For tuning in to today's fireside chat with Immunovant. I'm Sam Slutsky, one of the senior research analysts at LifeSci Capital, and we're joined today by Dr. Pete Salzmann, the company's CEO. In terms of format, there'll be a presentation on the background and positioning of Immunovant's FcRn inhibitors, and then this will be followed up with some Q&A. With that, I'll turn it over to you, Pete. Thanks, Sam. I appreciate the invitation to review a good amount of material. I'm gonna, as you mentioned, go through that material, then we'll have plenty of time for Q&A. I will be making some forward-looking statements today, and I direct investors to carefully read the statement, which is part of the 8-K when we released this slide deck this morning. Just for quick orientation, these are the programs that we have in development across our two assets, tocilizumab and IMVT-1402. Today I'm gonna focus the discussion on a lot of the clinical biology related to IMVT-1402, and then I'll also talk about chronic inflammatory demyelinating polyneuropathy or CIDP and our program there, which is clearly of a lot of interest given potential data readouts from rozanolixizumab in the first half of next year. We may touch on some of the other programs during the Q&A, but I won't cover them in this general overview. Here's what I'm going to cover, and, without reading everything, you'll see that, you know, the first 4 items relate to 1402, and also some foundational Fc analogy so that we can draw some conclusions and sort of interpret the data that we've shared with regard to our 1402 assets. I'll go into the CIDP design. Starting at the very beginning with autoantibody-driven diseases, this is a new slide put together because I think the class, which includes many, many indications, if you look at what is all being studied by one or more competitor, has grown to include not only classic autoantibody conditions like myasthenia gravis, which is a rare eye disease, or autoimmune hemophagocytic syndrome, but now also conditions where autoantibodies play a role. They play a role in disease pathogenesis directly, like they do in myasthenia gravis, for example, or they play a role through forming immune complexes with their antigen, and you get a multitude of autoantibodies to antigens kind of forming a larger immune complex, which then activates other components of the immune system. Those are, those biologies have some important differences, and probably most importantly that anything that's immune complex driven is likely to have a longer immune system activation and therefore may need a deeper and more prolonged reduction in the autoantibody in order to get the disease under control, given that the autoantibody is just one of the pathogenesis. We've already seen in our pre-submissive data that even in classic IgG autoantibody-driven conditions, there is a correlation between depth of IgG reduction and clinical response. Our takeaway is that it's important to be able to deliver a wide range, including saturating top of the curve reductions in IgG in order to address the full range of clinical symptoms in these different conditions. For those who are a little newer to the story, one of the things I love about this mechanism and what attracted me to Immunovant in the beginning was its simplicity. Many immunologic mechanisms are complicated. There's an interplay between different cytokines and cells. When you're at an early stage of development, there's a fair amount of uncertainty in terms of how the change in the biology that you affect with a new medication actually leads to clinical impact. In this case, it's very simple, which is you see the green antibodies here. These are endogenous antibodies being recycled by an endothelial cell. This would be a cell sort of lining a blood vessel, for example. This process of kind of constantly taking out of the bloodstream and then breaking it down into its amino acids is important so that proteins in the bloodstream which are Of IgG reduction that can be achieved and how easily that can be achieved. We'll get into that a little bit later in the presentation. Because we have unveiled a new anti-FcRn, and this is the first new anti-FcRn in quite a while, I have gotten a lot of questions back to the pre-clinical data, which was something I used to review in detail a couple years ago. Since there hasn't been a new anti-FcRn lately, this has not been such a topic of discussion until we unveiled 1402. We wanted to sort of dust this information off and kind of organize it all in one place. The first thing that you see is there are some differences in the backbone. The tocilizumab and 1402 have a very similar background. They are both IgG1s, but beyond both being IgG1s, they're very similar IgG1s. They come from sort of the same family of antibodies that were in both cases originally discovered or developed by HanAll Biopharma and both were licensed to Regeneron. Epratuzumab is an IgG1 fragment, nipocalimab is also a fully human IgG1, whereas rozanolixizumab and batoclimab, an antibody now owned by AstraZeneca are IgG4s. There's some differences in sort of the scaffolding or the structure of the antibody. In terms of Fc effector potential, you see the information we've been able to find from public sources. You know, importantly, nipocalimab, epratuzumab, tocilizumab, IMVT-1402, when you test them in vitro in standard assays, which are used to determine whether the effector potential has been sort of, you know, all scored negatively. The mechanism of deactivating effector potential is a little bit different, in the case of antibody by antibody, but the end result is the same for those four. We get to a topic that generates a lot of discussion and probably generates more discussion than it's than it is actually relevant. I think, yeah, because it generates so much discussion, it's worth reviewing, and that is what is the binding affinity at different pHs? The pH is 7.4, and that's important because that's the pH in the bloodstream, for example, with Fc receptors on the cell surface and in that endoscopic vessel that's first being formed. Once the vessel forms and is brought intracellularly, the pH drops. That's important, for the normal recycling of IgG because I don't have it on this slide actually, but the endogenous IgG does not bind to the Fc receptor at a normal pH of 7.4, but does bind to the Fc receptor at a acidic pH. That's what allows the recycling. Otherwise, the IgG, normal IgG, would just get stuck to the Fc receptor. Since it comes off the Fc receptor at a normal pH, it's protected intracellularly and released extracellular. That's for a normal endogenous IgG binding at its Fc site. The Fc inhibitors, of course, don't bind to their Fc sites, but they're describing that the antibodies bind in their variable regions. That was kind of shown in that slide as the other end of the antibody, which is where those variable regions are. What is the binding affinity between the variable regions of different antibodies and the Fc receptor, and does it change depending on whether you're at a neutral pH or an acidic pH? You see that for the antibodies, your tocilizumab, IMVT-1402, nipocalimab in particular, I'll focus primarily on those for today. The binding affinity is pretty similar whether you're looking at acidic pH or neutral pH. There's not a full order of magnitude difference. The largest difference, I guess, on a relative basis is for tocilizumab is a little bit more tightly bound at the acidic pH than at the neutral pH. For Epratuzumab, there is a pretty big difference. There's more than a 10-fold difference in the reading. The Epratuzumab can be less likely to bind in this in vitro analysis, just generally because a larger number is associated with a less tight binding and a smaller number is associated with a more tight binding. At the neutral pH, the binding affinity is a lot lower than what you see for these other ones as represented by a larger number with the acidic pH. Whether that has much impact or not on the ultimate thing we're all trying to do, which is lower IgG, it probably has some impact. From the perspective of Immunovant and our two assets, you'll see that if we compare 1402 to tocilizumab, that the binding KDs are a little bit lower for 1402 than tocilizumab, meaning that 1402 is a little bit more potently binding the Fc receptor than tocilizumab. I'm not sure these differences. In fact, I'm pretty sure these differences aren't gonna be big enough to matter, meaning that the amount of 1402 that we'll need to achieve the same degree of IgG lowering that tocilizumab has shown is probably gonna be pretty similar. I suppose if, you know, if they're gonna be different, I'd prefer for the 1402 one to be a little bit lower, and that's what it is. The other topic that generates a lot of discussion is half-life, and half-life is very tricky for FcRn since there's a target-mediated disposition, and there's a lot of variability based on the dose, on whether you've saturated the Fc receptor or not, which is involved in the disposition or recycling of the asset. This is an area that I think is generally just not too helpful, particularly because there is so much data on the pharmacodynamics. The pharmacodynamic curves, the slope of the curves are very similar across all these assets. The depth of the curve, meaning how much IgG you get, is dose-dependent and asset dependent. The time to peak reduction and the time to recovery is generally a matter of weeks for all these assets. We don't see big differences even though there are some big differences in the, in the PK half-life. Okay. This next section deals with crystal structure, and this I think is very interesting information. There is some data available that we found publicly beyond just batoclimab and IMVT-1402. To start out with, just the endogenous protein. Just to orient everyone here, the purple and yellow ribbon structure is the FcRn receptor. Here's a co-crystal structure of the FcRn receptor binding to the Fc portion of a endogenous IgG. You can see that the binding site is over here, 4 o'clock or so. On the left side of the slide, you can see the co-crystal structure between Fc receptor and albumin. Albumin is also recycled via the Fc receptor, albumin also has a much longer half-life than many other proteins. The binding site though for albumin is different. It's over here at sort of 10 o'clock on the Fc receptor in this orientation versus the IgG binding site with the other slide. When you put the two, when you overlay the two crystal structures, keeping the Fc receptor kind of the same so that you can do that overlay, you can see that the Fc and albumin don't appear to sterically interfere with each other, which makes sense given that, you know, these are recycled independently. How does 1402 and how does batoclimab bind to the Fc receptor? Here we have some other co-crystal structures. We have the co-crystal structure of batoclimab, the co-crystal structure of IMVT-1402 with the Fc receptor. Again, kind of always keeping this Fc receptor in the same orientation. You know, binding site and the batoclimab binding site are similar. They're not exactly the same, but they're slightly different epitopes within this general IgG binding site. IMVT-1402 binds in a steric orientation that's closer to this natural steric orientation of an Fc, an endogenous, Fc, IgG binding. Whereas batoclimab, although it clearly inhibits IgG binding very well, since you can get to saturating doses at reasonable milligrams, the 680 milligrams gets to maximum IgG reduction, which is about 80%. It completely blocks the IgG binding site very well. Its steric orientation is in a different direction. When we put, I'm just gonna skip ahead and then come back. When we put all four proteins together, you can see that the batoclimab is sterically interfering with albumin, which is probably how it why it causes a reduction in albumin. I'll come back to that in a second. Just looking at two other probably available co-crystal structures. The efgartigimod didn't have data that we were able to find. The Fc is in a slightly different orientation. You can see we put it in a different color. It's not exactly lined up like ours. I think you get a general sense that it binds probably very similarly to an endogenous IgG, which makes a lot of sense because it's binding in the same way as an endogenous IgG. Syntimmune also binds similarly from a steric orientation standpoint as does IMVT-1402 and efgartigimod and the Fc receptor. Batoclimab is kind of the outlier in terms of how it binds. We weren't able to find any publicly available information for nipocalimab's co-crystal structures, so we don't have any idea how nipocalimab binds to the Fc receptor. Returning to the R2 assets and kind of putting everything together. Starting on the right with batoclimab, which I already referenced briefly. Batoclimab binds to this IgG binding site. Its steric orientation is such that there's an overlap, probably overlap here between albumin and the batoclimab, and they're both going to bind the Fc receptor. Although it doesn't block the albumin binding site, it's bumping into albumin and probably inhibiting or making it a little bit more difficult for albumin to bind to the Fc receptor, which is why you get a dose to kind of reduction in albumin. On the other hand, IMVT-1402, which we'll see in a moment, did not lower albumin at saturating doses in a cynomolgus monkey model. That makes some sense given that its orientation is much more similar to an endogenous Fc, and it doesn't appear to be putting any more. Those are overall human co-crystal structures, and that's all human data. We don't have human data yet for IMVT-1402, but we do have data from cynomolgus monkeys. What we see in this head-to-head cynomolgus monkey study is data from 4 different test articles. We tested batoclimab at 50 milligrams per kilogram, which is about 5 times the saturating dose of batoclimab. When we study batoclimab in other monkey studies, at 10 milligrams per kilogram, that's a saturating dose in monkeys. 10 milligrams per kilogram of batoclimab 680 milligrams of batoclimab in the human. This was weekly doses of weeks, these gray arrows down here. We chose 50 milligrams per kilogram of batoclimab just to make sure we had a very saturating dose, and we wanted to be able to compare that very saturating dose of batoclimab to a likely very saturating dose of IMVT-1402 with regard to albumin and cholesterol. We wanted to flush any signal out if it were there. Because remember I showed you that the binding affinities between these two are pretty similar, so we expect the milligram per kilogram impact to be similar between batoclimab and IMVT-1402. What we see is that that saturating dose of, or super saturating dose of batoclimab does what we expected and what we've known from prior cynomolgus monkey studies, which is that it lowers albumin. These thresholds refer to upper and lower in the cynomolgus monkey. They're slightly different than in people. You can see that curve that goes down in 2 weeks and then recovers in weeks, which we're well familiar with. When we looked at that high dose of 1402, and we did also a lower dose of 1402, and that was more to see the impact on the V side, which we'll get to in a minute, and then placebo. If we look at albumin, you know, there's some variability in albumin measurement, for all 3 curves because there's just some variability of the assay. It's a good but very old assay. It has some variability. The placebo, the high dose, and the low dose 1402 all basically look the same. Particularly after 4 doses here, you know, you're looking at this 4th dose that was given here, and this the albumin right after the 4th dose was really pretty much overlapping central tendency between high dose IMVT-1402 and placebo. The low dose IMVT-1402 actually had a little bit higher albumin. I don't think that IMVT-1402 is raising albumin. Again, it just goes to show you the variability. They all start here at the same point. There's variability in cholesterol and LDL just as a measurement. Part of that probably has to do with the cynomolgus monkey biology and some of it may also have to do a little bit with the assay. Again, we see batoclimab clearly separating from the other three lines, whereas the high dose, low dose 1402 are more or less overlapping with the placebo. placebo. Particularly if we go out here at, you know, at day 4, they're pretty much overlapping. Okay. One of the questions I get a lot of questions on is, well, remind me what does the data look like for the other assets, and how much can we expect this data in the monkey to translate, in the cynomolgus monkey to translate to humans? I think the trends have always been consistent. Efgartigimod does not show change. This is all public data we were able to find and put the references down here. Did not show any change in monkeys, didn't show any change in humans. Bentamere, no change in monkeys, no change in humans for albumin. Nipocalimab, there's no published data published, but we were able to find some commentary from a nipocalimab that did show that they did show differences in albumin in the multiple early dose studies in the monkeys and that was shown in humans. Risatlinib has very small changes, 1%-13%, which is kind of within the range of variability in 1%-5%. Either it's sort of no difference or maybe a very small difference, but in any case, it was consistent. batoclimab observed differences and then observed dose-dependent differences with the same in monkeys and in humans. With IMVT-1402, we only have the monkey data. You know, if we can rely on these trends with these other five assets, then we would expect not to see a change. The reason they have no or minimal is because obviously you can't say exactly 0 with a study of this size. Again, if we look at the end of 4 weeks, look at that central tendency, it really looks like there's essentially no change. You know, whether there's a tiny little change in either direction, we can't exclude that, but we're not seeing much there. How about on the IgG side? You know, that's great as long as we're also reducing IgG as strongly as batoclimab. Here we have the comparison. Again, these are both high saturating doses, but they're essentially the same. 5 milligrams per kilogram is not a saturating dose. Per modeling what the batoclimab low dose is the amount we tested in monkeys with 10 milligrams per kilo. If you go to really low doses of a test article, you're doing safety studies in the monkey. But when we model what 5 milligrams per kilogram would do with batoclimab in a monkey, it looks like what 7 milligrams per kilogram does here, which is, you know, not quite as good as getting the saturated dose. Similar to I would think of this as kind of the 340 equivalent, and this is kind of the 680 equivalent for batoclimab. This all looks, you know, looks good and very consistent with what we would expect from an antibody that's likely to have very similar IgG. Why does that all matter? What do we get with IgG lowering? What we get is a nice continuous relationship between the degree of lowering and clinical response across a range of conditions. This is data from the efgartigimod myasthenia gravis phase 3 trial. We have a similar curve from nipocalimab phase 2 trial, which was a large phase 2 with multiple doses, so they were able to really define this well. Essentially, what you're seeing along the x-axis is change in IgG and along the y-axis change in MG-ADL, and there's a nice linear relationship. This one's just kind of a small picture, but the P value is very, very, very low here, very strong correlation with phase 2. Same with the efgartigimod data. I know it was a small trial, but even our small trial was consistent with this, where the degree from versus the 680 arm, 340 had lesser IgG reduction and, you know, lesser autoantibody reduction. Although it was different than placebo, and similar to what other antibodies or inhibitors have shown with a 65% issue reduction, the 680 is proven with better on IgG and better on MG-ADL. Which is why we included the 680 in the induction portion of our MG trial. In thyroiditis, we actually tested three different doses. Again, sort of same pattern, higher IgG reduction. This is through 6 weeks of the 12-week study. We're doing this post-hoc analysis at 6 weeks because that's when we had the most patients that completed 6 weeks since the start of study was interrupted. This line refers to sort of a threshold effect of the stimulating autoantibodies. When you get below 140, that's where they're thought to go from having a stimulating effect to no longer having a stimulating effect. At the 140, threshold means that you'd then be sort of similar to a normal person that didn't have thyroid-stimulating hormone receptor antibodies. You can see that a greater% achieved that sort of normalization on the 680 dose. That's not surprising because you had a lower overall reduction in IgG. Again, the apoptosis response was stronger in the 680 arm. We also have CT scan data that we showed previously, where you had a bigger impact than the 680 versus the 340 versus the 255. A lot of good results there. Different condition, ITP. This is a nice large study that UCB had with a lot of different doses, range of IgG reduction, and again, a dose-dependent platelet improvement. The Upartimab Pemphigus Vulgaris study, they had different cohorts in term s of duration of therapy and frequency. The two cohorts that had the most IgG suppression for the longest period of time had, you can see here, the new max IgG reduction was lower, and the complete response rate was higher, and the relapse rate was lower. A linear correlation across, you know, every disease where multiple doses have been tested between high therapeutic load and. We don't think that there's a threshold effect, by the way. There's not as much data when you get out to the lands of pretty reduction. I don't think that this curve suddenly flattens at 60% or 65%, and there's no benefit to be had beyond 60% or 65%, which is sort of what most FcRn inhibitors deliver. batoclimab at the dose that it's being studied generally delivers around a 65% reduction. At a much higher dose, it would probably also deliver a higher reduction in IgG, but the doses that are being studied deliver this 65%-ish reduction. We think of that more is going to be required in treating patients for different patients. That's a big advantage of tocilizumab for a period of time, induction, and potentially a big advantage for IMVT-1402 for long-term therapy. Again, multiple lines of evidence that greater IgG reduction yields greater clinical response. We're providing this column here of IgG reduction. This is sort of organized as the different, several different assets and then whether they impact albumin or LDL, what degree which they reduce IgG, route of administration, things like that. This is probably the most important column here because, efficacy, we believe, is gonna correlate to degree of IgG reduction. It's not gonna stop at 65%. Efficacy, differences are probably one of the biggest differentiators product to product but particularly in diseases that have a lot of unmet need. Most of the other assets are really delivering IgG reductions in the 65% range. The nipocalimab does get a little bit higher, but that's for short periods of time, and the higher doses are associated with a pretty high rate of headaches, so that may be dose limiting. It also has some limitations in terms of delivery mechanism with a subcutaneous infusion that takes quite a while. Although it does deliver a little bit higher IgG reduction, there's things that may limit that from a practical standpoint. Similarly, nipocalimab, when you give it in high doses intravenously, also can reduce IgG, up to 80% or even a little bit higher that they've reported. In the dose that's being studied, here this refers to the nipocalimab dose in their MG trial because that's the dose that's publicly available, and it's 15 milligrams per kilogram every 2 weeks after looking at it for 3 weeks per week. That dosing regimen, we estimate is gonna also be in the 60%. The tocilizumab can do that with the 340 milligram dose. What we can also do with the tocilizumab is achieve this 80% reduction, which indicated we believe is gonna be the difference for differentiating on efficacy. If IMVT-1402 pans out in humans, I think it's looking very productive. The cynos one is going to be able to do that similar reduction without having an impact on albumin and LDL, which is really significant in terms of a product profile. Both the tocilizumab and IMVT-1402, we plan to make available through the simple sub-Q. The tocilizumab is already, you know, being used in the clinic as a simple sub-Q. And by simple sub-Q, I mean it's normal preparation, normal like a lot of other biologics, concentrated with regular excipients and delivered in a epispecifique push. We have a similarly concentrated form of IMVT-1402 that we'll use in our phase one trial. The viscosity and needle. Same or similar thing for the needle gauge, similar for the scalp. We expect the dosing experience with 1402 to be very similar to tocilizumab and better than the dosing experience with competitors. Great. I'm just gonna touch on CIDP super quickly, and then I wanna leave a lot of time, Sam, for Q&A. I know that was a lot of information, we've been getting a lot of sort of second and third order questions, so I wanted to have an opportunity to go through a lot of detail across a lot of that, a lot of that data. With regard to CIDP, I'm not gonna run through all these slides. They're available on our website, and we've discussed some of this information. We see this as a really exciting opportunity for patients and commercially, given the amount of IVIG that's used for CIDP specifically. Although IVIG works well, it does have some significant limitations from a statistical standpoint and tolerability standpoint. The interesting thing about CIDP, of course, is that there's not as much clarity in terms of the autoantibody, which autoantibody is causing the disease. There's some nice science that our guides have reviewed, probably the most detailed, that shows the transferability of the sort of CIDP condition to animals using a sort of a serum solution which is acellular and suggests that there must be some protein that's present in patients with CIDP that's causing the disease, and that's got almost certainly an antibody. What the antibody is hasn't been identified. It's the antibodies that have yet to be identified but are probably causing the disease or some of the antibodies that have been identified are binding mostly to the myelin sheath, and that's gonna reduce nerve conduction and cause symptoms of CIDP. FcRn inhibition, of course, can, as we've already shown, reduce the autoantibodies by having them be degraded and not recycled, which then can allow your myelin sheaths to recover. That's the basic idea. We have a lot of respect for the careful thought that argenx put into their trial design. This is a tricky disease to design a study for some different reasons. We think there are a lot of things that they did which were really clever, and we copied. As we were looking to think, how could we make our trial even a little bit better, we made a few changes. The double enrichment, which is really the critical innovation, I suppose, that argenx brought to studying in this disease space, was not only it was possible to demonstrate that patients have disease activity, but being able to show a difference when you eventually get to the test portion of the trial, but also that they will improve on open label investigational product, which we should screen for those portion of CIDP patients that have a autoantibody-driven condition. That's that we think makes a ton of sense, and we did that as well. We added a third enrichment, which is we're restricting our primary endpoint just to the IVIG, subQIg, or flex cohort. The reason is that we believe the effect size is likely to be the largest for that group because you can completely remove that therapeutic agent. Whereas for steroids, it's a lot harder to fully taper steroids, assuming people are on multiple doses of steroids, because if you fully taper them over a short period of time, you're gonna have steroid withdrawal symptoms possible during the study. The other enhancement we made to our trial was to include more than one dose in this open label period. That takes advantage of the tocilizumab's ability to deliver that higher level of IgG suppression along with the standard IgG suppression of 65%. Really will be the, you know, first meaningful set of data that will allow us to understand whether there's a dose response or an IgG reduction response curve in CIDP. I think there probably is, but we don't know for sure. We don't know the size or magnitude of that. If it turns out that there is a response, which I believe there is, and that is significant, then that would even more so support not only tocilizumab, which can be used at that high dose in an induction period, but also potentially even IMVT-1402 in the maintenance period. For this trial design, I should probably just, you know, won't go through in detail here, but Sam, if you have questions, we can come back to it. It's something we've discussed previously. At the end of the day, you know, for CIDP specifically, we see this as a really exciting indication. We think that the argenx double enrichment trial design is a really attractive way to provide really meaningful scientific information to physicians and patients about the role of an FcRn in CIDP. We think we can improve on that even further with the changes that I mentioned that we've incorporated with the trial. Those changes not only are maybe some improvements to the trial design, but also take advantage of the unique properties of tocilimab, which is to deliver a higher IgG suppression and to deliver all the IgGs, right, to the sub-Q. With that, Sam, I will take the slides down. Awesome. Thanks, Pete. Next, you know, as mentioned, we'll go to some Q&A on some recent questions we've gotten. I guess first, regarding your crystal structures and preclinical data on albumin, with tocilizumab and 1402, there's been some questions recently on just minor amino acid differences between non-human primates and humans, and whether that could impact the translation of your data in cynos versus humans. I guess just any insights on this, in addition, just your confidence in the translatability of these animal data. Yeah. Yeah. You know, it's interesting, as we've unveiled 1402, I've gotten, you know, kind of reacquainted myself with a lot of the details of the preclinical models that are used by Immunomedics and others. With regard to non-human primate studies specifically, we're only using cynomolgus monkeys, not rhesus monkeys. Cynomolgus monkeys and humans have very high sequence homology for their FcRn receptor. With the IgG binding studies for both batoclimab and 1402, there's 100% amino acid homology between the cynomolgus monkey and the rhesus monkey Fc receptor. I understand from others that there may be some differences in the rhesus monkey, again, we're not using a rhesus monkey in our studies. Got it. In cynos, you showed multi-dose PD data earlier within the slide deck on IgG levels of 5 mgs per kg and then 50 mgs per kg for 1402, and then 50 mgs per kg for batoclimab, which was a super saturating dose to your point. I guess as we think about the translation of IgG lowering into humans, you mentioned that they're expected to be relatively similar. I guess is that kind of a per dose level in the sense that, you know, up to 680 mgs or whatever you can fit in, that amount of injection that should be relatively similar? Right. Exactly. I think there is probably likely to be some small differences that won't be in terms of the total milligrams and the milligrams per milliliter and those sort of things that we don't really care about. The advantage we have with batoclimab is we have a single prefilled syringe, 340 milligrams that delivers standard IgG suppression. Standard is 65%. That's what you're getting with, roughly with the argenx preparations and with others that are competitive. We have by using 2 syringes, we can get to a saturating level of FcRn suppression that gets you to the maximal IgG suppression of 80%. That's very simple. You got 1 or 2 shots. You don't have to have different syringes. You don't have to, you know, measure different amounts of drug. It's very simple and straightforward. We expect to replicate that for 1402. The exact amount of medication might be slightly different. It It might not be exactly 340, not exactly 680, but it'll be similar. I say it'll be similar. I predict it will be similar because the binding affinities are close, and to the best that we've been able to compare the, you know, a little bit larger set of monkey data we have in-house, batoclimab and 1402 look quite similar from a, from an IgG lowering perspective. That's That's in terms of the potency piece. In terms of the concentration, the concentration of 1402 in terms of the milligrams per milliliter that we will be testing in our phase 1 study is very close to what we're using for batoclimab, which is 170 mgs per ml. I think we're gonna have a very similar form factor for 1402 then as we're moving towards 1402 and batoclimab form factor preparation. Got it. Super helpful. Then going to indications, because batoclimab and IMVT-1402 should work in all the same indications more or less, how are you thinking about the best indications to advance IMVT-1402 in versus batoclimab? Right. Right. That's a really important question that we're spending a lot of time thinking about and we'll continue to spend a lot of time thinking about, you know, over the next six months as we prepare for success with our phase 1 trial and plan to be ready for that. I think it's both an important sort of short term and medium term question. The short term question is what to do with our current four programs that we're running for batoclimab. Let me start with that one because it's kind of concrete and I think relatively straightforward. If I take the two really straightforward ones first, for Graves' disease, that's a proof of concept which we need in order to know how to design a pivotal anti-FcRn trial in Graves' disease. That trial will finish... With batoclimab, we'll finish about the, you know, at a similar time frame that our phase I data is available for IMVT-1402. As I said before, I think there's a good chance that we'll pivot to IMVT-1402 for Graves' disease, run a pivotal trial with IMVT-1402 so that batoclimab proof of concept can accelerate our development program of IMVT-1402 in Graves', assuming that's important. The next one I think is pretty straightforward is thyroid eye disease. That's fixed duration therapy and over a 6-month period of treatment, the difference between batoclimab and IMVT-1402 isn't so significant. IMVT-1402's obviously just going into healthy subjects beginning of next year, whereas batoclimab is starting up a phase II program in thyroid eye disease. Running a phase 2 program on thyroid eye disease makes a lot of sense. CIDP, you saw that we have two doses in our open label lead-in, so that will give us a hint of dose response even before the final trial is completed with the, you know, the subsequent randomized withdrawal phase. Then we'll have data from argenx to give us also some information in terms of the effect size of FcRn inhibition in CIDP. At the end of the day, if we think that more is definitely gonna be better in CIDP, then we may pivot that program to 1402. On the other hand, we're surprised, and I would be surprised, but if we're surprised and 65% delivers kind of everything you could ever hope for in CIDP, and it seems that we've reached a ceiling of efficacy with 65% reduction, you know, batoclimab probably is we just keep going with batoclimab in CIDP, and it will compete on a better proof of predictor and with argenx there. That leaves myasthenia gravis. Myasthenia gravis is a really important indication for the FcRn mechanism. It's a little bit larger patient population than many of the others. It's, you know, there's the most data. The standard of care is far, I think, what an FcRn can offer. Our myasthenia program has many points of differentiation that take advantage of batoclimab's ability to provide flexible IgG lowering, kind of deep IgG lowering upfront, lesser IgG lowering over the long term. Both of those, I think that flexibility on both ends of the spectrum, I think is important. I see batoclimab as really competitive at the time of launch, assuming our phase 3 pans out versus 1402, which would be Halozyme-enabled epispecifique. That's why we're continuing that program with enthusiasm. Will we eventually develop 1402 in myasthenia? Yeah, maybe. I mean, it's a really important indication. Whether it's in the first wave of indications or it comes later, we'll have made a clinical decision on that. That's kind of a program-by-program answer. Conceptually, you know, IMVT-1402 has an opposite advantage whenever you need deep IgG suppression for longer than 12 weeks because we're using 6 to 8 just for 12 weeks of batoclimab. I think that's gonna be a lot of different indications where that could provide a benefit of, you know... If we take a couple of categories of indications where I'm quite certain there'll be that need for longer deep IgG suppression. It's indications in rheumatology because you have a lot more immune activation, and there's immune complexes I said earlier that take a little bit longer to bring to disease quiescence. Hematology, because you have a lot of allogeneic burden. There's just a lot of glycoproteins with many, many, many blood cells. In Graves' disease, based on the little bit of information we have from our thyroid eye disease program, it looks like deeper IgG reduction for a longer period of time is probably gonna be better than the 65% reduction. Given how exciting an indication that is because it's a little bit larger and it's first in class, there's really not much innovation there. That one's probably better for 1402. Got it. That's helpful. For the upcoming CIDP study, just kind of what gives you confidence that the trial could be registration enabling? Depending on whether it is registration enabling or not, how are you going to think about that switch between batoclimab versus 1402 for that next stage? Right. Right. Each division approaches the requirement for substantial evidence, you know, for the well-controlled trial data a little bit differently. The neurology division is generally amenable to a single adequate well-controlled trial that's clinically and statistically persuasive to use kind of FDA's language there. I think that's been shown to be true in myasthenia with our delivered assets, and it's probably true in CIDP as well. The reason I say probably is because, again, the effect size of CIDP is not as clear as it is in myasthenia. The randomized withdrawal trial design is a little less standard. All that being said, I think the... You know, you see from the action of sGenex, Janssen, and Immunovant, you know, three companies that care a lot about this condition and this class, and they've had a few interactions that we've all designed single pivotal trial. Our trial is a little bit smaller, and we designed that as a little bit smaller so that we could react to data that was coming out from competitors as they release data and anything else we learned along the way. That gives us the flexibility to either simply upsize the trial, which makes sense to have a little bit larger from a hopefully sGenex trial, which is a little bit larger. Alternatively, if we learn something along the way that says, you know, a different trial design might be complementary, either from the standpoint of achieving registration or from having a differentiated data package, we haven't, you know, committed to a very large trial, and then we're in a little bit trickier spot to add on that second trial. Having a smaller trial that's going to work because of the primary effect size that we predict in the IgG-only cohort, we have the flexibility to either upsize the trial or add a different trial. That's why I said we're fairly interested in CIDP. Since then, of course, we've unveiled 1402. The other option now that we have built in is, you know, if it looks like more is better for a longer period of time, then we can pivot the entire program to 1402. One of the most important things about our CIDP trial is we're just all in. I understood. For WAHA, I guess when can we expect an update on that indication and potential go-forward plans? Yeah. Thanks. Great question, Sam. We'll make an update in the next year. What we have been saying with WAHA is that we are going to make a decision on whether to study 1402 or batoclimab in WAHA based on an FDA interaction in the, excuse me, second half of this year, calendar year. That interaction has occurred, and we're now kind of taking a look at the feedback that we received. We had a very good discussion with the hematology division, which allowed us to explore, you know, different trial designs and some creative ideas that we had. Now we're taking that feedback together with, again, you know, what we know about batoclimab and what we predict for 1402 to make a final decision about how to go forward in WAHA. I expect we'll make that decision early next year. Okay. Then you showed some informative slides on just the correlation between IgG lowering and clinical activity. I guess is it expected that lower is better across autoantibody-driven indications, or is there a threshold effect in some diseases? I think, when you're trying to get initial control, to me, all the data suggests more is better. When I think about the fundamental biology, you have The disease causing autoantibody, and you're on average, you know, reducing it by 65%. I say on average, when you look across all the different assets, including the 340 with the ground tocilizumab, which is a good reduction, but it's not 95% or 98% or something like that. I would, I would have expected prior to seeing any data that, you know, more would be better, but particularly between the range of 50% or 60% reduction and 80% reduction. I think all the data supports that. I think, both the, you know, pretest belief and the test has shown that more is better. What about in the longer term? There, I think the answer could be different. There was a really interesting paper that looked at some of the more complete responders or people who achieved remission in the Pemphigus, in the phase 2 Pemphigus trial with batoclimab. Some of the patients who were treated with a higher dose, there were more patients who were treated with a higher dose and were treated longer who achieved a remission as defined by their disease activity, which was absent for a while, many weeks after stopping batoclimab therapy. When they looked at those patients who had had a remission or a deep response compared to those who improved and then relapsed or those who didn't have a response, the ones who had a deep response and stayed and had a remission, their autoantibodies didn't come back with that same pharmacodynamic curve that their total IgG came back. The total IgG recovered, but the autoantibodies stayed lower. They did some really interesting science where they actually looked at autoantigen-specific B cells and found them to be dramatically diminished after therapy was stopped. Potentially, the FcR inhibition was somehow sort of resetting the immune system, to use a kind of colloquial term, in those patients specifically around the autoantibody producing B cells. We do think that there's a lot of reason to believe that once you've achieved disease control, maintaining it will require less IgG suppression. Whether that, you know, is a step function, meaning you only need 50% or so, or whether just the curve shifts, and you just don't need as much, that's maybe a little bit semantics. I do think when you're trying to get patients well who are sick, more is gonna be better, generally speaking. When you're got people who've achieved a clinical response, you're trying to maintain it, I think in those cases, there'd be many examples where people would be able to go down or potentially even come off the FcR inhibitor at some period of time. Got it. I guess with that in mind, for the maintenance dose that you're using in studies with the tocilizumab, do you expect that it will compromise efficacy at all versus using a dose that is continually maxing IgG lowering, such as a 1402? Right. There are these fixed-duration therapy. MG, I think no, because MG is not a very inflammatory condition. I think if achieving deep clinical responses via deep IgG reduction in the first 12 weeks, I expect the 340 milligrams to be a strong reason to maintain a clinical response. Even 340 every other week, which we're testing, I think is gonna maintain response in many people probably. CIDP, I don't know. CIDP might be a little bit more like a rheumatology condition. It's a little bit more evidence that there's sort of the immune system is more activated. 12 weeks of deeper IgG suppression might not be enough. Sixty-five percent IgG reaction might not be enough to achieve the maximum that could be achieved with this mechanism in this disease. I think there's a decent chance that 1402 is better than the tocilizumab. The tocilizumab, even the 12 weeks, is better than other assets because you can get deeper reduction at least for 12 weeks. Got it. I guess just lastly, over the next year or so, what kind of important updates should we expect from Immunovant? Can I add one more after that, actually? Excuse me. Oh, yeah. No, problem. In terms of, you know, data we have, suppose that we'll have initial results from the phase I IMVT-1402 study in mid-2023. The reason that that is a little bit vaguer commitment than what you would usually hear from us is we unveiled the IMVT-1402 kinda data package before we had the protocol finalized. We're doing that now. We're finalizing the protocol, and that'll be submitted as part of the IND in the very early part of next year. Once we have that protocol finalized and agreed with the FDA, then we'll know kinda when which data is coming. What I've been saying is probably that mid-2023 data package is the single ascending dose data from the phase I trial. We'll see when we have that protocol finalized. The other important data from Immunovant specifically next year will be the Graves' disease data, the initial data from our Graves' disease proof of concept. Those are the two data points to expect from Immunovant. Just lastly, you touched on it earlier, over the years, there's been some discussion around pH-dependent binding for FCRN inhibitors, and kind of impact on PK/PD, albumin, et cetera. I guess at this point, you have a bunch of data points across assets. What's it kind of tell us in terms of those parameters? Does it really have that much of an impact just looking at IgG reductions across the board and so forth? Yeah. I think the short answer is no. You know, there's only one asset that has strong pH dependence, and that's upcarticimab. The antibodies are all pretty pH independent, meaning even at 7.4, the binding's pretty tight. The dose, all the assets, whether it's upcarticimab or the monoclonal antibodies, have dose-dependent reductions in IgG and time on, time off from a PD standpoint, time to max reduction, whatever max reduction is for that asset at that dose, and then time to recovery that are very similar. It's, I can't really see what the pH dependence or independence is doing in actual practice. You know, you can note in the, in an in vitro study, but I don't see a link to the clinical difference. Got it. Great. Well, Pete, thanks for joining us, and thanks to everyone for tuning in. Yeah. Thanks, Sam, for hosting this. I really appreciate it. Sure. Goodbye.