I think we're live now. Good afternoon, everyone. My name is Yatin Suneja. I am one of the biotech analysts here at Guggenheim. Welcome to our SMID Cap Biotech Conference. It is my pleasure to introduce our next presenting company, Zenas BioPharma. From the company, we have Chief Executive Officer Lonnie Moulder. Lonnie, why don't you maybe take five minutes, orient us, tell us about the company, you know, talk about some of the upcoming milestones that we should be focused on, and then we'll sort of go into the Q&A. That sounds good, Yatin. First of all, we're very appreciative of Guggenheim inviting us to the conference. It's been a productive day here, and I'll be making some forward-looking statements, so I'll just refer people to our SEC filings. For Zenas, as many of you may know, we're creating an immunology and inflammation franchise, really around our lead molecule, obexelimab, which is in a series of phase II and phase III global trials with some important milestones yet to be achieved this year, and the team that's operating the company has had significant experience and success in developing drugs globally, ultimately launching multiple products, and we're deploying that team to do the same thing here at Zenas. That lead molecule, obexelimab, is quite novel, as a potent B cell inhibitor, and we'll talk about the mechanism in just a moment, but it has some interesting features. As you may know, in a number of autoimmune diseases, B cell depleting antibodies are utilized. Unlike those antibodies, obexelimab doesn't eliminate B cells. It inhibits B cells, which means it can be turned off and turned off, which may have some interesting safety features associated with it. But importantly, it's a really potent agent. From a patient standpoint, it's quite convenient. It will be an autoinjection, a quick, less than 10-second autoinjection, ultimately at home once per week. That leads to target engagement and continuous exposure for high efficacy. That's how the dosing regimen has been designed. Specifically, what this antibody does is co-engage CD19 and a receptor called Fc gamma RIIb on B cell lineage. Fc gamma RIIb is also known as CD32b. This means that we are actually engaging the broadest part of the B cell lineage compared to, say, CD20, for instance, and then potently inhibiting B cells to impact autoantibody production, cytokine production, the processing and presentation of the antigen to T cells, and proliferation. So a really novel mechanism, as I said, across broad B cell lineage. Before we in-license this drug, actually five clinical trials have been conducted. And as you can see on this slide, a number of the studies were in patient populations. In fact, the multiple ascending dose trial was in a rheumatoid arthritis patient population, and those ACR scores there are quite respectable, which really supports the efficacy of this approach. Importantly, a phase 2 IgG4-related disease trial was conducted, and we'll talk about that, I'm sure, a bit more. and that was the basis for us moving to a randomized phase three registration trial. And in addition, a lupus trial that was unfortunately undersized by the prior sponsor but showed definite activity in this disease. And with our optimized dosage form, we feel like we have a path forward in lupus. So in summary, the trials that are ongoing today include the IgG4-related disease phase III registration trial that we refer to as INDIGO, completed enrollment in November of last year. Last patient out will be November of this year, leading to top-line results by year-end. But prior to that big milestone, we actually have the primary endpoint from our global phase two randomized trial in multiple sclerosis, reporting out in the third quarter of this year. Then finally, we'll fully recruit the SLE study this year, and those results will be available next year. I'll pause there. Very good, Lonnie. Thank you so much. I think before we dive a little bit deeper into your program and the studies that are ongoing, maybe just a few high-level questions. So what, I mean, you just touched a little bit on this concept of inhibition versus depletion. Like, what are some of the advantages, both as it relates to the efficacy and safety? What have we seen? Are there any data that you can put in context? Because your approach is obviously unique, you know, in terms of going with an inhibition approach. Sure. So, obviously the depleting approach is effective in a number of diseases. The anti-CD20 agents that are depleters are now the market leaders in multiple sclerosis. So that absolutely provides support to targeting B cells in multiple sclerosis. We know in other diseases that depletion is effective. The difference here, though, as we talk to clinicians, what's important to them, and you know, there are a number of other inhibitory approaches that are being pursued, APRIL-BAFF, BTK inhibitors. People are looking for a way to inhibit B cell lineage and not deplete. And this is because in these chronic autoimmune diseases, the option is to continue to deplete these patients every several months for decades. And it's been posited. Is that a good idea to do that? We know in the MS literature that those B cells that come back over time are more autoreactive, so is there an alternative to continuous depletion of the B cell compartment for decades, and inhibition is possibly the solution and an inhibition that can be reversible, so if you think about it, you know, patients that have comorbidities, patients that may have an infection or annually needing vaccination to be able to pause an inhibitor and then manage that patient and then restart, I think it is an advantage. The other thing is the B cell inhibitors, some of the leading products have a dosing regimen that frankly isn't optimized. If you look at some of the data sets, again, for multiple sclerosis, patients begin to feel symptoms as they approach their next dose for those that are dosed every six months. for a CD19 antibody that's depleting, we know from recent data that at the six and 12 month period, B cells are repleting, and in fact, some of the clinical data suggest efficacy is being lost at that point, so having a continuous inhibition could provide an efficacy advantage. The other thing with the depleters, of course, is that they typically require an infusion center to be involved. There are some that are headed towards subcutaneous administration, but the hypersensitivity has to be monitored at the infusion center. It takes a full day out of the patient's life, and it's complicated in many regions of the country and the world to actually get to an infusion center, and under, you know, Medicare payment, that's a Part B drug. Yeah. Patients are obligated to pay 20% of the cost of the drug as part of their copay under Part B. An inhibitory approach like this, which is a under 10-second, once a week autoinjection, that's a Part D drug. As you know, in January, Part D drugs were capped at a $2,000 annual copay. So there's a lot for the patient from an economic and an ease of use standpoint that I think favors an inhibitory approach over a depleter. Got it. One more question, again, staying with the inhibition approach. How do you measure the level of inhibition in plasma? And then what about across different B cell subtypes? Yeah. Obviously, there's a wealth of experimental data. Yeah. from this molecule from our licensor and also in our hands. We know that, of course, it binds and is active to activate resting B cells, across a variety of different subtypes that we've investigated. The key way of measuring this, as you know, Fc gamma RIIb is an inhibitory pathway. So phosphorylation of that pathway is what's looked at in the assays. We know that the level that's required to actually shut B cells down is five nanograms per milliliter or so, from those studies. With the dosing regimen we have in humans, the optimization we did by picking a subcutaneous weekly regimen, the C trough of our drug is about 15 + micrograms per milliliter. In tissue, it's a percentage of that. It's at least one microgram per milliliter. So you compare that in tissue relative to what's needed to shut down B cells at about five nanograms per milliliter. So we know we have a regimen that has target engagement and the exposure to be relevant in humans to dramatically shut down what I described before, autoantibody production. In our hands, we've shown inhibiting T cell antigen presentation, obviously proliferation, and also cytokine production. Very good. Very helpful. So then let's go into these three studies that you are running right now. The first one is the RMS study that's gonna read out. Could you just talk about how the enrollment is going? Maybe just walk us through the trial design and what the expectation there is for when this study reads out in Q3. Yeah. We don't guide on specific enrollment numbers. What we guide on is when the results will be available. And so the study's obviously on track because we've been guiding for some time now that we'll have top line results in the third quarter of this year. And this is the study design here. This is a classical design looking at comparing the drug obexelimab to placebo in RMS patients using an MRI endpoint, specifically looking at cumulative new T1 Gad enhancing lesions. This is what others have done. And those who have shown a 90%, approximate 90% reduction compared to placebo have gone on to have success in randomized phase III trials. So this is a really important endpoint. Third quarter, hitting that says we have a drug that works in this disease. And you, you know, you can frame or benchmark what others have done typically, you know, high 80% to well into the 90%. So there's a confidence interval there, but this is power 90% for 90% reduction. So that's 12-week endpoint, primary endpoint, third quarter. And then every patient in this study, both arms, the placebo arm, the obexelimab arm, continue forward all on obexelimab. And there we're looking at some novel imaging techniques and biomarkers that are a constellation of the science that says that this drug can potentially not only impact relapses, but the real unmet need is this silent progression that happens, which is actually independent of relapse. That's the opportunity to really differentiate. Got it. Are you stratifying it for RMS and secondary progressive in this? Are you enrolling those patients? And And then, yeah. Yeah. We expect results similar from prior data. So there's no need to stratify for that. Okay. I mean, we know that the B cell depleters work, right? If you see the CD20 data, you know, probably are the standard of care now. Where do you see the differentiation coming in here? Is it more on the safety side? Can push on the efficacy side? Just curious if you can articulate. Yeah. Let me, let me take you through that, ending up with potential clinical differentiation from a study outcome if you think about future registration studies. But to begin with, I think there'll be a mindset when a clinician is going to treat a patient, am I going to pick a depleting approach or inhibitory approach? And we know there's a number of, as I said before, inhibitory approaches. The MS docs really want BTK inhibitors to work here. It's an inhibitory approach. Unfortunately, they've been associated with some toxicity, liver toxin in particular. But ultimately, we think it'll come down to deplete or inhibit. And why inhibit? Again, do you do one of those? These patients are diagnosed at a young age, 30, 40, 50 years of depleting B cells every six months. You know, that's what some of these docs are struggling with, but they don't have alternatives. So inhibitory approach, then easy for the patient. MS patients, they have challenges to get their case of auto injectors. Less than 10-second autoinjection once a week, they take control of their own disease as opposed to having to get to an infusion center. Also I mentioned the economics of a Part D drug versus a Part B drug. Those are all really important factors. Ultimately, if you think about the unmet need in MS, and I put up a slide here, there's a clinical endpoint called PIRA, progression independent of relapse activity. You know this, Yatin. This is a clinical way that's been validated over the past few years to actually look at the decline that MS patients experience even when relapses are controlled. That's what we're trying to make a difference on. So we have the opportunity moving from the phase two to a registration program to actually include PIRA as a key endpoint. The currently approved CD20 agents weren't able to do that because the endpoint really hadn't been fully validated. So it's not part of their labeling. But we do know from at least one anti-CD20 antibody, Ocrevus, that, after some time they took the two RMS phase three study data sets and they put 'em together in a post hoc mechanism and retrospectively applied the PIRA calculation. And it looks as if it was actually impacted, but it's not in the label. It was post hoc. We have an opportunity to do it prospectively and actually differentiate in this unmet need, which is silent progression. I see. Okay. And then, in terms of, you know, when you go, then once you have this study, you will likely stick with this patient population or you sort of carve out another niche within the RMS or the PPMS patient population? That's an excellent question. Today we don't have to make that decision, but obviously we're working through the plan. You know, the base plan would include RMS. Yeah. You know, you might think, well, hold on, there are agents that are effective in RMS and preventing relapse, but we wanna do more than just prevent relapse. We're talking about PIRA. So yes. That would typically be two large randomized phase three RMS studies and then a PPMS study. Whether or not we can do just one there is, you know, something we're discussing internally and with our advisors. Ultimately you'll have the discussion with the agency. Got it. But it would typically be at least three registration trials to get a broader label. Got it. Very good. So then moving on to the IgG4-RD as an indication. I mean, obviously we have seen data from Uplizna there. I think the key focus from our discussion with investors have been, you know, number one is that the bar that has been established, which you have to meet. And two, what are the commercial dynamics there, right? You know, how big of that opportunity that is. So if you can just walk me through, you know, when we get data, let's say in December timeframe or later this year, like what we should be looking at, should we even compare to Uplizna or not? And then how the commercial setup there is. Let me start out with the trial that was already conducted because there was a phase II trial of obexelimab that was conducted at Mass General. Interestingly, the same group did a trial with rituximab, which is a depleting antibody. I'll get right to your question, but I think it's important to take a look at this data set first. The trial had similar patient populations. The trial was an induction and maintenance trial. Patients were in flare, put them in remission, then maintain them in remission. The control of flare was similar. You see that. Yeah. The time to control flare was quicker with obexelimab than a depleter, which I think goes to the point of how potent this inhibition is. In fact, in humans, pulling B cells out one day after administration of the drug, they are 80% inhibited one day after administering the drug, one dose. So quick onset, but something that stands out here in this study that, we find really interesting, and this applies to your question. We look at an important secondary endpoint in this study, sustained disease response. This measures patients beyond flare. This measures patients that just have disease activity. They may not have a score of a flare, so they're beyond, below that score, but they're still above zero. So they have disease activity that can lead to fibrosis and organ damage. It's measured in the study at the end of the study, you know, how many patients had sustained response, disease response or had complete remission to the end of the study. Here's where you see a real difference between our continuous administration with full target engagement, protecting the patient versus an every six-month drug where you're losing control at the end of the dosing interval. A 20% difference in disease response. If one goes to, you know, the trial setup with INDIGO, that's the obexelimab phase III and MITIGATE, which is the trial that you referred to that reported out, they're quite similar in design. Obviously, we did a larger trial over 190 patients and we completed that enrollment in November and the team did a great job. The primary endpoint are the same. It's time to disease flare. We know from the reported trial that 60% of the patients in the control arm flared and that is not unexpected, and 10% in this study arm. Yeah.i Go back to the obexelimab phase 2 and less than 10% flared, so we feel good about that flare rate. A difference may be, though, this concept of complete remission. Whereas the trial that reported out protected 90% of patients from flare, it only protected 57% of the patients from disease. So there's a difference there, and one looks at a depleting antibody that's dosed every six months. You can see that even in the blood, B cells are starting to bounce up at that six-month point, which means in secondary lymphoid organs and in tissue, they're clearly present causing disease. We think the opportunity with our continuous dosing is to impact that complete remission endpoint and protect the patients from disease, not just flare. Yeah. Yeah. I remember the chart or that figure, I don't know if you have it here, where the flares in Uplizna was around when the B cell depletion would be minimum in that study, around the 26 and 52-week timeframe. Very interesting. So those are the things that we should focus on. What about the commercial dynamic? You know, you will be, you know, second to market. Just curious how are you thinking about that? Yeah, I think it's interesting. We're second to market. I can't think of many categories where there's only two players. You know, we feel pretty good. You know, to us and the other company in this arena, we're doing a lot to educate clinicians, support the single patient support group that's now been established. This is an orphan disease that's newer, and I think those of you that have followed orphan diseases that didn't have a therapeutic, and then once a therapeutic was approved, how the whole disease progressed and the community built up and a lot of education happened, many more patients were diagnosed and the drugs ultimately become significant revenue producers, and this disease, we believe, and this is in the literature, and I think a variety of people have published on this, there are 20,000 diagnosed patients in the U.S. Many people in the field believe there are many more, but that's what's diagnosed today, and of that, the way we think about the market opportunity, about half of those patients will probably be managed with intermittent steroids, occasionally some rituximab. It's the other half that flare more, more often, so 10,000 patients annually with a remitting, relapsing disease, that's what this is, requiring the continuous therapy, and at the pricing that's in the market now for that, the other agent, that would be about a $3 billion U.S. opportunity for that subgroup of patients, and then what share do we get based on our profile? And I've listed the key points of our profile from a patient convenience, patient cost, safety, and potential efficacy standpoint. We think we can do well. Our team has successfully launched multiple products in the U.S. and Europe in the past in other company settings and are already engaged in Europe. We have our medical science liaisons everywhere. We have our market access people. In Europe, as an orphan drug, there's a different pricing paradigm. It's tough to negotiate prices in Europe, but when you have an orphan drug, benchmarks are different. We see an opportunity that's quite substantial there too. It's the first revenue generator. We think we have a really good opportunity to make a difference for patients and build a business. What would be the requirement in terms of the commercial build, sales force? So that's one. And then if we get the data by the end of this year, what is the timeline for you to file and get it on the market? Yeah. So as I described, we already have medical affairs initiatives, market access initiatives underway with the team. But when we look at an actual sales force and all the support around a sales force, that's under a hundred people in the U.S. and about half of that in Europe, we'll get that done. We've scaled sales forces before. We're kind of prudent about when to pull the trigger on that. There's a lot of work that can go into preparing the marketplace without having a sales force. But if you think about the drug being, having top line results, obexelimab from the IgG4 RD phase three trial about the end of this year, you know, historically, we file our BL, BLA several months later, and that would be the case. Europe is within a few months of that. And then we help our partner BMS in Japan file their submission. And, obviously with a drug with orphan drug designation, we would have the opportunity for a, you know, a reasonable turnaround from the agency, so that we would be launch ready by the end of 2026. That's not telling you when we'll launch, but the team has to be ready. Be ready around that time. Okay. Very good. Okay. Then moving on to the SLE, I mean, there has been some remarkable data with CD19, specifically, you know, this, the CAR T cell therapy. So I think there's limited doubt that the CD19 would work there or not. But maybe if you can just walk us through the initial data, I think there is some exposure-related data that you're showing here. Like just put that in context in terms of how this phase two study is set up and what would be the bar here you were looking at. Yeah. So the prior study, in an attempt to treat standpoint on the endpoint of flare, had about a 17% benefit over placebo. Our dosing regimen that delivers full target engagement, when looking at patients that had that C trough and target engagement in the same study, the effect size doubled to 35%. So we think we have a dosing regimen that's much more effective than the prior trial. And this is the trial design, randomized, placebo-controlled, BICLA primary endpoint, 24 weeks. And, using the new dosing regimen, and importantly in screening, all patients screened in the study have to go through a three-person adjudication committee to ensure we're getting true moderate to severe lupus. That's what has caused trials not to go well, getting mild lupus. We eliminate those patients and the trial sized at 95 per arm, has the power to be successful. Got it. How is the enrollment? So that data is gonna come in first half of next year? We'll finish enrolling this year. This year. In the first half of next year and we reiterated that again. That again. We passed on. Very good. Yeah. I think we're out of time. Thank you so much, Lonnie. It was very helpful. Big year this year with readouts. Yeah. Two really important readouts here and ending last year with $350 million in capital, we can deliver all of these endpoints through lupus, with the cash we have on hand. So very good. Thank you so much. Thank you.