covering biotech in the U.S. And the next, our company is IGM Biosciences. Welcome, Fred. Thank you. Appreciate the opportunity, Roger. Absolutely. Or, the updated elevator pitch for IgMS, given you have pretty, kind of, robust updates, during the year. So just a general update on IgM? Yeah. Sure. I think we continue to make really good progress, I think, in our clinical development programs, as well as our research programs. So interestingly, you know, we continue to be, to the best of our knowledge, the only significant commercial effort anywhere in biotech or pharma on IgM antibodies. And we continue to think that they have some really important intrinsic advantages as compared to the classic IgGs that everyone else is developing. And we think those advantages can probably be easily separated into two categories. The one, you know, Roger, as you well know, the IgM is very different than the IgG because it has the 10 binding domains, as compared to the two binding domains of the IgG. And that gives us the ability to bind really well to low-expression cell surface targets. Also, the ability to bind really well to difficult targets, carbohydrates, and so forth. That's what IgMs are intended to do, is to bind to targets that your body has never seen before. But what that 10 binding domains allows us to do, is to do a really good job of binding to multiple targets on the surface at the same time, cross-linking those targets, and sending a strong agonistic signal. And so, the ability of an IgM to be a much better agonist than an IgG, we've seen across our pipeline, and that was the basis for the Sanofi investment. The Sanofi deal that we did last year, was the principle that an IgM can be a better agonist than an IgG. And so, as a result, that inherent advantage is what we're taking into our Death Receptor 5 program. that we think is. We'll talk about that in a moment, but that's one of the intrinsic advantages that we think we're playing out right now in the clinic. Similarly, the IGM platform and our bispecific execution of that platform has allowed us to create a bispecific platform that we think has an intrinsic advantage in terms of safety relative to the IgG bispecifics. And we're executing on that in our autoimmune applications. And so those are the two intrinsic advantages of IGMs that we're most focusing on developing right now: agonism and the intrinsic safety of the bispecific platform. Excellent. That's a very good overview for the entire platform and also teed up for your lead programs now. Let's maybe understand, you know, we've been... This is a kind of biotech world, and we have so many modality out there, but so far, you're still the only IGM company in the public domain, kind of doing this in the, you know, kind of commercial scale or the clinical scale. So, which is amazing, right? You are really in a very unique spot for our complete new modality here. So, and then, you know, with this very differentiated platform and, you know, as you said, a couple unique advantage as well. So you do have a few in the clinical programs. Maybe we'll focus on the first, the lead program, IGM-8444. So understanding earlier this year, you provided a pretty kind of a comprehensive update for the initial phase I, phase II kind of expansion cohort in the third plus line, metastatic CRC. So how should we know, the data have been for a while, but maybe you can summarize at a very high level, how do you think that data support your ongoing potential pivotal second-line CRC randomized trial, and that give the investor some confidence, that can be a successful story? Yeah. We continue to be, very pleased with the data that we're seeing in our single-arm studies, both with, 3 mg/kg and the 10 mg/kg, and both with bevacizumab and without bevacizumab. So you recall that in June, we showed a very significant increase in, progression-free survival in those patients who had had, you know, median third line, who had, did not receive aplitabart, but not bevacizumab. Mm-hmm. That gave us a pretty good basis for believing that in second-line, we would be able to improve on progression-free survival in that second-line setting, particularly in the setting where patients had never received FOLFIRI previously. So we continue to feel quite optimistic that we will see a significant improvement in progression-free survival, which is closely linked with overall survival in that second-line setting. Yeah, I think, a couple key points from that single-arm trial. One is this with or without BEV- Mm-hmm. It's still kind of the efficacy is pretty kind of comparable and even, you know, kind of potentially improving. I think we, we discussed that before, and a little bit kind of mechanism why the mechanistically how BEV potentially will improve, which- Right ... we'll talk about the BEV triple, triplets, the data, in a moment. And also, in terms of the PFS versus response rate, very clear your progression-free survival is, pretty kind of impressive, in terms of the compared to the standard of care. And the last point, the FOLFIRI-naive versus the progression. You see activity from both, although the patient number a little bit low, small in the, kind of a FOLFIRI-naive population because that's supposed to be third plus line. Right. But your second-line population, the ongoing pivotal study, is for the FOLFIRI-naive population. Exactly. Okay, awesome. And another thing you didn't mention, but I think we should not take that for granted, but also we all know the DR5 agonist, which is IGM-8444, mechanism, you don't see any clinically meaningful liver tox. So maybe tell us a little bit about the safety even in that program. Yeah. It's probably one of the things that we're most confident of so far- Mm-hmm ... is we've dosed a lot of patients, you know, more than 100 patients with aplitabart right now, and we've not seen any significant liver toxicity. And so we're feeling pretty confident that we're not going to discover something downstream here. And that's been an issue that has killed a lot of programs in this space, most recently, the Genmab HexaBody program. Mm-hmm. So, it's really important that you create safety. And it's one of the things that people lose sight of perhaps, or perhaps they focus on too much, I'm not sure which, is that pharma has been trying to address this target for 20+ years now. You know, you had Genentech, I think, has taken three swings at this target, and you had Amgen and Daiichi and Human Genome Sciences and just a panoply of companies who've tried. And I think most folks would now agree that the only way you're going to make this work is not with an IgG. You're only going to make it work with some sort of multivalent antibody, or antibody-type structure. And so right now, as far as we know, the only significant players who are still out there trying to address DR5, Inhibrx, which has its two heavy-chain only antibodies on each arm of the Fc, so they create a tetravalent as opposed to a bivalent approach. And then you have AbbVie, which has the TRAIL ligand on an Fc. So, I think it's pretty well accepted now that in order to get something that works with this target, you've got to have multivalency. We think IgM is nature's answer for multivalency, so we're optimistic that this may be... This and frankly, all the members of the TNF receptor superfamily, which by and large, all of them require trimerization or something like trimerization on the surface of the cell in order to send the agonistic signal. We think IgMs are really well suited to that application, as well as we're going to hopefully get a chance to talk about bispecifics in a moment, too. Yeah, absolutely. We definitely will touch on the- Yeah ... autoimmune and, bispecifics. That makes sense. You know, so IgM is, you know, control the clustering, so that's the terminology we have been circling. And then I think that's the very natural kind of application for- Mm-hmm ... IgM format for this type of the target. Okay, so let's take some kind of forward-looking perspective here from here. So in the upcoming couple months and within a year, so you will have quite a few kind of data updates for us. If I, you know, count this correctly, firstly, you maybe have this 3 mg/kg kind of BEV triplets data. Mm-hmm. And then you potentially will have the 10 mg, which is higher level, dose level of the BEV combo as well. And then, most importantly, the ongoing second-line CRC pivotal study, potentially pivotal study, you're going to read out next year. So maybe just give us some flavor, what should we expect from there? Maybe from the first and then to the, to the later- Sure ... to the readout. Well, clearly, the most important data is obviously the randomized data. So we feel very good about the single-arm data, but it's always still going to be single-arm data and subject to question. But when you've got randomized data, 110 patients, you should see a pretty significant... You know, you should see a pretty clear signal one way or another, that you've either got something here or you don't. We focused folks primarily on progression-free survival because that is highly correlated in colorectal cancer with overall survival, which is correlated with-- obviously, that's the approval standard. It's going to-- ultimately, it will be approval on the basis of overall survival. Mm-hmm. We think that if we have a really strong progression-free survival signal in a randomized study, that that could potentially serve as the basis for accelerated approval. Response rate is going to be interesting. Mm-hmm. And I'm certainly hopeful that we're going to see, continue to see a response rate that's significantly better than what you see in the control arm. But it's less well correlated in colorectal cancer with overall survival. So you'll see, you'll have a sense of response rate earlier, but the real numbers that are going to provide confidence are going to be the progression-free survival. I think that's what allows you to say, "Okay, this is likely to get approved. Yeah. This is exciting, right? So it's potentially you can support the accelerated approval based on the PFS, and maybe in the more nearer term, in terms of the 3 mg kind of mature data, and then for the 10 mg, both of them coming from a single-arm trial, take it for a grain of salt. So how investors should look at those data, particularly for the 10 mg/kg? Yeah. Because, no, so for the ongoing pivotal trial, you are doing the 3 mg, and why you still do 10 mg, and how this will incorporate into your potential kind of filing package? Yeah. So I think that the way I would look at it is, at 3 mg/kg, hopefully, we will see a good significant signal of improvement over control. So then the question is, does 10 mg/kg give you more than 3 mg/kg? Yeah. I think it's quite unlikely it's not going to be at least as good as 10 mg-- as 3 mg/kg, but does it give you enough more to be worth the extra infusion time, you know, maybe some more infusion reactions, and of course, cost of goods? Is it worth it? We announced on Monday that we expect to have the 10 mg/kg single-arm study fully with, with BEV, fully enrolled by the first half of next year. So at the same time that the data are coming in for PFS with the 3 mg/kg, we're going to have those data in the single-arm with the 10 mg/kg. And so while the 10 mg/kg is going to be third line and beyond, and the 3 mg/kg is going to be second line, we'll still be able to compare those two and make a decision. Well, first, and perhaps most importantly, we'll be able to talk to the FDA about 10 mg/kg and say, "You know, gee, it looks good, but doesn't look that much better, and so we don't think we need to run this in our pivotal study for approval." On the other hand, if the 10 mg/kg really looks significantly better, then we would probably throw a 10 mg/kg arm and a 3 mg/kg arm into that final approval study. Yeah. I think that's also sufficient for the Project Optimus- You're right -from the, from the FDA. Yeah, it is Project Optimus. On the other hand, we're very much following Project Front Runner, which is, you know, let's do these randomized studies early. Let's get a sense in earlier lines of treatment, and I think the FDA is onto the right track here in thinking that randomized data is what really matters here. Let's quit trying to interpret this third and fourth line, single-arm data, and let's look at randomized data. So we're fully on board with Project Front Runner, and that's what we're doing. Yeah. Yeah, a lot, lot of the oncology company have some, you know, trouble kind of interpreting the kind of single-arm trial- Yeah ... and all with the how does it work clinically meaningful. And eventually, they need to do the confirmatory study. In your case, you may need to do another trial to- Yeah ... PFS still going to be the accelerated approval pathway, but at least, as you said, PFS correlates with the OS, you should have a better sense of how the final endpoint will look like. Yeah. We're big believers in trying to do randomized studies as early as you can. Okay, before we talk about the autoimmune and the bispecific, we promised we would talk about this, but you do have some other combination therapy for the IGM-8444 in other indication. Mm-hmm. Maybe my question is: What-- Because it's had been ongoing for a while, you always say, you know, "We will have some stay tuned for the, for the- Right ... data update," but we haven't seen anything. So what will trigger you to announce some data and the potential timing-wise, we will, Yeah. So we, we want to make sure we've got enough data with those, those cohorts to make it meaningful. Right now, we, we like what we're seeing with the venetoclax combination- Mm-hmm ... and the birinapant combination looks really interesting. But in this environment where capital is really constrained, the thing that's going to create the most value in 2024 is going to be the FOLFIRI combination in, you know, the 3 mg/kg and the 10 mg/kg. And so we have to make some hard decisions about how much do we expand in the venetoclax combination right now, and when do we get to, you know, 'cause you have to expand, and then you need to get to a randomized study in that combination. Similarly, with birinapant, we have to make a decision, well, what indication would we expand in? And then what is the standard of care that we need to compete with? And so as we look at those things, we think that where we should focus most of our capital and energy is on this FOLFIRI combination. It's not that those aren't great things, but they're not going to pay off in the short term the same way that the 3 mg/kg and the 10 mg/kg data; we're going to have something definitive. And assuming that those work, then I think everyone will be pretty excited about the potential for this drug, not just in combination with venetoclax, but in combination with a whole bunch of other chemotherapies and in a whole bunch of other indications. And you saw at AACR, we presented a lot of synergy data with other chemo combinations, and we have additional synergy data coming that'll be presented about, you know... So we think that, aplitabart and the DR5 pathway has broad application across many tumor types and in many different combinations with chemotherapies, with ADCs, with a variety of different things. But we got to, we got to take one step at a time. We got to prove to the market that, no, this is real, and then once we've proven that this is real, then the world opens up. Yeah, I think that's the right approach, particularly in the current environment. In the current environment. Yeah. Yeah. Yeah. I think, you know, once you have the data, and particularly for the randomized trial, meaning, okay, you can safely dose DR5, and also you potentially will have the clinically meaningful benefit over the standard of care, and then people will give you more credit- Sure ... in terms of other combination therapy. That's exactly how we see it. Awesome. Yeah, that, totally understood. Okay, we save the rest of the time, not much. We're going to talk about the autoimmune because it's in earlier stage, right? So I, I believe most of the investors for the next probably years or so focus on still the aplitabart, in terms of the, the FOLFIRI, combo in the CRC. But the autoimmune, a lot of cell therapy and generated by POC and a lot of other companies starting to move into this autoimmune disease. So how do you think IgM-based, bispecific will have some advantage of what... And you mentioned the safety, and what the other key factors make you feel, "Hmm, I want to move that as well," and potentially will be the front, front runner in terms of leader? Yeah. So it's really interesting how much interest we have seen from investors and from pharma companies about the use of our bispecific platform in autoimmune disease. As far as we know, right now, the only other, there's like, I can't count how many cell therapy companies have decided they're going to go into autoimmune disease right now. Most everyone. Yeah. Basically, almost every single one. Yeah. But with respect to T-cell engagers, as far as we know. Mm-hmm ... the only other company that's in autoimmune disease is Roche- Roche ... with their mosunetzumab and, and SLE. So we think we stand an opportunity to be a real leader in T-cell engagers in autoimmune disease, and we think that T-cell engagers have some real intrinsic advantages over CAR-T in terms of treating these diseases. First of all, they're a lot easier to give. We can give this on an outpatient basis. You don't have to go in the hospital for two weeks and lymphodeplete these patients, and you don't have the cost of CAR-T, and you can retreat over time using T-cell engagers. It's a drug in a bottle, and you can... You know, we expect we'll have sub-Q formulations and so forth. It's just going to be so much easier to treat with a T-cell engager than with a CAR-T. So we think there are lots of intrinsic advantages. And the key is safety. So I think some of the T-cell engagers that you've seen used in oncology, you know, they have 60% CRS rates, they've got ICANS deaths, they've got a lot of significant toxicity and safety associated. And that's all fine in the oncology setting, but in the autoimmune setting, particularly where the vast bulk of the patients are in the, you know, mild to moderate disease, that's just not going to be acceptable, our view, from most rheumatologists. So safety is key. You know, you followed us. We believe that imvotamab showed really good efficacy in oncology. We showed complete responses in all four of the major subtypes of non-Hodgkin's lymphoma, and we believe that we showed a best-in-class safety profile there. Our most recent data disclosure showed a CRS rate of below 10% in our step-up dosing with 100 milligrams and you know, no ICANS, et cetera. So we think it's the perfect opportunity for this platform. And not only are we very excited about imvotamab, the CD20, but we're very excited about the potential for our CD38 x CD3 in autoimmune disease. And you know that people have struggled with CD38 as a T-cell engager target, struggled primarily on the basis of safety issues with a lot of fratricide of both NK cells and T-cells. And you've seen our preclinical data that we presented in various presentations, where we've shown that we seem to have avoided that fratricide and seem to have a much hopefully safer T-cell engager. So we think that that safety advantage that we've shown in imvotamab with CD20 extends across to CD38 and to CD123 in AML. Excellent. Okay, maybe just last minute, what's your cash runway? What is the current cash position and the runway? Yeah, I think we just announced more than $380 million. Misbah would correct me on the exact numbers in the press release. But importantly, plenty of cash to get through into the second half of 2025, so. It's great. That's appreciated. Great. Yeah. Okay, awesome. Thanks for the time today, and thanks for everyone attending. Thanks for the opportunity. Appreciate it. Thank you.