Good morning. My name is Shelley, and I will be your conference operator today. At this time, I would like to welcome everyone to the Biogen Thematic Pipeline Seminar, Rare Kidney Disease. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during this time, simply press star one on your telephone keypad. Please limit yourself to one question to allow other participants time for questions. If you require any further follow-up, you may press star one again to rejoin the queue. Today's conference is being recorded. Thank you, and I would now like to turn the conference over to Mr. Tim Power, Head of Investor Relations. Mr. Power, you may begin your conference. Thanks, Shelley, and good morning, everyone. Welcome to Biogen's Thematic Pipeline Seminar, where today we'll focus on felzartamab and rare kidney disease. During this call, we make forward-looking statements which involve risks and uncertainties that may cause actual results to differ materially. We provide a comprehensive list of risk factors in our SEC filings, which I encourage you to review. We've also posted the slides to our website that we'll be using during the call. On today's call, I'll be joined by our President and Chief Executive Officer, Chris Viehbacher, Dr. Priya Singhal, Head of Development, Dr. Travis Murdoch, Head of Biogen's West Coast Hub, and Dr. Uptal Patel, Head of Development for Biogen's West Coast Hub. Our discussion today will focus on our felzartamab opportunities across multiple nephrology indications, and each section of our presentation will be followed by a pause for some Q&A, with time for additional Q&A at the end. To allow us to get through as many questions as possible, we kindly ask that you limit yourself to one question, and I'll now turn the call over to Chris. Thank you, Tim. Welcome, everyone, to our first investor seminar. As you know, we have been focused on generating sustainably growing revenue, building a new Biogen. Over the past two years, we have restructured our business through our Fit for Growth program, and that has brought a lot of focus and generated significant resources. We have launched four first-in-class and indeed first-ever disease-modifying treatments in the past two years, and they now represent a significant and increasing share of our total revenue. We also critically reviewed our portfolio of development assets, and we now have a pipeline that I think is more diversified and one in which we have growing excitement and confidence. Now, Biogen is where breakthroughs happen. We are proud that we tackle some of the hardest problems in medicine, but this brings challenges even when we succeed scientifically. Breakthroughs mean a market has to be developed since often there has been no treatment in the past. That is also difficult for investors to assess since there are often no analogs. The rare nature of the diseases and lack of analogs means that we have to work harder to educate physicians and patients, our own teams, but also you, our investors. Today is an opportunity to do a deeper and more focused dive into a very promising part of our pipeline. We've expanded our therapeutic horizon of interest to include immunology. Our acquisition of HiBio last year accelerated this expansion. We're currently in the process of initiating three phase III studies in rare nephrology indications with felzartamab. In fact, we have already enrolled the first patient in two of the three studies, and we expect to have the first patient enrolled very shortly in the third study. Now, although the indications are in nephrology, the path to treatment goes through the immune system. I think you're going to hear that the CD38 is not only an ideal approach in these three indications, but there are many other potential indications. Dr. Travis Murdoch and Dr. Uptal Patel will take you through the three initial indications for felzartamab, and Dr. Priya Singhal, sorry, will conclude the presentation. Before we do that, I would just like to point out, in addition to innovating in immunology, we're also innovating a business model. I'm really pleased and proud to say that the HiBio team has elected to be part of Biogen, and the team is now the foundation of a new West Coast Hub. We recently recruited a new head of immunology research, Dr. Nick Wilson, who is building out a research team alongside our HiBio colleagues. We hope to leverage the passion, the entrepreneurial spirit, and the knowledge of this team and wrap around the benefits of a larger company in terms of procurement, CMC, global clinical trial recruitment, as just some examples. Now, this is not easy to do organizationally, and I'm grateful for the collaborative leadership of Priya, Travis, and Uptal. I am now going to turn the presentation over to my colleagues, and if I could have the next slide, please. Our two colleagues are Dr. Travis Murdoch. He is a Rhodes Scholar, where he studied immunology. He trained as a physician first. He was a consultant, then had a period as an investor at Third Rock and SoftBank before founding HiBio. Uptal is a nephrologist by training. He has spent 20 years at Duke University. He is also the chair of the board of directors of the Kidney Health Initiative. He was Head of Clinical Renal and Executive Group Director, Early CVRM Research at AstraZeneca before becoming the Chief Medical Officer at HiBio. I think you'll find these are two extremely well-qualified people to really present the strengths of our immunology and nephrology pipeline. Travis, I'll turn it over to you. Thanks for the introduction, Chris. Let's start by talking about how we've brought real depth of expertise in nephrology to Biogen. As some of you know, HiBio was established to address severe immune-mediated diseases by developing targeted therapies. We built a team with many years of expertise in immune-mediated diseases, with a focus on nephrology given the high unmet need, but also compelling proof of concept data for our lead program, felzartamab. Following the acquisition by Biogen, the vast majority of the team has remained part of our West Coast Hub and grown over the last year with an intense focus on advancing our immunology and rare disease efforts, including advancing felzartamab into three pivotal studies with further expansion opportunities underway. Today, we'll be speaking to felzartamab and why we think this is such an exciting opportunity for patients and for the company. Let's start on CD38, which we believe is a very interesting target in immune-mediated diseases. As you can see on the slide, there are multiple diseases caused by autoantibodies that attack the body's tissues. While the end organs affected vary, the mechanisms that underlie these diseases are shared. Most autoantibodies are generated by two types of cells, plasmablasts shown on the left and long-lived plasma cells shown on the right. Both these cell types, which are the professional antibody factories, have high expression of CD38, which makes it a very interesting target for treating antibody-mediated diseases. Now, there's additional history here in that there's strong validation of CD38 in multiple myeloma, which is a cancer of plasma cells. The mechanism by which CD38 works is by directly depleting the cells that produce autoantibodies. We believe this has the potential to treat antibody-mediated diseases in a more durable and targeted way, which our clinical data that we'll share have borne out. At the same time, and critically, we avoid earlier B cell lineages, and this has the potential to provide a differentiated safety profile, given that CD38 does not target B cells. What we've shown, for instance, is that patients can maintain vaccine responses while they're receiving felzartamab. This is a different approach than those targeting CD20 or CD19 that deplete precursors to those cells or April, which really act by inhibiting those cells. Hopefully, you can see why we believe that CD38 and targeting CD38 via a monoclonal antibody is a differentiated approach to treating these diseases. Let's turn specifically to felzartamab and why we believe it's the right anti-CD38. First, felzartamab binds to CD38 in a unique way, which has some important consequences. It was engineered to not have complement-dependent cytotoxicity. As a result, infusion rates can be as fast as 30 minutes, and we've seen a lower rate of infusion-related reactions. Additionally, felzartamab binds to CD38 in a way that doesn't inhibit the ecto-enzyme, which we believe could have safety benefits. Secondly, and uniquely, we have a complete chronic tox package for felzartamab, including a reproductive tox package in marmoset monkeys. Now, the marketed CD38 programs, which are used in oncology, do not have chronic or repro tox packages that are important to support chronic use in immune-mediated diseases, and that's because they don't cross-react to relevant non-human primate species. Our current focus is on nephrology indications of high unmet need, including AMR, IgAN, and PMN. As we'll share, these indications have compelling proof of concept data. We additionally have an ongoing lupus nephritis signal-seeking study. Now, we've seen some compelling data off-label in lupus and in lupus nephritis with daratumumab that appears in some ways similar to data generated off-label with CAR-T therapy, including durable remissions off therapy. As you can see with this indication landscape, what's unique about the anti-CD38 approach is that there are a number of other indications shown here with off-label case series using other anti-CD38s, and this really provides us a roadmap for future potential indications where there's already some existing clinical validation. Now, I'd like to hand it over to Uptal to walk us through the felzartamab opportunity in AMR. Thanks, Travis. Let's start with an overview of AMR in kidney transplant recipients on the next slide. Antibody-mediated rejection, or AMR, is a disease with a very high unmet medical need, and that's because it's one of the leading causes of kidney transplant failure. As you can imagine, patients are thrilled and rejuvenated when they receive the gift of life from a kidney transplant, but absolutely devastated when they lose their new kidney to rejection. This disease is driven by alloantibodies to antigens on the donor cells, as well as by damage from natural killer cells that cause microvascular inflammation in the kidney. This process can occur either shortly after a kidney transplant, referred to as early AMR, or in the case of late AMR, more than six months following the transplant. What's important is that despite the potentially devastating impact of AMR for these patients, today, they have no approved options, and experimental treatments so far have had limited success. Let's take a deeper look at why this is such an important opportunity for patients as well as for Biogen. First, patients who need kidney transplants tend to be younger, meaning there is a productivity impact to having this disease, and there are costs associated to the healthcare system for managing their disease over time. Now, unfortunately, while transplant is the answer for these patients and a preferred treatment for kidney failure, kidney transplants are hard to come by. Only around 1/3 of patients on the waitlist will actually receive a kidney transplant, and the cost of the procedure itself is almost $500,000 here in the U.S. This further drives the importance of protecting a transplanted kidney once patients have actually received them. Let's take a minute to look at the numbers in late AMR more closely. As you can see on the right, approximately 4% of transplants develop late AMR and are therefore at significant risk of losing the kidney transplant. Furthermore, it can cost somewhere around $160,000 to treat and manage AMR per year. Knowing there are no effective treatments today, I hope you can appreciate why we view AMR as an important opportunity. Let's take a moment to look at what characterizes AMR. While identification of AMR begins with routine post-transplant surveillance, the diagnosis is defined by a kidney biopsy exhibiting features of active microvascular inflammation, or MVI. More specifically, MVI is characterized by infiltration and accumulation of immune cells within the kidney microvasculature made up of glomerular and peritubular capillaries. Traditionally, AMR has been viewed as the result of high affinity donor-specific antibodies, or DSAs, that bind to alloantigens, primarily HLA antigens, on the endothelial surface of these capillaries. This triggers a cascade of effector mechanisms, particularly natural killer, or NK cells, leading to inflammation and injury of the microcirculation. Resolution of AMR is achieved when the active features of MVI and other histopathological features resolve. As I mentioned, the options available today have had limited efficacy, but let's take a closer look at that on the next slide. With no approved therapies for AMR, the existing standard of care relies upon the use of therapies that remove DSAs or reduce their production, such as plasmapheresis or intravenous immunoglobulin, both of which have lacked efficacy in late AMR. Unfortunately, phase two data from multiple investigational agents have also failed to meet the bar for what transplant physicians want for their patients. In our research, we've heard from these physicians that they need a drug with much higher biopsy resolution. Anything greater than 45% would be clinically meaningful, but they actually told us that a drug that would deliver more than 75% would not only be good, but transformational. With that in mind, a phase II study was conducted to look at what felzartamab might do in AMR. Let's look at that next. Because felzartamab has a distinct capability of selectively targeting not just the CD38-expressing plasma cells, but also the CD38-positive natural killer cells, this phase II study had the potential to demonstrate greater efficacy than prior therapies. It included 22 patients randomized to either felzartamab or placebo dosed over 24 weeks. The primary endpoint of the study was safety, but key secondary endpoints included resolution of AMR features on biopsy, including MVI. Let's take a look at that on the next slide. In the felzartamab arm, over 80% of patients demonstrated AMR resolution by biopsy. Six months versus placebo, where we observed only 20% resolution. This was accompanied by an improvement in kidney function, as measured by the estimated glomerular filtration rate, or eGFR, in the felzartamab arm out to one year. As a reminder, expert transplant nephrologists told us that anything over 75% would be transformational, so these results were very encouraging. Underscoring the significance of these results, the phase II study was published in the New England Journal of Medicine last year. On the next slide, you'll see that this is also a well-tolerated medicine. The majority of treatment-emergent adverse events were mild to moderate in severity. The most frequent adverse events observed in the felzartamab arm were infusion-related reactions, with the majority occurring after the first dose, and there were no treatment-related discontinuations. This is why we're excited about the potential for felzartamab in AMR, where no treatments exist today, and why we started a phase III trial earlier this year. Let's talk a bit more about that on the next slide. The Transcend phase III study will enroll approximately 120 kidney transplant recipients with late AMR. The primary endpoint of Transcend is the percentage of participants who achieve resolution of AMR at six months, as assessed by biopsy. Key secondary endpoints include changes in the MVI score and the percentage of patients achieving an MVI score of zero. You'll notice that unlike the phase II, we're including the potential for chronic treatment here because we believe this will reduce the risk of relapse in the future. Remember, in this disease, the constant presence of a transplanted organ drives persistent stimulus for alloimmune responses. The study is expected to read out in 2027, and we look forward to sharing updates as the study progresses. In summary for late AMR, it remains the leading cause of kidney transplant loss, posing a significant unmet need in transplant care. Despite extensive efforts, no approved treatments currently exist, and previous agents in development have consistently failed to demonstrate sufficient efficacy to gain confidence among transplant nephrologists. However, felzartamab has shown promise as a potential breakthrough therapy, and the phase II data showed a transformational over 80% resolution of AMR, offering new hope for improving long-term outcomes in kidney transplant recipients with the potential to address a critical gap in treatment options. I'll pass it over to Tim for Q&A on felzartamab in AMR. Thanks, Travis. As Uptal alluded to, we're going to take some questions on AMR now, and then we'll come back and we'll pause for questions after IgAN, PMN, and then at the end of the call as well. Operator, could we just go to the first question for AMR, please? Yes, thank you. If you would like to ask a question, please press star one on your telephone keypad. Again, as a reminder, please limit yourself to one question. Your first question will be coming from Eric Schmidt with Cantor. Thanks for taking my question and congrats on a very lucid presentation around the felzartamab and this indication. I guess my question's on the schedule and dose in AMR and maybe in particular whether felzartamab is going to be formulated as a sub-Q. I assume that's going to be important when we talk about the IgAN opportunity in particular. Thank you. I'll take that one, Uptal. Sure. Thank you for the question. In the phase III AMR trial, in part A, we're going to have participants randomized to receive nine intravenous infusions of felzartamab or placebo over five months, like we've done in our other studies. The efficacy and safety will be evaluated compared to placebo at 24 weeks. In part B, all participants will receive felzartamab during this open label period from six months through 52 weeks. At this time, I'll maybe hand it over to Travis to share how we're thinking about sub-Q. Sure. Thanks, Uptal, and nice to hear from Eric. We will share this later in the presentation, but we certainly are, you know, we're currently pursuing sub-Q. That said, and as we'll share, you know, and certainly the case in AMR, these patients have no options. You know, an infusion initially, you know, weekly and monthly, and then every eight weeks, which is the schedule, we believe is, you know, highly tolerable in this patient population and one that, you know, given the potential for transformative efficacy, would really result in IV form potentially becoming an important part of standard of care. Thanks, Travis. Could we go to the next question, please? Next question will be coming from David Amsellem with Piper Sandler. Thanks. I might be putting the cart before the horse here, asking a commercialization question, but on slide 14, you have the patient funnel down to 11,000 patients with late AMR. Of course, IgAN is, you know, quite a larger market. You know, I guess with that in mind, you know, you have these different addressable markets of different various sizes. How does that play into your thinking about pricing, you know, the extent to which you will, you know, price it in sort of deep orphan territory versus something more geared to a larger population? Might be early to ask the question, but it is something that I am thinking about as you are going through these slides. Thanks. I'll take that one, Travis. Sure. Thanks for the question, and certainly something that we've been thinking about, albeit, as you've mentioned, it's early. What's unique about AMR? Certainly, it's a smaller patient population today than IgAN. What's unique in the data that we've seen is that patients clearly have evidence of relapsing off therapy. We see that both through biomarkers such as cell-free DNA, but also recurrence of MVI at 12 months, because in the phase II study, patients didn't have therapy between six and 12 months. We think that in this disease, actually, the dosing schedule will be more intense, and there will be chronic dosing. In contrast, in IgAN, as we'll share in the next section, after a nine-dose, five-month course, patients had durable disease control out to two years. We think that, you know, from a relative dosing point of view, there is an opportunity to commercialize this product across multiple indications of different sizes. Yeah, if I could just add on. Thanks very much, Travis. I was just going to add on, David, you know, one of the things that, as we look across, we're just because of what Travis said, I think we're looking at an annual cost basis. Actually, just because of these different dosing regimens, and it is early, and it all needs to be validated in clinical trial, but we actually think that that will actually help us, even though there are different populations. When you look at it in an annual cost basis, this works out. Thanks, Chris. Let's go to maybe one more question on AMR, please, Operator. Your next question comes from the line of Jay Olson with Oppenheimer. Oh, hey, this is Sean on the line for Jay and for hosting the event. I'm just curious about the diagnosis of AMR. It seems like you need to have biopsy. Just wondering, do you think like a biopsy will be required on the label for felzartamab? Also, maybe I can just ask about the following strategy, whether you need to wait for the part A and part B, or you can just follow based on the part A result. Thank you. Uptal. Sure. Thanks for the question. The biopsy-based diagnosis is pretty critical and defines the disease. You know, this microvascular inflammation, there's really no other way of diagnosing that without a biopsy. Fortunately, in kidney transplantation, biopsies are routine, particularly for complications and assessing the efficacy of treating rejection. There's precedence for this. As far as filing strategy, you know, our intent is to file on the six-month data, and we'll, you know, we've got breakthrough and orphan drug designation to allow some ability to sort of add to those packages as we move forward with the program. Terrific. Thanks, Uptal. Let's move on, Uptal, if you don't mind, to our next section on IgAN. Go ahead, Uptal, whenever you're ready. Turning to IgAN. IgAN. IgA nephropathy or IgAN is the most common type of primary glomerulonephritis worldwide, and it's a serious disease and a leading cause of kidney failure. What's clear is that today, patients need new options that deliver durable disease remission. IgAN is mediated by immune complexes composed of galactose-deficient IgA1 and its IgG autoantibody, both of which are believed to be produced by CD38-positive plasma cells. These immune complexes deposit in the kidney, resulting in tissue damage and nephron loss with subsequent progressive kidney failure. Most patients who get this disease are typically diagnosed in their 20s- 40s. Their lifetime risk of developing kidney failure or death from kidney disease is really high. Now, while some countries perform regular screening for IgAN, most patients are typically diagnosed through incidental findings such as increased proteinuria or hematuria, and then the diagnosis is confirmed by a kidney biopsy. Current treatments are evolving, but generally involve nonspecific therapies to reduce proteinuria with or without chronic generic or branded steroids. We all know that this landscape is increasingly competitive, and there are many new assets being tested in late-stage development. To better understand this landscape of desired therapy and IgAN, we spoke to nephrologists and patients about what they would want to see, and we learned some interesting things. As expected, there's a focus on the need for more effective options that have an acceptable tolerability profile. What we thought was interesting was that physicians and patients are also telling us there's a real need for a novel therapy that provides durable disease remission without chronic administration. On this slide, you'll see on the top right, this is nicely captured by a comment from a patient, really highlighting the psychological impact of chronic treatment for this disease. Knowing that felzartamab would deplete the long-lived plasma cells that produce the antibodies causing IgAN, we ran a phase II study to see how felzartamab might work in this disease. Let's take a look at that next. Here's an overview of the phase II study we ran to assess the depth and durability of felzartamab or MEPS effect on proteinuria out to two years. This study schema looks a little complex, but it's basically a placebo-controlled trial evaluating different durations of treatment from one month out to five months. As I mentioned, we wanted to see how durable the benefit from felzartamab would be. Let's take a look at that next. First, we looked at what was happening to antibodies of interest, and these are pretty interesting. What you see is that felzartamab or MAPS treatment resulted in robust and sustained reductions in IgA more than 18 months after the last dose. This is important because this is the primary antibody that's implicated in the disease. What's also important is that levels of IgG and IgM antibodies, vital for fighting infections, quickly rebounded after treatment. We believe that we may have a differentiated profile here that might have the ability to manage the disease with a durable effect while maintaining the ability to fight infections. Let's take a look at what happened to kidney function next. Looking at kidney function on this slide, what we found was in line with the reductions observed in IgA. We observed robust and sustained reductions in proteinuria, as shown in the chart on the left. In the nine-dose arm administered over a five-month period, we observed ongoing reduction in proteinuria with a roughly 50% reduction at 24 months. Again, it's important to remember that this is now 18 months off treatment. This level of proteinuria reduction is both clinically meaningful and may translate generally to kidney preservation based off epidemiologic data. To confirm this and consistent with it, we also observed sustained placebo-adjusted stabilization of kidney function as measured by eGFR out to two years as well. Overall, these data were really encouraging and seemed different from what is seen with other approaches. To that point, when we look at the emerging IgAN landscape, the sustained response observed with felzartamab is different from many other investigational programs in IgAN, such as the April or BAFF agents. For those agents, the data so far shows that when therapies are stopped, you begin to see an increase in proteinuria and loss of eGFR within just a few months. What we're seeing with felzartamab is different. We're clearly seeing efficacy in the same neighborhood as the other effective approaches, but without the need for continuous treatment. You can see why we're excited to launch the phase III study in IgAN. Here's the design of our phase III study for Prevail. It's a placebo-controlled trial examining the nine-dose regimen over five months versus placebo. The primary endpoint is change in proteinuria from baseline to month nine, with a key secondary endpoint being change in eGFR from baseline to two years. Prevail's now underway, and we expect data to be out in 2029. In summary for IgAN, many patients progress to kidney failure over their lifetimes, highlighting the urgent need for treatments that deliver durable disease remission. This represents a significant unmet need for patients with IgAN. Felzartamab has emerged as a promising therapeutic candidate, with phase II data demonstrating sustained clinical benefits following just five months of treatment, with effects persisting for up to 18 months off therapy. Again, these results underscore felzartamab's potential to transform the treatment landscape for IgAN and deliver a differentiated treatment option for patients. Let me pass it back over to Tim for Q&A on felzartamab and IgAN. Great. Thanks, Uptal. So, yeah, let's go take a couple of questions on IgAN. Shelley, can we go to the next question, please? Yes. Your next question comes from the line of Mohit Bansal with Wells Fargo. Hi, this is Sadia Rahman from Mohit. Thanks for the question. In this phase II data, there seems to be some rebound in IgA antibodies after the six-month dosing period. There also looks to be a decline in eGFR, similar to the slope you're seeing in the placebo arm after nine months. Just curious how you think this, you know, felzartamab or MEPS could look in phase III with this drug holiday compared with competitor B-cell agents that are dosed chronically. Thanks. Sure. Let me take that. Thanks for the question. I think one of the things to, you picked up on an observation sort of after the six-month point, a little bit of rebound in the proteinuria. You know, that may be in part related to noise. This was a small study. You know, I think what we see overall is consistent with, you know, pretty consistent reduction. That is shown in the Japanese subcohort that we only have one-year data of. Again, small numbers in each of these cohorts, which is different than some of the other studies out there that were larger phase II. As far as progression goes, this was a high-risk population. What we saw was progression that was quite rapid in the placebo group, but stabilization across the different doses, in particular for the nine-dose arm in felzartamab. Thanks, Uptal. Shelley, can we go to the next question, please? Next question coming from the line of Laura Chico with Wedbush Securities. Good morning. Thank you very much for taking the question. I'm not sure if this should be directed towards Travis or Uptal, but maybe if you could talk a little bit about the registrational study. The phase III study is enlisting the primary endpoint of a% change from baseline in proteinuria at week 36, which is consistent with what we've seen from other players. At the week 104 secondary analysis, what are you looking at in terms of, I guess, magnitude of effect to remain competitive? Would it be ideally seeing kind of that stabilization persist on eGFR, or are there other measures that you're kind of looking to see? Thank you. This is Uptal. Yeah. Thanks, Laura. Hi. For the two-year endpoint, I think what, you know, everyone is interested in, patients, companies, treating physicians, and the regulatory authorities, is stabilization of kidney function. Preservation of kidney function is the goal. When you look at proteinuria as a surrogate of that, you know, that allows a sort of a faster pathway to approval and having the drug be available to patients sooner with the nine-month data. The ultimate goal is really reducing the loss of kidney function. We are very interested in the amount of preservation we'll be able to achieve at two years with felzartamab. Thanks, Uptal. Shelley, let's go to one more question on IgAN, and then we'll move on to Beilan. Your next question comes from the line of Brian Abraham with RBC Capital Markets. Hi, this is Kevin Owen for Brian. Thanks for taking our questions. Maybe just to follow up a little bit, how are you thinking about sort of phase II- phase III translatability for IgAN for felzartamab on biomarker and kidney function? Can you maybe talk a little bit about that specific eGFR 20-30 cohort that you have built in the phase III program? What are you hoping to learn from that dataset? Thanks so much. Uptal, you're going to take that one. Sure. Thank you. In terms of translatability, look, we had a relatively small phase II study, but the totality of the data we have that we're sharing today on felzartamab suggests that, you know, reducing the antibody production driving these diseases leads to durable disease-modifying effects. Although there is some noise from our small study, we're, you know, very pleased to see the reduction in proteinuria and that translate to stability of kidney function. You know, that needs to be validated in this larger phase III study that's now underway. As for the additional cohort, you know, there's interest in understanding what happens to people who've already lost a fair amount of kidney function. The goal is still to help stop and preserve the remaining kidney function those patients have. Rather than have that confound the primary assessment, we've created a separate cohort to look at the effect in people with eGFRs between 20-30. Hopefully, that will also translate there. The disease mechanisms are a little different there because there's activation of sort of chronic pathways that lead to progressive kidney disease. We're hoping to also find stabilization of kidney function there. Thanks very much, Uptal. If you're ready, let's move on and talk about PMN. Great. Thanks, Tim. To PMN, you know, primary membranous nephropathy, it's a severe antibody-mediated disease of the kidney that's the leading cause of nephrotic syndrome and carries a significant risk of kidney failure. Patients with PMN and nephrotic syndrome often present with very severe swelling and fatigue related to the high-grade proteinuria, which also causes them to be at increased risk for infections. This disease is characterized by autoantibodies that are produced by CD38-expressing plasma cells. It's estimated that up to 80% of PMN patients have autoantibodies specifically against PLA2R. Those with high titers are at increased risk of poor outcomes. There are no approved treatments for PMN currently, and the standard of care includes everything from immunosuppressants to chemotherapy. Still, up to 40% of patients do not achieve remission, and 30% of patients progress to kidney failure within 10 years. Let's take a closer look at how it's managed today. On this slide, we have a simplified view of the treatment algorithm and the outcomes for different treatment options. Here, the treatment decisions are based upon risk evaluation, which is largely determined by assessing the degree of kidney dysfunction using eGFR and proteinuria. Looking at high-risk patients, you can see that their options include cycling through a series of medications, including the use of steroids, as well as chemotherapy. Each option has anywhere from a 20-50% relapse rate with other safety and tolerability considerations over the long term. Knowing that felzartamab could potentially be a better option, we ran a phase I two study. Let's take a look at the design of that. This study utilized our nine-dose regimen in two cohorts of patients, both of whom had anti-PLA2R autoantibodies and were in need of immunosuppressive therapy. Cohort one consisted of newly diagnosed or relapsed patients with high PLA2R autoantibodies, while cohort two consisted of refractory patients who showed no immunologic remission to prior immunosuppressive therapy. While the primary endpoint was safety, we were very interested in the secondary clinical endpoints. Let's take a look at those data next. On this slide, we see the impact on changes in the autoantibody involved, PLA2R. Looking at anti-PLA2R titer response across both cohorts, the graph on the left shows depth of response at the six-month time point. Felzartamab led to a robust reduction of PLA2R autoantibodies in newly diagnosed, relapsed, and refractory patients one month after the last dose of Felzartamab. The graph on the right shows a sustained response without additional therapy. Most patients actually had a response that was maintained at the 12-month mark. What's interesting is the response in cohort two, which included highly refractory patients, including some of whom were refractory to multiple rounds of prior anti-CD20 therapy and cyclophosphamide. Now, let's turn to what the impact was on relevant clinical assessments. Felzartamab led to improvement across various parameters in most patients in both cohorts one and two. This includes the recovery of serum albumin levels, decreased proteinuria, and stable eGFR through the end of one year. While there's some heterogeneity in these individual patient populations, we believe the robust and sustained immunologic response and improvements in kidney function suggest evidence of the potential efficacy of felzartamab in PMN. Now, you can see why we're also encouraged by the opportunity to advance a phase III study in PMN as well. Based on these findings, we're initiating Prominent, a phase III study to confirm the efficacy of felzartamab in moderate to high-risk patients with PMN, inclusive of newly diagnosed and relapsed patients, similar to cohort one in the prior study. This study will include two courses of felzartamab separated by a drug holiday so that we can fully elucidate the clinical profile of felzartamab in patients with PMN over two years. Prominent's now currently underway with a readout expected in 2029. In sum, PMN is a symptomatic and progressive condition with approximately 30% of patients advancing to kidney failure within a decade. Current treatment options are often limited by insufficient primary efficacy, relapses to therapy, or severe side effects such as those associated with chemotherapy. At the same time, felzartamab has shown promise in addressing these challenges, with phase II data showing robust and sustained reductions in anti-PLA2R antibodies and sustained clinical improvements across newly diagnosed, relapsed, and refractory patients. Together, we believe these findings highlight felzartamab's potential to redefine the treatment paradigm and improve outcomes for patients with PMN. Let me pass it back over to Tim for Q&A on felzartamab and PMN. Thanks, Uptal. Shelley, can we just go to a couple of questions on PMN? Maybe go to the first one on this one, please. Okay. Yes. Again, if anyone would like to ask a question, it will be star one on your telephone keypad. Your next question comes from the line of Paul Matisse with Stifel. Hey, this is Julian Uptal. Paul, thanks so much for taking our questions. Just for the phase III, can you talk about in PMN, what are the proportion of newly diagnosed to relapsed patients? I guess, just across these three indications, would you be able to just opine on what you believe is the level of potential for chronic dosing? Any information on that would be really helpful. Thank you. Uptal. Yeah. No, thanks for that question. You know, this study is just getting started. We do not have any targets for the newly diagnosed versus relapsed populations. Based on what we see clinically, you know, there is some variation of this around the world. We expect that, you know, these will be balanced across the two arms. Maybe for the second part, I can hand it over to Travis. Sure. So, I would say, you know, what we're seeing in IgAN certainly is patients are having durable responses up to two years. Given the underlying pathogenesis of this disease and of PMN, we do expect that there will be recurrence in some patients. And so, you know, our thinking is that we'll pursue a long-term extension study to really understand, in both these diseases, to understand retreatment. But we do expect that, you know, a portion of these patients will require retreatment just given the underlying pathogenesis of this disease. Thanks, Travis. Shelley, can we go to the next question, please? Next question is coming from the line of Evan Seigerman with BMO Capital Markets. Hey there. This is Connor on for Evan. Thanks for taking our question and for the really comprehensive presentation here today. Maybe just one follow-up to the previous question there. Can you maybe discuss a little bit about the importance and differentiation of the durability of the responses you're seeing here in PMN? And maybe discuss a little bit your sort of decision to redose at week 52 and kind of the profile of a patient who may require chronic dosing? Thank you. Travis, you want to take that one? Sure. One thing that's really important to note in the employee study, which was the, you know, the signal-seeking study, is that these patients had some of the highest anti-PLA2R, so the autoantibody titers. In this disease, what we see typically is that patients who are higher titer tend to not respond as well to a CD20-based approach. We believe that that's because these patients are more plasma cell-driven. They end up getting, unfortunately, cyclophosphamide, which is really toxic. These are also the patients who tend to be at highest risk for a relapse. Given that, you know, obviously, we only have one-year data, but given the fact that we were seeing deep responses immunologically in many patients, but not all, we decided to redose patients at 52 weeks, as you point out. I think it's going to be really the long-term extension study and really understanding those patient segments based on risk, which helps us understand how many of those patients ultimately will relapse and require retreatment after the two-year period. Thanks, Travis. Let's go to one last one on PMN, please, Shelley. Your next question is coming from Phil Nadeau with TD Cowen. Good morning. Thanks for hosting the webinar. It's very helpful. Question for us on the PMN phase III trial. The primary endpoint's complete remission. How is that defined in the context of the trial? And what% of patients would you expect to achieve remission under tacrolimus? Thank you. Maybe Uptal for that one. Sure. The complete remission definition is something that, you know, is pretty standard with thresholds of proteinuria that are achieved, whether that's 0.3, 0.5, with stable GFR. And then for, you know, the proportion of patients who then relapse, you know, that's—sorry, I'm blanking on the second part there. Yeah, I think the question was on TAC, the TAC arm, what we expect in terms of. Oh, the TAC arm. Sorry. So, the responses there. Yeah. So, the tacrolimus arm, you know, that's by two years, we expect that there'll be a smaller proportion of those patients who achieve complete remission without the need for rescue therapy. If they've, you know, if they've got worsening proteinuria, progression of their kidney function, they would be eligible to receive rescue, similar to many other trial designs. That'll be a relatively small proportion. Thanks, Uptal. Maybe I can hand back to Travis to take us to the next section and conclude with Travis and Priya. Thanks, Tim. To summarize, we believe that the selective and unique targeting of CD38-positive immune cells may provide felzartamab with a differentiated profile across important nephrology indications. This really includes potentially becoming the first approved treatment in AMR with transformative efficacy, as was demonstrated in the phase II, a highly differentiated option in IgAN with a durable treatment-free remission, and the first B-cell-sparing and preferred agent for high-risk patients in PMN. This provides us with three phase III studies, two of which are already dosing patients with our first data expected in 2027. To be more specific, although these three indications have different estimated patient numbers, we view all three of them as commercially attractive. Starting with AMR, even though the population is smaller, this is an indication with the potential for chronic dosing with no approved therapies, and where the value to patients and the healthcare system can be very meaningful with the potential of protecting the transplanted kidney. In IgAN, we understand this is an increasingly competitive market and potentially more fragmented. We believe the potential to bring a differentiated therapy to market with a non-chronic option and shorter dosing will be one that patients and physicians appreciate. Finally, with PMN, this market is slightly larger than AMR. Even though we expect there to be continued use of the anti-CD20s, we have an opportunity to be the first B-cell-sparing agent in high-risk newly diagnosed and relapsed patients. We believe we can address a significant fraction of the market. In sum, we believe for each of these opportunities, we have a significant commercial potential for the company. Now, importantly, given the rare nature of these diseases, there's a finite commercial footprint that we believe will be required to be successful. AMR is a disease that's managed and closely monitored in transplant centers. Therefore, there's a concentrated footprint of physicians. IgAN and PMN, as you expect, are treated in the broader nephrologist community, but nearly half of nephrologists are treating the majority of patients. For these indications, there's still quite a focused commercial footprint that we believe will be required to succeed. We're not satisfied with just these three diseases. Remember, we told you how broad the applicability of anti-CD38 could be. Let me take a moment to tell you how we're thinking about that. Starting with lupus nephritis, we also believe there's an opportunity to deliver a differentiated treatment option in LN without the type of side effects associated with other investigational agents that deplete cells, such as CAR-T or T-cell engagers. The existing data demonstrate that an anti-CD38 approach is active in this disease. We are executing a phase I study with data expected in 2026 that's intended to inform next steps, including the potential to move forward with a registrational study. Beyond lupus nephritis, we are looking at other opportunities that will allow us to build our CD38 franchise. I'd like to share two objectives. We have a unique opportunity, given the knowledge base and development expertise, to further expand and strengthen our anti-CD38 franchise. Felzartamab has already shown promise as a non-chronic treatment in diseases like IgAN and PMN. We are actively advancing a subcutaneous formulation that could further enhance patient convenience and accessibility. Additionally, we're developing a next-generation anti-CD38 designed to provide greater commercial flexibility and continue to unlock potential for CD38 targeting across multiple indications. We believe the existing data, and in particular PMN, which is very much a prototypical IgG autoantibody disease, suggests that we could have deeper and more durable antibody and clinical responses without globally impacting IgG to the same degree as other classes, importantly, the anti-FcRns. Together, these advancements position us to maximize the potential for CD38-based therapies and deliver innovative solutions to patients in need. In summary, we believe the data generated to date highlight the potential for felzartamab to be a best-in-class treatment option across multiple serious immune-mediated renal diseases with significant unmet need. We're expecting a regular cadence of data readouts over the next few years. We will gain increased clarity into the clinical profile of felzartamab and the potential it holds for patients. Now, the three phase III studies we have today, we believe, are just the beginning of what we can do with CD38. I would like to hand it now off to Priya to provide some concluding remarks. Good day, everybody. Excellent. Thank you so much, Uptal and Travis, for that in-depth look at felzartamab. I hope that our audience shares our enthusiasm for felzartamab's potential to be an important medicine for patients and further bolster Biogen's high-conviction late-stage pipeline. Now, turning to our overall late-stage pipeline, as you can see from this slide, felzartamab is an important asset in a broader set of several compelling opportunities across these late-stage, high-scientific conviction programs. What I hope is also evident is that there is depth in the pipeline across key franchises. This includes our anti-Tau ASO in Alzheimer's, as well as BIIB115, our next-generation ASO in SMA, which has the potential for a once-yearly administration. From this slide, I hope it is clear that our pipeline momentum is increasing. In fact, since our earnings call last month, we have now dosed the first patient in the Prevail phase III study of felzartamab in IgAN and started screening for the Prominent phase III study of felzartamab in PMN. I believe this progress demonstrates our focus on execution as we continue to employ a highly disciplined scientific approach to R&D. With several important milestones expected over the next 18 months, we have the potential to continue to further strengthen the profile of our pipeline and deliver new meaningful therapies and options to our patients. I hope you'll see why our confidence in, therefore, delivering the new Biogen is growing. We believe that our pipeline will continue to play a key role in this journey, and we remain focused on advancing and expanding our pipeline to deliver the sustainable growth. We also look forward to continuing to share updates with you as we progress in the future. Now, I'm going to hand it back to Tim for our final Q&A session. Over to you, Tim. Thanks very much, Priya. Shelley, could we go to our next question, please? Your next question comes from the line of Marc Goodman with Leerink Partners. Hi, good morning. This is Basma on the line for Mark. Thank you for taking our question. We had a question on IgAN, please. We'd like to hear your opinion and commentary on the other competing asset, the early phase that aimed to be even more selective by targeting the pathogenic autoantibody. How much does it really matter, this additional level of selectivity for the? Does it really impact the differentiation from felzartamab? That's it for us. Thank you. Travis, you want to take that one? Sure. So, just to clarify, I gather you're speaking to some of the IgA degrader approaches? I think that's right for us. Yeah. I think the important piece here is the mechanism, which is that we are directly depleting cells. We're depleting, you know, we believe, and our data suggest, both the IgA-producing cells, which are largely in the mucosal-associated lymphoid tissues, as well as antibody-producing cells in the bone marrow. Whereas these other approaches really are, in a way, taking those antibodies out of the system, but not dealing with the root cause. While I think there'll be multiple tools in the toolbox for physicians, we believe that many physicians and patients would prefer to have an option where you're directly depleting the pathogenic cell rather than really only dealing with the downstream mechanisms. Travis, could we go to the next question, please, Shelley? Your next question is coming from Jeffrey Mechant with Citi. Hello. Hey, it's Ross on for Jeff. Thanks for taking my question and the presentation. I guess we were curious about indications moving forward. Obviously, this can have some broad applications. I guess, how is the company thinking about going into certain indications over others? Specifically, if the company was considering prioritizing going into rare disease indications over others? You want to start with that, Travis? And then maybe Priya, you want to add on the prioritization? Sure. We're actively looking at prioritizing new indications. Certainly, lupus nephritis is an indication where HiBio had already initiated a signal-seeking study, but one that has a ton of industrial logic, given the building lupus franchise here at Biogen. Beyond that, I think we're looking for indications that are large but rare markets, but ones that certainly we think could be highly de-risked already, given data for off-label use of daratumumab and other anti-CD38s, but also, frankly, some of the plasma cell-targeted CAR-T therapies. You can imagine that there's a broad swath of antibody-mediated diseases, but we can quickly narrow down to those where we think we could have a commercial differentiation and where we already are heavily de-risked by virtue of those other data. Thanks, Travis. I agree completely with what you said. Actually, I just offer that this is very similar to our approach across any indication mapping. We're always looking for the scientific conviction, biomarker data, external and internal, and looking at the value proposition and the unmet need. We're really putting all of that together and prioritizing. That's the disciplined approach we're taking. Thanks. Yeah. I would just add, we're certainly prioritizing a next-generation CD38 as well, because while we are certainly looking at rare indications, they're all going to have some differences and potential pricing differences. Having two separate molecules would enhance the optionality around this. We are in the space of immunology. I think we prefer to follow the pathways here. That leads to whatever indications that they lead to. As Travis said, the commercial investment is manageable. They're not huge investments in commercial to go after any one of these indications. In our view, anyone where we can gain conviction, and we think there's an unmet need between the two molecules, the subcutaneous formulation, we do think we can build out a portfolio. That might be relatively diverse in terms of indications. As I say, we're betting more on the science and let the commercial chips fall where they may, essentially. Thanks, Chris. Shelley, could we go to the next question, please? Your next question comes from the line of Miles Minter with William Blair. Hi. Thanks for taking the question. I had one on slide 28. It's on IgAN again. I think the radar study that John Barrett's on seems to suggest that an eGFR decline of 2.0 for a year is a pretty increased rate of ending up with renal failure. I had a question on your eGFR data that doesn't seem to line up with the proteinuria data in the trial, in the IgAN trial. Can you just explain how you're getting a 50% proteinuria reduction with your nine-dose arm, but it seems that eGFR is still declining? I'm just wondering whether that's just a small amount of patients and variable eGFR, or whether that's something that you're actually seeing and how you kind of reconcile that to long-term benefit in this patient population. Thanks very much. Sounds like one for Uptal. Yeah. No, thanks for the question, Miles. You're highlighting the disconnect between sort of our data and maybe some other phase II data with larger study populations. I think what we are seeing is noise and more progression than we would want. The greater progression is true in both arms, not only the placebo arm, but also the treatment arm. The relative reduction is important. What we're hoping is with the adequately powered phase III trial, what we know to be true about the disease is essentially that reducing the drivers of disease then manifests with a reduction in proteinuria. That essentially indicates that you've got a decrease in the disease drivers that then also lead to declining kidney function, and that would be evident in our phase III study. We're very comfortable launching this and expect that we'll be able to demonstrate clinically meaningful benefits. Thanks, Uptal. Let's go to the next question, please. Your next question comes from the line of Umer Raffat with Evercore. Hi, guys. Thanks for taking my questions. I have a set of three questions. If that's appropriate, I'll go ahead. Otherwise, I'll limit it to one. Tim, what do you say? You can go for the three here. Okay. Thank you. I was just looking to clarify how the phase III is structured. First, is the dosing through week 24 and then beyond as well? I ask because in phase II, we saw three out of nine patients that were responding started being non-responders when you went past week 24 when they were no longer dosing. That's number one. What's the dosing profile? If you could speak to the durability of response. Secondly, is the actual dose still about a gram per infusion and four infusions in the first month? If you could just speak to how the dosing is being done, the volume, and whether it's subcu or not. Finally, the primary endpoint that's being used in phase III, which is the histologic resolution, was that ever reported for phase II? This may be my lack of understanding here in AMR. Thank you very much. Sounds like good questions for you, Uptal. Sure. Thanks. As far as dosing and continuing that, you're exactly right that what we observed was a few of the patients who had responded by six months then had evidence of AMR activity by 12 months. That is why we're going to continue dosing in the phase III part B. During that second part of the year, we'll have ongoing dosing for those initially randomized to felzartamab. Those initially randomized to placebo will receive the standard nine-dose regimen over five months. We're using the same dosing regimen that we've seen in all three diseases that we just shared data on: PMN, IgAN, and AMR. That is essentially five weekly doses followed by four monthly doses. A total of nine doses over about five months. Currently, all of the dosing will be administered IV, like Travis and Chris described. We're working up subcu, but that'll take some time. In terms of the primary histology—sorry, primary endpoint, it was actually demonstrated and reported in the New England Journal paper. We demonstrated resolution of AMR. The subtlety is that—it doesn't really change if you use a different classification—the way AMR is graded is with an international classification system called the BAMP classification. We used the 2018 version for this trial, which was started several years ago. It's been revised. There's a 2022 classification that's going to be used for the phase III study. I think one thing to add here is that when you look at the New England Journal paper and you look at microvascular inflammation, we have many patients who achieve an MVI of zero at six months. This is all on biopsy. This is all histologic resolution. That's never been demonstrated in any AMR study. To Uptal's point, we do see that start to come back at 12 months off therapy. In both the BAMP classifications, MVI reduction is sort of the main driver of resolution. We feel very confident in the translation into phase III. Terrific. Thanks, Travis. Let's go to our next one, please. Your next question comes from the line of Michael Yee with Jefferies. Hey, guys. Great. Thanks. A couple of questions. For these indications, are you planning to file each of these on one study on accelerated approval endpoints for AMR, IgAN, et cetera? And specifically for IgAN, it says that it's a two-year readout, although it's a 36-week input endpoint. And that's to 2029. I was just trying to get my timelines there. Is that actually a 36-week endpoint, or is that the two-year endpoint in 2029, which seems quite far for just 36 weeks? Two questions there. Thank you. Maybe Travis? In the case of AMR, given we have BTD, we're expecting to file on six-month data. The last six months of the study is an open label. That's where we expect data in 2027. I think we intend to, if possible, use the accelerated approval pathway in IgAN. What we're providing is really full approval in two years. The study is designed to enable that 36-week endpoint. Thanks, Travis. Let's go to the next one, please. Your next question comes from the line of Sumant Kulkarni with Canaccord. Hi, Mike. Thanks for taking our questions. I have a two-parter on AMR. Beginning July 1, 2025, our understanding is that Medicare will be starting up a program called IOTA or Increasing Organ Transplant Access Model, which means hospitals could receive upside risk payments in year one or be eligible for downside risk payments beginning in year two based on performance. Given this dynamic, could felzartamab and AMR help position hospitals for success and incentivize its use? That's the first question. The second is, on AMR, is it fair to assume that the 45%-70% clinically meaningful to transformational thresholds on biopsies translate very well to actual functional improvements for patients, or are there any nuances we should be aware of there? Travis? Sure. Thanks for those questions. I think the two questions are, in a way, related. Unfortunately, in AMR, we've never seen a study that showed resolution on biopsy. What we expect, given that patients that have microvascular inflammation—and there was a New England Journal paper in October of last year that really shows this—is highly associated with loss of graft, even with or without evidence of antibodies. What we understand about this disease is that if you have AMR and MVI on your biopsy, you're likely to lose your graft. The community feels very strongly that if you were able to reverse that, given that the disease is defined by those features on biopsy and that ongoing inflammation, which is what we showed in our phase II study, that you'll be able to reverse that course to read on the client. For hospitals and treaters who are being judged by outcomes, we do expect that this will be a helpful driver. Frankly, for patients who see this sort of a result in a phase II, what we're already hearing from sites that are active is a ton of enthusiasm and excitement about enrolling into our phase III study. That is certainly because there's been nothing for these patients, but also because we're seeing very significant clinical impact in the phase II. I'll just add the median time from transplant in our phase II study population was about eight years. That's sort of past the period of the year one, two, where IOTA is going to have the biggest impact. That said, late AMR is defined as after the first six months. There will be some people who have AMR within a year or two of transplant that could be impacted by this. To Travis's point, there is no effective therapy that exists right now, and these could have a really big impact for patients. Thanks, Uptal. Let's go to the next one, please. Your next question comes from the line of George Farmer with Scotiabank. Hi. Thanks for taking my question. On slide 27 of your deck, the selective and sustained reduction of IgA is quite striking relative to IgG and IgM in the IgAN study. How relevant is that across the other two disease indications, as well as other indications that you're thinking about? Take that one, Uptal. Sure. It was striking, and we're pretty fascinated by that. It may be related to the fact that IgA is produced, like Travis mentioned, primarily by cells in the mucosal-associated lymphoid tissue, which may be more accessible, and so they're depleted. For IgA nephropathy, it's really important. Like we said, it's the GAD-deficient IgA that's driving the disease. These are likely produced in the same compartment. Reductions in these antibodies that are producing some of the reaction is critically important. What's also important is the improvement in IgG and IgM. Across all of our diseases, we do see this pattern. In terms of the impact of the sustained reduction in IgA for the other diseases, it's not clear there's any benefit there, nor a downside. What we do see is also the return of IgG and IgM, which is important for those diseases that are essentially treated with greater levels of immunosuppression in the background. Maybe one thing to add here, not related to IgAN, but related to PMN, is that, and you saw this in the data we showed, but also in the data we've published, you see sustained and deep reduction in the IgG autoantibody while at the same time you see normalization of IgG and of other protective immunoglobulins like antitetanus. When you think about PMN as a prototypical IgG disease, and as I mentioned earlier, the anti-FcRns have gone after these diseases, but have not been able to show sustained reduction in autoantibody, we do believe that there's an opportunity to potentially have a differentiated approach in other IgG autoantibody diseases. Thanks, Travis. Let's go to the next question, please. Your next question comes from the line of David Amsellem with Piper Sandler. Thanks. Just wanted to clarify how you're thinking about expansion opportunities for felzartamab. I know you talked about different indications, but I guess, and maybe it didn't come through quite as clearly in the slides, but what, beyond the three that you've articulated, are you most excited about, and how are you thinking about further advancement in these additional indications that you are most excited about? I just wanted to clarify how to think about the setup in terms of additional studies and what you're prioritizing. Thank you. Travis? Sure. Thanks for the question. I think it relates to the last question as well, which is, where are there IgG autoantibody diseases that we believe we could show a clinical impact and also one that has the sort of durability and depth of response that we're seeing? Naturally, that leads us, frankly, into a number of indications where the anti-FcRns have been active, but clearly where they show, let's say, a 50%-60% reduction in autoantibody, but in the PMN study, we show an 80% with normal IgG after a year. You can imagine some of those indications spanning both neuroimmunology, hematology, and dermatology. We're actively prioritizing those, which we'll expect to be coming back and saying more to in the coming months, but believe that there's a role really for felzartamab and potentially for a next-generation CD38 across those indications. Thanks, Travis. I think we've got time for maybe two last questions. Can we go to the next one, please, Shelley? Your next question comes from the line of Laura Chico with Wedbush Securities. Thank you for taking the follow-up. This is more of a strategic question, kind of along the lines of the last one. I understand the goal is to really continue to build out the immunology franchise, but I'm curious if there are other assets that would perhaps complement or be beneficial to bring into the portfolio that could kind of boost the footing in the nephrology space with felzartamab. Anything else from a mechanism or target perspective that would be something that would be sought after? Thank you. Yeah. I mean, I'll take that one. I think there's always two axes to these things. One is you've got a commercial presence, and you're building up relationships, and we certainly will be doing that with nephrologists. On the one hand, it will make sense to say, "All right, are there other assets through business development that could come in and enhance that nephrology space?" The other is, and this is what we've really started to appreciate since the acquisition of HiBio, and that is just the significance of CD38 as a mechanism. I'm not a scientist, so I think I'm allowed to say this, but to me, this feels like precision immunology. The immune system is very important. We don't want to modulate it any more than we have to. That's why I think CD38 seems to be such an elegant solution here. I think we're mapping out, and Travis and his team are really doing that. We, in fact, had a first conversation about some new indications yesterday. It is going to be a function of, look, there's a period of biologics exclusivity for the current molecule. We've got a follow-on molecule. We're going to be looking across at where do we think this mechanism really would fit. That is where you sort of divorce the commercial aspect of this. You really look at where does this mechanism really potentially offer the biggest benefit. Then we'll tool the commercial side to fit that. I think it'll be both. I think we're going to be going horizontally in nephrology, but I think going back to the mechanism, looking across in that direction, another indication. Travis, you're much more expert on that, and I invite you to complement anything here. Yeah. I mean, there are a lot of different upstream/downstream mechanisms that one could think about. I think what we like about the direct targeting, especially as it pertains to these sort of rare diseases of high-emit need, is that you are really depleting the pathogenic cell. And so, you have the potential to really be disease-modifying in a way that some of the downstream mechanisms, be it the anti-FcRns as an example or other degrading approaches, do not have. I think we also recognize that as we continue to generate clinical data across these indications, we will see where there are pockets. For instance, some of these diseases are mixed B-cell plasma cell diseases, where others seem to be more pure plasma cell. You could imagine how we may want to start thinking about other mechanisms that are complementary in the diseases that we have of interest. Thanks, Travis. Let's go to our last question, please, Shelley. Your next question is coming from Jay Olsen with Oppenheimer. Oh, hey. Thanks for squeezing me in and taking the follow-up question. This is Chung on the line for Jay. Maybe a two-question from us. First, on IgAN, given that you are thinking maybe felzartamab may enable a non-chronic dosing, are you planning to maybe run some type of a solution study to transition patients from other agents to felzartamab eventually? The second question is on the next-generation CD38 antibody. Is that like a monoclonal antibody or it's like a multi-specific antibody? Thank you. Travis? Sure. I think naturally in our IgAN study, and I invite Uptal if he's got additional comments, we do allow patients who've been on other therapies but have washed out. I think if the profile holds up, I think commercially, one thing to consider here, as you see what we believe, which is plasma cell-targeted agents are likely to become a backbone of therapy, I think there's a real question as to if patients could, in first line, take a therapy and know within the first 6 to 12 months if they've had a response and then be able to be off therapy. I think for many patients, that could be a very compelling opportunity. While naturally, I think there's going to be a switch pool, and we believe that as a different class of plasma cell-targeted agents, we could potentially be an important switch agent for patients who are on APRIL inhibitors. I do believe there's a reason to believe that physicians and patients would rather have a durable option upfront. That's maybe the first question. Could you repeat the second question again? What type of answer are you going to ask? Sorry, I didn't hear that. Whether next-gen CD38 is an antibody. We have not disclosed publicly exactly what that molecule looks like, but I think there are a ton of learnings from the felzartamab experience. What we learned at HiBio is that not every CD38 is built the same. I think we will continue to build on that expertise with our next-generation molecule. That's great. Thanks very much, Travis. And thanks, everybody. Sorry, go ahead, Uptal. I was just going to add a little bit about the IgAN. I think one of the clear mandates in the kidney community is now in this golden era of multiple therapies is that the goal will likely be to try to start with disease-modifying therapy. From that perspective, like Travis mentioned, you could try felzartamab, see if that works. The other goal would be depth of response, right? I do not think the current thresholds are going to be satisfactory. I think what we want to achieve is stopping progression for patients, and that might require sequential therapy. To your question about are we going to be studying that, like Travis said, there are ways people can get onto our phase III with the appropriate washout, and we will continue to study the effects of felzartamab in our long-term extension where some of those options could be explored. That's great. Thanks. Thanks very much, Uptal. Look, we're out of time. Just want to thank you all for your time and taking part in our webinar today. Hopefully, it was informative. The IR team is around. If you have any follow-up questions, we'll leave it there. Thank you. This concludes today's call. Thank you for your participation. You may now disconnect.