Ladies and gentlemen, thank you for standing by, and welcome to the fourth quarter and year-end Xencor conference call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session, to ask a question during the session you'll need to press star one on your telephone, please be advised that today's conferences is being recorded, if you require any further assistance please press star zero. I would now like to hand the conference over to your speaker today, Charles Liles, Head of Corporate Communications and Investor Relations. Please go ahead, sir. Thank you, good afternoon. Earlier today, we issued a press release which outlines the topics we plan to discuss today. The press release is available at www.xencor.com. Today on our call, Bassil Dahiyat, President and Chief Executive Officer, will provide a corporate overview and will review recent partnership news. Allen Yang, Chief Medical Officer, will review updates throughout our clinical portfolio. John Kuch, Chief Financial Officer, will review financial results. Then we'll open up the call for your questions and will be joined by John Desjarlais, Chief Scientific Officer. Before we begin, I would like to remind you that during the course of this conference call, Xencor management may make forward-looking statements, including statements regarding the company's future financial and operating results, future market conditions, the plans and objectives of management for future operations, the company's partnering efforts, capital requirements, future product offerings, research and development programs, and the impact of the COVID-19 pandemic on these topics. These forward-looking statements are not historical facts, but are rather based on our current expectations and beliefs and are based on information currently available to us. The outcome of the events described in these forward-looking statements are subject to known and unknown risks, uncertainties, and other factors that could cause actual results to differ materially from the results anticipated by these forward-looking statements, including, but not limited to, those factors contained in the Risk Factors section of our most recently filed annual report on Form 10-K and quarterly report on Form 10-Q. First, some housekeeping. We have renamed our programs that do not yet have confirmed non-proprietary names. In general, where there were five digits, we have shortened to just the final three digits. For example, XmAb20717 is now XmAb717. With that, let me pass the call over to Bassil. Thanks, Charles, good afternoon, everyone. Xencor's approach to creating antibody and cytokine therapeutics is based on our XmAb protein engineering platform. It's built on our extensive protein engineering knowledge, combined with our suite of XmAb Fc domains, which we use to build novel molecular structures, improve natural protein and antibody functions, and create new mechanisms of therapeutic action. The plug-and-play portability of our XmAb Fc domains and the speed of our protein engineering capabilities enable us to rapidly explore different targets and biologies so we can select the most promising programs to take forward. We're focusing our R&D on the expansion and use of our XmAb bispecific platform to create antibodies that bind to two or more different antigens simultaneously, and also to engineer cytokines with structures optimized for particular therapeutic use. We're currently running six phase I studies evaluating such XmAb bispecific antibodies. This way, we are taking multiple simultaneous shots on goal in the clinic, the proof of concept data we generate will guide which programs we independently advance, which we partner, and which we will terminate. Last quarter, we provided program updates for our plamotamab bispecific antibody program targeting CD20 and CD3, including plans for a potentially registrational phase II trial we expect to start later this year. We presented interim phase I data for XmAb717, our PD-1 by CTLA-4 bispecific antibody, which showed activity in multiple advanced solid tumors, including prostate cancer. We announced that we are starting a multi-arm prostate cancer trial this year. We also presented updated data for vibecotamab, a CD123 by CD3 bispecific antibody in AML, where we identified a marker for patients more likely to respond to therapy, lower baseline leukemic disease burden. Shifting to the preclinical front, we expect to begin the phase I clinical trial early this year for XmAb564, our wholly-owned IL-2 Fc fusion engineered to selectively activate regulatory T cells for the treatment of autoimmune disease. It will be our second cytokine in the clinic and will join XmAb306, our engineered IL-15 for oncology, which is partnered with Genentech. Following behind that, we expect to file an IND for XmAb819, our ENPP3 by CD3 bispecific for renal cell cancer later this year. We are beginning development of our first CD28 bispecific, a B7-H3 targeting molecule for potentially broad solid tumor use, including in prostate cancer. Our broad XmAb platform also drives our partnering strategy, which provides revenue streams, but also the opportunity to expand our clinical development scale and combination therapy options. For example, our Genentech partnership for XmAb306, which initiated dose escalation in combination with atezolizumab, Genentech's anti-PD-L1 antibody, last quarter after starting monotherapy escalation last March. Our recently started CD28 prostate cancer discovery collaboration with Janssen against an undisclosed tumor target also gives us access to their industry-leading prostate cancer portfolio for clinical combinations with our agents. Before we move on to our clinical portfolio today, I want to state that we did not experience significant COVID-19 disruptions to operations during the last quarter. We'll continue to update you on impacts from COVID-19 if and when they emerge. With that, I'll let Allen Yang, our Chief Medical Officer, review updates to our clinical portfolio. Allen? Thanks, Bassil. Today, we'll provide a few brief clinical updates, and we'll be happy to address your questions in the Q&A session. Really dating to late 2019, we have been presenting early stage clinical data across many of our bispecific antibody programs, and the data have guided our decisions to advance several candidates into new studies scheduled to start in 2021. First, plamotamab is our CD20 by CD3 bispecific antibody that we are advancing for patients with B-cell malignancies. Preliminary safety and antitumor activity from the phase I dose escalation study in patients with relapsed or refractory non-Hodgkin's lymphoma were presented at ASH 2019. Initial data indicated that plamotamab was generally well-tolerated and demonstrated encouraging clinical activity as a monotherapy. Across this competitive class of molecule, we have observed similar efficacy and toxicity profiles, though some datasets have been smaller or more selective than others. We believe that the differentiation for CD20s will bear out through which combination strategy elicits strong, durable efficacy, and maximal tolerability for patients. This past November, we entered a clinical collaboration with MorphoSys and Incyte to investigate the chemotherapy-free triple combination of plamotamab with tafasitamab and lenalidomide in patients with relapse or refractory diffuse large B-cell lymphoma. Plamotamab's mechanism of action as a CD20-directed CD3 bispecific redirects T cells to tumors. Tafasitamab is a CD19-directed XmAb antibody that we engineered with our cytotoxic Fc domain and subsequently licensed to MorphoSys in 2010. These two antibodies combine powerful and distinct immune pathways. Tafasitamab itself is easy to use, tolerable, and can generate prolonged durable responses. It's the first agent approved for second-line diffuse large B-cell lymphoma. It has already received NCCN listing. MorphoSys and Incyte will provide tafasitamab for the studies, which we will sponsor and fund. We anticipate the first study will start this year. Other studies additionally planned include triple combination in relapse or refractory follicular lymphoma and first-line diffuse large B-cell lymphoma. Next, XmAb717 is our most advanced tumor microenvironment activator. Its mechanism is a dual selective targeting of T cells that express the checkpoints PD-1 and CTLA-4. In November, we presented updated interim data from an ongoing phase I study at SITC last year. 717 was generally well-tolerated in patients across multiple types of advanced solid tumors. As of the September 2020 data cutoff, a complete response was observed in a patient with melanoma, and partial responses were observed in multiple tumor types, including melanoma, renal cell carcinoma, non-small cell lung cancer, ovarian cancer, and castrate-resistant prostate cancer, or CRPC. In the first half of this year, we plan to initiate a phase I-B study of XmAb717 for patients with certain molecular subtypes of castrate-resistant prostate cancer as a monotherapy or in combination with other agents, depending on the subtype, as these patients represent a high unmet medical need. This year, we also look forward to presenting more data from the phase I expansion cohorts as data was rather early at SITC. We have continued to mature in the prostate, renal cell, and basket cohorts, for example. Moving on, we have previously discussed initial dose escalation data from the ongoing phase I study of tidutamab, a CD3 bispecific antibody that targets the somatostatin receptor in patients with neuroendocrine tumors, or NETs. NETs are an indolent slow-growing tumor type, and we are following these patients to evaluate progression-free survival and clinical utility of tidutamab in this patient population. From the early data, we know that tidutamab was generally well-tolerated at the dose identified for the study expansion, and biomarker analysis are consistent with its proposed mechanism of action. We're in the final stages now of initiating a new clinical study in patients with Merkel cell carcinoma and small cell lung cancer, which are somatostatin expressing tumor types known to be responsive to immunotherapy, and we would anticipate a much shorter time for tidutamab to potentially demonstrate clinical activity in this patient population compared to neuroendocrine tumors. We expect to dose the first patient early in 2021. Finally, some brief updates on two other programs. A new study of XmAb698, which was formerly known as Amgen's AMG 424, is being planned to start later this year, and we'll update you on the indication closer to the study's initiation. For vibecotamab program in AML, we presented updated data at ASH in December of last year, where the efficacy and biomarker analysis indicated that responses appeared to be associated with lower baseline disease burden. We continue the dose escalation study, we are reviewing the data with our partner, Novartis, and planning additional studies. Bassil? Thanks, Allen. We're always looking to grow this pipeline with new programs, and the next entry into the clinic is XmAb564. That's our IL-2 that we engineered to have a bias towards activating regulatory T cells, a promising new mechanism to treat autoimmune diseases. It also has reduced potency to improve tolerability and duration of action for this normally toxic cytokine and is fused to an XmAb heterodimer Fc domain that has our Xtend technology for longer half-life. Both of these are key elements of the design for XmAb306 also, and that's our IL-15 in oncology. We expect to start dose escalation in healthy volunteers shortly and study, in addition to tolerability, changes in levels of regulatory T cells and other immune cells. Following 564 is XmAb819, which is a bispecific agent against ENPP3 and CD3 and is designed to recruit cytotoxic T cells against renal cell carcinoma. We expect to file the IND this year. It uses our 2 + 1 bispecific format, which has two antigen binding domains to the tumor target, providing for more selective binding to the high ENPP3 density expression on tumor cells compared to the lower density on normal cells. The binding selectivity of the 2 + 1 format extends the range of targets amenable to CD3 bispecifics. For example, our partner Amgen's AMG 509 program in prostate cancer uses this format. On to partnerships. A core part of our business is to complement our internal development portfolio with partnering. These partnerships generate payments from the licensing of XmAb technologies, the clinical advancement of XmAb candidates, as well as royalties from sales of approved products. There were no COVID-19 impacts to partnering revenue during the fourth quarter, we'll continue to monitor potential impacts, of course. Our many partnerships really highlight the plug-and-play nature of the suite of XmAb Fc domains we've created. Currently, there are 13 ongoing partnerships for XmAb technology, which have resulted now in two marketed products to date. Alexion's ULTOMIRIS for rare blood disorders and MorphoSys' MONJUVI as the first second-line treatment for patients with diffuse large B-cell lymphoma. Last year, for ULTOMIRIS, we earned $16.2 million in royalties, and in the fourth quarter, a $10 million sales-based milestone payment. MorphoSys has guided the decision on MONJUVI's European Marketing Authorisation Application should be in the second half of 2021. We also entered several new partnerships last quarter, spanning the different approaches we use to expand our pipeline, to enhance our clinical development programs, or to extend the use of our XmAb technology. First, we announced an agreement with Janssen to discover a CD28 bispecific antibody against a prostate tumor target. This partnership, where we received $50 million upfront in addition to potential milestones, royalties, and an option to co-promote the drug in the U.S., it highlights the excitement around this new mechanism of action. Targeted CD28 stimulation can potentially boost the activity of T cells in a tumor-specific way and enhance both checkpoint inhibitor therapy and CD3-directed bispecific antibodies. A key part of this collaboration is that both parties have the right to access each other's prostate cancer development agents for combination trials with their own agents. Getting access for combinations with Janssen's leading portfolio in prostate cancer will help us in our expanding work in castration-resistant prostate cancer, an area with very high unmet need. Also expanding our development reach is our collaboration with MD Anderson Cancer Center to execute additional clinical studies with our XmAb drug candidates. Over a five-year term, we will work closely with investigators in MD Anderson to start clinical trials in additional indications, generate new clinical insights, and accelerate development timelines across our entire oncology portfolio. We expanded this relationship in December to include the discovery and development of novel drug candidates that combine MD Anderson's biological insights into novel antibodies and targets with our plug-and-play XmAb bispecific technology. We have an exclusive option to develop these candidates and hope to access novel targets to create a new generation of XmAb bispecific antibodies. We entered license agreements that extend the use of our platform technologies in therapeutic areas that we are not pursuing internally. We announced in December an agreement with Viridian for a license to apply Xtend Fc technology to antibodies targeting IGF-1R in exchange for common stock valued at $6 million and potential future milestones and royalties. We also entered into a license agreement with a new privately held company, giving them worldwide rights to develop three preclinical programs incorporating XmAb Fc domains for development in autoimmune disease. We received a 15% equity interest in the company and are eligible for royalties. With that, I'll hand the call over to John Kuch, our Chief Financial Officer, who will review key highlights from our 2020 year-end financials. John? Thank you, Bassil. During 2020, our partnerships, collaborations, and licensing arrangements continued to generate strong cash flow with $165 million in upfront payments, milestone payments, and royalties received, which helps offset the growing investment in our portfolio of clinical and early-stage drug candidates. We ended the year with cash equivalents, and marketable securities totaling $604 million, compared to ending 2019 with $601.3 million. Based on current operating plans, we expect to have cash to fund research and development programs and operations into 2024 and estimate we will end 2021 with between $425 million and $475 million in cash and cash equivalents. Total revenue was on a GAAP basis for the year end December 31st, 2020, for $122.7 million, compared to $156.7 million for the same period in 2019. Revenues earned in 2020 included royalties and milestones from MorphoSys related to approval of MONJUVI and Alexion royalties and a sales-based milestone related to ULTOMIRIS sales and several licenses of XmAb technologies and drug candidates, compared to 2019 revenue, which was earned primarily from our Genentech and Astellas collaborations. Total research and development expenses in 2020 were $169.8 million for the year, compared to $118.6 million in 2019, an increase that was primarily attributable to increased spending on Xencor's bispecific antibody and cytokine candidate technologies, specifically on additional studies for our plamotamab and XmAb717 programs and our IL-2 program, XmAb564. General administrative expenses were $29.7 million for the year, compared to $24.3 million in 2019. The increase was primarily attributable to increased staffing, professional expenses, and spending on intellectual property. Non-cash stock-based compensation expense for the year was $31.6 million, compared to $31.9 million in 2019. Net loss for the year was $13.7 million or $0.24 on a fully diluted per share basis, compared to net income of $26.9 million or $0.46 on a fully diluted share basis for 2019. The net loss report for 2020 compared to the net income report for 2019 is primarily due to higher collaboration and licensing revenue reported for 2019 and higher research and development expenses and lower milestone revenue reported in 2020. With that, we'd now like to open up the call to your questions. Operator? Thank you. Our first question comes from Ted Tenthoff with Piper Sandler. You [audio distortion] with your question. Great. Thank you very much, and really excited about all the progress and everything going on at the company. I just wanted to get a sense of what you might be showing at AACR this year, and I know it's a little bit early to be calling out specific conferences with respect to clinical updates, but do you think that the 717 update might be at ASCO? What do you think you'll be showing in June? Thanks. Hi, Ted. I'll take that one. This is Bassil. For AACR, we can't disclose what we're going to be presenting until, of course, the abstract's published. We always try to use various oncology conferences to highlight both our preclinical progress as we continue to expand our platforms, as well as clinical programs. We have guided for XmAb717 will have data this year. We'll get more specific and granular on timing as we get closer. To be clear, the kind of information we're going to present should be the mature data from the expansion cohorts that were really quite immature at SITC last November. Those would be in particular the prostate cancer cohort, which was quite early, as well as the renal cell carcinoma cohort, and then rounding it out with the basket cohort of other indications where there's no PD-1 approved. It'll be that full data set, and we'll be able to also guide much more specifically on our prostate cancer trial that'll be starting this year, as well as other trials. Awesome. Great. Thanks, Bas. Thanks, Ted. Thank you. Our next question comes from Mara Goldstein with Mizuho. You may proceed with your question. Yeah, thanks. Just on the molecular subtypes in the CRPC study, can you maybe just give us a little bit more granularity as to what that is and just conceptually what that looks like in terms of patients on demographics and populations? Then I'm just curious about the private company transaction that was in the press release and when you'll be in a position to disclose some more details on that and how that relates to just sort of strategy from a BD perspective. Sure, maybe I'll take the second one first. That's a fairly easy one. I'll touch on the molecular subtypes, me and Allen. On the private company, when we can announce more granularity, it's really up to them. They're currently in stealth mode and working very hard to move the company to the next steps. From a BD perspective, we've had just a suite of different molecules we've characterized pre-clinically over the years that use different Fc technologies to try to gain an advantage. These all happen to be an autoimmune disease. They were all molecules we made a number of years ago that were never part of our plans developed clinically that really make sense for this particular company to start pursuing. We help them get going by licensing these assets. It's again about non-core assets, things that aren't core to our focus on oncology, on bispecific antibodies, and on cytokines, that we want to see moving. We think taking equity in a company where we like the leadership team is a great way to see value from that. It's again, it's about from a BD strategy standpoint, how to use the depth of our technology to non-core assets and create value and hopefully value for patients. On the molecular subtypes, the trial hopefully will be up and running in the coming months. We'll be able to get into all the gory details, but until they're certain, we want to be cautious, but I'll say, and maybe lead into Allen, that we are going to be talking about the CRPC setting, and there's just a variety of places where there's either small molecules or chemo. Allen, you want to comment on what we know about that field and defer the specifics of our trial until we're certain? Yeah. Bassil, I think first of all, we're very excited about the early 717 data in prostate cancer. Without giving details of the trial design that we've established, I can just talk about prostate cancer in general. After we saw clinical activity, when you look at prostate cancer in general, it's really breaking down by molecular subtypes. Remember, this is a phase I-B, so 717 will either be given as a monotherapy or as a combination therapy. If you think about what's approved for prostate cancer in terms of checkpoint inhibitors, for MSI-high people are using checkpoint inhibitors already as a monotherapy. In other subgroups like homologous recombination deficient prostate cancer, PARP inhibitor is now approved. There are other forms that are more aggressive that may be treated with chemotherapy more aggressively, and there you might want to think of a combo with chemotherapy. Without saying much on the trial design, which we'll disclose later in the year, that's sort of how we're thinking about it. Okay. If I could just actually ask one question for John, and it's about ULTOMIRIS and the sales-based royalty, rather sales-based milestone payment. Should we think about additional payments for 2021? We don't guide on those. We do have $20 million in sales-based milestones remaining under the agreement, your model's probably better than ours as far as predicting what their sales are, to be honest with you now. Okay. Thank you. Thanks, Mara. Thank you. Our next question comes from Gregory Renza with RBC Capital Markets. You may proceed with your question. Thank you. Hey, Bassil and team, thank you so much and congrats on all the progress. Bassil, maybe just taking a step back, and certainly a question that we've received is really what Xencor could look like in say three to five years. Certainly a great deal going on, a lot, as you alluded to, a lot of programs advancing, a suite of them actually, and understanding the management of risk and opportunity assessment. I'm just curious how the current profile of so much going on would sort of translate to opportunities going forward as these programs advance and potentially de-risk. Thank you. The strategy, that's really a question central to our strategy. Thanks for asking. The strategy is about trying to find different molecules we can make that have differing scientific and business risks to put into the clinic that have a good hypothesis for how they could help patients, then letting the data guide us. As the data guides us, some programs we will out-license or terminate. For example, we out-licensed our XmAb7195 IgE reducing antibody when it didn't make sense for us to proceed anymore. We did that deal with Aimmune, it's now Nestlé. It's about data driving the decisions. We now have data for plamotamab and XmAb717 that gives us a clarity on the next step of development, and we hope to continue letting the data from those programs either drive them forward or result in maybe an out-licensing or even a cessation. It all depends on the data and having a rich pipeline behind it so we don't feel tied to any one program at the early stages of development. However, as we start moving into mid and later stages and we're starting a potentially registrational trial with plamo, we'll see how that goes. But as we start moving to those stages, we'll commit more and more resources to the programs that pull us, make sure we apply stringent filters to the earlier programs. I think our profile will change, if all goes well in the clinic, to a company that is really focusing on getting mature assets through approval and ultimately to market by ourselves if all goes well, always maintaining a rich early clinical base, but being pretty ruthless about culling that. I think that the early rich early clinical data or program base will always remain. It'll just start becoming only a piece of the puzzle as our later-stage programs or program even, emerge and really solidify. That's great. Thank you so much for the call. Appreciate that. Thank you. Our next question comes from Alethia Young with Cantor. You may proceed with your question. Hey, guys. Thanks for taking my questions. Congrats on all the progress. I want you to take a step back and kind of talk a little bit about the IL-15 program. I know there's some others in the space and kind of the promise of that potential target. If you have any update with the Roche collaboration, that'd be great. My second question is just as it relates to PD-1 CTLA-4 program, just kind of wanted to get a broad picture of how enrollment timelines are going in light of some of the COVID volatility that we've seen. Thanks. I'm sorry, which program was that you were asking about timelines? CTLA-4 PD-1. Got you. For the first one, I'll comment on our collaboration with Roche, and maybe John, you can touch on the design philosophy we use that we hope differentiates us. The collaboration with Roche is a 55/ 45 P&L split. We're sharing clinical development costs and hopefully profits. We share decision-making in the clinic, and right now they're executing the phase I escalation study. They did advance from just doing monotherapy escalation to escalation in combo with atezolizumab last quarter. We can't disclose data until we've agreed on a publication plan with Genentech, which we're working on, but we really can't say when information would come out. I think we can say that as new studies emerge or as we engage in different new steps of the existing study, we will, of course, announce those as makes sense. As for data, publication plan will come. Maybe, John, you want to talk about how we fit in the space. Probably the molecule that's been out there the longest is the ALT-803. That's an IL-15 Fc fusion. There's also an earlier-stage molecule, a pegylated IL-15 from Nektar. We also compare ourselves to the NKTR-214, which is a pegylated IL-2 that basically acts like an IL-15, right? Because it talks through the same receptors. The key distinction with XmAb306 is that we started with an IL-15 Fc fusion using our Fc heterodimers, made a nice stable molecule, and then based on observations we had in terms of PK with that molecule, as well as just understanding the way that these molecules work in terms of their mechanism of action, we kind of did the audacious thing of actually dramatically reducing the potency of the molecule. We took the wild type IL-15 Fc fusion, made a few mutations, took the potency down a couple orders of magnitude. The idea being that these things get cleared through the receptors when they interact with them. What we found pre-clinically is that with that potency reduction, we actually got dramatically better half-life for the molecule in vivo. Because the molecule lasted longer, we actually got better pharmacodynamics. We got a higher peak of peripheral NK and T cell expansion in cynomolgus monkeys, as well as a longer duration of that peak. We hope and we think everything's pretty well set up for those kind of properties to translate well into humans. Great. Next question. Yeah. Bassil, do you want me to take the interruption? Oh, I'm sorry. I completely forgot about her question about enrollment and COVID on [audio distortion]. I apologize. Sorry. Go ahead, Allen. No problem. Lisa, in terms of the PD-1, CTLA-4, or 717, we haven't noticed really any sort of decline or delays in our enrollment. First of all, I'd like to thank all the teams at Xencor. They've been working really overdrive during the pandemic, and COVID has interrupted hospital supply chains and hospital systems, but the teams quickly adapted to things like remote and virtual monitoring. I think there's two factors here. Cancer is a large unmet need. If you have cancer, despite the pandemic, you need to be treated. We have an active molecule, which is also very important. We've noticed that the studies are enrolling well and to our schedule. We haven't noticed any delays in that program. [audio distortion] Great. Thanks. Thank you. Our next question comes from Jonathan Chang with SVB Leerink. You may proceed with your question. Hi. Thanks for taking my questions. First question on B7-H3, how does your CD28 approach and program compare to other B7H3 approaches and programs in development? Sure. I can answer this generally, I guess. The hope here is to use B7-H3, a marker that's expressed on many tumors and is particularly bright in places like prostate, as a way to overcome T cells, maybe quiescence or resistance to activation from things like checkpoint therapies or CD3. It's not bringing a cytotoxic payload, it's bringing a good co-stimulatory payload. Hopefully that doing so in a targeted way can assure a tumor-specific effect and avoid side effects. I think the attractiveness of CD28 is really about its centrality in the immune system, and John, maybe you can comment on that. Yeah. The way that T cells are activated are, they need multiple signals. Signal one, they get through the T cell receptor, interacting with MHC or artificially through a CD3 bispecific, a classic T cell engager molecule. In this case, we're triggering signal two, right? CD28 is the textbook signal two. If you want to expand T cells in vitro, you couple signal one and signal two with CD3 and CD28 on [audio distortion] and expand T cells. We're just trying to make that happen in the tumor microenvironment, specifically at the tumor cell T cell interface. Since B7-H3 is brightly expressed on a lot of different tumors, we're trying to promote that interaction and that triggering of signal two right at that interface. In contrast to a lot of the other programs that are out there, the nice thing about a CD28 bispecific, at least this is our philosophy, is that, and we can show this, signal two all by itself doesn't actually accomplish anything. From a safety perspective, we believe that broadly targeting a broadly expressed tumor-associated antigen like B7-H3 should be safe, and then we're going to couple that with either PD-1 blockade or a CD3 bispecific to promote the signal one that you're getting through the T cell receptor. Got it. Thank you. Just final question, when could we see additional plamotamab clinical data? We expect to have more plamotamab data later this year. We're wrapping up the dose regimen setting. That's hopefully near complete. We should have it at, we hope, at a medical conference right after that. Got it. Thank you. Thank you. Our next question comes from David Nierengarten with Wedbush. You may proceed with your question. Hey, just a quick follow-up on that updated clinical data for plamotamab. That's the monotherapy data presumably, right? A couple questions on the combo studies with Incyte and MorphoSys. Do you plan on reporting data that year? Who is it under control of, what are you thinking of as a bar for success comparing amendedly across clinical studies to the other CD3, CD20 bispecifics that are in development? Thanks. Yeah. The plamo update would be for monotherapy. For the combination studies with Incyte and MorphoSys, we control the studies and obviously there's a collaborative element to the data. We remain committed to presenting data when it's meaningful and interpretable. This is not a partnership that is likely to hold that data back like a large company and some of our other partnerships that we had. The bar for success in relapse refractory DLBCL, I think it's great you have two highly active regimens coming together, the CD20, CD3, and the tafasitamab plus len. Maybe, Allen, you can comment on how ORR and PFS play off of each other here? Let me back up and answer a couple questions. How we're going to put the molecules together, we're not going to disclose the study design, but I think the way you think about these is there's actually three agents here. They have slightly different mechanism of actions. The lenalidomide likely synergizes the CD19. It probably will synergize the CD20 as well. That's one way to think about it. The other thing to think about is toxicity profiles. CRS mainly for the bispecific T-cell engagers, and for the lenalidomide, it's really cumulative neuropathy and maybe some myelo suppression. Could you put them together in a way to sort of minimize the toxicity and increase the efficacy? That's something that we have been actively thinking about. In terms of milestones, I think, or sort of reference benchmark, it's highly dependent on the disease population. Is this second-line diffuse large B-cell lymphoma? Is it third-line or after two other therapies? Is it monotherapy or single agent? I think the data from monotherapy, you're seeing good response rates. How durable they are is not clear. That's why I think everybody is after sort of their monotherapy data is moving quickly to combinations. The different companies after ASH have declared what their combinations are. I sort of like our combination because I think it's really novel and it's chemo-free. Got it. Thank you. Thank you. Our next question comes from Arlinda Lee with Canaccord. You may proceed with your question. If your line is on mute, please unmute. Hi, guys. Congrats on the progress. I think I had some questions on some of your other IO-IO combinations, whether you still think that you're going to have data on those, and if you could provide an update on 104 and 841? Thanks. Yeah. You're talking about our XmAb104 and XmAb841 programs, the respectively PD-1 by ICOS bispecific for tumor microenvironment activation and the CTLA-4 by LAG-3 bispecific. Those are both in dose escalation. They started dose escalation about a year after 717, so they're just a little bit behind. We are expecting to announce data when dose escalation is complete. We have a package. We haven't guided yet on that. I will point out that it was about two years from the start of the 717 trial to data, and we're at about 18 or 19 months now from those trials starting. Without committing to a specific date, I think we're starting to approach when we'll be able to guide on new data from those, or data period from those. Okay, great. Thank you. Thank you. Our next question comes from Tom Schroeder with BTIG. You may proceed with your question. Hi, this is Kaveri Pohlman for Tom. Thanks for taking our question. My first question is for CTLA-4. There are other approaches in the clinic that include Fc enhanced molecules. Can you share your thoughts on the role of active Fc domain for this drug? With the data expected for Fc active molecules this year, do you plan to develop your own Fc enhanced antibody? I'll say that we don't have any plans for developing an Fc enhanced anti-CTLA-4 antibody. In fact, our molecule, our PD-1 CTLA-4, as well as our other one, our CTLA-4 LAG-3, both have Fc receptor binding silence, so there's no effector function drive there. They rely on the co-target, whether it's PD-1 or LAG-3, to give us selectivity and also to drive further activity by hitting another checkpoint. Yeah, we'll be interested to look at other kinds of data that comes out from other programs and go from there. I think we're excited by having a dual checkpoint approach that I think drives down different pathways than trying to use enhanced effector function for clustering or cytotoxicity. John, did I miss anything there? Yeah, I would just emphasize that the Fc enhanced approaches are mostly built off of mouse data, where a significant MOA for anti-CTLA-4s is through Treg depletion, since Tregs are bright for CTLA-4. The current consensus based on clinical biomarker data for ipilimumab is that it is not actually depleting Tregs in humans. We prefer the approach on our molecule. Of course, you wouldn't want to do this with a PD-1 binding arm anyway of having silent effector function and no ability to promote depletion. Got it. Just the last one. The search for tumor-specific targets is so extensive in the industry. What does MD Anderson bring that's novel? Do you think you need deeper biology to get targets? Does the deal help you to move the programs to phase I trials? I'll answer on the deal structure. Maybe John can chime in on why he's excited about working with MD Anderson scientists. On the deal structure for the discovery partnership, they pay for all of their discovery costs and all of their preclinical costs. We have an exclusive option to take rights to the program. We've agreed to contribute our XmAb technology and assist them, if necessary, making molecules. We would imagine the typical kind of deal would be if they show exciting preclinical data, we would take it over for clinical development, though I think a natural collaborator for that clinical development that you'd probably want to consider would be the MD Anderson folks. Maybe John, on why their data's so exciting. Yeah. I guess the best way to put it is, I'd love to have relationships like we have with MD Anderson set up with every major research university, because there's a lot of different ideas out there. We prioritize for MD Anderson because it's one of the top cancer institutes in the country, or in the world. That's a really great place to start. We're hoping to get new eye, fresh ideas from them. They've got a lot of discovery efforts ongoing at MD Anderson, and it's a very, like you said, it's sort of teed up for a further clinical relationship downstream. I'll also point out, we are definitely eager to find novel targets. We've announced our collaboration with Atreca for exactly the same reason. Great. Thank you. Congrats on the progress. Thank you. Our next question comes from Etzer Darout with Guggenheim. You may proceed with your question. Great. Thanks for taking my questions and congrats on all the progress in 2020. I guess the first one may be a sort of a 2 + 1 strategy question with the program moving forward. Interesting data so far in avidity tuning, I guess, where do you see the technology positioned versus other emerging technologies like conditional activation, epitope masking, et cetera, aimed at enhancing tumor selectivity? The second question, just wondered if you could talk a little bit about what's baked into the end of 2021 cash guidance, and can we assume that it's predominantly maybe a step up in R&D from the breadth of plamotamab activities that are planned for 2021? If you could help with those. Thank you. Yeah, maybe I'll touch on the second question, your question on what's driving the spending in the 2021 cash guidance. It's going to be increases in development programs, not just plamotamab, which, as you move to the next stage of trials, absolutely, you're correct, it's going to drive increased spending. It's also increased spending around XmAb717 as we go into prostate cancer with its own trial and probably start additional studies and other indications, as well as additional spending in our XmAb306 collaboration with Genentech for IL-15 as that program progresses. I think those are the primary drivers of new R&D program spend, R&D program spend is absolutely the big driver of the cost growth. on the 2 + 1, where does this technology position relative to these other approaches for sort of getting that more selective antibody activity? I would say using avidity and that kind of binding property to get to different target densities is kind of a very well proven phenomenon in antibody engineering, going back to the days of the designs of Herceptin and Erbitux. I think these novel approaches, while extremely exciting, and I think they have a lot of potential, really have yet to bear out that the selectivity is going to be there, and that in real practice, in vivo, it's going to play out. We're very excited to watch those. We're certainly open-minded. We think that an avidity approach not just has the advantages, though, of selectivity, but there's other ones. John, you want to touch on the different tricks you can do with a 2 + 1 format that's, by the way, very stable and very straightforward and easy to make? Not only that, back to the original question, I would say that what I like about the avidity tuning approach is I feel like I can confidently translate from some in vitro assays in terms of binding selectivity as well as killing selectivity of bright versus dim reagent cell lines. I feel like I can confidently translate that information with putting it to other various pieces of information together, like IHC data from human tumors, and feel like that's going to translate well. I've always felt like with the other conditional activation approaches, they're a little bit more faith-based. There's certainly data out there that, yes, there are a lot more proteases, certain proteases in the tumor than the periphery, but at the end of the day, you're crossing your fingers hoping that that all plays out well in terms of toxicity and therapeutic index. Got it. Well, thank you. Thanks again, and congrats on all the progress. Thank you. Our next question comes from Dane Leone with Raymond James. You may proceed with your question. Hi, thanks guys, congratulations on the updates. For me, I just want to go back. Can you clarify, is the IL-15 program, the 55/45 P&L split with Genentech, is that for the U.S. only or is that global? That's global. Okay, that is global. Okay. Can you remind us on the ULTOMIRIS and JUVI royalties, are you lagged in terms of how those get paid out? John, you want to take that one, John Kuch? We record the royalties as they record the sales. For both of them, we have to estimate what the sales are to book our royalties. Alexion reports ahead of us, so it's real easy to pick it up. For purposes of MONJUVI, we have to estimate what the sales are. In this case, we picked it up off of the Incyte earnings release. Okay. Does that answer your question? Yeah. Basically, it's real-time, so it's not on lag basis. Okay. Correct. I think we're all just trying to figure out where the blended royalty rates are coming in as these sales ramp. Okay. In terms of this year, we've kind of bounced around on this subject a bit for what the updates are going to be. Going back to plamotamab for a minute on the monotherapy data, what's going to be the focus of this update? I guess, what are you hoping to tease out within the monotherapy setting at this point from a more mature data set that's going to be informative? Are you planning on taking this asset forward as a monotherapy from this study out, or are you going to be more focused on the combination with MONJUVI? Yeah. The data update would be just to really wrap up the phase I dose escalation and give a clear picture of regimen and what you can learn about tolerability and efficacy from these small escalation data sets. It's just to really wrap it up and finish it, and we expect to be fully rolling with our combination study with tafasitamab lenalidomide. We do think combinations are the focus of the strategy, because that's where you're going to have the regimens that have the most efficacy, and that's what's going to win the day in lymphoma ultimately. We are going to continue monotherapy development, and we plan to have multiple expansion cohorts in this phase I while we go into combo with tafa- len in DLBCL. We'll also continue monotherapy DLBCL in expansion cohorts and accrue a number of patients, and that can track along in its own bucket and continue the development. If the data looks really promising and exciting, you could potentially go with that data and advance to later development or even just accrue a lot of patients, and that data set could be, if the data looks amazing, registrational itself. We'll also look at other indications like follicular lymphoma and others. Okay. That makes sense. In the prostate cancer cohort for this CTLA-4 PD-1, how large of a group is that? I just can't remember what the dose expansion group was in general, what the patient disposition was. This is separate. Oh, the 20 patients in the phase I expansion cohort in prostate. Yeah. What was the disposition of those patients generally at baseline, or what were you generally accruing? For prostate cancer? Yeah. Yeah. This is Allen. How quickly pre-treated? Yeah. Yeah. Go ahead. Yeah. We didn't select for certain molecular subtypes in the expansion cohort. They were castrate-resistant prostate cancer, they had to exhaust standard of care. Most of them had seen chemotherapy, this was really not a chemo naive group. They were a difficult group to treat. Okay. Sorry, just to clarify your comments around the landscape and prostate, where do you think the unmet need is with certain new therapies coming in? PSMA would be one of them, I guess. Well, they're not in yet, right? I would say that there's a big unmet need in post-chemo after failed salvage in castration-resistant prostate cancer is a big unmet need still. Okay. You're thinking about it broadly, not more specifically to a subtype or? Not unless the data guides us. Okay. Sorry, I was just trying to understand what you were talking about with the subtypes earlier, whether that was something you already have in mind to focus on or whether that was just something you're exploring. Oh, no, it's multiple ones that we're going to explore to see which signals, if any signals emerge across subtypes, if there's a particular one or other that's great, right? Right now we're agnostic. Oh, okay. Basically you have this mixed expansion cohort of 20 patients. You're going to interrogate that cohort for like base lead. I'm sorry. No, we were unclear. We have this expansion cohort of 20 patients that's mixed. We're going to report that data. Also, this year, we're going to start a completely new trial just in prostate cancer patients with multiple parallel cohorts of different molecular subtypes. It's a whole other set of patients. Okay. All right. Awesome. Thank you for getting me over the line with that one. No worries then. I will stop harassing you guys. Thanks. Take care. Thank you. Our next question comes from Peter Lawson, Barclays. You may proceed with your question. Yeah. Thanks for taking the question. Just a follow-up on Dane's questions just around that molecular subtype you're looking for, is that kind of like PD-1 levels or PSA levels, or like BRCA scores, HRD scores you're thinking through? I guess it is across kind of sub-indications, whether it's post-chemo, et cetera. Well, Go ahead, Allen. I think, again, without having disclosed the details, which will be coming out soon enough, I suppose. Yeah. Maybe the best way to think about this, Peter, and sorry for the confusion, is we treated sort of an unselected cohort as an expansion, and that was all comers that were castrate-resistant prostate cancer. Because of that, many of them got chemotherapy because that's a standard of care. The challenge is moving forward in prostate cancer is that people are molecularly subtyping the disease. The question we have is, where could we be effective? Where could we generate the most value for patients? It could be across all arms. From a logistics standpoint, you would want to have a clinical trial that anybody with prostate cancer who walked through that door that's metastatic could qualify for the study. Castrate-resistant prostate cancer. They'd come through the door, and we would want to have an arm or a basket. Some of the baskets, like recombinant deficiency, they would normally get a PARP inhibitor. You want to include those patients somehow. Some other patients, like MSI-high, would just be a monotherapy. Some of the other ones that have biomarkers may have more aggressive disease, and you may need a chemotherapy. Eventually you would want to include everybody that comes through the door and just have an understanding of the activity of 717 in each little basket molecularly. We're not really narrowing the indications at this point. We're sort of studying all the indications with the appropriate combination if needed based on the molecular subtype. Sorry if that wasn't clear before. No, that's perfect. Thank you so much. Really helpful. Just a question around, I guess, the equity investment in an emerging stealth company. Is that a new thing that you're thinking through? Just the ideas about potentially selling royalties. I don't know if you can. It just seems to be an increasing trend in the space. Yeah. On the equity piece we get in these private companies or even new public companies, we don't think of them as investments. We think of them as getting stock in lieu of cash upfront payments for licensing of our technology or licensing a preclinical asset, for example, in these cases. It's really when an entity wants to conserve its cash and when we think the company has promise and could grow in value, in part based or maybe wholly based on the technology we're licensing, we like the equity piece in lieu of upfront payments. It's really just changing one element of a deal we would have, and we have royalties on all of those and milestones built into those deals also. It just broadens the pool of people that we can get our technology into the hands of. On the selling of royalties, we're always assessing the options of how to maximize value in the different assets we have, whether they're financial assets like royalties or our own programs. Those are the kinds of things that so many different considerations, we really can't say anything specific. Okay. Perfect. Thanks for taking the questions. Thank you. Thank you. Our next question comes from Zhiqiang Shu with Berenberg. You may proceed with your question. Thank you. Good afternoon, everyone. Thanks for taking my questions. My first question is on plamotamab, the first-line DLBCL combination study. I know MorphoSys is running their own front line study. I guess, just want to hear your thoughts there, why you want to run your own front-line study, and why do you think potentially that can beat R-CHOP in the frontline DLBCL? Second question is on the 564 program, IL-2. I guess I want to hear your thoughts on why do you think your molecule potentially is better than any other IL-2 for autoimmune diseases out there? I guess for this year, do you see a venue for you to present some of the biomarker data or even some of the activity data this year? Thank you. On the frontline DLBCL, we think that how these CD20, CD3 agents combine with other agents is really completely unknown now. The opportunity to create a chemotherapy-free regimen, as opposed to using R-CHOP, but that opportunity, we think is very compelling because of the drive and the interest in removing chemo from lymphoma therapy. Toxicity concerns, long-term toxicity concerns. We think just that strategic driver of having a chemo-free regimen that potentially has very high activity is worth that shot to compete with the chemo-containing R-CHOP regimen. Why is it better than R-CHOP? I think aside from being chemo-free, we're going to be very interested in seeing the synergies we have with an immune stimulant like lenalidomide, right? With what happens with tafasitamab hitting CD19 versus the CD20. Great. Yeah. Allen, you want to add anything or is that sufficient? Should I go to the IL-2? No. I guess the only thing I could add is, if you look at the data from the tafasitamab lenalidomide combination, the response rate in relapse refractory was approaching what Coiffier observed in his original R-CHOP study in the front line. There is this possibility that adding a CD20 bispecific instead of a CD20 antibody could sort of potentiate that. Again, it's very early, but we are excited, and it's something that we're very keen on doing. Sorry, Bassil. Back to you. No, it's great. IL-2, we believe that the lower the potency you can design into your cytokine, in this case IL-2, the better tolerability you'll see and the longer duration of action, and in particular, when you fuse to a long-acting Fc, extend the pharmacodynamic effect. That's the hypothesis we've seen proven preclinically with both our IL-15 and our IL-2, and we believe that does create a potential for a best-in-class therapeutic profile on both the tolerability side as well as the duration of action of boosting your target cells. That's the hypothesis. Again, preclinically, it's the exact same strategy with our IL-15 XmAb306. We hope it plays out here as well. On data this year, we can guide on that, and we plan to what our initial data timing is going to be as we start the trial. We'll give further updates. Great. Just to clarify, both for IL-2 and IL-15 program, the Fc domain is inactivated. Is that correct? It's got no Fc gamma receptor binding. That's been completely ablated, and it has long half-life from our Xtend technology. Got it. Okay. Thank you very much. Thank you. Thank you. I'm not showing any further questions at this time. I would now like to turn the call back over to Bassil Dahiyat for any further remarks. Thanks so much. Thank you everybody for joining us today. Have a wonderful evening, and we look forward to updating you more over the course of the year. Bye-bye. Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.