This covers the cut out tagging in the US. It is my great pleasure to introduce our next presenting company, Zenas BioPharma. We have the CEO, Lonnie Moulder. He will give us some corporate presentation, and then we're going to have some Q&A toward the end. Welcome, Lonnie. That sounds great, Roger. Thank you. Good afternoon. We really appreciate being invited to the conference, Roger. As we go through this, I'll be making some forward-looking statements. I refer you to our SEC filings. As you probably know, we are an I&I-focused company. We're just about five years old, and we're making some great progress in the clinic with our lead molecule, Obexelimab, which is in several studies I'll review today. In addition, this team that we have in place is one that has great experience in not only developing globally and registering products, but also launching products in key markets in North America and Europe. We're poised to do that with our program, Obexelimab. Here are the near-term milestones. It's going to be a big year for us. Our IgG4-related disease program for Obexelimab that I will speak about is, of course, fully enrolled. The last patient out will be in November. That means from an analysis and release standpoint, about year-end, those results will be available. Our multiple sclerosis global phase two program actually completed enrollment yesterday at over 110 patients. It is a 12-month readout, and that indicates a data release in early fourth quarter. Finally, our systemic lupus program, SLE program, is enrolling patients. That should wrap up about year-end. That is a six-month readout. That means mid-year next year. Three really important data readouts over the next year or so. You may be familiar with this molecule. It is rather unique. There are no other molecules with this specific mechanism in the clinic. This mechanism combines the binding to two markers on B cells, one being CD19, which is broadly expressed across B cell lineage, the second being FC gamma R2b, also known as CD32b. This is really the natural inhibitory pathway to shut down B cell response or B cell activity, specifically after an infection with antigen-antibody complexes coming back and binding to that pathway. That's been leveraged in the design of this antibody. This antibody is highly potent in decreasing B cell function, which includes antibody production, cytokine production, proliferation and differentiation, and the presentation of antigen to T cells. When we brought this molecule in, we already had data in hand to review from five clinical trials. You can see here, three of these were in patient groups, one in rheumatoid arthritis with respectable ACR scores for a B cell agent, a compelling phase two IgG4-related disease trial that served as the basis for us moving into phase three, and also a phase two A lupus trial we'll talk more about in just a moment. We stepped back. We looked at these data sets. We thought about how to actually get the greatest value for patients and for our stakeholders out of this molecule. Came up with about 40 indications, narrowed that down based on scientific merit, clinical path, regulatory path, commercial opportunity. We landed on several that are listed here. Obviously, we're in the clinic in a few of these, and we have some others in mind. First of all, we moved towards an Obecsilamab IgG4-related phase three trial. Just quickly, this disease, you may know, although a newer disease, is one that affects typically multiple organs in patients. It's inflammatory, leading to potential fibrosis and organ failure. These patients from time to time will flare. Once a patient's in a flare, they have to be treated. There's no resolution of a flare without significant pharmacologic intervention. Typically, it's been steroids. These patients, from a journey standpoint, will usually show up first at a primary care physician's office with some symptoms. Some laboratory parameters will be evaluated, maybe a scan. Using certain criteria determined by the rheumatologist, IgG4Rd is determined to be the disease that the patient has. How many patients have this disease? The experts believe there are 30,000-40,000 in the U.S., the same number in Europe. We are confident in a prevalence that is diagnosed today of about 20,000 in each of those key markets. The way the disease progresses here over time, if not treated, there are periodic flares. The flares, for clinical trial purposes, use something called the ACR-ULR criteria listed on this slide and a score of 20. Patients below 20 still have inflammation. They still have disease. It's important to control that disease and push it down as far as possible because even the lower level disease can lead to organ damage. We thought about that in how the trials were designed. First, the phase two trial that I mentioned before, if you look at this pretty simple graphic explaining the outcome of the trial, you'll see on the y-axis the IgG4Rd responder index. That's a measure that determines flare. Anything over three is a flare. The median here was 12. These patients had significant flares. The drug was then used to induce remission and then maintain remission. You can see how quickly the onset was. The primary endpoint of the study was a two-point decrease. Obviously, all of these patients met the primary endpoint. One patient dropped out early because actually they weren't qualified. They were below three. One patient had a flare in the study, only one out of all the patients in the study. Under a 10% flare rate on drug. These are impressive results and again, served as the basis to move to phase three. To give you context, the same site, Massachusetts General Hospital, conducted a study with Rituximab, whereas Obexelimab is a potent inhibitor. Rituximab is a depleter of B cells using an ADCC mechanism. It has activity here. If you look at these two columns, the patient population was similar in both, and both drugs were reasonably effective at controlling flare. There are some differences, though. Look at the onset of action. The onset of action of our potent inhibitor was half the time of Rituximab. Look at the sustained response. This is measured at the end of the study. Rituximab in this setting is dosed every six months. Apparently, the benefit wears off over time in certain patients where their B cell compartment is repleted and they have disease activity again. Whereas with Obecsilamab that is dosed repeatedly, it will be available in an autoinjector under 10-second subcutaneous at home, but continuously provides drug exposure, target engagement, and protection from disease. You see that the sustained disease response was 20 percentage points better than Rituximab. That is because of the continual dosing to protect patients. That led us to a phase three design. This phase three design was agreed to with regulatory bodies throughout the world. It is similar to a phase three design of a now-approved drug in this area that we will talk about in just a moment. The way this works, patients are in flare. They're adjudicated by a committee to determine they're truly in flare, then treated with steroids. Once they're put in remission, again, centrally confirmed, they are randomized one-to-one, Obexelimab to placebo. The steroid is tapered per protocol over eight weeks in both arms, similar to the competitor's study, actually identical. We monitor for flare. The study, as I said before, completely enrolled last November. The full cohort of patients are on study. The last patient out of the study will be this November, leading to the results. We monitor for flare. The primary endpoint is actually time to disease flare. We know from prior work that the placebo flare rate will be about 60%. We know from our phase two study that the flare rate was under 10%. That would lead to quite compelling results. As you can see here, looking at the two large studies in this field, our study of over 190 patients being the largest ever conducted in IgG4-related disease, the other study, 135 patients producing results with this study's design that led to an approval in April for this B cell depleting agent. You see an 87% reduction in risk or a hazard ratio of 0.13. We would expect with a hazard ratio or a flare rate on our drug in the 10% range and a placebo comes in at 50-60%, which would be anticipated, a similar hazard ratio in the teens. Where we may see some differences, if you recall the slide on Rituximab, because it's dosed every six months and there's a loss of benefit from the drug at the six-month point. On this slide, the flare-free rate in that other drug's study was 90%. That's very impressive. The complete remission rate at six months was 37%. At 12 months, it was 59%. Not as many patients are being protected from ongoing inflammation. We think that relates to the fact that the drug loses some benefit by the six-month time point, the 12-month time point. We can obviously, with our continual dosing, address that. Where does this lead to from a market opportunity? As I said before, there's expected to be 30,000-40,000 patients in the two largest markets, U.S. and Europe each. We do know, though, that there are 20,000 that are today defined as the diagnosed prevalence. About half of those flare frequently enough that they should have continual therapy. If you dollarize that to the current market price in this field, that would lead to a $3 billion opportunity in the category in the US and about $2 billion in Europe. We believe our profile could lead to a good share of that. Let me just briefly touch on the multiple sclerosis program and the lupus program, and then we'll move on to a discussion, Roger. This is the Moonstone phase two trial. This is a classical design, randomizing drug to placebo, two-to-one ratio, and looking at MRI results at 12 weeks, specifically cumulative new T1 GAD-enhancing lesions. It's what others have done. Those who succeed then usually succeed in randomized trials. For us specifically, it's taking the week eight scans, adding them to the week 12 scans, that cumulative number of GAD-enhancing lesions, and comparing drug to placebo. As I said, those results will be available early in the fourth quarter. Let me just go to the next slide. The decision will be at the appropriate time, where do we take this next? Do we take it into the classical two RMS studies, or do we move to secondary progressive and primary progressive MS? A decision yet to be made. Finally, the third program, which we'll report out middle of next year, the lupus program, is really building upon the work that was done once before with this drug in a phase two A study where the intent to treat population on the primary endpoint actually had an effect size or a benefit that was 17 percentage points better than placebo. That's in the range of the two marketed drugs for lupus, but it's not good enough for patients. We can do better than this. What we identified in this study is that patients who received the proper exposure, the right CTROF level, actually they had double the effect size. This would be game-changing to have a drug that has a 35% benefit over placebo, which was demonstrated in that population. The dosing regimen we selected for all of our studies provides a CTROF that is in the range of those patients that had this substantial benefit at the 35% level. That is the regimen we brought into all our studies, including the lupus study. A more effective regimen. Importantly, that prior study was a bit undersized by the originator at 50 patients per arm. Our study is almost 100 patients per arm. In addition, something that's really important in lupus studies to ensure you're getting the right patient population, which is a moderate to severe disease state. The physicians, obviously, that are participating, the investigators, have inclusion-exclusion criteria. Sometimes it's right on the edge. We have an adjudication committee that reviews them. Actually, that adjudication committee takes patients that investigators otherwise would have put in the study and deletes them from the study before they get in. We're protecting the study so we don't get this overperformance of the placebo arm. I think we've set up a study to potentially win here. We're excited to continue to execute on that. Finally, what is the opportunity overall across these three indications? It's quite significant. We're building a serious franchise in rheumatology based on IgG4-related disease, followed by lupus. Of course, pending the results of the MS trial, determining what our regulatory strategy will be and neuroimmunology strategy. I'm really pleased to have the team we have in place to deliver on this. I'll come over and join you now, Roger, for some questions. Thank you, Lonnie. Yeah, please join. All right, great. Great overview of the company. Very exciting. We're going to have three major readouts in the coming six months and then 12, 18 months. Maybe we start with the IgG4-related disease because that's one of the major pivotal data you will report, although it's maybe the second readout among those three. In terms of the profile, you laid it pretty clear, right? We have one approved drug, and we're going to see the sales for that drug. It's a pretty distinct profile. In terms of the phase three data, you say, "Okay, we can differentiate on a couple of efficacy endpoints and then also the safety profile." Based on your market research or the feedback from your advisor, how would you rank those differentiations in terms of importance to drive the clinical use? Understand it's $3 billion. Maybe you can take one-third of the market, $1 billion. How do those kind of play into the future treatment paradigm? Yeah, let me respond to that in a sort of a holistic way. If you think about the overall profile, with depleting antibodies that target B cells in the hematology-oncology setting, obviously, there's a certain mindset for that patient population. But when we move to autoimmune disease and we're looking at patients that are going to have a journey that's two, three, four, five decades with whatever that autoimmune disease happens to be, MS patients are frequently diagnosed at a very young age. IgG4-related disease, many patients are actually younger. The first decision is, as a clinician, do you want to delete the B cell compartment continually for the next two, three, four decades? A lot of people are coming down on, "Well, it'd be great to have an alternative, an inhibitor that we could use. We could pause, have the B cells come back. We want to vaccinate the patients annually for their annual vaccines. If there's any comorbidity we need to consider. That right there, there's an important differentiation. Do you want to deplete B cells for decades, or do you want an inhibitor that you have some flexibility with? I think that's an important consideration. The administration. Most of the B cell depleters require infusions or even monitored long subcutaneous. That has to go to a center because there's the potential for hypersensitivity, even anaphylaxis. The patients are predosed with medications, this pre-medication to protect them from hypersensitivity. They get their infusion. They're monitored in the center for a while. Our drug, the case pack, is sent to the patient's home once a month, and they have their autoinjectors. Less than 10 seconds, once a week, autoinject. I think the world of GLP-1s have shown us that patients can get very comfortable with periodic autoinjectors. I think that's an important consideration right there. To your point, could there be some efficacy differentiation? We believe there could be because we're continuously putting pressure on B cells in tissue to decrease their hyperactivity. Depleter versus inhibitor, convenience of at-home administration, and then potentially, because of the continuous exposure and coverage, some efficacy advantages. As I mentioned before, this ability to vaccinate after pausing, I think, is an important safety advantage. I think the profile offers a lot to clinicians and patients. Got it. Okay. Yeah, that's pretty line and clear. Then you will report a phase three, and then you do have the primary endpoint. That's always investors and everyone going to take a close look at that, understanding you can differentiate on other endpoints potentially because it seems the bar is not too high. We have to admit, right, the competitor or the current approved drug, they have a pretty robust primary endpoint data. What's your expectation on that primary endpoint? I believe some of the KOL give some reasonable expectation for that bar because you don't need to be exact the same given the totality of the profile. I think the data from the other drug, the hazard ratio was 0.13. If we had a hazard ratio of 0.18 or 0.08, I don't think that's different than 0.13. Anything in the teens is really the same. There's a confidence interval around it. At the end of the day, if you look at this and the placebo arm comes in at 50-60% flares over 52 weeks, and the drug arm comes in at about 10% flares, the drugs are similar on the primary endpoint, and the hazard ratio should be about the same. Got it. Yeah, great. All right. Let's touch on the MS as well because that's the first data readout you're going to have early fourth quarter. That's 12 weeks, and then the imaging data. I understand this is obviously the imaging data. It's not clinical endpoint, but it seems the coloration between the imaging and then the clinical phase three endpoint is pretty robust. Just give us some teaser there and then how you think about the coloration. When we see the data, I believe you have powerful 90% reduction. How this will translate into the phase three clinical readout? Yeah, so this correlation, even though it's a surrogate, it's an MRI measurement, I think there's one standout that had good phase two results but didn't succeed in a randomized trial. That drug had issues. The trial was conducted during COVID. There were missing data points. There were a lot of issues with the study execution. We're very comfortable, and the field is very comfortable that if you have a meaningful change in a phase two MRI endpoint, T1 GAD-enhancing lesions, you will succeed in the clinical measures in a randomized phase three trial. We're quite confident in that. The question is, where do we want to go? Do we want to go to RMS, or do we want to think about the unmet need in PPMS or secondary progressive MS? There's a lot of confidence in the phase two predicting success in phase three. I know your powerful 90% reduction. What's the effect size? Is that effect size matters to translate into the clinical endpoint? Yeah, I think the effect size, there's been a broad range that then translated to success in phase three. There are two considerations. There's the absolute number of T1 GAD-enhancing lesions in your drug group, and then there's the effect size, the difference from placebo. The closer your drug pushes the number to zero, the effect size might shrink a bit because you can't go below zero with your drug. Some studies varied where the effect size was 90%, where the placebo arm might have been four or five, and the drug arm was 0.5 or 1. There are other studies where the drug arm was less than 0.05, and the placebo arm was more just 90% above that. The studies vary, but it's interesting how they move together. The placebo and the drug arm move together. It depends on where it's going to fall out in this patient population, but there should be a substantial effect size. Historically, it's between 70-95%. And then the actual absolute number in the drug arm varies a bit, but it's always tied to the placebo. Interesting. Okay, 75%-90% effect size is translated into. But the placebo seems with the drug arm move together. Move together. Yeah, got it. Okay, that's very helpful. Also, given this inhibition mechanism and subcutaneous weekly dosing, you may be able to show some other endpoint, including the PIRA. That's one of the major kind of development areas to focus for MS population. Tell us a little bit more and when we're going to see that. Sure. The concept of PIRA, which is progression independent of relapse activity, we know there's a phenomenon here in MS that patients that don't have relapses still decline. It's called silent progression. There's a clinical measure that's been validated over the last number of years called PIRA that would be utilized in a large phase three program. You need the power of a large phase three to show PIRA. In our phase two, there isn't a PIRA measurement that can be done, but our phase two has a 12-week readout, but then a 24-week readout. The 24-week readout is well over a dozen exploratory endpoints looking at biomarkers and novel scanning techniques that build the translational medicine data set that the drug's doing more than just controlling relapses. That would tell us scientifically that we can impact PIRA. The other reason to believe that this approach hitting CD19 can impact PIRA in large randomized phase three trials is that actually the market leader, Ocrevus, which is a multi-billion dollar drug in this disease, many patients benefiting from it. The phase three programs did not include PIRA, but there was a post-hoc retrospective analysis combining the data set from the phase three trials that actually showed that targeting B cells will impact PIRA. Does impact and reduce this silent progression. It just was not prospectively done, so it is not part of the label. We would have the opportunity, if we move to phase three RMS trials, to put it into our clinical trial now as a key secondary endpoint. Excellent. Okay, that will be very differentiated. Okay, we have limited time, but let's talk about FLE as well, which is a third, but also large population. So understanding you when you designed the study, you have some biomarker embedded, but you also have the all-common population. Maybe just how you power the study and then what you want to show benchmarking the current approved drug. Yeah, so in that study, we have an all-common population. So patients come in, but we're actually taking samples and doing sequencing, which was done in the phase two A, and some interesting data was produced from that, and looking at some biomarkers. Prospectively, that's set up such that if we learn anything from the phase two study, we could potentially consider a biomarker strategy in a phase three registration program. That will all be captured here. The study itself, the BICLA endpoint is what we're looking at. That's an endpoint that's important, an endpoint that can be used in registration studies. The current drugs on their primary endpoint had effect sizes or improvement over placebo in the high teens, mid to high teens. We don't think that's good enough, as I mentioned before. Our study is powered such that if we came in in that range, the study would succeed. What we would hope to see is something greater than that. I showed a slide that said the phase 2a primary endpoint intent to treat population had an effect size of 17%, but with the right dosing, the patient population had a 35% effect size. If we are north of 20% effect size, I think we have a drug that is differentiated. Got it. And then the 20%, that's all in the all-common or that's in the biomarker population? The 35% was in the all-common. In that phase two study, I didn't mention it was also in the slide that in the biomarker population, the effect size was over 50%. That was retrospective. It was a small study, right? That needs to be repeated, and that's what we're doing in this study. We're going to have that data from the entire population. If we find there's a biomarker that would show you that you could have an improvement over placebo by 50%, then it'll be a decision. Do we do an all-common population or do we do what we learned in oncology studies that you could test the biomarker population first in your hierarchical statistical analysis, lock that in, and then take a bit of an alpha hit, as you know, and then do the overall population? That could lead to the potential to utilize a biomarker and inform physicians. The term is a complementary biomarker. It's not required. Got it. Okay. Yeah, hopefully we can see both effects. That's right. The biomarker will be even higher and so that would be more patient would be benefiting, right? Okay, maybe just last minute in terms of the corporate strategy because you have one product and three indications and then large, small, relatively small. How do we think about the commercialization and then the late-stage development? We know MS takes years and then a lot of money to do. Yeah, so we have a team of about 150 people, a very experienced senior team. A number of us have worked together before. We've built commercial organizations and successfully launched drugs in the U.S. and Europe and built companies that had value for patients and ultimately got acquired. This team is well prepared to commercialize. We're well funded right now. We have about $315 million on the balance sheet that gets us into the fourth quarter of 2026 through all these data points, allows us to do all the initial commercialization activities. We have MSLs in Europe and the U.S. now. We have market access, leadership in marketing, and in market research in place. We're preparing for the launches. Now, how about the indication-wise? So all the indication you're going to launch by itself or? Yeah, we're thinking of others. We're assessing some others. Sjogren's could be interesting. People have suggested sclerosis. That could be tough. Vasculitis, that could be tough. We're looking at others. We're also looking at business development opportunities to leverage this team we have in place to bring in more molecules. Excellent. Thank you, Lonnie. All right. Thank you, Roger. Thank you, everyone. Thank you, everyone. Thank you. Thank you.