inhibitors and one of only two to be studied in a controlled dose range finding study in phase II. It is the only program to study at-home self-administration. As the only program with two-year data in phase II, we anticipate being positioned with the most robust dataset at commercial launch. Vera today is in a strong position financially with pro forma cash of $677 million and 63.4 million shares outstanding.
Dual BAFF/APRIL inhibition has gained increasing validation as an attractive target in a variety of autoimmune disease, and Vera has created broad optionality to expand our clinical investigation of Atacicept to other autoimmune kidney diseases and beyond. Last October, we shared our current activities to expand Atacicept beyond phase III ORIGIN population to a broader IgAN population, where prevalence in the U.S. is estimated to be about 160,000 patients. We have initiated the PIONEER study used to explore Atacicept in several non-IgAN autoimmune kidney diseases, including membranous nephropathy, focal segmental glomerulosclerosis, or FSGS, and MCD, or minimal change disease. Further, dual BAFF/APRIL inhibition with Atacicept has the potential to treat autoimmune diseases in other areas of medicine, including hematology, rheumatology, and neurology, in which a shift from steroids and B-cell depletion to a more targeted modulation could provide positive risk-benefit and substantial impact on patients' lives.
Vera has multiple potential value-building catalysts in 2025. Next quarter, we anticipate reading out our primary endpoint of our phase III pivotal trial, ORIGIN 3, and a BLA filing in the second half, enabling commercial launch in 2026. In addition, initial clinical data from our EXTEND and PIONEER trials, which I'll describe, will read out initial results later this year. Atacicept's mechanism of dual BAFF/APRIL inhibition has broad therapeutic potential and are substantially driven by abnormal B-cell function. Atacicept inhibits the two known circulating cytokines, BAFF and APRIL, which are both important for the survival and maturation of the B-cell lineage. Elevation of both BAFF and APRIL are found in patients with IgAN, lupus, and other autoimmune diseases, and both play a role in disease pathophysiology driving autoantibody production.
In preclinical models, dual inhibition of APRIL and BAFF have been shown to be more potent than blocking BAFF alone or APRIL alone, which may translate into more robust and sustained B-cell modulation and approaches to B-cell modulation in autoimmune disease. Inhibiting both known B-cell signals minimizes the possibility of signal escape, in which a compensatory increase of the uninhibited pathway reduces potency or durability. Atacicept is a nice example of rational drug design. It's a fusion protein that makes use of the native receptor, unaltered, TACI, bound to an inactivated Fc domain of IgG1. It has low nanomolar affinity to both BAFF and APRIL, as expected from TACI's natural role in B-cell biology, and a half-life of approximately 35 days in humans.
IgA nephropathy is a B-cell-driven autoimmune disease, and therapeutically, we hypothesized that by inhibiting both BAFF and APRIL upstream of the dysfunctional B-cells that drive disease, we could cause a reduction in disease-causing autoantibodies and relieve downstream kidney damage that ultimately leads to kidney failure in young patients. Therefore, we designed the phase II-B ORIGIN study to determine whether atacicept's known effect on the upstream causes can translate into improved kidney function as measured by multiple measures: reduction in proteinuria and stability, ultimately, of estimated glomerular filtration rate, or eGFR, which is what your doctor measures to measure your kidney function in the clinic. The phase II-B ORIGIN trial is a multinational randomized double-blind placebo-controlled dose-ranging study evaluating atacicept versus placebo, empowered to demonstrate a statistically significant difference in proteinuria.
Key inclusion criteria include both adults with biopsy-proven IgAN with a minimum GFR of 30 who are optimized and stable on RAS inhibition with or without SGLT2 inhibitors and still producing over 0.75 g of proteinuria at screening. The randomized phase was 36 weeks, during which three doses of atacicept were compared to placebo, and then all subjects were switched to atacicept 150 mg for up to 96 weeks, representing the longest duration of a study of a B-cell modulator and IgAN in a phase II trial. Importantly, of the 116 subjects randomized and treated, the discontinuation rate through 96 weeks, or roughly two years, was low, and 90% of the study population completed the full study.
Now, by blocking BAFF and APRIL with Atacicept, we would expect to observe four downstream effects: reduction of immune complexes as measured by Gd-IgA1, or galactose-deficient IgA1, the autoantigen. Resolution of nephritis as measured by hematuria, which is what nephrologists use to assess inflammation of the kidney and glomerulonephritis . Reduction of proteinuria, a sign of glomerular dysfunction associated with kidney function decline. And stabilization of kidney function as measured by GFR. In totality, such evidence would support a clinical profile of disease modification. And that is what our clinical trial results demonstrated through a duration of two years. Galactose-deficient IgA1, the autoantigen. Atacicept reduced it by 66%, a degree of reduction substantial enough to normalize Gd-IgA1 in almost all patients receiving Atacicept 150 mgs. Hematuria, the clinical measure of active glomerulonephritis , resolved in 75% of patients.
We observed statistically and clinically significant reductions in proteinuria, which through 96 weeks showed a robust 52% reduction. Remarkably, in these high-risk patients, kidney function as measured by GFR remained relatively stable through 96 weeks, with an annualized GFR slope of minus 0.6 mL/ min/ year. In totality, this quartet of findings supports a clinical profile of disease modification. The natural history of these patients with IgAN on current supportive care shows an inexorable decline in kidney function of roughly 6 mL per minute annually, leading almost all patients to kidney failure in their lifetime. In our trial, Atacicept-treated patients had an eGFR slope consistent with this general population without biopsy-proven kidney disease, a slope at which over decades end-stage kidney disease is not reached.
The x-axis on this figure represents only two years, and if you think about the average age of a patient at 35 years old, we're hoping for decades of stable kidney function. Halting kidney function decline in this population is completely novel in the IgAN field, and the implications for young patients facing dialysis are profound. Draft KDIGO guidelines currently call for agents that can target the source of the disease and deliver an annualized slope of less than one. Currently available therapy, both supportive CKD therapies such as SGLT2 inhibitors, steroids, or endothelin receptor antagonists, have not yet demonstrated that treatment effect. Thus far, we have shown the results of chronic dosing of Atacicept over two years. However, in our Phase II ORIGIN trial , after 96 weeks of therapy, all patients were asked to discontinue Atacicept.
A safety follow-up visit was performed 26 weeks later, providing an opportunity for us to assess some measures of disease after discontinuation of therapy. This is data that has not yet been publicly shown. As expected, after discontinuation of atacicept, a rapid return to disease progression was observed. We observed a pronounced increase in Gd-IgA1 of over 100%, along with a concomitant decrease in eGFR, a return to the natural history of eGFR decline of about 4 mL/min/ year in these high-risk patients. These new results underscore a drug treatment effect and support the paradigm of chronic treatment of atacicept in IgAN patients. Our phase III ORIGIN pivotal trial is progressing very well. ORIGIN 3 is a multinational randomized double-blind placebo-controlled trial comparing atacicept 150 mgs to placebo with a primary endpoint of proteinuria at nine months and a secondary endpoint of eGFR at two years.
In both phase II and phase III, Atacicept is studied as an at-home self-administered 1 cc subcu injection once per week. Entry criteria are very similar to phase II, and Vera has utilized the global experience in phase II to rapidly progress into phase three and make use of operational efficiencies. Last year, we announced full enrollment of our first 200 subjects, and we're on track to read out the primary endpoint just next quarter. In addition to our registrational program in IgAN, Vera has moved rapidly to expand the exploration of Atacicept, and we've initiated a longer-term study called ORIGIN Extend, which provides long-term access to Atacicept for all ORIGIN volunteers. Because of the pause in chronic dosing between our registrational and enrollment and this extension study, we expect to be able to provide further clinical profile of patients before and after reinitiation of Atacicept.
In addition, Atacicept is being studied in addition to the weekly dosing interval, which has demonstrated an attractive use profile of over 90% of patients continuing self-administration on a weekly basis. We will further explore Atacicept's potential for other administration formats, given its 35-day half-life, and we're conducting a monthly dose-finding study this year to explore extended dosing. Much broader, the rationale to study Atacicept in additional autoimmune kidney diseases is based on the emergence of substantial clinical evidence that several kidney diseases are driven by autoantibodies against a variety of antigens. In the case of IgAN, that antigen has been determined to be galactose-deficient IgA1. In the case of membranous nephropathy, anti-PLA2R antibodies are associated with disease severity and progression in the vast majority of patients, and the reduction of anti-PLA2R antibodies is associated with a slowing of disease progression.
More emerging evidence suggests a similar paradigm of autoantibodies and the glomerular antigen nephrin, suggesting an attractive target for certain patients with FSGS and minimal change disease. We've initiated the PIONEER study of phase II basket trial designed to assess Atacicept's potential benefit in IgAN patients who did not meet our phase three entry criteria, and specifically moderate and low-risk patients: patients with low eGFR, with high proteinuria, adolescents, and post-transplant patients with recurrent IgAN who may benefit from Atacicept treatment. PIONEER also expands our investigation of Atacicept into new autoantibody-driven nephritic diseases that I've just described, such as MN, FSGS, and MCD. Initial clinical data from these populations in PIONEER are anticipated later this year.
Following the success of our phase II ORIGIN trial in 2024 and momentum into 2025 with our phase III pivotal trial readout and BLA filing, we have been building Vera's capacity and extending our leadership position as we continue to innovate in the B-cell modulation space. Current approaches to modulating B-cell biology in the setting of autoimmune disease include monoclonal antibodies that bind BAFF or APRIL alone, and Fc fusion proteins that utilize the TACI receptor, like Atacicept or make use of TACI receptor mutants. Currently, Atacicept has the longest duration of B-cell modulator data to date, and IgAN and eGFR stabilization sets a high standard for other approaches. The known biology of B-cell survival and maturation offers an alternative approach to binding BAFF and APRIL, namely through the BCMA receptor, which represents a novel B-cell modulatory unlock for therapeutic potential in this high-profile emerging therapeutic space.
This morning, Vera announced the completion of an exclusive license agreement with Stanford University for a novel preclinical next-generation dual BAFF/APRIL inhibitor known as VT109, which represents an important new part of Vera's lifecycle management strategy to extend our leadership position within B-cell modulation. VT109 has highly desirable preclinical characteristics, including low picomolar binding affinity for both BAFF and APRIL, and a very attractive pharmacokinetic profile in rodents. This novel molecular composition may offer a differentiated clinical profile in the future based on frequency or even route of administration or other characteristics to enhance patient convenience in the future. This recent addition and acquisition adds a third molecule to Vera's pipeline. Given the potential to improve patient outcomes for patients with IgAN and autoimmune renal disease in the near term, Vera is focused on advancing atacicept to patients as quickly as possible.
Atacicept for IgAN is reading out phase III next quarter, BLA filing later this year, and we anticipate a PDUFA date in 2026. The phase II PIONEER basket study in the broader IgAN population in MN, FSGS, and MCD will begin readout later this year, and VT109 will advance in preclinical characterization for MAU868, our phase II anti-BK virus monoclonal antibody. We'll receive ongoing regulatory feedback for the next stage here in 2025. It's an exciting moment for patients. Vera is leading a paradigm shift in how we treat patients with autoimmune disease, beginning with Atacicept for IgAN, as our robust clinical data support the potential to target the source of several autoimmune diseases and affect a functional cure profile. I want to thank all of you for your attention and interest, and happy to answer questions. Thank you, Anupam.
Thanks, Marshall. Just want to remind folks that there are three ways to ask a question. You can raise your hand. I'll call on you. You can submit a question in the portal, and I'll ask it on your behalf, or you can email me. Marshall, I just want to talk a little bit, maybe with the first question about the deal that you announced this morning. Just, why was this the right time to bring in an additional asset versus maybe focus on Atacicept indication expansion broader? You have this new asset that gives you maybe some optionality on indications, modality. What was the rationale there?
Yeah, I would describe it in the following way. Serial innovation is the best way to win in therapeutic advancement. The window of opportunity to advance medicine is not infinite, and we have a multi-pronged strategy to win in the BAFF-APRIL space. The first one is with Atacicept weekly, which we plan to take to market in 2026. We're looking at longer interval dosing, and then this opportunity, of course, is to be explored preclinically first. Now is the time. We've built an incredible team, and now is the time to adjudicate and build the pipeline.
Got it. And then thinking about Atacicept, just about the 26-week top-line proteinuria data, what's the regulatory bar on sort of an absolute or placebo-adjusted change, and how do physicians view this?
Yeah, excellent question. So it's important to recognize that there is now a precedent to achieve accelerated approval based on nine-month proteinuria reduction, which compared to placebo, the bar is roughly 30%, and there is already a precedent with three approved medicines according to that pathway.
FDA would like to see, and we certainly have communication with FDA, would like to see a confirmatory secondary endpoint of GFR separating from control over two years. That's the standard format. That's the format we're taking. We see this upcoming phase III readout in Q2 as an important unlock to file a BLA. What we think physicians care about is GFR stability, and that's really the key and why we've made sure that the phase II study ran for two years, and we were able to capture that quartet of findings that we see as disease-modifying as a profile. It's very clear that physicians have responded to it in that way.
We're actively discussing that in advisory boards, both with KOLs and community physicians, but it really is about GFR. That defines whether someone gets to use their own kidneys or needs to use a machine or a transplant in the future, and that's precisely what's on the minds of these 35-year-olds.
I hear you on the GFR, and you guys have the data that you presented at ASN out to 96 weeks from the phase II-B on GFR. Is the plan to submit those data as well for maybe some claims in the label on GFR ahead of the 104-week data?
Yeah, a good question. I'm happy to give a little color here. As the space has evolved in the last few years, you wouldn't be surprised to know that FDA is going to look at eGFR, but they'll keep that really confidential and ask sponsors to do so at the primary endpoint, 96-week data point, in order to protect the blinding of a confirmatory secondary endpoint at two years, so shouldn't be no expectation that eGFR data is shared publicly, but rest assured, FDA will be interested, and I think that's a key question around what will Vera potentially launch with.
We'll have a phase III trial with a nine-month endpoint, but we already have two-year data in a peer-reviewed manuscript that's already out in the public domain, and it's not uncommon for clinical experience beyond the phase III trial to be included in a label. We can't make comments on what will or will not be in the label, but it's important that it's known that we already have that two-year data, and that separates us from the rest of the field.
Questions from the audience? So what does your market research suggest about a B-cell modulator project placement in an accelerated approval strategy on proteinuria, right?
Yeah, great question. Our market research is really based on the emerging profile for Atacicept, so I can't speak generally to B-cell modulators. Again, to be a B-cell modulator that targets one or the other inhibitor or doesn't yet have the clinical profile is truly a different question. We've got two-year data. We have done market research.
We have spoken to patients, providers, and payers, and there's a lot of attraction about a GFR that hits a normal curve, and I can share with you that there's real excitement about that, and we see that as really a fundamental therapy. As you look across other modalities that are in therapeutic development for IgAN, some purport to reduce inflammation, and I've shown data now where 75% of patients have full resolution of hematuria. So the question is, what other agents need to be given to get this profile? The data you're seeing today is atacicept on top of standard renoprotective therapy. That's ACE inhibitor and ARB, ± an SGLT2 inhibitor, and you're achieving a normal GFR. That's the value proposition that our phase 2 data offer,
And one of the pushbacks that we get, because you talked about the convenience of weekly at home, right? One of the pushbacks is, well, IgAN patients are probably followed monthly, so why not in the clinic sub-Q like Otsuka? So what do you see from physicians in the marketplace about that dynamic?
Yeah, so we're familiar with pushback, and I think the best.
I'm not sure if you heard.
The best way to answer pushback is with data. We've got 90% of patients who continue to take once weekly. It's the same format as Ozempic. That's an Ozempic-like approach, and I think that it's pretty clear that IgAN patients don't come in every month. So in our phase II trial, it's a major advantage and potentially why we enrolled phase II so fast and phase III so well, is that patients don't have to come in every month. They can come in once a quarter and over time less. These are young patients. They're 35 years old.
They've got jobs and families. We, based on our market research, would object to the idea that patients come in once a month. They don't want to do it.
We have an email question here, which is to clarify your prior comment that at 30% placebo-adjusted is your regulatory bar for proteinuria in IgAN.
Yeah, that's the precedent. I think it's important for those of you following Vera closely that that 30% reduction relative to placebo, and proteinuria is an important endpoint to measure in a double-blind placebo-controlled trial because proteinuria is a confoundable endpoint. So adjusted for placebo, 30% is associated with a substantial reduction in your risk of disease progression, and that's why Tarpeo and Filspari were approved despite a continued reduction in GFR.
These patients are so sick that if you show a drug that just extends the declining slope even by a few years, you're reducing morbidity and saving costs. So there's no question that's an important step forward for patients. What they haven't seen yet is a drug that actually extends that by decades, and these are young people who don't have to think about a life on dialysis. That's a really different value proposition. So 30% is an important regulatory threshold. When you compare 30%- 40%, is it any different? We'll tell you now that there are multiple drugs that have a 30%-35% reduction in proteinuria, but they're of different mechanisms, and they have very different profiles for GFR. So to overly focus on UPCR is a mistake, and we've already gone beyond that with the two-year ORIGIN Two data. Yeah.
Questions from the audience? Just thinking about the 2Q update, how much data are we going to get sort of in the top-line, and what could we see at a future medical meeting scientific forum?
Yeah, I think it's fair to say with the timing, this is more likely to be a press event as opposed to a medical meeting for our top-line phase III data. It will be nine-month data where the primary endpoint is proteinuria, and we plan to share a number, and we won't plan to share GFR data. As I mentioned, FDA has been very clear that that needs to stay confidential so that we protect the blind for the confirmatory GFR endpoint.
And then safety. Yeah. Any more granularity when in -
2Q. We can't be more specific at this point, and important for us to focus on. These are now standard timelines. The team is a fantastic team that we pulled together that has a lot of BLA filing experience, so getting from phase III readout and database lock to BLA filing is a major focus for the company. We know how to shorten that. It's an expert team, and the priority for the company is getting this drug to patients.
And then what are the gating factors to starting the monthly sub-Q program for Atacicept? Your guidance is pretty broad for this year.
Yeah, there's nothing gating. We just haven't been specific on data flow because it's in process, but there's nothing gating there. It's just operating the study.
And then how should we think about the milestones around ORIGIN Extend as well as PIONEER in 2025?
Yeah, we can provide more specificity once we have a better handle on how enrollment is going. We just turned the page into the new year. Remember, think about Extend as another interesting snapshot at the baseline of patients who've been off of Atacicept for a while. So we hope to look at that and share that with the nephrology community to continue to underscore what I've just shown you for the first time today, this clear evidence of drug treatment effect, and really the reason why chronic dosing is justified in a risk-benefit profile over time. So that's a really key outcome for the Extend study that could come relatively early. And then over time, I think the dividends from Extend is longer term. What does two, three, four years look like over time? PIONEER, I think of as really two buckets.
One is the extended IgAN population, and the other is the non-IgAN autoimmune renal disease MN and the like, and we can provide updates once we have more enrollment information for you.
Maybe final question from me. You talked about your cash position at the end of the quarter. Maybe just talk to us about the runway and what milestones are assumed in there.
Sure. We haven't been specific on guidance other than $677 million in pro forma cash after the financings we did last year. It puts us in a very good position, funds us through launch and beyond, and allows us to expand the pipeline as I've been describing it. So we're comfortably financed to execute on our first launch, and we feel great about the ability to really explore the clinical utility of atacicept.
All right. Any final questions? All right. Thank you, Marshall.
Excellent. Thanks so much, Anupam