All right. Welcome, everyone, to the last day, day three, Jefferies London Healthcare Conference 2024. My name is Roger Song, one of the senior analysts covering medical biotech in the U.S. It's my pleasure to introduce our next company, IGM Biosciences. Welcome, Misbah and Lisa. All right. Roger, great to be here. Thank you. Yes, so maybe before we kick off some questions and then to start this fireside chat, Misbah, why don't you give us some most recent updates for the IGMS and what's the latest? Yeah, I'm happy to. And again, thanks for having us here. For folks who are unfamiliar with IGM, and even for folks who have been following the story, there's been quite a bit of change over the last couple of months. So let me give you a brief overview. IGM is a biotechnology company focused on the development of IgM antibodies. We are exclusively focused on autoimmunity. We're a clinical stage company. We have three phase 1 trials underway and one about to be initiated. All four of these trials are in areas of large unmet medical need in autoimmunity. We also have a pretty significant research collaboration underway with Sanofi, where we're focused on the development of IgM agonist antibodies. So that, in a nutshell, is IGM today. Awesome. Yeah. So we definitely got to go into all the details. But at a high level, right, so you're IGM Biosciences IgM format biologics, and then the lead program is the CD20 CD3. Maybe just at a high level, how IGM format CD20 CD3 is different from other formats of the CD20 CD3, given we see a lot of the new development in this field, particularly for the CD20? Happy to. Well, I think this is certainly an exciting time for B-cell depletion therapies, and that's where we're positioned with imvotamab. And I think the opportunity for differentiation and as a way to kind of talk a little bit about imvotamab, I think the opportunity for differentiation is fourfold. First, it starts with the opportunity to deeply deplete in tissue. And as our new CEO, Mary Beth Harler, likes to say, that's where the game is going to be won with respect to B-cell depletion therapies. So we have some encouraging preclinical cyno data with imvotamab that shows that imvotamab, it gets deep into tissue and depletes in tissue and organs of interest. We also have some clinical data from one of our legacy programs that shows us that the IgM antibody can get deep into tissue. So that opportunity certainly exists. Second, we're encouraged by the potential to deplete low-target expressing cells, and this is where we may have a particular point of differentiation vis-à-vis existing drugs such as rituximab. In our corporate deck, we show that in low-target expressing environments, imvotamab can be much more potent than rituximab. Third, there's potentially a wide therapeutic window within imvotamab, and we benefit from the existing clinical experience that we have within imvotamab. As many of you may know, we started testing imvotamab a number of years ago, first in NHL, and there we dosed nearly 100 patients, and that gave us a really good understanding of the drug. We were able to dose up to 1,000 milligrams with no dose-limiting toxicities. That gave us quite a bit of information as to how to develop an appropriate step-up dosing regimen to minimize the risk of CRS, Cytokine Release Syndrome. And we think that could be particularly helpful in the autoimmunity setting where safety is certainly an important concern there. And fourth, within imvotamab, there's an opportunity for more convenient administration. And I think this is something that's different for bispecific T-cell engagers, especially when you compare them to potential CAR T therapies. You don't have the burden of predosing regimens or lymphodepletion. You also have the opportunity for redosing if needed. And you don't have all the burden of potential hospitalization, et cetera, when we're talking about a T-cell engager. So that's in imvotamab in a nutshell. Excellent. Yeah, I think that's a good magnitude of preclinical and the clinical evidence to suggest the differentiation. Okay, so we're just coming off of the ACR. I know Imvotamab has some preclinical data update there. It's incremental. You show us most of the preclinical data already. So maybe some of the key highlights in ACR. And then we do see maybe one clinical data from the T-cell engager for B-cell from a Chinese company, and then quite a few preclinical data from the T-cell engager and the CD20 monoclonal antibody. So tell us what you have been seeing and then any research too in Imvotamab from the ACR. Yeah, I'm happy to take that. Thanks a lot, Roger, for that question, so let me step through. First, it was really great to see the wealth of companies involved in B-cell depletion. We made this pivot with our T-cell engager just about two years ago now, and at the time, we were one of the first companies to do it, so we view it as incredibly validating to see the number of people coming into the space and starting to generate that early data, which to us really speaks to the potential of what B-cell depletion can do in an autoimmune context. From our preclinical work that we presented at ACR, we did have the opportunity to show some very nice data in both mouse models and in vitro assays, where we show that imvotamab is able to kill, to deplete low CD20 expressing cells better than the ADCC mechanism antibodies, such as rituximab, which are approved for rheumatoid arthritis. In addition, in some mouse models, a humanized mouse model, we were able to show that imvotamab was able to similarly deplete the target cells in the periphery, but more importantly, in the tissues, in the spleen, which is really going to be important for any successful agent in the depletion space to really be able to get into the tissues and deeply deplete those tissue-resident B-cells. It's interesting that we find ourselves in a position where we have multiple clinical programs running within imvotamab, and we are essentially backfilling the preclinical work. We jumped right into the clinic in autoimmunity without sort of doing the normal linear progression of the preclinical work. So that's a little bit of the summary of the work that was in that poster at ACR. Excellent. Yeah, I do agree all the preclinical evidence. Luckily, it still very much supported all the clinical development then and all the research and validation for other pipelines. Okay, let's zoom into your clinical program. Maybe start with the timeline, because recently you officially got this initial data readout going to be mid next year. So what made you make the decision to do that? And then how you make the decision to release the data at that point? We're really pleased with how enrollment's going across all our imvotamab studies. In our recent quarterly earnings update, we announced that we had cleared the third dose cohort in rheumatoid arthritis. We announced we had cleared the first dose cohort in lupus and enrolling in the second cohort. We also announced that we had dosed our first patient in myositis. That's a trial that's underway in collaboration with Stanford University. Enrollment is going well and in some cases exceeding expectations for us. We did update our guidance with respect to when we're going to release initial data to data by middle of 2025. That was really done with an eye. We have new leadership now, a fresh set of eyes looking at our development program. We wanted to give ourselves the time and opportunity to release a more robust data set. We want to make sure we have the time to answer the questions that we have internally and the questions that are in the mind of folks externally as well when we release that data. We're certainly not going to do drips and drabs. We want to have multiple cohorts and be able to capture not only the depth and extent of B-cell depletion and also talk about the safety profile, but also talk about the B-cells that come back, the reconstituted B-cells, and that can take a little bit of time for that type of data to mature, so hence, we thought it would be good to push out the timing and just give ourselves that time to develop that quality data package. Got it. Yeah, robust data set is always welcome. We want to see informative data set for the initial data readout. Then, so to the extent you can disclose to us, because we know this is RA is a randomized trial, the lupus is a single arm, the treatment arm only. Then it's mostly kind of unblinded to the company. So what have you been seeing and then to the extent you can disclose to us? So safety, maybe some signal, understanding your three-weekly dosing. So the B-cell biomarker change probably happened pretty early on, but you probably want to see a little bit longer-term follow-up to see the B-cell reconstitution. So that may be the things you are waiting for. I think I can say with confidence what we've seen with these phase 1 studies is that there's significant patient and investigator interest in exploring B-cell depletion therapies. We've been, as I alluded to with enrollment, really pleasantly surprised by the progress of enrollment and the level of interest. We've certainly observed that. I think as we've announced various cohorts clearing the right read-through cohorts, that there are no safety issues that prohibited us from moving on to the next dose cohort. The studies are unblinded to management, but we don't want to release any type of data in drips or drabs. Rather, we focus on that full data set and wait until middle of 2025. Yeah, that makes sense. That makes sense. And then since you want to make this data set as robust as possible, what would you consider as a winning scenario for the initial data set? You have a long enough follow-up, and then you have a big enough N to tell the safety activity. So what would be considered, okay, wow, this data set is what we're looking for. Yeah, I'm happy to take that one. So what we're really aiming to show when we come forward with that data set is, of course, the ability of imvotamab to deplete in the periphery. We will have through RA and lupus indirect measures of the ability to deplete in the tissues because we're not actually taking biopsies in those studies. Our myositis study with Stanford has a very heavy translational component in which we'll be taking skin and muscle biopsies. So if the data is ready, there may be an opportunity to have some biopsy data from the tissues. So depletion is, of course, key. We'll also be talking about the biomarkers that we have observed, such as autoantibodies, as well as inflammatory cytokines and any changes that we saw there. Importantly, we want to understand some of the kinetics of the response, how long it takes to deplete, how long that depletion is maintained, and then what is the phenotype of the reconstituted B-cells? Are they coming back as naive cells? Are they still the same memory B-cells? To really give an example of that indirect measure for what tissue depletion may be occurring. And then, of course, we will be looking at disease assessments to see if there's any indication that the level of depletion that's being achieved and the duration is having any impact on symptoms that a patient might be experiencing. As for what we constitute as a win, we really are using rituximab as our benchmark. Rituximab is the only approved CD20 in rheumatologic indications. And so we would be looking for a significant, meaningful improvement over what was observed with rituximab and trying to match the data as closely as we can for like to like. Okay. And then just set the expectation appropriately, understanding all the translational B-cell biomarker as deep as possible. And obviously, when the B-cell eventually reconstitutes, you want to see more naive versus the memory. That part is pretty clear. And then in terms of the clinical activity, given this is small and rituximab approved, and then they have a wealth of the data there, so how should we think about the significant improvement over rituximab? And what's the right expectation there? Yeah. And also we know you have a multiple dose cohort. So what's the dose response look like? Yeah. So we really are engaged right now in doing that very thoughtful, careful drug development to really make sure that we're optimizing dose and regimen. So to answer your question specifically, Roger, for what we'd be looking at, we will be talking about DAS28 scores in the rheumatoid arthritis context to really understand if there's a significance of improvement. And again, by taking this time to really understand the data, come forward with a robust data set, we hope that we will be able to inform not only on the potential of imvotamab as a drug, but importantly, what next phases of development would look like and be able to accelerate the next phase, the phase 2 development of imvotamab. So that's really our strategy that we're employing right now with the development. Yeah, absolutely. That's right into my next question, the next step. So, this is the initial data readout, dose escalation. How should we think about the next step? You will have enough information to move into the phase 2 expansion? On what kind of dose cohort you're looking for? Any regulatory interaction you need before you can initiate the next stage? Yeah, absolutely. So my last question did dovetail perfectly for this question, Roger. We really do anticipate that the data that we're collecting right now will enable that rapid development of phase 2. We're actively thinking through what the various options are. Importantly, this really is the data that we're collecting right now, primarily about safety and how to safely dose that T-cell engager to drive for the best efficacy. And we look forward to bringing data sets forward to the agency to have conversations about next steps once we have that robust package. Okay. And then given this dose escalation, next step, should we expect to see mid stage phase 2 randomized trial before you can go into the pivotal? Is that the right expectation there? Yeah. So I think it certainly is highly likely and possible that the phase 2 will be randomized with placebo or possibly even an active comparator to really quantify the magnitude of effect, of treatment effect of imvotamab. Excellent. And then that's a typical question for biotech in terms of moving to the later stage development. How do you think about you develop on your own versus a partner when you will start to entertain the partnership, if at all? Yeah, I'm happy to take that one as well. So as you might imagine, it's a very hot space. A lot of people are interested. Our strategy has been all along and will remain. We really want to collect that data set that will inform as to the potential of the drug. And once we understand the potential, we can then have a better understanding strategically what we may or may not want to do in a partnership context. I think it's possible we could decide that this is something we could progress with, or we may in fact want to decide to progress with a partner if we feel as though that partner would enable us to really maximize value of the asset. So we're really excited to have the opportunity to engage with folks. And we will see what happens when we get there. Yeah. No, that's fair. That's fair. We're just a little bit looking ahead of ourselves. And then just quickly, given you have a real IGM platform, you do have another asset also in the autoimmunities, CD38. Recently, you just started phase 1 and started going to the clinic. So tell us why you think CD38 is also a good target for autoimmune, given you already have a CD20 and then many other companies doing CD19, even BCMA. So how CD3 fit into the future autoimmune T-cell engager space? So when you think of the spectrum and the lineage of B-cells, as B-cells terminally differentiate into plasma blasts and plasma cells, they start to downregulate markers such as CD20. CD19 is not expressed on plasma cells. So if you want to go after a disease, which the primary driver is an autoantibody-mediated effect, going after plasma cells is really the right approach in our opinion. And CD38 is highly expressed on those plasma blasts and plasma cells. And we believe that IGM-2644, our CD38 x CD3, complements our portfolio very nicely with imvotamab because now we have two assets that can essentially cover the spectrum of the B-cell lineage. And each may have their role in addressing autoimmune diseases depending on what the main driver, an underlying driver of any given disease is. We may be thinking about a combo in the future, but let's get the monotherapy for each individual asset first. But in terms of CD30, what are the more appropriate indications for CD38 versus the CD20, more plasma-driven disease? Our initial studies are going to be focused on myasthenia gravis. Once we start to collect that data set, and again, as we're taking T-cell engagers into an autoimmune context for the first time, those initial studies are by design and very intentionally focused on safety signals. We will have some other endpoints to start to look at PD as well, of course. But once we have confidence that we can safely administer a CD38 x CD3 in a patient population, we can start thinking about what the full development plan might look like. Myasthenia gravis is one potential indication, but there are others that come to mind, such as autoimmune kidney diseases, et cetera, in which a plasma cell-specific targeting agent really could drive for very strong efficacy. That makes sense. Okay. Last couple of minutes, Misbah, you mentioned earlier recently IGM has had some leadership change. So my question is how confident this new team can push this pretty kind of exciting space forward for the IGMs and then any high-level strategic thinking, maybe updated strategic thinking you can give us for the new leadership team? Yeah. No, I think we are at this point all in on autoimmunity, and we are redesigning our company to give us the best chance of success in autoimmunity. We've got a pretty full pipeline with respect to we've got imvotamab being studied in three indications currently. Lisa talked a little bit about IGM-2644, the CD38 x CD3 T-cell engager. And then we also have the Sanofi collaboration in three undisclosed research targets. That entire pipeline is focused on autoimmunity. So I think we have our hands full in the near term, and we are laser-focused on generating clinical data and answering a lot of the questions we have internally and what we know people want to know externally as well. We're always on the lookout, of course, for new opportunities in the pipeline areas where an IgM antibody and our IgM antibody could be differentiated from traditional IgG-based antibodies, but in the near term, we're laser-focused on what we have. Excellent. By the way, you are representing the continuity there, so between the leadership team. So glad you stay with the company, so kind of with the institutional knowledge. So maybe just lastly, in terms of your cash position and what's the runway, what's the operational plan building to the current runway? So we ended last quarter with $219 million in cash, and that gives us runway into 2027. So all the programs I walked through in imvotamab, IGM-2644, the Sanofi collaboration and those targets, we've designed our runway and restructured our operations to be able to turn over the initial data cards and really see what we have, particularly with imvotamab in the near term, do we have a play with respect to a B-cell depletion therapy? So we're funded to turn over those data cards and excited to continue to execute against those goals over the coming months. Excellent. Look forward to that. Thank you, Misbah, thank you, Lisa. Yeah. Thank you, everyone. Thanks, Roger.