Everyone, I'm Brian Abrahams, Senior Biotech Analyst at RBC Capital Markets. Thanks for being here in this session. We're really pleased to have IGM Biosciences, represented by their CFO, Misbah Tahir. Thanks, Misbah. Thanks, Brian. Really appreciate you joining us. Thanks for having us here. Thank you. So, maybe we can start on the autoimmune side, 'cause I know that's one of the data points that we may start to see roll out by the end of this year. Can you talk maybe broadly about the potential for imvotamab in autoimmune disease, and just the way that this approach may address the limitations of the current B-cell depletion therapies? And I guess, I'm also curious what prompted you to pivot the development away from cancer towards autoimmune for this asset, and how excited are you about the autoimmune potential? Yeah, great place to start. Yeah. I think we're, we're really excited about the potential of imvotamab in autoimmune diseases. Many of you may recall we were testing imvotamab in non-Hodgkin's lymphoma not too long ago. We made a strategic decision to pivot that program over to autoimmune diseases, and our pivot really started before some of the seminal work came out of Germany with CD19 CAR-Ts. But certainly, the publication of that research in late 2022 really catalyzed our efforts, because we saw there was an opportunity for imvotamab in autoimmune diseases and certainly with B-cell depletion. So we made that decision. We announced early last year that we were ceasing development in non-Hodgkin's lymphoma and went all in on autoimmunity. So we think there's a big opportunity here, not only because of the large unmet medical need in autoimmunity, but also because of imvotamab specifically. So what we've seen is that with the CAR-T data, if you can deplete deeply and reset the autoimmune system, you can actually make a meaningful difference in various B-cell-mediated autoimmune diseases. And the challenge with traditional IgG antibodies is that they're not able to get at tissue-resident B cells, and in situations where we have low-expressing CD20, CD19, they're not as effective. And a lot of the ADCC-based traditional IgG antibodies, they really require the availability of complement and effector cells to be effective. Whereas with imvotamab, which is a bispecific T-cell engager, a CD20, CD3 T-cell engager, it can get to the site of activity and bring the T-cells to that site of action, and that's what can lead to deep B-cell depletion. So I think that's the opportunity for us and what we're going to be testing, what we are testing in the clinic now in a variety of autoimmune diseases. We've started testing in Lupus. Last week, we gave an enrollment update there. We're actively enrolling in the first of three dose cohorts in Lupus. In rheumatoid arthritis, our second clinical indication, we announced last week that we've completed the first of three dose cohorts in rheumatoid arthritis, and we're getting ready to initiate a third study with imvotamab in an autoimmune setting, and that's going to be in Myositis. But this autoimmune pivot also goes beyond imvotamab. We transitioned another one of our drugs, a CD38 x CD3 bispecific T-cell engager. We were testing that last year in multiple myeloma. We've stopped that program, and we're moving that into autoimmune diseases later this year. One of the questions we get asked the most about the program is how translatable some of the really remarkable CD19 CAR-T data and experience would be to imvotamab, just given different targets and degrees of depletion. Like, what can we take from that CAR-T data, and what might be similar or different about using an IgM-based CD20-targeted bispecific approach versus a CD19 CAR-T or versus a traditional CD20 mAb? You know, we get that question. Yeah Quite a bit these days, and it feels like the world has divided into the CD19 only versus folks. Yeah - that are more open to, to CD20. But look, I think we're, we were excited about the data coming out of Germany. Certainly, CD19 has the most clinical data right now in autoimmune settings, but I think that's going to change as we begin to publish data towards the end of this year, early next year. So there certainly is some translatability, but you know, let's start with a couple of the differences, and I think you hit the nail on the head, CAR-Ts versus bispecifics. And this is a debate that has been ongoing, you know, even going back to our days in NHL. There's going to be a place in the treatment landscape for all these therapies, and I think, you know, CAR-T has some advantages, but also some inherent disadvantages. It may not be as scalable, it may not be as applicable to a broad swath of the population, whereas an off-the-shelf bispecific doesn't have all that logistical complexity and may be more applicable to a broader swath- Yeah of the population. So certainly, there are some advantages there if we can show efficacy. It doesn't have to be exactly the same as CAR-T, given the benefits of administration and whatnot. There may be a place for it in the treatment landscape if it falls somewhere between the ADCC IgG antibodies and the CAR-T therapies. So with respect to CD19 versus CD20, it may be a false choice at the end. Mm-hmm. Look, we need to run the experiment and see what we get. But if you look at the B-cell lineage map, CD19 and CD20 are co-expressed on the vast majority of B cells, over roughly 95%. And at the far end of the spectrum, where you have the plasma cells, we're not sure, you know, CAR-Ts are even getting at that end of the spectrum there. So it may be a false choice, given the broad expression of CD20. But if you look at the plasmablast, where maybe there's a tapering of expression of CD20, it's not a binary on or off, no CD20, but it could be a tapering of expression. That's where imvotamab may have an advantage because what we've shown preclinically is that in environments in which there's low expression of CD20. Imvotamab can be quite effective at depleting, certainly more so compared to rituximab. So we think, you know, CD20 could, our imvotamab drug could do really well in these diseases. How much do we know about the safety profile? I know you've tested it, this at various doses, but maybe slightly different type of administration regimen in Non-Hodgkin's lymphoma. What can we take from the safety data in the NHL experience? And obviously, there's, there'd be a different safety bar in a cancer versus autoimmune. And I guess, how should we think about the step-up dosing scheme that you're using in autoimmune and the finite dosing? What do you hope to see? What do you expect to see from a safety standpoint? Yeah. Now, can't overstate the importance of safety in an autoimmune setting, certainly compared to an oncology setting. And that's where the experience that we have in NHL with imvotamab really comes into play. We're not starting from scratch. We've tested imvotamab in over 100 patients, and we have that data. And so these autoimmune studies, they're not first in human studies, and we've been able to use our oncology experience to inform the doses at which we're starting. So these doses that we're using in Lupus, RA, Myositis, we believe they could be meaningful doses at a very early point. And what we did in our experience from NHL also helps inform our step-up dosing regimen. We wanna make sure we play it safe. We wanna make sure we're taking appropriate precautions and whatnot in autoimmune, given the importance of safety. But I will mention what we saw specifically in NHL, and you may recall this, is that among all the CD20, CD3 bispecifics that were tested, imvotamab experienced the lowest level of CRS, which is a huge factor in the dosing of these drugs. So at a 100-milligram dose, we showed a CRS rate that was below 10%, which certainly was the lowest CRS rate among the bispecifics that were being tested. So that gives us a huge leg up in autoimmunity. There are certain CD20, CD3 bispecifics that you really, you gotta think really long and hard of whether you're gonna bring them into autoimmunity. If you're talking to rheumatologists, they're not really set up to deal with high-grade CRS, and it's not something they wanna be thinking about. So safety really comes into play here. So when you look at imvotamab, and you have the combination of deep B-cell depletion and potential for efficacy, combined with the tolerability and the safety profile that we've shown in NHL, and we hope will translate over to autoimmunity, could make for a nice, good, effective treatment. So it sounds like we're well underway with the clinical studies, at least in lupus and RA, and with myositis right around the corner. So what should we be expecting in terms of the data cut we'll see later this year? I guess, first off, should we still expect to see some data this year? And can you just I guess, what should we be looking for in terms of the degree of maturity of that data and interpretability of the data? Yeah. So we haven't made any firm decisions, but I think we're probably gonna steer clear of reporting out on just one or two patients. We wanna make sure that what we disclose publicly is a robust data set. And, you know, certainly what I've observed over the last couple of years, I'm sure you've observed the same, any company that reports out interim data, they always seem to get burned. So you know, we're gonna wait till we have a nice, robust data set. That probably means one or two cohorts worth, worth of data, either in RA or SLE or both, and report out on that data. We're certainly gonna know, and, and I think the timing of that would be towards the end of this year or early next year. We're certainly gonna know early on in the clinical studies whether or not safety is aligning with our expectations, and we're gonna know whether we're impacting the biology of interest. You know, from a, one of the things we're looking for, we're gonna be looking at how the depth of depletion and how well we're depleting. We're gonna look at the duration of depletion, and we'll be looking at the reconstitution of B cells and what's the phenotype that they come back with. And certainly, you know, that can take approximately three months or so. So using that, we'll probably given where we are with enrollment, I think end of this year, early next year, is probably a good timeframe for a data readout. Should we expect any sort of, I guess, clinical outcome or functional signals, or should we be primarily focused on depletion kinetics? Haven't firmly decided yet, but I think those are all things that we're looking at and we could report out on. How are you guys feeling about enrollment overall? I know that, you know, with, at least with some, with cell therapies, some of the autoimmune studies have maybe taken a bit longer to enroll. But I guess, are you guys seeing similar challenges, or do you think a bispecific approach may be able to get around, some of the, I guess, the safety issues that have narrowed the populations eligible for the, the CAR-Ts? You know, I think we're seeing very strong site interest, investigator interest, and certainly, given that we are, imvotamab is dosed predominantly in an outpatient setting, it's a little bit of a different audience there. We do have a little bit of overlap with some academic centers and folks who are also dosing CAR-Ts, and certainly, we hear loud and clear, the advantages and preferences for having an off-the-shelf. Yeah Bispecific, given the inherent logistics involved with CAR-T therapies. Look, I think RA seems to be enrolling pretty well, especially given our completion of enrollment in our first dose cohort. There's certainly a number of patients out there, and we seem to be doing well. Lupus, aware of the challenges that other companies are facing. We've actually experienced a pretty high level of patients screened. And I was saying earlier today in another meeting, if all those patients had converted into enrolled patients, we'd be in great shape. What we've seen is because this study is designed for severe patients, that not all the patients are able to qualify for the study. Right. and eventually don't make it. So we're still actively enrolling that first dose cohort, but we're bringing on new sites, specifically in Europe, so we expect that enrollment curve to increase. Could you loosen the criteria versus, say, a CAR-T in terms of the level of severity of patients that a level of severity a patient would need to have to qualify for the study? We certainly hope so, but that'll be. Yeah. Over time. Okay. We'll engage with the FDA. You know, our hope is certainly to broaden the patient population for this drug. Okay. And then as you sort of think strategically, larger scale rheumatology studies, as was discussed in our keynote panel, can be expensive to conduct. Would your vision be to take this forward independently on your own? Do you envision partnering this out? How do you see this, the mid and late-stage development playing out, assuming that the drug shows the promise that you hope it will? Yeah. I think it's too early to say. Okay. We want to see what we have. The good news is that imvotamab is currently unpartnered. IgM owns worldwide rights to imvotamab. Right. And so if we show the data that we hope we're going to show, I think all options are on the table for us. You know, we're certainly mindful of and aware of the cost of bringing this alone to market. Yeah. It's not insignificant. We assume there will be significant interest in the drug from large pharma, but at the moment, I think we're just keeping- Right All options open. Okay. Got it. Maybe shifting gears to the cancer program, aplidabart. Bigger picture, can you talk about maybe some of the challenges that have been observed in the past with other approaches using IgG antibodies to agonize the DR5 receptor, and what specific properties an IgM could bring to the table and advantages there? You know, the drug industry has been trying for a couple of decades now to find a solid drug to go after DR5 as a target. It's been a target of interest for a while now, and I think the first generation of DR5-targeted agents they all failed for a couple reasons: liver toxicity. Mm-hmm. just lack of efficacy, and those were IgG-based antibodies. Right. Our takeaway from that is that folks were going after the right target, but perhaps going after DR5 with the wrong tool. Right. Because of the nature of DR5 as a target, in order to trigger cell suicide, cell apoptosis, you need to trimerize DR5, and so that calls for more of a multivalent approach, and that's where we've seen the second generation of DR5 agents come forward. An IgM antibody is really well positioned to go after DR5 because of the ten binding domains. You can trimerize DR5 quite well and trigger that cell suicide signal. So it's a really nice application of our IgM platform, and so we've been at this for a few years now. We showed some single-arm data last year of aplidabart in combination with FOLFIRI and bevacizumab. We showed some good and some encouraging PFS data, aplidabart plus FOLFIRI at 5.6 months in third-line metastatic colorectal cancer patients. That compares to standard of care, roughly two months. Yeah. PFS. And so that gave us the confidence to move forward with a randomized trial that we're currently executing. Can you give us an update on, I guess, how enrollment's going in the randomized study, as well as the non-randomized work that you're doing, and when we might expect the next update there? Yeah, we actually provided an update. Yeah Last week in connection with our quarterly earnings release. Yep. Maybe just remind us, yeah. And so we achieved our targeted enrollment of 110 patients. We're still enrolling a few patients. We expect at the end of the day that we'll exceed 120 in total. So the clock has started to tick with respect to our PFS readout, and we're hoping to provide an update on that and provide that data by the end of Q1 2025, subject to events. How have the event rates been tracking so far, versus your expectations? Yeah, we have. I know the study's blinded, but just in terms of understanding when the data will mature. Yeah. It's actually unblinded, I'm sorry The randomized study. I'm sorry. Yes. We haven't really. I'm sorry Talked too much about the events. I think what we want to do is wait until we have the full data set and really go out with that, early next year. Okay. Can you talk a little about the Sanofi collaboration? I know that had some recent, there have been some recent updates there. It sounds like it's been a fruitful and productive collaboration, but there's a lot going on behind the scenes that I guess hasn't been publicly shared. Can you maybe just remind us the core objectives there, how things are going, how it's evolved and changed, and what, when we might learn more about the discovery and development of new IgM antibodies in I& I? Yep. So, as background for folks who may not be as familiar, we entered into this collaboration with Sanofi in early 2022. It was, you know, one of the largest collaborations of the year at that time. They gave us $100 million, $150 million dollars upfront, took an undisclosed equity stake in the company, and the collaboration covered 6 targets, all research stage targets. So we didn't partner any of our clinical stage or IND stage candidates at that time. 3 of the targets were in oncology, 3 of them in autoimmunity. So, the collaboration's been ongoing for a couple of years now, and Sanofi, as many people know, has been undergoing a little bit of a strategic or a change in strategic focus. That's been going on for a little, quite a little bit of time now. And so we announced a few weeks ago that they informed us that they were pulling out of the oncology portion of our collaboration. From our perspective, I think from their perspective as well, the collaboration has been going really well. The teams have been working well together. No issues with the targets per se, or the collaboration itself. I think it's just a change in strategic focus for Sanofi, and both of us remain excited about what we're doing on the autoimmune, autoimmunity side of things. So we still have the potential for over $3 billion in milestones, and that portion of the collaboration remains very much intact. The teams are working very well together, and we're looking forward to reporting out on that, at some point down the road. Sanofi controls the information. Right. disclosure on that, so there's not much we can say. Okay. Aside from these are all early-stage research candidates. Okay. All agonist candidates, for that matter. Great. And then you alluded to this before when you were talking about the CD38, CD3, but maybe you could talk more about 2644 and what autoimmune indications you're most enthusiastic about exploring with that asset, and would that be positioned primarily as a combo agent with the CD20? Or do you see particular indications where, as a standalone, a CD38 bispecific could be interesting? Yeah. I would say we probably have more questions than answers on that at this point. So CD38 x CD3 is a drug that we were testing as recently as late last year in multiple myeloma. As I alluded to earlier, we decided to pivot that drug over to autoimmunity indications. We have not yet announced which indications we're going after, but when you look at that B-cell lineage chart and you see the coverage of CD20 versus CD19 versus CD38, there's a noticeable gap for both CD20 and CD19 on the far right end of that. Yeah. that spectrum there with plasma cells. Yep. That's where CD38 may have a role. So you can imagine a number of plasma cell-mediated autoimmune diseases where we may want to test CD38 x CD3 and see how it does. So it could be as a single agent, it could be dosed in sequence with imvotamab, potentially. I think these are all things we wanna explore over the coming years, but our goal right now is to get that CD38 x CD3 autoimmune trial up and running. Okay. You know, hopefully, we can, we can initiate it at some point this year or early next year. Got it. And then maybe just lastly, can you give us an update on the financials, your cash burn, your projected runway, and how you're thinking about capital, capital prioritization? We feel good about our balance sheet currently. We just reported out Q1 earnings, and as part of that, our cash balance at the end of Q1 was $294 million. That gives us runway into Q2 of 2026. You'll recall, we did a small raise last June, and we also did a restructuring last December. Mm-hmm. That was all with the goal of extending our cash runway so that we didn't feel the pressure to release data prematurely. Right. Or single patient data or whatnot. We wanna make sure we have sufficient buffer to let the data mature and make sure we have a robust data set for both aplidabart and imvotamab. So we have the runway to do that, and feeling good on where we are. Just maybe on that point, can you remind us what will be the point at which you would report out the aplidabart data? Is there sort of a set point, or is it more sort of gauging based on whether or not the data, in your view, has matured sufficiently? I think it's more the latter. Thanks for raising that, 'cause one of the things we didn't talk about is just kind of expectations for that PFS read. Yeah. You know, primary endpoint is PFS. We're testing aplidabart in combination with FOLFIRI and bevacizumab versus a control arm that is standard of care treatment- Yeah. FOLFIRI plus bevacizumab, and this is all in the second-line metastatic colorectal cancer. The standard of care for the control arm expectation in terms of PFS is roughly six months. So you know, certainly, we would hope to do at least 20% better than that, as a minimum. We certainly hope to do better. And so we'll be tracking events, we'll be looking at when we achieve PFS for the control arm and then decide when it makes sense to release data after that. Median PFS for the full enrollment. Median PFS. Okay. Okay, great. Well, with that, I think we're just about out of time, so I think we'll wrap up. Thanks so much. It's been really informative. Thank you, Brian.