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

Let's go ahead and get started. Welcome, everyone, to the JPMorgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by my squad, Malcolm Kuno, Priyanka Grover, Rati Pinge. Our next presenting company Vera Therapeutics and presenting on behalf of the company is CEO, Marshall Fordyce. Marshall?

Thanks so much, Anupam. Good afternoon, and welcome. I'm Marshall Fordyce, 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 2 years, patients taking atacicept have kidney function similar to healthy individuals without a biopsy-proven kidney disease. EGFR normalization over 2 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 2-year results were published last quarter simultaneously with a 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 1cc subcutaneously once weekly. And over 2 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 nonclinical 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 in development for treatment of IgAN, dual inhibition of BAFF and APRIL with atacicept has established a high bar for safety and efficacy over a 2-year period. Of the 4 B-cell modulators in Phase III, atacicept is anticipated to be first to market among the 2 BAFF/APRIL inhibitors and 1 of only 2 to be studied in a controlled dose range finding study in Phase II, and it is the only program to study at-home self-administration. As the only program with 2-year data in Phase II, we anticipate being positioned with the most robust data set 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 2 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 IIb 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 IIb ORIGIN trial is a multinational, randomized, double-blind, placebo-controlled dose-ranging study, evaluating atacicept versus placebo and powered 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 grams of proteinuria at screening. The randomized phase with 36 weeks during which 3 doses of atacicept was compared to placebo. And then all subjects were switched to atacicept 150 milligrams 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 2 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 4 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 2 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 milligrams. Hematuria, the clinical measure of active glomerulonephritis resolved in 75% of patients. And 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 mls per minute per year. In totality, this quartet of findings support 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 mls 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-proving kidney disease, a slope at which over decades, end-stage kidney disease is not reached. The X-axis on this figure represents only 2 years. And if you think about the average age of a patient at 35 years old, we're hoping for decades of stable kidney failure -- 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 1. 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 2 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. And 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 GFR, a return to the natural history of GFR decline of about 4 mls per minute per 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 milligrams to placebo with a primary endpoint of proteinuria at 9 months and a secondary endpoint of eGFR at 2 years. In both Phase II and Phase III, atacicept is studied as an at-home, self-administered 1cc 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 III 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 nephrine, suggesting an attractive target for certain patients with FSGS and minimal change disease. We've initiated the PIONEER study, a Phase II basket trial designed to assess atacicept's potential benefit in IgAN patients who did not meet our Phase III entry criteria and specifically moderate and low-risk patients, patients with low GFR, 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 includes 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 in IgAN and GFR 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 VT-109, which represents an important new part of Vera's life cycle management strategy to extend our leadership position within B-cell modulation. VT-109 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 a broader IgAN population in MN, FSGS and MCD will begin readout later this year. And VT-109 will advance in preclinical characterization for MAU868, our Phase II anti-BK virus monoclonal antibody, will 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.

Just want to remind folks that there are 3 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 e-mail me. Marshall, I just wanted 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 and 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?

Yes. 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 multipronged strategy to win in the BAFF/APRIL space. The first one is with atacicept weekly, which we plan to take to market in '26. 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?

Yes. Excellent question. So it's important to recognize that there is now a precedent to achieve accelerated approval based on 9-month proteinuria reduction, which compared to placebo, the bar is roughly 30%. And there is already a precedent with 3 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 2 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 2 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.

And I hear you on the GFR, and you guys have the data that you presented at ASN out to 96 weeks from the Phase IIb 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?

Yes. 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 GFR, 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 2 years. So shouldn't be no expectation that GFR 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 9-month endpoint, but we already have 2-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 important that it's known that we already have that 2-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 product placement in an accelerated approval strategy on proteinuria, right?

Yes. 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 a truly a different question. We've got 2-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 renal-protective therapy, that's ACE inhibitor or ARB, plus or minus an SGLT2 inhibitor, and you're achieving a normal GFR. That's the value proposition that our Phase II data offer.

And one of the pushbacks that we get because you talked about the convenience of weekly at home, right? But one of the pushbacks is, well, IgAN patients are probably followed monthly. So why not in the clinic subcu like Otsuka? So what do you see from physicians in the marketplace about that dynamic?

Yes. So we're familiar with pushback. And I think...

I'm not sure if you've 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 e-mail question here, which is to clarify your prior comment that 30% placebo adjusted is your regulatory bar for proteinuria and IgAN.