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All right. Good morning, everyone. I'm Stephen Woolley, one of the senior biotech analysts here at Stifel, and glad to have with us as part of the next session, Vore BioPharma. We have Dallin Murray, who is the chief commercial officer, and Jeremy Sokoloff, who is the Chief Medical Officer. Thanks for joining us today, guys. Any opening remarks you'd like to make before we jump into Q&A? Well, firstly, thanks for hosting us, Steve. We are very excited to be here. We're very excited to be in the position that we're in. It's just about a year since we've created this iteration of VOR, VOR 2.0. We've just recently announced the completion of our global phase three study, and we have exciting data coming up in ANIM that Jeremy can point to later. And we believe we have best in disease data in our beachhead indication which is one of the most exciting dynamic and rapidly growing markets out there the mg market and jeremy also has a global study running very well in children's to date so lots of lots of progress in our first year but even more opportunity looking forward to future so looking forward to the discussion. Yeah, me too. Great. So maybe just broadly, you can talk a little bit about how you think about the mechanistic differentiation of teletassosept, specifically within myasthenia. I know when you look at the current treatment landscape, there are novel therapies that are targeting either upstream B-cell depletion or downstream circulating IgG. You're kind of the first to combine, you know, the two via BAF and April inhibition. So how do you think this differentiation reveals itself in the China data that we've seen to date and then potentially positions you for commercial success and what is obviously kind of an increasingly competitive marketplace? Yes, that's a great question. So telotacicept obviously is a dual BAF April inhibitor. And as such, it covers that upstream and downstream targeting of the B-cell developmental pathway, autoantibody production, all the way back to early B-cel maturation. And we think that often we're asked, why would there be such a differential efficacy from your mechanism versus a downstream mechanism such as FCRN or an upstream mechanism such a CD19? And the answer is exactly as you implied, which we think is that dual mechanism, and it's the ability to have that additive benefit where we first initially see relatively rapid improvement in acetylcholine receptor antibody reduction, acetyylcholine receptor antibody production. And it's that initial effect that is very similar, not identical to that seen with FCRN. But all that time, we're remodulating the upstream B-cell repertoire, and that does two things. One is it prevents repopulation of that autoreactive B- cell pool such that we don't get or we've really turned off the source of that auto-reactive B cell clone and auto-antibody producing plasma cell. But also, we think that the more we see, the more We're convinced there's an antibody-independent mechanism for B-cell-driven pathology in MG, and we think that the evidence for that is really drawn by the success, reasonable success, of CD19 targeting. Uplizna has a very nice efficacy profile, relatively similar to the FCRNs and the complement inhibitors, but it has a Very Minimal Reduction in Immunoglobulin, 9%, you know, total immunoglobulins. We don't think there's a directly disproportional reduction in pathologic immunoglobulin. Thus, there must be another mechanism by which this B-cell modulation is resulting in that magnitude of efficacy. So we think that when we look at the curves for the two different mechanisms, FCRNs tend to improve relatively rapidly and then have a period of stability where you don't see further improvement, or you might see a wave pattern where patients actually do get worse between cycles and then get better, versus the CD19 upstream B-cell depletion mechanism, where you see slow but gradual improvement, which tends to further separate even between 18 to 24 and 24 to 48 weeks. And if you look at those two patterns and you superimpose them, that's the pattern we see with telotacicept. So we think what we're capturing is that early momentum and increased depth of the FCRN mechanism, and then similarly the durability and continued remodulation of the B-cell response through the upstream B-cel targeting through the BAF mechanism. So we think it's that additive mechanism. One investigator used a term, he said, we're really looking for combination therapies in MG and telotacin may be the first combination therapy. Again, it's one drug, but it has that dual targeting mechanism. Yeah. And Steve, to your question of where it positions us in the market commercially, We think this dual mechanism will, you know, it's all going to come down to the data. And we think it will allow us to come into the market with best in disease data. And I think you can look to Argenix in the market earlier who came in in 2021 with a differentiated profile. If you can show differentiation on efficacy and or safety, the market, you know, they're dominating the market now. So while it's an orphan market, there's no, you know, one-time gene therapies. If there's a better profile of a drug coming in, the physician and patient community will move to that new option. Maybe just another quick commercial question. So I know that we've seen some recent literature that's been talking about the contribution of IgA and IgM antibodies to the pathology of MG. What are the commercial implications of these findings for TELI, and is this something that clinicians are looking for via serology at time of diagnosis, or is it just really you're an adequate FCRN responder, it might be due to this? Yeah, it's a great question, and Jeremy can talk to what's available diagnostically today. This data that's come out of Yale showing IgA and IgM is resonating with the physicians because about a third of patients have these antibodies that are fixing acetylcholine, and it correlates with about a 3rd rate of non-response to the FCRNs. There's not a commercially available assay to test this, but I think that this advantage that we have that we target IgG, but in addition we target IGA and IgM, is a key advantage and it speaks to the unique opportunity we have here. even if you are on the conservative side and you don't believe we're going to come in with best in disease data we have a response rate that uh that we think is driven by this broader immunoglobulin coverage and 100 of patients are getting at least a two-point or greater response on the mg adl and that's significant that's unique and differentiated in the market and and we think this is what's driving that and so even if your um a little bit more conservative on the expectations of what our efficacy might be, this IGA and IGM coverage positions us very well for second line use, even if we don't replicate the delta from China. Even if we come in with a delta, we lose it entirely. That looks similar to the rest of the market. We have a $3 billion opportunity in second line that we can target. So that speaks to how de-risked the asset is. And the recent launch of uplizna um gives us a even more conviction on this opportunity because um the delta on mgadl was was um lower than what you see in the market was so true yeah and their their launch is exceeding all expectations and the company themselves have said they're getting about 50 percent of their usage is in first line patients so it really speaks to the appetite in the market for targeting upstream, a new modality. Until Blizna launched in December, the biologic market in MG had really just two modalities of FCRNs and complement. So it speaks to that unmet need and the demand in the market für different modality für, you know, clearly the current options are working for all patients. Okay. So I know you recently completed enrollment in the upstream MG trial. Congrats. I believe this study was already actively enrolling patients when you assumed control from Remagen. What can you just say about the consistency about the types of patients that were enrolled throughout the change in sponsorship here? I know it's a question that we get from investors sometimes. Yeah, there was very few patients enrolled during Remagen's ownership of the study. So the vast majority of patients were enrolled during our oversight. The patients are not particularly dissimilar. I think there was a more rapid uptake in Europe and South America early on during the Remagen phase. The U.S. sites hadn't really come on board and been aware of the mechanism. I think one of the things that we did, which I think was helpful, was really engaging with U.S. investigators, key opinion leaders, scientists, and really showing them why a Bath-April mechanism scientifically was a good opportunity in MG, and also making a good partnership with all of our sites and investigators. I think there's so many good sites and investigators globally, they're just looking for a good partner. So I think really what it was, was making that partnership both operationally and scientifically. And so most of the patients were enrolled under our leadership. And I think that that really will represent a typical, potentially optimal global population by final analysis. And then what are some of the key differences in terms of the patient baselines in the global phase three in the upstream study relative to the phase three China trial? And how should we think about these differences potentially impacting expectations on the clinical efficacy side? Yeah. So I think the two demographics that are different are the age is a little younger in the China population than the global population. The disease duration's often a little bit shorter in the China population. And so I think that's a little different. I think it's a lot more than the global population. And that just really represents the referral patterns in China. Patients are referred to tertiary care academic centers that conduct clinical trials very quickly, community neuromuscular docs. So I think that's the main reason we see that. But really, I think the other difference is just the, there's some cultural differences. Dallin and I traveled to China, went to a couple of the largest sites that were involved in their study and are also involved in our study as well. And what we learned was, you know, patients in general in China have a slight reluctance to over-represent reporting, to over reporting. So they tend to be a little more stoic, which is why the placebo rates tend to Be a little bit lower. And it also tends to blunt the active response in patient reported outcomes. What we find is that in the physician administered outcomes, like called the QMG in Gravis, they tend to be pretty similar to the global population. So we hope that, you know, the results observed in China will be very similar to the results that are globally for the QNG and the results for the MGADL. We anticipate some increase in the placebo globally relative to the China study, but we also anticipate a relatively proportional increase in The Active Arm relative to The China study. So hopefully that delta, that effect size is maintained in the global study. Okay. I know in talking to KOLs, we've heard kind of more of an emphasis on this minimal symptom expression. So MSE is kind of an important differentiator on the efficacy front. Just given that the disease itself is kindof so heterogeneous and kindof all of these phase three studies are kindof delivering this 2.MGADL delta. But so how do you think about the competitiveness of Tally on this MSE endpoint? And then maybe particularly as it pertains to this sustained MSE and not just kind of MSE at any time? Yeah, I think that's really important. So MSE, just minimal symptom expression, just for reference, is an MGADL of 0 or 1. Basically, it's remission. And it's great that that's the goal. And that should be the goal, everyone wants to be free of disease. The reality is the way MSC has been reported has been very variable. It's attainment at any one point over 24 weeks, any one point over 48 weeks, any one point over four years. And again, that's really not the best way to think about it. So again, like you suggested, we think that patients want to be in MSC and they want to stay in MSE. So that's the sustained durability of minimal symptom expression of remission. So that'S how we're measuring it. So I think one thing that, I don't want to speak to how other people did it, but I'll just say that anytime you have an MSE report, the question is over what duration and of what consistent magnitude do you want to see that MSE maintained? In our study that we'll be reporting out at the AANEM meeting next week, actually, we'll be showing both the rate of MSE, but also the durability of MST. So of those patients who attain MSE, who gets to keep it? And, you know, the analogy we use is like giving a child a toy. If you give a child toy and take it away, you really didn't do them any favors. They get pretty upset. Whereas if you let them keep it, I think that's really the goal for minimal symptom expression and disease remission. Okay. And I know this similarity in, I guess, MGADL effect sizes across a lot of these studies has placed a bit of an emphasis on things like safety, convenience, administration. I know there's a lot of patient data to support the safety profile of tele at this point, but can you just talk about where you are with respect to formulation, the longer-term administration profile you're hoping to bring to the commercial setting and just what the timelines are to get there? Yeah. So right now, we're giving two subcutaneous injections weekly. So they're low volume injections, one and a half mils. But at the end of the day, we are looking to reformulate. In fact, we have a reformulation which is active right now. So we will launch, anticipated to launch with the current formulation, which is the two shots weekly. That will rapidly be replaced by a single pre-filled syringe weekly and an auto injector option as well. We're leaving both options on the table because we know patients like to have that optionality, both for the providers as well as for the patients. So again, we haven't had a whole lot of complaints about the double injection right now. We don't think that the double injection will be very long in its launch cycle, and we're excited to get a single injection weekly. Notably, the single injection is kind of the timetable that most people are comfortable with for myasthenia gravis, and so we think that by following that cycle, we're not at a significant disadvantage. That said, you know, we are doing everything we can to make it more convenient for patients to administer at home. Yeah. And, you Know, given our confidence about our value proposition in the market, Steve, we're actively doing lifecycle planning. And once we have that one once a week shot, we'll move very rapidly into an auto injector for more convenience for patients as well. So and more to come. We're in this market for the long term. Maybe, Dallin, where are we with respect to just the percentage of MG patients who are on a biologic now? Do you think a disease like MS, where I think three-quarters of patients are on the biologic, is that a good proxy for where the MG market expands to over the longer term? I guess, if so, what are the TAM implications of that? Yeah, it's certainly where we would like to go. We would love to replicate the success of the MS market. And it's a great question, Steve, because you do hear different numbers from different companies out there. But general consensus is that there's a huge runway still to go in MG, that about 20% of the patients with MG are currently treated. And so as the market leader, Argenix, starts to expand out, different companies may have different denominators because there are genics is moving to ocular mg as we will be doing as well and seronegative mg but generally speaking the you know the we spend a lot of time talking about differentiation between the the drugs here but the biggest opportunity is the is the penetration in the market and and i think there is a pathway to get there the market's been growing at a rate of about 60% per year. It's an orphan market with high value therapies in the market. And so as in any market, there's friction, and that friction slows the rate of patients getting on therapy. But as we see, there has been a predictable 60% or so growth every year. And so I think the docs are fighting for access for their patients. And just through new entrants like Amgen coming into the market and we will come into the market, you're going to see that grow and the penetration hopefully get to levels similar to what you see in the MS market. And we'll keep fighting for patients and for access for patients. And we think there is a huge existing unmet need in this market, both in the biologic treated portion, but more even in the in the biological naive segment of the market. Okay. Yeah. I know that there's another dual April bath competitor that's following you into MG. This is Vertex's Povitacicept. I Know that they're guiding to, I think, a disclosure of phase two data in the first half of next year. How would you characterize the differences between Povie and Telly? And I guess, how do you think about that data reading through to what you're doing in MG, specifically if we happen to get that before your phase three. Yeah. So telotacicept and povitacicect are similar. They're both based on that TASI framework. Teletaciceft is more similar to the native TASi, which has a two to one BAF to April potency ratio. Povitacicezt is slightly more engineered for higher potency, but it ends up with a higher potancy for April relative to BAF. and that becomes relevant in a moment. I think operationally, I can't anticipate too much. What we know publicly is that they're doing a 12-week study. At a 12 weekend point, I think you may see some significant efficacy, but what you won't have a chance to see is the amount of continued reduction after 12 weeks from that upstream BAF mechanism, as well as the durability of response. So I wouldn't read through too much from either a highly successful or a highly unsuccessful study with povitacicept. Should they read up before us? I think the key thing to understand is that April is a good mechanism for decreasing autoantibodies. We see it with our mechanism, and we'll see it mit povitazicepti. The real ability to differentiate, we think, comes down to the ability to remodulate that upstream B-cell pathway and get that long-term durability that's seen, you know, similar to the CD19s on top of what's seen with the FCRNs. So we think that there may or may not be the ability to get that Long-Term Durability and continued improvement over time with a molecule that has less targeting of BAF relative to April. We all dose to April as our goal and can't overshoot April because if you do, you end up with hypogammaglobulinemia, and that's been a risk with several BAF April inhibitors. We don't see that because we dose exactly to the right level of April, knowing that we're overdosing on BAF because BAF is a relatively safe area to go higher than your target and supersaturate that target. Ben Lista taught us that one milligram per keg, 10 milligrams per kegs, similar efficacy, similar safety. Whereas with April, if you go over on April, even by two or three fold, you can very easily end up with hypogammaglobulinemia. So when we all dose to April, some molecules may under target BAF relatively and end up with a loss of some of that long-term remission and that long term remodulation that we're looking for. On a timeline perspective, again, we think there's an advantage to being roughly three years ahead. We're completing phase three. They're somewhere middle of phase two. Dallin can speak to some examples of where that first mover advantage, especially in a rare indication like MG, has just really been a massive separation commercially. Yeah, Steve, we think the first mover advantage is huge here, especially in this orphan market where you've got a small number of neuromuscular KOLs driving the market. And again, we don't need to look beyond MG to see the importance of that. Argenix was the first FCRN. They had less than half the lead we'll have over Vertex. And the second and third FCRMs have hardly made a dent in their market leadership positions. So we think it's very important here. As Jeremy said, there's important mechanistic differences. And then Jeremy alluded to the dosing to April and the safety potential implications. One of the underappreciated advantages we have is the 3,000 patients that have been studied in randomized control trials with this mechanism in multiple indications and tens of thousands of patients treated in China. So very well characterized safety profile as we're going in. And in MG, it's our higher doses, the 240 mg per week. And so I think that is going to be important in a market like MG, that long-term safety data and the reassurance that comes with it. So in addition to the three-year head start, we have a lot of other advantages that will set this out. Okay. Maybe just on the ocular opportunity that you talked about. So I know a lot of patients will initially present with ocular symptoms. And then most of those patients will progress to the generalized form. So when you enroll this phase three, are you going to be including some of these early presenting patients with occular symptoms, or is it just going to be kind of like the pure documented ocular pathology. And then do you think that there's a scenario whereby like if you intervene early and treat the ocular symptoms that you can somehow prevent progression to generalized disease? Yeah. So in general, our approach is to enroll MGFA class one, which is basically an ocular population with minimal generalized symptoms. The goal is really to show the ability to improve ocular systems and access that early patient population, which is a gateway to the larger junk GMG population. Your second question is a great one, which we do think that our mechanism gives the opportunity to have some degree of abrogation of progression from ocular to generalized MG, and that is one of our exploratory outcomes. We're running a 24-week randomized study. We'll have an open-label extension for at least a year, and so we will hopefully be able to see some separation. We're not counting on that as our primary approval point, but it's definitely something we think is both mechanistically probable, but also something we can potentially demonstrate during that long-term extension period, which is something that probably won't be demonstrated with FCRNs. Yeah, we're super excited about OcularMG. We're going to be third to market here, and we're going be first with the upstream targeted mechanism of action. So we feel like we got fortunate with Ocular MG because if you talk to the KOLs, they'll tell you, you know, Ocular Mg is just an earlier, it's all on a spectrum. It's all Mg. And I think probably part of the reason that there's only two other companies there is that people probably felt that you were going to get the OcularMg opportunity by default. but the payers have made it such that you need to do the work here. You need to do the studies and you need the get the indication for these patients. And so that has all resulted in us going from being 12th in generalized MG to third in ocular. And so we're really, really excited. And as Jeremy alluded, it does get us access to these patients earlier. It puts us on an even footing with Argenix in what we believe will be a battle for the first-line patients in this market. Okay. I know we're running out of time here, but maybe you can squeeze a children's question. So I know you have the phase three that's ongoing. The placebo response, I think, also comes up here. And I think you've got kind of two disparate examples, right, where you havethe phase three tele-China data that had a very muted placebo response. You had the Novartis-Neptunis data, which had a very inflated placebo response, so how do you connect the dots on the differences between those two studies, and then how do you just incorporate those assumptions into your power? Yeah, so we obviously are powering for an effect size that's lower than the one observed in the China study. We don't think we will phenocopy the China of study in terms of Sjogren's. We know we're going to have a higher placebo. If you look at the Neptunus study, it was obviously the high end, somewhere in the range of five. The population tends to, when you remove Neptunas, be somewhere inthe range of two to three. And so I think, you know, we would anticipate that that would be a global population placebo that we'd observe. Whether our active goes up proportionally, we maintain the delta, that'll be ideal. But even if it narrows, you know having a delta that's two and a half to three and a half would be really still a game changer in the field of MG. So we anticipate a higher placebo. We're doing a lot of things that we learned from the Neptunus studies and from other studies, how to mitigate that placebo. We've incorporated them into our clinical design, into our study oversight, and we're just going to do our best to make sure that we enroll the right population of patients. We think we have the right investigators on our team, and And we're fairly confident that mechanistically, this teletastasep will demonstrate significant efficacy and presumably differentiate efficacy from the two reportedly successful studies that we've heard about, Ionalamab and now more recently, the CD40 from Amgen. Yeah. Any quick thoughts in the last 30 seconds on CD40 ligand as a target? Again, so the nice thing about the Bath-April mechanism is it targets the breadth of the underlying immunobiology of Sjogren's. So Sjогren's, yes, there's autoantibodies, and those autoant antibodies cause disease. But there's also a significant amount of antibody independent B-cell driven pathology. One of the things that those B-cells do is T-cell co-stimulation. So that's something that also is abrogated by telotacicept. And then there's just the upstream biology of cytokine production and B-cell hyperactivation, the whole lymphoma risk spectrum, which is a small portion of the pathology-driving Sjogren's. We think that autoantibodies and FCRNs and those type of mechanisms are limited to a proportion of the underlying pathology of Sjогren's, and we think that Ionalamab targeting BAF and B cell depletion targets only a small proportion of the methodology underlying the Sjogn's pathobiology. We think really to get that maximal efficacy in Sjogren's, you need a mechanism that covers the breadth of that B-cell immunopathology, and we think Baf-April is an ideal mechanism that does that. There's translational data to support that. There's the China efficacy data, and hopefully there'll be our data shortly to show that as well. Wonderful. Well, we are a little bit over time, but I appreciate you guys taking the time to speak today, and мы really looking forward to what should be incredibly interesting next six to nine months. so we're really excited for our readout in the spring and we're looking forward to taking you along with us thank you so good guys thanks for hosting us bye