Good morning, and thank you everyone for joining us today. I hope everyone is enjoying the third day of the conference. My name is Tarun Soni, and I'm a Vice President in JP Morgan's Healthcare Investment Banking group. Before I introduce you to our presenters for the session, I want to call your attention to the blue button on your screen which says Ask a Question. This is where you can submit your questions and will be addressed during the Q&A session. With that, I'm very pleased to introduce you to Fred Schwarzer, CEO of IGM Biosciences. I know he is very excited to tell you a little bit about this, their story. Without further ado, over to you, Fred. Thanks very much, Tarun. Appreciate the introduction, and we really appreciate the opportunity to present here at the JP Morgan conference. Welcome to all of you, and thanks for taking the time to listen to our presentation. I sincerely wish we were in person, but maybe next year. This presentation will contain certain forward-looking statements that are based on information available to IGM Biosciences as of today's date, but we must advise you that these forward-looking statements are subject to many factors that are beyond our control, and we have to caution that these forward-looking statements should not be relied upon as predictions of future events. We also direct you to the risk factors in our filings with the SEC. With that out of the way, I'd like to introduce you to IGM Biosciences. For those of you who are not familiar with the company, we are the global leaders in the development IgM antibodies for therapeutic uses. We are presently, our first area of focus has been oncology. We're now expanding into autoimmunity and inflammation as well as infectious diseases. Excuse me just one moment here while I change some. Oops, sorry. I need to try to change something on my screen. My apologies. Well, it may not happen. There we go. Thank you. Had to be able to see my own slides. Our strategy is to extend that global leadership in the development IgM antibodies and to advance our product candidates and increase our R&D efforts over time. We're expanding our manufacturing capabilities. We're also expanding our intellectual property portfolio. When the time comes, we hope to participate in commercialization. Importantly, with respect to that intellectual property portfolio, we have 38 patent families right now. I think we have a quite remarkable intellectual property position IgM antibodies. to the best of our knowledge, we're still the only significant commercial effort anywhere in biotech or pharma focused IgM antibodies. as I like to say, we're running as fast as we can, but as far as we can tell, no one's chasing us yet. We have 145 research development manufacturing personnel based in San Francisco and the Philadelphia area. We just opened our East Coast facility in Philadelphia this year. We've got about $230 million in cash on the balance sheet as of the end of December, which gives us plenty of cash to get through 2021 or 2022 and into 2023. We think 2022 is gonna be a very exciting year for us. Let me talk a little bit IgM antibodies, for those of you who are not familiar. On the left, you see the traditional IgG antibody. You see it has two binding domains in yellow, and on the right you see an IgM antibody, and it has 10 binding domains in yellow. That what that does is it gives you much more binding power relative to an IgG antibody. You see the cryo-EM image over there on the right-hand side. You see where the little red semicircle is? That's what we call the joining chain or the J chain. You see it's a little bit like taking one slice of pizza out of a six slice pizza. You can really see that on the cryo-EM on the right-hand side. What that J chain allows us to do is to create bispecific and bifunctional antibodies, and we're gonna talk about that in a little bit, and those are very different than the bispecific and bifunctional antibodies that are created using the IgG format, as you can obviously tell. Also really important, if you focus back on the two binding domains for the IgG versus the 10 for the IGM, we like to say it's like the difference between holding on to something with two fingers and holding on to something with two hands. We think it just gives you much, much more binding power. Here's a little bit about our leadership IgM antibodies. first, on left-hand side, protein engineering. That is we take the IgG binding domains, those little binding domains, and I see something's happened to my microphone, but hopefully you can still hear me. Excuse me just a minute. Okay, sorry for the. Not sure what happened to the microphone there. The IgG binding domain's in yellow, and we take those and put them onto the IgM backbone. What that does is it gives us the benefit of much higher affinity and specificity of those IgG binding domains while on the IgM backbone. The backbone gives you the binding power of ten. We've also done a lot of protein engineering to extend the half-life IgM antibodies, and as I said, we've created some very novel, bispecific formats. In addition to that, we have the manufacturing abilities that have been traditionally the plague IgM antibodies in terms of the ability of other companies to, or anyone, to manufacture IgMs at scale and with high yield. You see on the right-hand side, you see our manufacturing facility. We have a brand-new manufacturing facility that's come online in Mountain View, California, and, it's a state-of-the-art manufacturing facility. We're able to use relatively industry-standard manufacturing techniques, but adapted for IgMs and very cost-effective purification. Here's our pipeline for right now. Focused on oncology first. Our lead program is IGM-2323. Following that, we have our IgM that's a CD20 x CD3 T-cell engager. Following that, we have our death receptor 5 antibody receptor cross-linking. We'll talk more about these. Following that, our targeted cytokine. We have two more T-cell engagers coming that we'll talk about, as well as our first infectious disease program, which is in COVID-19. First, we're gonna talk. We have three different mechanisms of action in oncology. The first is T-cell engagers, and we'll talk about those first. IGM-2323 is our lead program there. What you see on the upper left is the IgM antibody with the 10 binding domains to CD20 and the CD3 binding domain on the J chain there in yellow. A very different format as compared to IgG antibodies. We think that this product candidate can be a backbone therapy in hematology for B-cell proliferative diseases. Now, obviously, first we'll start with monotherapy in late-line non-Hodgkin's lymphoma. We'll then be expanding into combination therapy in earlier lines. We think that the safety profile as well as the efficacy profile that we have with this candidate can make it a really important backbone therapy in earlier lines of therapy, as well as in the late-line therapy. Here you see some of the data that we presented at ASH in December concerning our safety profile in our phase I clinical trial. You see the relatively quite low rate of CRS that we've seen, as well as a very low rate of neutropenia that we've seen, and no ICANS or immune effector cell-associated neurotoxicity that we've seen. We think that this safety profile is arguably better than any of the competition. Obviously, we need to show this with many more patients, but we're very, very encouraged by this safety profile. With respect to efficacy, you see here at 100 mg that we had a complete response rate of 50% with respect to DLBCL, and a complete response rate of 67% with respect to follicular lymphoma. We think that these response rates, obviously, those are small numbers, but if these response rates are established overall in our phase II trial, we believe that these are response rates that are competitive with any program, any CD20 by CD3 program. We did have questions as to why we didn't see higher efficacy at the higher doses. We've been doing research on that to try to understand what might be happening here. What our initial preclinical, in vitro data has demonstrated is that when we go above an optimal dose, we actually see a reduction in T-cell activation. Now, this is not necessarily surprising for an immuno-oncology space. We've seen this with a number of other agents where as you go above an optimal dose, you actually see a lower response. We're continuing to develop these data, expanding our research, particularly trying to create conditions that are similar to the conditions around the patient tumor, which is a setting that is more difficult, an environment that's more difficult for the T-cell. We hope to present these data later this quarter. The most important thing will be to establish clinically that these response rates are reproduced in our phase II clinical study, which is starting this month. That study will involve testing two different doses and consistent with the FDA's Project Optimus advice, we'll be testing 100 mg and 300 mg. Over the course of the first 30 patients in each randomized arm, we'll determine which dose appears to have the most efficacy. Assuming that the 300 dose does not have more efficacy than the 100, we will be proceeding with the 100 to 60 or 70 additional patients, and that could potentially be a registrational cohort for us. Now, our dosing is once a week through the first 12 weeks. If a patient has a complete response or partial response after 12 weeks, then they have the option to move to every three-week dosing. We're also planning to start combination studies this year. We think there's some very interesting potential combinations for IGM-2323 given our safety profile as well as our efficacy profile. Those combinations obviously could include rituximab plus GemOx, and a number of other potential combinations that you see here on the left. What I think I wanna focus on here is some differentiation that we have with respect to the IgG bispecifics, which are, in most cases, one binding domain to CD20 and one binding domain to CD3. Now, what happens in that case is when they are being dosed in combination with Rituxan, the Rituxan, which has two binding domains to CD20, can outcompete the 1 binding domain to CD20 on the bispecific CD20. As a result, there may be limitations on the efficacy of those bispecifics in combination with Rituxan. What you see here on the right is because of the 10 binding domains of IGM-2323, it can outcompete the Rituxan for binding. We think that it will be potentially less impacted. Its T-cell-directed cytotoxicity will be less impacted by the presence of Rituxan than perhaps some of the one-on-one bispecifics might be. We also believe that this 2323 safety and efficacy data that we've generated supports our broader T-cell engager pipeline, most particularly, IGM-2644, which is a CD38 by CD3 bispecific. That will go into the clinic this year, is our anticipation. Then IGM-2537, which is CD123 by CD3, we expect that to go into the clinic next year. Both of those represent very significant patient needs, as you see there on the right. We're very excited about those, and we think that our safety profile that we've shown with IGM-2323 bodes very well for both of these two programs because safety is gonna be a very important issue, we believe, in both CD38 by three and CD123 by three. You've seen that the competition, in many cases, has struggled with safety issues with these two targets. Moving on to our second mechanism of action. This is multi-receptor agonism. This is something that an IgM antibody does really well. You sort of can see in that image there, an IgM with its 10 binding domains can bind down onto a cell surface and can really aggregate receptors together. When receptors are aggregated together, the signal that those receptors give into the cell, which is called agonism, is creating that signal. It's much stronger than if you just hit one or two receptors. If you tend to cross-link, it's called, those receptors, bind them together, it tends to send a much stronger signal. This is particularly true with our first lead program. Death Receptor 5 is a receptor that is highly expressed across many different tumor types. As you might guess from the name Death Receptor 5, the purpose or what happens when you agonize this receptor is it sends a death signal or an apoptotic signal into the cell. You see on the left-hand side the way the natural ligand binds three of those receptors together, and that's what sends that apoptotic signal. In the middle, you see how an IgG antibody doesn't necessarily do a very good job of binding three together, since it only has two binding domains. It tends to send a relatively weak signal. On the right-hand side, what you see is with an IgM antibody, we can bind three receptors together, and we can even bind clusters of three together and send a relatively quite strong signal. This is demonstrated in the graph on the right-hand side, where what we did was we took the same two yellow binding domains from an IgG antibody against Death Receptor 5, and we formatted them into an IgM antibody. You see that we had a 5,000-fold increase in efficacy, even on a weight basis. Don't forget whether one weighs more than the other. On a weight basis, more than 5,000-fold increase in efficacy. Just by changing the format from two binders to 10 binders. In addition to that, activity as monotherapy, what we've seen is when you combine IGM-8444 with chemotherapy, for example, in this case, irinotecan, you see significant increased activity. As we'll talk about in a moment, that's what our first combination study is in combination with irinotecan or FOLFIRI. If you combine two pathways, if you attack or address two apoptotic pathways at the same time, you see some remarkable synergy. DR5, we saw that image on a couple of slides back where you... DR5 is on the surface of the cell, and if you address DR5, you're addressing what's called an extrinsic apoptotic pathway. There's also an intrinsic apoptotic pathway. If you address that pathway through a target called BCL2, which is the target of venetoclax, if you address both of those pathways at the same time, you see the kind of remarkable synergy that you see here on this slide in an AML model. We will be moving venetoclax and IGM-8444 into clinical trials in AML very shortly. Now, there's another way to address the intrinsic pathway, and that's through using a SMAC mimetic that also addresses that pathway. I won't go into the detail of exactly where it interacts with the pathway. The really interesting thing here is if you combine the extrinsic pathway approach of IGM-8444 with the intrinsic pathway approach of birinapant, you see this remarkable synergy here on triple-negative breast as well as fibrosarcoma. Last year, we licensed exclusive worldwide rights to birinapant, and we are now in dose escalation, a combination of birinapant and IGM-8444. Here is where we stand in terms of our clinical trial. We have completed our monotherapy dose cohorts up through our highest dose of every two weeks. We have completed our second FOLFIRI dose cohort, and we've seen no DLTs to date. We're expecting that we will clear our third FOLFIRI dose cohort in the next month or so. We have our first dose cohort open for a combination with venetoclax, and we have we're finishing up our first dose cohort in combination with birinapant, and we hope to clear that dose cohort next month as well. To date, we've treated 38 patients with IGM-8444. 13 patients remain on treatment, no discontinuations, no maximum tolerated dose defined, and most importantly for this class of agents, we've seen no clinically significant liver toxicity. This includes patients who have been on treatment for over 9 months. We've still seen no clinically significant liver toxicity. We've seen signs of biological activity that are consistent with activation of that extrinsic pathway by a DR5 agonist. This is my favorite slide in the entire presentation. What you see here on the left-hand side, you see these are both monotherapy patients. On the left-hand side, you see 3 mg/ kg of IGM-8444. On the right-hand side, you see 10 mg/kg of IGM-8444. These are matched biopsies, pretreatment and post-treatment. What you see is the amount of brown, excuse me, on the bottom post-treatment. What that brown is showing you is the cleaved caspase-3. To simplify this, cleaved caspase-3 is generated when you activate that extrinsic apoptotic pathway. What we're seeing here is IGM-8444 is getting into these solid tumors. It is activating this pathway and creating the apoptotic signal that we want to see. We're very pleased with these data. Moving on to targeted cytokines. Our first targeted cytokine is IL-15. Here's a different form of a J chain-based. In this case, we would call it a bifunctional antibody. You've got 10 binding domains in yellow to PD-L1, and you've got on the J chain IL-15 and the sushi domain there in order to make it effective. How this works, I love this because it's really elegant. You're reproducing the natural way that IL-15 is presented to a passing NK cell or CD8 cell in order to stimulate those cells to expand. We believe that this targeted delivery may increase toxicity and potentially reduce activity. Increase efficacy and potentially reduce toxicity. My mistake there. We expect this to go into phase I this year. Here's some preliminary data from IGM-7354. You see on the left-hand side that we see quite a significant efficacy signal here with eight out of 10 tumor-free. Really quite interesting is then when you take those eight mice that have been tumor-free and you go re-challenge them with CT26, they all stay tumor-free. Somehow through the use of this IL-15, they've created an immune response that allows them to fight off the cancer, which we think is just obviously very, very interesting. To finish up here for a moment, a third program that's in the clinic right now is IGM-6268. This is a nasally delivered IgM antibody for the treatment and prevention of COVID-19. Very interesting application of IgM technology against the target, the type of target that IgM was evolutionarily designed to address, which is infectious diseases. Now, IgM antibodies were your first line of defense against infectious agents, viruses and bacteria, and they use that great, much greater binding power of an IgM to neutralize any of those invading agents. We're trying to take advantage of what IgMs do best naturally without engineering. Here you see how we've taken some of those yellow binding domains from the IgG. We've converted them to an IgA, which is a four binding domain antibody, and as well as an IgM, which is the 10 binding domain. You see that the IgM is more potent than the IgA, which is again more potent than the IgG. On the right-hand side, you see how that potency really has been applied across many variants that we've tested, and the additional avidity of the IgM antibody makes it much better against mutants than the corresponding IgG. If you have an IgG, it might lose some potency against a mutant, but the IgM tends to retain much more potency than the IgG does. We're planning a completely different way to make this available to patients. Rather than an infused or an injected antibody, we're trying to go with an intranasal approach, which will be much less invasive, will be able to be much less expensive, and we think it will be a terrific product, assuming we get through to approval, both for acute treatment and acute prophylaxis to prevent, if your spouse or partner comes home with a positive test, you could squirt this into your nose and potentially prevent getting infected. Similarly, if one of your employees at work gets infected, you could provide this to the other employees nearby, and hopefully that would prevent infection. Or if you were gonna go to a Knicks game or something like that, you might well decide that you wanted to squirt this. Now, obviously, we need to demonstrate all of this, but that is the potential for this program, is to be a very broad prophylaxis and acute treatment. Go to where we're at right now. In terms of what we hope to see happen in 2020, we expect to disclose initial data from our phase II trial of IGM-2323. We expect to disclose initial combination data from our IGM-8444 DR5 agonist program. There we think that we should be through our follicular combinations and have gotten through a couple of dose escalations with respect to birinapant. We're currently targeting probably ESMO in early September to have an adequate data set to be able to show the efficacy in combination. With IGM-6268, we have cleared our first dose cohort of healthy volunteers, did that in December, and we are continuing our phase I clinical trial there. With respect to IGM-7354, we expect to start a phase I this year. With respect to IGM-2644, we also expect to start a phase I this year. By the end of this year, we should have five programs in the clinic, and we think it's going to be a very exciting year in terms of data and in terms of milestones for IGM. Maybe I'll quit right now and, Tarun, see if there are any questions we wanna address. Thanks a lot, Fred, for the great presentation. You know, I just want to draw attention to the audience that if you want to ask any question, please use the blue button on your screen, which says, "Ask a question," and you can submit your question. We have our first question from the audience, Fred. You know, on IGM-2323, there wasn't a dose related response rate. Is the drop in T-cell activity at higher doses due to aggregation preventing T-cell engaging? Well, what we think is probably happening, what we're continuing to explore is remember the IgM antibody, when it sits down, when it engages a T-cell, what it does is it sits down on the cell surface, and then the J chain comes up and engages the CD3 on the T-cell. We think that it's possible when you get into significant antibody excess at the site of the tumor, the tumor is spherical, it only has a certain amount of surface exposed. Remember, each IgM antibody has 10 CD20 binding domains. We think what might be happening is when you get way too much antibody there, the antibodies are fighting each other, and they're not able to lie flat and expose that J chain to the T-cell. As a result, we're not getting the kind of T-cell activation that we get when they're not greatly in excess of what's needed. Now, obviously, we've seen really nice efficacy at 100 mg, so we think at an optimal dose where that IGM can lie flat and engage the T-cell, we can get very good efficacy. I think we think right now that when you get above that, the antibodies start to fight with each other and just aren't able to get to the position that's appropriate for full T-cell activation. That's our hypothesis right now. Got it. Thank you. That makes sense. So at this point, we do not have any questions from audience, so I would like to ask like one question, which is, you know, how do you see this data on CD20/CD3, which is the IGM-2323 read-throughs for your other T-cell engagers, such as the CD123 and the CD38. Yeah. We think that our data with respect to 2323 is very positive as a read-through with respect to CD38 and CD123. As I said, we've seen very nice efficacy there at an optimal dose. I think we hope that that indicates that we'll see similar efficacy at an optimal dose with CD38 and 123. Obviously, in both cases, we're gonna dose up starting at minimally active biological effect level or MABEL, and dose up and see how our activity increases as we go up in dose. To be clear, with 2323, we saw significant increases in efficacy up until 100. We didn't see increases in efficacy beyond 100. So there clearly is a dose response here. It's just a question beyond which, when does the dose response not continue? We think that with CD38 x CD3 and CD123 x CD3, if we see comparable efficacy, that's gonna be terrific. If we see comparable safety, that's gonna be really important in both of those targets where safety has been. It hasn't been so much a question of efficacy with bispecifics there. It's really been a safety question, I think. Got it. Makes sense. No questions again from the audience. You know, how do you differentiate your CD20/CD3 compared to your competitors? There's a lot of data, you know, and there's a lot of from the big pharma as well as from some of the small- to mid-cap. There's a lot of agents. What are some of the differentiating factors, and is there a specific patient population where you think IGM-2323 provides a great benefit? And do you- We see IGM-2323 as being really important, particularly in the community oncology setting to start with. We think that the safety profile, the ability to use this on an outpatient basis, the fact that we're gonna have this, hopefully, very low rate of CRS and relatively low grade of CRS and no neurological symptoms at all. We think that's gonna give community oncologists a good comfort level with using this drug. Similarly, we think in combination IGM-2323 is going to be potentially the partner of choice in combination. If you look, for example, at the neutropenia, that's gonna be an important factor in those cases where you use other drugs that do cause neutropenia. A number of chemotherapies and lenalidomide and so forth will cause neutropenia. You don't wanna combine two agents, both of which cause neutropenia. We think we hope it will be a really good drug for the community oncology setting as well as academic settings, both in third line. More importantly, we think it'll be a really good drug in combination. Got it. Thank you. We have a question from audience, and just in the interest of time, we would like to take that. Have you compared your IgM PDL1 IL-15 with IgG PDL1 IL-15, and have you seen any advantages of one over the other? What we have done. First let me make clear. Was it the primary IL-15 that's out there, is the Roche Cibisatamab molecule, which is not targeted to my knowledge. There's one PDL1 IL-15 that Kadmon had that I'm aware of. But I don't believe we've done any comparison, head-to-head comparison with that molecule. Maybe you could repeat the question. Was it with respect to targeted IL-15 or untargeted? What we're bringing to the table, we think that's most, perhaps most important, is the targeting to PDL1. Obviously with the IGM against PDL1, we think that targeting will be very strong. Got it. Well, they haven't specified whether targeted or non-targeted, but if you would say that, you know, it is targeted, then how would you compare it? And, you know, have you done any internal comparisons within, you know, your own discovery or externally as well? Yes, we've done some internal comparisons with untargeted IL-15, and we look very good in comparison. We haven't shared those data, but yes, we're feeling that we are definitely bringing something new to the table here with respect to the PDL1 targeting of IL-15. Got it. I think it was targeted with Kadmon, and probably this will be our last question just in the interest of time. Right. But- Yeah. I don't recall whether we've done a head-to-head comparison with our Kadmon version of a Kadmon-generated PDL1. I don't recall if we have. All right. Obviously, the big difference here is ours is going to be an IgM, and it's gonna have much stronger targeting to the PD-L1 expressing cell than an IgG we believe would do. All right. Well, thanks a lot, Fred, for your time, and it was great speaking with you. I hope everyone in the audience is enjoying the conference. Talk to you later. Thank you. Have a great day. Yeah, sorry for the headset problem here. I'm not quite sure what happened, but hopefully you could at least hear me through the conference. Thank you. Cool. Thank you. Thanks a lot, Fred. Okay. Take care. Take care. Bye bye.