Good day, everyone, and welcome to the IGM Biosciences fourth quarter and full year 2020 financial results call. Today's call is being recorded. At this time, I'd like to turn the call over to Misbah Tahir, Chief Financial Officer of IGM. Thank you, operator. Welcome and thank you to those of you joining us today to discuss IGM's fourth quarter and full year 2020 financial results. With me this afternoon to discuss the financial results and to provide a general corporate update are Fred Schwarzer, Chief Executive Officer, Bruce Keyt, Chief Scientific Officer, Dan Chen, Chief Medical Officer, and Lisa Decker, Chief Business Officer. Please note that we will be making forward-looking statements on this call, including statements about IGM's plans, expectations and forecasts, and about future events. Actual results may differ materially as a result of various risks and uncertainties, including those discussed in the company's most recent annual report on Form 10-K, as well as its other filings with the SEC. Any forward-looking statements represent IGM's views as of today, March 30, 2021, only, and the company disclaims any obligation to update these statements except as required by law. Following this call, a replay will be available on the company's website, www.igmbio.com. With that, I will now turn the call over to Fred. Thank you, Misbah. Good afternoon, everyone. Thank you for joining us on this call to discuss our fourth quarter and full year 2020 financial results. Before we begin, it's my great pleasure to introduce Lisa Decker as our new Chief Business Officer. Lisa brings a wealth of life sciences business development experience to IGM, and I'm very pleased to welcome her to our executive team. 2020 was an important year for IGM. Among our milestones last year, we presented the first clinical data from our phase I trial of IGM-2323, our bispecific IgM antibody targeting CD20 and CD3, and these were presented at the ASH 2020 annual meeting. We were highly encouraged by these initial data from both an efficacy and a safety perspective. We continue to make good progress through our IGM-2323 dose escalation cohorts, and we are pleased with the safety and efficacy profile that we have seen so far. We look forward to completing enrollment in the phase I dose escalation and initial expansion cohorts and establishing a recommended phase II dose later this year and provide an operational update on this ongoing trial. During 2020, we also began clinical development of IGM-8444, our IgM DR5 agonist antibody, which we believe may have application in the treatment of a broad range of cancer types. As Dan will shortly describe, we have now cleared the second dose cohort in our monotherapy dose escalation protocol, and we are ready to expand into higher dose cohorts and combination therapy. Bruce will describe some of the exciting preclinical data we've generated concerning IGM-8444 in combination with birinapant, a clinical-stage apoptosis drug, which is synergistic with IGM-8444, and to which we obtained exclusive global rights earlier this year. Finally, as Bruce will also describe, we are very excited about the prospects for IGM-7354, our targeted IL-15 immune cell-stimulating antibody, as well as our broader pipeline. We plan to file an IND for IGM-7354 towards the end of this year and to file an IND for our CD38 by CD3 T-cell engager candidate next year. With that, I'll turn the call over to Dan, who will discuss IGM-2323 and IGM-8444 and the current state of our clinical trials. Thank you, Fred. As Fred mentioned, 2020 was a particularly exciting and important year for us, as we presented our first clinical data from IGM-2323 in non-Hodgkin's lymphoma at the 2020 ASH annual meeting. We continue to make rapid progress with both of our clinical programs, IGM-2323 and IGM-8444. By end of 2021, we hope to file an IND to begin the clinical development of IGM-7354. I'd like to first discuss our lead clinical program, IGM-2323. As a reminder, the ongoing phase I study is a global multi-center open label dose escalation trial intended to assess the safety, pharmacokinetics, and preliminary efficacy of intravenous IGM-2323 as a single agent in patients with relapse and refractory B-cell non-Hodgkin's lymphoma. Since the ASH 2020 presentation, we've now cleared the 300 and 600 titration dose escalation cohorts, and we are currently open to enrollment for the 1,000 mg cohort, which is our planned top titration dose. We are very encouraged by the safety and efficacy signals that we continue to see in our clinical trial, and we expect this program to continue to progress quickly in clinical development. From a safety perspective, we have not yet experienced a dose-limiting toxicity, and we have not seen any cytokine release syndrome to date at either the 300 mg or 600 mg doses. We are very excited by our ability to dose at these higher levels without cytokine release syndrome. So far, we have also not seen any sign of neurotoxicity at any dose in any of the patients treated in our clinical trial. Overall, we believe we are well on our way to demonstrating a best-in-class safety profile. Of the 25 patients we have treated, only two have experienced cytokine release syndrome beyond Grade 1, one case of which was described in our ASH presentation. Those two patients have some striking similarities in that both had prior treatment with CAR T and also had circulating peripheral B-cells. The more recent patient had been treated with an experimental CAR T, which has since been removed from clinical development. Interestingly, testing of samples showed that the patient had non-detectable levels of circulating CAR T prior to treatment with IGM-2323, but then had detectable levels of this experimental CAR T circulating following treatment with IGM-2323. This event occurred at a first dose of 50 mg. This 50-mg first dose has not demonstrated CRS of any grade in any of the other 12 patients who also received 50 mg as a starting dose. While the numbers are still small, we believe that there may be something special about the combination of prior CAR T treatment and circulating B-cells. As a result, we plan to adjust our dosing scheme for that relatively small subset of patients who have previously received CAR T drugs and have circulating B-cells. However, we do note that we can achieve both efficacy and low-grade CRS in post-CAR T patients with circulating B-cells. In this regard, the only other patient we have treated with both prior CAR T and circulating B-cells was a DLBCL patient who is now in a complete response. This patient had only Grade 1 CRS. As to our overall safety profile, we are very encouraged by the fact that to date, we have not had a case of CRS beyond Grade 1, except in that very small subset of patients who had both prior CAR T treatment and circulating B-cells at baseline. We believe we are on track to develop a drug that oncologists can use with confidence. We have been very pleased to note that some of our complete response patients did not have any CRS, which demonstrates that CRS is not a prerequisite to efficacy. We have also been very pleased to note that we have seen an exceptionally low rate of CRS in those patients who do not have circulating B-cells. With respect to efficacy, we are excited by the fact that we have seen additional complete and partial responses since our ASH presentation, including among some of the patients that were described in the ASH presentation, as well as in patients only dosed more recently. As you can tell from the fact that some of these additional and new responses were patients covered by the ASH presentation, we are seeing deepening of responses over time. We are also very excited by the fact that some of our more recent responses have been very quick to develop. We look forward to discussing these responses in more detail later this year. Now that we have cleared the 600-mg dose cohort, we are enrolling to our 1,000 mg escalation dose cohort and to expansion cohorts at 100 mg, 300 mg, and 600 mg dose levels, and we expect to determine a recommended phase II dose and schedule this year. We are also making plans to begin clinical testing of single-agent IGM-2323 in situations where there is low CD20 expression in the disease, such as chronic lymphocytic leukemia and multiple myeloma. We are planning on combination therapy with IGM-2323, looking at combinations with standard of care and novel therapies in NHL. Our success with IGM-2323 makes us very excited about aggressively moving our T-cell engager pipeline forward in both hematologic and solid tumor applications. As Bruce will describe shortly, we expect to be able to begin clinical testing of our CD38 and CD123 T-cell engager molecules for multiple myeloma and acute myeloid leukemia, respectively, in the relatively near future. We are also focused on beginning to test our T-cell engager platform in the clinic against solid tumors, which we believe will be a particularly good way to utilize the features of this technology. Now, turning to IGM-8444, our IGM DR5 agonist antibody, it also continues to make good progress in dose escalation. As a reminder, the ongoing phase I study is a multicenter, open label trial to evaluate IGM-8444 intravenously administered as monotherapy and in combination with chemotherapy in patients with relapsed or refractory solid tumors or non-Hodgkin's lymphoma. The first two dose levels of the monotherapy escalation portion of this trial have now been completed without a dose-limiting toxicity. We are currently recruiting to our third monotherapy dose escalation cohort, which is 3 mg/kg, and our first chemotherapy combination cohort. To date, IGM-8444 looks safe and tolerable and hasn't shown any signs of hepatotoxicity with single or repeat dosing. If this is sustained, we believe that that would represent a particularly important step forward for a DR5-targeted agent. We hope to report initial data from this dose escalation portion of this phase I trial in the second half of this year. As you know, we also obtained exclusive global rights to birinapant, and we are working towards starting an IGM-8444 plus birinapant combination clinical study set for later this year. On the basis of some very intriguing data, we are also looking at possible combinations of birinapant with other agents in our pipeline, and we are very excited by these possibilities. This clinical stage asset has already established safety, dose, and schedule in extensive clinical testing, and it appears that it may be able to further enhance the benefits of several of our engineered IgM approaches. We are moving forward quickly to evaluate its potential for other important combinations in the clinic. In summary, we are very pleased with the progress, growth, and expansion of our clinical development efforts, and we look forward to sharing additional updates as milestones are achieved. At this point, I will turn the call over to Bruce, our Chief Scientific Officer. Thank you, Dan. I'd like to stay with IGM-8444 and discuss the scientific rationale behind a combination approach with birinapant. As a reminder, birinapant is a bivalent, small molecule SMAC mimetic that binds to and degrades Inhibitors of Apoptosis Proteins known as IAPs. By inhibiting IAPs, we believe SMAC mimetics can greatly strengthen the effectiveness of the apoptosis signal sent by an apoptosis trigger, such as our IGM-8444 DR5-specific agonist antibody. For that reason, we believe that SMAC mimetics can be synergistic with 8444, which generates a strong apoptotic signal. We tested IGM-8444 pre-clinically in combination with a number of SMAC mimetics, and the combination of IGM-8444 and birinapant was striking. Full synergy. In combination with IGM-8444, birinapant showed the greatest cancer cell killing amongst the SMAC mimetics we tested. Needless to say, we are eager to explore this combination's potential to deliver antitumor activity in patients with solid tumors. Finally, with respect to IGM-8444, I would also like to mention that we have an interesting AACR presentation coming up on April 10th this next month. We'll provide an update on our preclinical studies. We're also excited about IGM-7354, our targeted immune-stimulating IL-15 IgM antibody, which we hope will have broad oncology applications. This product candidate demonstrates another use of our novel J chain-based bispecific technology. In this case, immune-stimulating IL-15 is attached to the J chain of an anti-PD-L1 IgM antibody, which serves to display the IL-15 to passing nearby CD8 T cells, also called killer T cells, and to natural killer cells, the NK cells. This results in proliferation of the killer T cells and natural killer cells, which can play critical roles in the immune system's response to cancer. Our pre-clinical studies also suggest that IGM-7354 provides durable immunity in tumor rechallenge models, which is consistent with the formation of a long-term immune memory response. In this recent study, the same mice who achieved complete tumor regression with initial treatment with a murine IGM-7354 remained tumor-free upon being rechallenged without the benefit of additional treatment with IGM-7354. We expect to file an IND with the U.S. FDA for IGM-7354 towards the end of this year. We're also very excited by our pre-clinical pipeline of T cell engagers against both hematologic and solid tumors. We expect that our next T cell engager to enter the clinic will be CD38 by CD3, and we plan to file an IND on that product candidate next year. We hope that our CD123 by CD3 product candidate will also enter the clinic relatively soon thereafter. We are developing a broad pipeline of solid tumor T cell engagers, and we hope to file INDs on several solid tumor T cell engagers in the next few years. Finally, we continue to make excellent progress with our manufacturing efforts. Construction is now complete on our GMP manufacturing facility in Mountain View, California. We are in the process of bringing this facility online and preparing for an initial GMP run later this year. This 14,000 sq ft facility is modular in design and quite flexible. Although we will continue to utilize contract manufacturers for some time, we believe that having a GMP manufacturing facility under our control will be a very important advantage in managing our clinical supply requirements for new and existing programs. With that, I'll turn the call over to Misbah. Thank you, Bruce. In addition to the brief financial overview I will provide on the call today, you can read additional detail on our fourth quarter and year-end financial results in our press release issued prior to this call and in our 10-K, which was filed with the SEC. We are fortunate to be in a strong financial position. We raised gross proceeds of $230 million in a follow-on public equity offering in December. As a result, our cash and investments total $366.3 million as of December 31, 2020. In the fourth quarter, our research and development expenses were $19.6 million. For the full year of 2020, R&D expenses were $65 million. General and administrative expenses for the fourth quarter of 2020 were $5.1 million and $18.3 million for the full year of 2020. Our net loss for the fourth quarter of 2020 was $24.6 million, or a loss of $0.79 per share. For the full year of 2020, our net loss was $81.4 million, or a loss of $2.65 per share. Turning now to the financial guidance for 2021. We expect our full year 2021 GAAP operating expenses to be between $175 million and $185 million. This includes estimated non-cash stock-based compensation expense of approximately $25 million. We also expect to end 2021 with a balance of over $200 million in cash and investments, providing IGM with an expected cash runway into the second half of 2022. With that, I'll now turn the call back over to Fred. Thank you, Misbah. In closing, I would like to thank all of the employees of IGM for their work over the past year, all of our principal investigators, their teams, and their institutions, and most importantly, the patients and their families, all of whom have made the progress we've described today possible. All of us at IGM sincerely hope that the accomplishments of the past year represent a critical first step in the process of bringing new and important treatments to patients. We appreciate your interest in IGM, and we look forward to keeping you all informed as to our progress. With that, operator, I'd like to open the call for questions. Thank you, sir. As a reminder, to ask a question, you would need to press star one on your telephone. To withdraw your question, please press the pound key. Please stand by while we compile the Q&A roster. I show our first question comes from the line of Stephen Willey from Stifel. Please go ahead. Yeah, good afternoon, guys. Thanks for taking the questions. Was wondering if you could maybe provide a little bit more color just around the 50 mg dose cohort patient receiving 23-23 in terms of the severity of CRS that was observed specifically in that patient? I understand the context of prior CAR T and circulating B cells, but if you could just let us know what the graded severity of CRS in that patient was, that'd be helpful. Sure. I'll turn that question over to Dan. Thanks, Fred. Thanks, Steve. I think one of the keys here is that the vast majority of patients that have been treated aren't showing CRS or aren't showing CRS greater than Grade 1. In fact, of the 13 patients that have been dosed at 50 mg, the other 12 haven't even demonstrated Grade 1 CRS. I think that has put us in a pretty strong position in terms of the safety and tolerability of IGM-2323. It is interesting that this one patient receiving 50 mg did experience a higher grade of CRS by ASTCT. That was a grade 3 event, but the patient was well managed, well tolerated through it. I think one of the really important parts for the development of IGM-2323 is that we've been able to very specifically identify and isolate a very small subset of patients, prior CAR T with circulating B cells that seem to behave differently. That allows us to relatively easily just implement a different way to treat and manage those patients. We do think it's important to still treat those patients. As you know, the prior CAR T, prior B-cell patient population also includes another DLBCL patient that had a complete response to IGM-2323, and that patient only experienced a Grade 1 CRS, so essentially just fever. I think where we've come to now is we've implemented titration dosing. The vast majority of those patients have done well without even experiencing even Grade 1 CRS. We've identified just a very narrow subset of patients with whom we can manage those patients differently. We'll likely just increase pre-treatment steroids, slow infusion, and maybe even fractionate their first dose to make sure that we don't have other high-grade CRS events. Yep, that's understood. It sounds like the disclosure of the DLBCL patient now becoming, I guess, a CR is incremental. Can you just maybe talk a little bit about, I guess, how soon post the ASH presentation, that previous PR, I guess, flipped to a CR? I guess, I ask the question only just because there's a lot of interest regarding just the kinetics of response that you guys have been seeing at the clinic. Yeah. I'm going to actually take your broader question here, which is, we're seeing a host of new responses. That's obviously really important to our program as we continue to dose escalate and expand our experience. We've seen additional CRs, PRs, and interestingly, we do see different patterns of response. Some of these patients seem to evolve over many weeks, and I think you've seen that. We described several of those at ASH, including patients evolving into their CR at 24 weeks, for example. Half a year to CR. That's obviously a slower response pattern. We've also started to see the complete opposite of that, meaning very fast CRs. You can imagine how that may look on a first scan. We see that diversity, and I think it's important for us to continue to think through the different mechanisms that IGM-2323 can engage as it induces these different responses. Right? I think that's one of the things that's kind of special about IGM-2323. Remember, we talk about three potential mechanisms of action. The T-cell dependent killing, which we know can happen fast, the complement-dependent killing, which can happen really fast and doesn't even require the presence of T-cells to engage, and the interferon gamma dominant and repeatable stimulation, which we would expect to take longer. As we look at these different response patterns, we generally are looking at it through the lens of those different mechanisms of action, and we continue to be very aggressive about collecting biomarkers, because we want to understand it. We think that this type of a depth of understanding about our drug, our technology, and our platform will help with the success of the IGM T-cell engager platform. I think it is interesting to note that as we've seen these different kinetics, you saw that at ASH, it seemed like as we got to higher doses, we were seeing faster kinetics of those responses, and we've continued to see that pattern as we've gone to higher doses. Okay. That's very helpful. I guess just lastly, I think prior guidance had suggested that maybe there was a chance for us to get a disclosure of the phase I development program for IGM-2323, kind of in and around the mid-year timeframe. I guess, is that possibility still on the table, I think, as you look at the medical conference calendar, obviously with ASCO and EHA. Then, just in terms of incremental patients that have been enrolled post ASH, I know that there seem to be a fair balance between indolent and aggressive lymphoma patients. Has that been kind of a consistent pattern with the incremental patients that you've observed or with that you've enrolled thus far? That's it for me. Thank you. Thanks, Steve. I would say that we continue to focus on identifying that recommended phase II dose, and that would be our trigger for the next clinical presentation, for IGM-2323, and that's definitely on the table for middle of the year, as you can probably recognize, it's going to be data-driven. Right. I don't think we can sit here and promise yet exactly when it'll happen. It'll be based upon the data that we see in the phase I. I think it's important to note that we will focus on that next clinical presentation at a future scientific or clinical meeting, obviously, additional operational updates could also happen at forums outside of medical meetings such as this one. Okay. In terms of the histologies, as you've noted, we're enrolling a full range of different types of histologies with non-Hodgkin's lymphoma in the phase I. It's part of our belief that a CD20-directed T-cell engager like IGM-2323 is likely to have similar types of activity across a broad range of CD20 expressing malignancies. Obviously, our numbers are still small. The numbers of patients with the different histologies are even smaller. I would reserve any further characterization until we have a greater experience. In general, I think we continue with the belief that a drug like IGM-2323 should work relatively similarly in the different histologies. Great. Thanks for taking all the questions and congrats on a great year. Thank you. I show our next question comes from the line of Michael Schmidt from Guggenheim. Please go ahead. Oh, hey, guys. Thanks for taking my questions. I had a couple more for Dan, maybe just to clarify some of the new information. Did I hear you correctly in saying that you have now 20 patients treated in total? If that's the case, I would assume that the DLBCL patient with this case of grade 3 CRS had already been assessed at ASH. Thanks, Michael. Our total number of treated patients on the IGM-2323 phase I is 25 patients. It continues to increase as we both dose escalate, but remember, we also have dose expansion cohorts enabled, right? As you know, we've already seen CRs at the 50, 100 dose level and even in a patient on the 30 mg level. Clearly we have strong activity at dose levels that we've already cleared. That gave us the confidence to go ahead and start to expand those doses as we think forward to the recommended phase II dose recommendation and decision, right? If you already have CRs at lower doses, you know as you look forward to that decision that you're going to want a pretty good understanding of the activity and safety at that lower dose that was already generating CRs. That's partially responsible for the number of patients dosed. Okay. Understood. Yeah. To your second question about was this 50 mg patient at ASH, the answer is no. That was subsequent to ASH. Okay, understood. I guess, how do you think about identifying the recommended phase II dose? I think I heard you mention that the 1,000 mg dose was the top titration, the top planned titration dose in this phase I. I guess, do you have plans to going beyond that should you not see MTD or DLTs and how do you think about determining the recommended phase II dose? Yeah. 1,000 is our planned top dose. We're right around the corner from completing the planned dose escalation. As you know, we would certainly be open to going higher if the data suggested we should. I don't know that we have that data today. I would say today, we continue to plan to have 1,000 as our top dose. In terms of making that decision, obviously you can have possibilities where it's black and white and very easy, and you can also have shades of gray. We feel very fortunate that we're not in a position where our lowest target dose didn't show activity. We already have CRs at the lowest targeted dose, which is what we consider the 100 mg dose and schedule. I think that we have a lot of interesting decisions to make. Number one on our decision tree will be, what efficacy are we seeing? What are the kinetics of that efficacy? What is the safety we're seeing? Below that, and I think you've heard us say this before, we do have a really deep interest in the underlying science. That has pushed us to build in a very aggressive biomarker program underneath that clinical program. The way we fully intend to use all of the data available to us to help make that recommended phase II dose decision. One of the things I think you've heard us be very interested in is, okay, as we go up in our dose, 100, 300, 600, 1,000, is there a difference in how T cells are being stimulated? Is there a difference in the interferon gamma dominant and repeatable signal? Do we start to engage more complement-mediated killing of cancer cells? What do we wanna do with that balance? I think we're in a pretty promising position in that we get a chance to really set that dial. Once we've completed this dose escalation, we're gonna push with expansions across these doses, and I like our chance to be able to set the dial just right. To your question, Michael, just to reiterate, we've not seen a dose-limiting toxicity to date, and so it would not be surprising if we do not see a maximum tolerated dose. That's right. We would call that a maximal administered dose level. Right. Okay. Then just going back to the two cases with CRS higher than Grade 1, just hypothesizing, are you suggesting this is a scenario where patients might potentially experience reactivation of pre-existing CAR T cells? I think you raise a really interesting scientific point. The only two patients with higher than Grade 1 CRS that we've seen both fit a very similar profile, right? The idea of prior CAR T, now, if you overlay that on IGM-2323, which again, we believe leads to a more physiologic T-cell stimulation than other approaches that we're aware of. Right? Now you imagine you're giving this maybe more appropriate level of T-cell stimulation. You add in some interferon gamma. Could that lead to a more physiologic stimulation of any existing CAR T? What does that do in a patient? Well, here, we recognize the manifestation of CRS, and we feel like we have a pretty good way to manage that, right? We can increase the levels of steroids. We can lower the dose so that you can see that signal as a more mild and easily managed signal. I think that the part that really interests us is, I think, what you're suggesting, which is, what does this mean for the ability to treat patients either with prior CAR T or even with CAR T? I think it has piqued our curiosity around could this type of more physiologic stimulation lead to a different kind of activity of CAR T, a different kind of stimulation of CAR T? You can imagine how interested we were in the finding that we have a patient here without detectable prior CAR T that when we gave them IGM-2323, very acutely, we were able to measure evidence of that CAR T. Now, obviously, we didn't make that CAR T appear out of nowhere. There was likely a niche where there were a few persistent CAR T, so they must have seen and felt the effect of the stimulation with the IGM-2323. This is something we fully intend to continue to interrogate. We don't plan to exclude these patients from our trial. We'll just manage them in a way that we think is appropriate. We look forward to the possible discussions around how to develop IGM-2323 in those patients that either got prior CAR T or may get CAR T. I think it's a really interesting line of thinking for us to continue to work on. Okay. Very interesting. Then just a question on 8444. Good to see progress here as well in the dose escalation. I was just curious if you could remind us at what dose level 1 might start to see clinical activity here and what type of patients might be most likely to potentially respond to DR5 agonists. Dan, would you take that one? Yeah. As you know, we're very pleased to have moved quickly from having our second program, IGM-8444, in the clinic to clearing two of the dose levels in the dose escalation, which puts us now just over halfway into the dose escalation of IGM-8444. This is a program that's moving very quickly. These were also key cohorts to clear because they ungate a lot of additional activity. Not only do we now continue on to complete the dose escalation for 8444, this dose cohort will be 3 mg/ kg. We only have one planned cohort above that. Also that it ungates the development in combination initially with chemotherapy, and that'll be with FOLFIRI. This is a really important time in the development of IGM-8444. I'd say all these doses fall within likely active dose ranges. Again, we are dosing across a complete range of solid tumors. We'll add on heme malignancies once we've completed the single-agent dose escalation. We look forward to the next few months of development in the phase I of IGM-8444, but right now, it's full steam ahead. I guess, high level, are there any predictive biomarkers when it comes to DR5, or are there certain types of cancers that are more responsive than others, potentially? Yeah, I think that we can look across the field and recognize that certain patients are just exquisitely sensitive to stimulation of this pathway. I think Bruce and his team have done an amazing job figuring out sort of the why behind that. If we were going after this as just a biomarker-driven play or an indication-specific play for development, I think that we would be more focused on very specific subsets. To us, the real opportunity around DR5 agonism is much broader than just that narrow, super exquisitely sensitive to single agent DR5 agonism. That's how we're playing out our development plan. That doesn't mean we're not going to take a look at those patients. We will in dose expansion. Our primary focus is to understand safety and efficacy across a very broad range of cancers and play the sensitization play, right? If you know there's only a subset of patients in cancer that are exquisitely sensitive, you either go after that narrow group or you say, "How can I make the rest of these patients sensitive?" We know DR5 expression is there across the broad range, we know this biology is not limited. It is broad, sort of in the way that VEGF is a broad target, PD-1, PD-L1 is a broad target. We look at DR5 very much through that lens. We're going to get a chance, I think, to play to that understanding of the biology, right? The first chemotherapy combination is intended to help sensitize these patients. You know that we're very excited about the birinapant combo because we think it does exactly that. It plays to biology that just makes sense. You give a death signal, you take away that survival signal, and I think you've seen a little bit of Bruce and his team's data around just very synergistic activity there. Great. All right. Well, thanks for that detailed answer. Really appreciate it. Thank you. I show our next question comes from the line of Brian Abrahams from RBC Capital Markets. Please go ahead. Hey, guys. Thanks so much for taking my questions and congratulations on all the progress. It sounds like you're rather encouraged by what you're observing with 2323. I'm just curious, as you have continued to see the data evolve, how would you characterize your level of confidence that you'll be able to achieve response rates, rapidity, and durability akin to the other CD20, CD3 bispecifics within the currently planned dosing range? Thank you. Yeah, go ahead, Dan. Why don't you take this one. Rates, rapidity, and what was the third one? Durability. Durability. Yeah, I think those are good questions. I think that, look, we're very excited by what we're seeing here. I think that we're well-positioned. I think we have the potential to be best in class. I think the easiest place to see that we've always guided towards this is look, the safety and tolerability signal will come first. I think you've clearly seen that differentiation, right? Like if you look at other molecules in the CD20, CD3 T-cell engager class, they generally have a CRS rate of 50%, 60%, 70%. My personal belief was we're not going to be anywhere close to those rates, that our CRS rate is going to be very low. You've heard us talk about, I mean, if you look at what we've said about the CRS that we're seeing in dose titration. I mean, that's a fair number of patients now in our experience. I think you've heard us describe not even cases of CRS. Even though our target isn't to say, "Hey, we're going to deliver a no CRS rate," I mean, our experience in dose titration has seen very little clinical CRS. I think we're well-positioned to be clearly differentiated around safety and tolerability. That gives us confidence that this is a drug that outpatient community oncologists should likely feel confident in their ability to use. While we need to generate more data to continue to support this, again, I think the early data has put us in a very strong position here, and it's one where I think that we've pushed that acceleration button on our T-cell engager pipeline because we do feel confident. Rapidity, we're clearly now seeing rapidity of responses. Even though I don't hold that as a goal, I would never say, Oh, we need to optimize the rapidity of responses. That I don't think is something we're trying to achieve because rapidity may or may not be the best thing for patients, right? If you have to trade off rapidity for durability of immune stimulation, I would take durability of immune stimulation. It's not a goal, but clearly we've seen some very fast responses here. Finally, durability. That's going to take time to show. If you can already show that responses evolve over time, that tends to tell you that you have a drug that continues to work over time. Even though we have limited follow-up, our sense of the ability to generate durable, complete responses, I think is off to a good start. Got it. That's super helpful. Then I guess on the safety and tolerability side, it's really interesting. I know there's been a theory that the switch to complement from T-cell driven killing at higher doses may have been part of the reason why you're observing such low CRS rates. Is that still the dominant view, or has that changed now that you have a more detailed understanding of the patients experiencing CRS. Do you think it may be more about baseline characteristics like prior CAR T? I guess I'm curious if this might steer you towards exploring higher starting doses than 50 mg. Yeah, these are good questions. I think the theory around a shift to more complement-dependent killing is definitely in play. We'll need to study this better with more patients and more data and more biomarker activity. I think it definitely stands as a potential hypothesis. Now, separately, is there a sensitive subset that we should be careful with and just manage differently? I think that's probably true, too, and is consistent with how we look at clinical development. Patients are very different. We need to be prepared to understand our drug in many different types of patients and be able to figure out how to manage those patients as a whole. I think I feel pretty good about where we stand with that today. Great. Maybe one more quick one from me. I'm wondering if you had a sense yet of the extent of data we might look for IGM-8444 in the back half of the year, and in what forum those data may be presented. Thanks. Yeah. I think that we're targeting getting up through the IGM-8444 single-agent dose escalation, and that would largely trigger presentation of first clinical data from that program. Recognize that in the background of that, we're already starting the chemo combo, any available data there could be packaged together at a later meeting. I think it's too early to say which meeting, certainly we have some nice choices coming up in the second half of 2021. We'll just need to take a look at which ones to choose from when we have the data. Great. Makes sense. Thanks again. Thank you. I show our last question comes from the line of Asthika Goonewardene from Truist. Please go ahead. Hi, guys. Thanks for taking my questions, and excuse me at the end. I'm curious, Dan, how is that gamma dominant cytokine profile holding up after repeat doses? I remember at ASH, you presented some data, or in the analyst meeting, you guys presented some data that showed that it held up quite nicely. I'm just wondering, how have you seen that with more follow-up in-house? I got a couple of follow-ups on dissociations and kinetics. Yeah. Thanks, Asthika. Interferon gamma, that whole concept of repeatable interferon gamma-dominant T-cell immune activation is still one of our primary hypotheses. It's something we incorporate into our thinking about how to best develop a drug like this. Absolutely, I would say today, even with continued dosing upwards, that we continue to believe in that, and we continue to believe that that is something we want to be optimizing. As we define and select our RP2D, that is one of the key pieces that we're looking to optimize. Yes, that is fully in play. I'm sorry, your two follow-up questions were? Yes. For the patient who had the prior CAR T that had the CRS after the 50 mg dose, I'm just wondering when would be last dose with the CAR T? Yeah, that was a fair amount earlier. It wasn't like within a short number of one month. We actually exclude patients that had very recent CAR T. Got it. Okay. Thank you. Lastly, again, squeezing in. What are you seeing regarding 2323's dissociations from tumor cells? Just wondering because the pre-clinical data suggested that 2323 is really sticky. You're talking about dissociation, you mean off rate. I think that one of the things we've said is that that off rate has been unmeasurable in some of the preclinical studies. I'm going to turn it over to Bruce here. I don't think anything in our clinical data set has made us believe anything other than that concept being true, which is that IGM-2323 binds to a CD20 expressing lymphoma cell and doesn't come off. That's right. Thank you, Dan. The dissociation rate for the IgM to the tumor target cell is just irreversible. There will be eventually internalization of that antibody on the tumor cell. Obviously, we will continue to redose. The durability of that antibody on cells and the effect is much longer than any other bivalent I'm sorry, it's a bispecific antibody, but they most have single binding sites to the tumor antigen. We get very durable effects in vitro and in vivo. Great. Thank you very much, guys. Thank you. This concludes the Q&A session. At this time, I'd like to turn the call back over to Mr. Fred Schwarzer, Chief Executive Officer, for closing remarks. Thank you, operator, and thank you to all of you for joining the IGM conference call. We really appreciate your interest in IGM, and we look forward to updating you on our progress as the year progresses. The year passes, shall I say. Thank you. Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect. Good day