Good afternoon and welcome to the Xencor Fourth Quarter and Year End 2019 Financial Results Conference Call. At this time, all participants are in a listen-only mode. Following the formal remarks, we will open the call up for your questions. Please be advised that this call is being recorded at the company's request. At this time, I would like to pass the call to Charles Liles, Associate Director and Head of Corporate Communications and Investor Relations at Xencor. Please proceed.

Thank you, Sydney, and good afternoon. Welcome to Xencor's fourth quarter and year end 2019 financial results conference call. Earlier this afternoon, 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 business overview and review our licensing partnerships; Allen Young, Senior Vice President and Chief Medical Officer will review our clinical stage programs and John Kuch, Senior Vice President and Chief Financial Officer will review the financial results from the fourth quarter and the 12-month period, then we will open up the call for your questions. 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, and research and development programs. These forward-looking statements are not historical facts, but rather are based on our current expectations and beliefs, and are based upon 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. With that, let me pass the call over to Bassil.

Thanks Charles and good afternoon everyone and thanks for joining us. Xencor approach to creating antibody and cytokine therapeutics is centered on our XmAb protein engineering platform by making small changes to an antibody structure specifically in its Fc domain, we can improve its natural functions and performance and create new mechanisms of therapeutic action. The plug and play nature of the suite of XmAb Fc domains that we've created allows us to engineer nearly any antibody to have improved activity, longer half-life or bispecific structure. This flexibility and portability enable us to take multiple shots on goal simultaneously in the clinic and generate proof of concept data to guide which programs we will independently advance, which we will partner and which we will terminate. In the last few years, we have focused our R&D on the expansion and use of our XmAb bispecific platform to create drug candidates that bind two or more different therapeutic targets simultaneously. And we've initiated six Phase 1 clinical studies evaluating XmAb bispecific antibodies. Our plug and play approach to engineering enables a rapid design and simplified development of antibodies and other protein structures like cytokines. Bispecific antibodies and cytokines are a rapidly emerging area of therapeutic development, particularly in oncology and in order to stay at the forefront of innovation in this space, we use our engineered heterodimeric Fc domain as a robust scaffold to rapidly develop new candidates that we group into 3 classes; T-cell engagers, tumor microenvironment, activators and cytokines. The first and most advanced classes, the T cell engagers. These are tumor targeted bispecific antibodies that contain both the tumor antigen binding domain and cytotoxic T-cell binding domain, specifically a CD 3 binding domain. These T-cell engagers which we also call CD 3 bispecifics, activate T-cells at the site of…

Thank you, Bassil. Just briefly to touch on my background since I'm new. I'm an MD PhD by training and was a board certified oncologist practicing as an academic oncologist for many years before joining industry. Most recently I was at Jazz Pharmaceuticals where I originally joined as a Therapeutic Area Head for Hematology/Oncology and was eventually promoted to Head of Clinical Development and Acting CMO. Prior to Jazz I worked at other biopharma companies including Amgen where I worked on several development products including BLINCYTO, the first approved bispecific antibody in oncology. During my career, I've been fortunate to work on and lead several new drug approvals. I'm delighted to join Xencor for its strong foundation and protein engineering, multiple platform technologies that are in high demand by industry partners and its broad internal portfolio of bispecific antibodies bispecifics which have rapidly emerged as an important area in oncology and drug development. So onto a brief overview of our internal clinical development portfolio of bispecific antibodies and cytokines. First XmAb14045 is our CD-123, CD3 bispecific antibody that's being developed in collaboration with our partner Novartis. It's in an open label Phase 1 dose escalation study to assess its safety, tolerability and preliminary antitumor activity in patients with relapsed or refractory AML as well as other CD-123 expressing hematological malignancies. In the second quarter of 2019, we resumed enrollment in the study following the lifting of a partial clinical hold. We continued dose escalation in this study and are planning to initiate additional clinical studies evaluating XmAb140545 this year pending alignment with our partner Novartis. Our second hematology program, XmAb13676 has received the non-proprietary name Plamotamab. It's a CD20, CD3 bispecific antibody and is being evaluated in a Phase 1 study for patients with advanced B cell malignancies like non-Hodgkin's…

Thanks Allen. We'll now switch to reviewing some updates from our partnerships which continue to provide revenue in the form of upfront payments, milestones and royalties that helped fund development of our own internal pipeline candidates. The plug and play nature of our XmAb technologies enables us to license access to these platforms with partners needing very limited resources and effort from us. We won't review each program, but we have 10 ongoing partnerships for XmAb technology, which resulted in one market, a product, 70 clinical stage candidates and more in earlier stages of development. Most advanced of these is Ultomiris, a compliment inhibitor with improved half-life using our Xtend technology, which Alexion launched last year and it has seen significant progress in conversions of patients from Soliris, their first-generation inhibitor. Ultomiris is the first antibody to incorporate an XmAb technology to be marketed. Ultomiris has now received multiple global marketing authorizations in the U.S., Japan and Europe for the treatment of adult patients with PNH and in the U.S, for aHUS. We're receiving royalties on net sales in all indications in geographies worldwide. New among our technology licenses, last month we entered into a tech license agreement with Gilead who will access our extended half-life and cytotoxic Fc technologies for developing and commercializing GS9722, their first in class broadly neutralizing anti-HIV antibody in Phase 1 clinical development as well as up to 3 additional anti-HIV antibodies. This is the second license for antiviral antibodies using our Xtend technology. We've also entered licensing agreements with exclusive worldwide development and commercialization for our own pipeline candidates. MorphoSys in 2010 license from us tafasitamab, which was previously known as MOR208 and it's XmAb5574 before that. It's an anti-CD19 antibody that we designed and initially developed incorporating our cytotoxic Fc domain for high…

Thank you, Bassil. During 2019, Xencor continued to strengthen its balance sheet, which enables us to continue supporting development of our bispecific antibody and cytokine programs technologies. First, I would like to provide an overview of 2019 financial results and then some thoughts on 2020. Cash, cash equivalents and marketable securities totaled 601.3 million as of December 31, 2019, compared to 530.5 million on December 31, 2018. 2019 year-end cash balance reflects upfront payments in milestones from our partners and collaborators of 155 million received net of spending on operations during the year. For the fourth quarter ended, December 31, 2019, revenues were 3.5 million compared to 11.6 million for the same period in 2018. Fourth quarter 2019 revenues were primarily from Alexion royalties or revenues for the same period in 2018 were primary milestone payments received from Alexion. Research and development expense for the fourth quarter 2019 were 27.3 million compared to 27.1 million for the same period in 2018. General and administrative expenses for the fourth quarter of 2019 were 6.7 million compared to 5.5 million at the same period of 2018. The fourth quarter of 2019 net loss was 26.9 million or $0.47 on a fully diluted per share basis compared to a net loss of 18.2 million or $0.32 on a fully diluted share basis for the same period in 2018. The higher loss for the fourth quarter 2019 over the loss reported same period 2018 is primarily due to lower revenues reported in the fourth quarter 2019. Turning to full year results. Total revenues for the 12-month period ended December 31, 2019, were 156.7 million compared to 40.6 million 2018. Revenues earned in 2019 reflect collaboration, milestone revenue earned from our Genentech, Astellas, Alexion, Amgen, and Novartis partnerships compared to milestone revenue earned from Alexion…

[Operator Instructions] And our first question comes from Alethia Young with Cantor Fitzgerald. Please proceed with your question.

Maybe a couple for me. One, I just wanted you to talk about the CD20 x CD3 and the data you had. I know there are a lot of kind of assets, they're similar out there and I just want you to talk a little bit about how you think about future studies, which could lead to differentiation, whether that be through combinations? My second question is just administrative, is just on 18087 and on the 2717, so we expect data in the first half of the year or is that, or should we expect it now that we are kind of in somewhere over 2020? And then, my last question is just can you talk a little bit about the Gilead's and the deal you did with those guys and how you think about your technology and its applicability in HIV thing?

Sure. So, I guess we will start-off with a housekeeping question, we're expecting for 2717 midyear update along the lines of what we said in our press release, biomarkers and initial Phase 1 data from just escalation for 18087, we're guiding towards in the second half. So mid year, second half. Let's see, for the CD20 data, maybe I'll also let Allen comment here a bit. There are a number of programs that use bispecific technology to engage CD20 to try to sort of move the ball in B cell malignancy, specifically lymphoma at first beyond where Rituxin combination therapies have gone. I think you're right the combination therapies the only way forward to really advance regimens that are going to move the needle. So, there's a variety that we could think about and I think it's about the right biologies. And you had a comment Allen, on the different kinds of biologies and how we'll guide specifically later this year.

Yes. So, first let me start off with an overview of B cell malignancies. There a lot of B cell malignancies and what I want to remind everybody is where we're at with our Phase 1 study. We're still in dose escalation. We've seen good activity in diffuse large B cell lymphoma and enough activity that we're encouraged about that and want to move forward in diffuse large B cell lymphoma. We continue to dose patients in follicular lymphoma, Waldenström's, CLL and so forth. I think that there's still a lot of activity that we need to explore. But with that said, you're right, in diffuse large B cell lymphoma. It's still a very large unmet need. I think there's a lot of opportunities, if you look at previous approvals for other agents in the relapse refractory diffuse large B cell lymphoma space, they've been improved with either single arm studies or accelerated approvals or breakthrough therapy designation more specifically. So with that said, we are exploring our opportunities. We think combinations are a key way to go. I think there's a lot of opportunities with other agents that are targeted as well and have different mechanisms and action.

Yes. So we're really focusing on things that already have their own data showing they can kill B -- tumor cells that are B cells, right? So to focus on that rather than thinking of IL/IL combinations. To address the Gilead points. So the technology they licensed was good old Fc engineering technology to extend half-life and to induce ADCC function. In this case, an antibodies that are broadly neutralizing for HIV. So they stick onto the HIV. One of the proteins in HIV, we can't disclose which one that's up to them. And there's sort of two things you want from our Fc engineering. One is just to have the antibody last longer. An antiviral antibody is essentially, it's what's called passive immunization. Your body is not making the antibody, there's no vaccine to make it to have an antibody forced to be made. So you give the body sort of artificial immunity by giving people a neutralizing antibody exogenously. Obviously, in that case, you want it to last as long as possible. The use of our Xtend technology has sort of spread throughout the academic community in anti-infective antibodies quite widely. And I think Gilead sort of was following along with that lead because you'd rather give somebody a passive immunization shot every three months or every six months or what have you depending on, what the antibiotic can give you. In addition, the ADCC technology, because of the way the biology of HIV works, you often have budding virus particles on immune cells and you'd like to kill the immune cells that are harboring that virus. So that's also been a modality that's been studied in academic labs for a number of years, how antibodies can kill HIV bearing cells. So a GS9722 happens to incorporate both of these approaches in one Fc domain. And we're very, very happy to have them go forward earlier in the year we announced a partnership, our half-life extension Xtend technology with [indiscernible], an early stage company looking at a variety of different anti-infective antibodies or sorry, antiviral antibodies. So we think there's a lot of utility for our approaches in antivirals.

Thank you. And our next question comes from Ted Tenthoff with Piper Jaffray. Please proceed with your question.

Just picking up on PD-1 CTLA-4, when should we be expecting that preliminary? Have you already started dosing that in combination with any other agents or is that what we really see the opportunity to dose sell on a sort of an enhanced checkpoint inhibitor? Thanks.

Yes. So we'll guide on what kind of next phase strategy we're contemplating mid-year. I guess that the initial development is in a single agent because the goal here is to add functionality to PD-1 inhibition within the same molecule and hopefully in a way that using our avidity hypothesis creates a regimen it's more tolerable by focusing on just T-cells that are double checkpoint positive. That's hypothesis. We're excited to see some initial data to see whether we can get that kind of T-cell activation function but without some of the immune-related adverse events that seem to really bedevil PD-1 CTLA-4 combination therapy. So, it really, initially it's about single agent. I think when you think about combinations, it's about what indications you go into -- some indications you're going to want to combine with chemo. So indication you're going to want to combine with targeted therapies. The milieu of solid tumor indications each one has its own specific drivers and we're going to be able to guide on what directions we're taking later in the year.

Thank you. And our next question comes from Mara Goldstein with Mizuho. Please proceed with your question.

So I have a question on and it's essentially a similar question for 18087 and 2717. And that is really kind of understand the threshold for advancement in particular with 717 and whether the focus ends up being more on sort of safety aspects or efficacy aspects and how you think about that. And then also a housekeeping question on the Novartis payment in December, is that booked, is it a deferred revenue item or should we anticipate that being booked in the first quarter of the year?

I'll take care of that. Hi Mara. How are you doing? Address the first question with respect to the Novartis payment, that milestone was not in for revenue, that's a separate item. It's sitting in receivable, the $10 million sitting in receivable as December 31, totally separate from any deferred item in that arrangement.

And so again, your question Mara on 717 and 087 or PD-1 CTLA-4 and our SSTR-2 CD3 antibodies was around what sort of data you would -- how are we going to assess the data, I guess and define plans for going forward? Again, these are initial dose escalation datasets. We're looking for all sorts of indications. I mean, Allen, do you want to give it a shot?

Yes. Let me start with the 717 first because I think you were asking the question of, are we trying to improve better efficacy or better safety? And just from my experience, I won't tell our strategy, but just from my experience proving safety is challenging in a clinical trial design. And so the way that the molecule is designed, we believe it's going to be improved tolerability, which will allow us to escalate where we can get better efficacy. Now note it's sort of targeting PD-1 and CTLA-4 which has already approved targets in terms of checkpoint inhibitors approved agents out there and so they're well entrenched. And so what we would want to do is sort of benchmark it against those sort of previously completed studies and we should have a high bar to move forward given the entrenchment compared to our other molecules in that space. Going to 087, I don't know, should I take that question about…

Sure.

Okay. Going to 087, no, clearly somatostatin is expressed in neuroendocrine tumors and GI stromal tumors and we're studying those. In addition, it's expressed in other tumors to a lesser extent, but larger tumor population, small cell lung cancer, liver cell cancer to name a few. And so we're evaluating those right now and we'll hopefully give guidance on a more complete strategy later on.

Just to sort of come back to the sort of strategy around it for our PD-1 CTLA-4 molecule XmAb 2771 that the strategy for the Phase 1 design was expansion cohorts as we've established a go forward dose and those are going to be in the relapse refractory setting of post PD-1 exposed patients in PD-1 approved tumors things like melanoma, non-small cell, et cetera, where the high bar that Allen is referring to is actually a fairly low number in terms of response right now. We won't have expansion cohort data by mid-year, but we should be well along in those cohorts by then. And so that's our one-ins go for that relapsed refractory population to PD-1 therapy where there's a very high unmet need and even modest activity could be a very big opportunity. The second area we're looking at is, we'll be able to guide more later on is, indications where PD-1 therapy alone is not had resounding success. But where the addition of CTLA-4 there's good biological rationale and we'll be exploring that set of opportunities as well and be able to give specifics on what indication we want to pursue. So I think for both, and I guess this will -- [indiscernible] 18087 as well as we want to establish that you can give these agents that they're safe and tolerable, that we're seeing some initial activity and then use that as a launching point for how we can exploit them. For 1887, you've got the rare tumor and [indiscernible] tumor and you've got other ones like Merkel cell that are rare or small cell that are less rare. So, it's just how do we get from the starting point we've gotten to with our biology the best strategy, we'll guide more later.

Okay. And if I could also just ask on Plamotamab just in the discussion around looking at things like clinical trial design for accelerated approval and whatnot. Is there an opportunity or is it something that the company is interested in pursuing looking at you know, post car T as a sort of speed to market strategy?

I'm not so sure there's enough there to make that a speed to market strategy in terms of patient volumes. We've treated post car T patients. We have had response for post car T patients as a separate standalone strategy that's not something super high on our list. So we will continue to enroll them and evaluated -- as we see enrollment trends and see if there's enough need there.

Thank you. And our next question comes from what Gregory Renzo with RBC Capital Markets. Please proceed with your question.

Bassil and team, my question is related to the fact that 2020 looks like a very busy year with early stage programs and certainly as you touch on the plug and play for your technology. Just curious if you could touch a little bit about -- commenting about, the plug and play of your resources, and operationally how you're staying nimble to essentially enable matching some of these goals ahead with the right resources and capabilities. Thanks.

Yes. We've built an organization that can very capably handle a pretty large volume of early phase clinical trials, specifically in oncology where there's a lot of portability of skill sets, of talent, of the infrastructure from CROs that you need to access as well. And so we've built that part of the organization to really feed our strategy of exploiting a very broad and capable platform and having that produced the shots on goal we need to hopefully produce winners in our clinical portfolio out of the reality that biology is very hard to predict as our competitive landscape three, four years in advance. And so we want to have the highest likelihood as possible, one or more of our programs coming off the other end in the late phase development and hopefully one day commercialization by Xencor. So we built an early phase broad capability and we're building now out off of that internal clinical development and preclinical capability. The tools to do a late phase development that'll -- that ought to be ready in time for one of these programs to jump into in the next year or two. So we're very, very mindful of that and that's why we've expanded the management team and added people with a lot of late phase experience and commercial experience into the mix.

Thank you. And our next question comes from Arlinda Lee with Canaccord. Please proceed with your question.

Hi guys. Thanks for taking my questions. I guess maybe just follow up on those discussions that Bassil just had. I was curious about how many programs do you think you can take forward yourself to advance to a registrational trial and beyond and how you think about the mix of your pipeline as it's advancing through?

Yes. I'll say for the first one, it, I have no idea because it depends on the specifics of which programs go forward, whether that's one, because it requires multiple broad phased 3s or whether it's two or three because each one is a relatively small well-focused clinical study in a smaller population. So you can't really say what you've got to do is build all the pieces for late phase development, which include altogether additive kinds of capabilities. Everything from biometrics and data handling to market assessment to clinical data management and medical monitoring. So it's more of the capabilities rather than just the numbers of people. And now, sorry, what was the second part of your question?

I think that actually addressed both of them. Can you maybe talk about what kinds of like the scope of the data that we might expect for Plamotamab that we're going to get later this year. Is that going to help explain what your strategy is or kind of talk about early indications of what might be interesting to pursue a little bit further before you commit to doing a registrational program?

So we're going to be guiding on what our next stage clinical trials and strategy are later this year. We're not committing to a data release this year. It's a little bit early. We're just coming off of ASH. So we'll guide more on when we'll have our next data release, but the strategy we want to be able to articulate more clearly.

Arlinda, this is Allen Yeng calling. I just want to address something that you and Gregory alluded to. So first of all, I want to say that, in my short time, we have a fantastic clinical development team and I think Bassil is right. It's really dependent on the data. Some of the agents you can get approved, let's say if they're highly active in a rare tumor type, that's a large unmet need. We don't need that many patients and a lot of resources to get it approved. However, if it's a more competitive space and it'll be a larger program, then we would probably have to commit more of our resources to that. But again, as Bassil alluded to, it'll be based on the data. We're actually suffering from a very good problem, which is multiple agents that are exciting to develop. And I think that's a good place to be at right now. Sorry, Arlinda, I interrupted your question, go ahead.

Yes. I guess I was also curious about whether this update was specific to promote a matter or might we get some of indication of where you might be going with some of the combinations that you have that are maybe perhaps less common in the competitive landscape? Like your CTLA like 3 or PD-1 or something like that?

We're not anticipating having specific guidance on next phase clinical trials this year outside of Plamotamab and XmAb 14045 where we expect to have additional information on the next set of trials that we're launching, the specific indications in myeloid malignancy.

And this is Allen. The teams are busy, very busy. Again, sort of progressing all the programs in parallel.

Yes. But, for this year, next, next phase guidance would be on the two that I just mentioned, the heme programs.

Thank you. And our next question comes from Dane Leone with RJF. Please proceed with your question.

I just want to touch on a couple of things. Can you give us a little bit more detail in terms of where you think the clinical hurdles going to be for 18087 just in kind of a tricky indication with some pretty specific things that you need to look at? Then, can you give us a little bit more detail on where you hope to get to the 14045 program this year? And then just anything you can tell us in terms of potential partnerships on Obex. Thank you.

So I'll talk, I'll sort of go to reverse order real quickly. We can't really guide on potential partnerships for obexelimab, partnerships, as I've said is they're hard to define. We're working hard to both continue to educate people on the continued analysis from our lupus study where the rich biomarker work that we did in that study is, is, is maturing more and more, but as well, look at other opportunities to advance it with different kind of financing arrangements. So we're busy at work there, but it's very hard to predict how that's going to land. I mean, we didn't have a good timeline for XmAb7195, and we're very happy with the partnership with Aimmune in food allergy, which I think is a tremendous opportunity for that kind of molecule. With regard to 14045 details, with our Novartis partnership, we can't speak to when we can announce results details, but we can, we should be able to guide pretty specifically on the next set of plans for that. For the clinical hurdle for 18087 for that one, I mean that's, you're right -- it's an unusual rare tumor with an interesting bar. I think it's as much as anything about what we learn in net and just and how we position it broadly and the other tumor types that might be benefited form it.

Yes. I would like to add, this is Allen Yeng. Neuroendocrine tumors and GI stromal tumors, there have been some recent approvals, so we know the pathway for the approvals in terms of a clinical development program. I think the challenges, these are tumors that are not highly responsive in terms of CR. So you would have to sort of plan larger studies based around PFS. There are other tumors that express somatostatin, we're sort of exploring those types of tumors, more recently Merkel cell, which is a much smaller unmet need but clearly is responsive to immunotherapy. So these are things that we are sort of mulling over, I would say. We're thinking about very carefully right now. And hopefully we'll have more details for you later in the year. And as for 045, without sort of disclosing any confidential information, AML is a area that I know very well. CD-123 in my previous company we actually had a partnership for a CD one 23 target agents. So I seem to know the space pretty well and reviewing the data, it's very interesting and hopefully we'll have sort of scientifically driven and clinically sort of considerations into the clinical market space. And we'll have a plan around that shortly…

That we can talk about publicly once that moves forward. So with that any other stuff, Dane or…

Oh yes, sorry. Actually, on that note, could you just remind us how the partnership works on 14045 with Novartis, like how does the decision-making done in the disclosures?

Yes. So Xencor U.S. commercial rights, Novartis has x-US commercial rights. We split the cost 50:50 for development. We have to have really agreement. It's 50:50. Nobody has a veto power on decision-making. So you have to agree, which is both challenging and good and that you means you get full dialogue on things. And on disclosure, both parties have to agree to a disclosure, which means either one can be to any disclosure. As we've said in the past. Novartis is not a company that is into disclosure when it doesn't have to.

Thank you. And our next question comes from Shanshan Xu. Please proceed with your question,

So I have actually two questions for Allen. Hi, Allen. Welcome to Xencor earnings call. So for your Plamotamab that's your CD20 CD3 molecule. You were very clear that combination is the only way to move the needle as right now. And in terms of this drug partner, you seem to have shied away from an IO/IO combination. So if I understand you correctly, you don't want to combine it with PD-1. So Roche actually presented some very interesting data at ASH 19 for their CD20 CD3 in combination with Gazyva. So how do you like that strategy? Would you consider your CD20 CD3 in combination with your tafasitamab? And I have two follow-ups.

Okay. Hey, Shanshan. How are you doing? So getting back to 676, I think I'm very happy that the molecule is very active as a single agent in diffuse large B cell lymphoma. So saying that we wouldn't develop it and other indications as a single agent, I think it's too early to commit to that we just don't have enough data. In terms of combinations and competitive landscape, you have to look at what's going on in Car Ts, the MorphoSys compound as well. So I think combinations make a lot of sense in terms of value, in terms of what's going to be initially in the relapse refractory space and eventually what you would like to do in the front line where combination is the standard of care. So, I know that's not a lot of detail, but I don't want to disclose what our plans are at this point. But yes, we are thinking combinations. We are thinking of broader indications. And what was your other, Oh, the checkpoint inhibitors. I think it's still early and I think there's a lot of combination potentials in other immunotherapies, antibodies without a payload that seem to have high activity, whether they be CD20 or CD19. So I think there's a lot of opportunities, chemotherapies, ADC as well. So I think there's a lot of opportunities and I think the checkpoint inhibitors are sort of a class that we wouldn't consider at this point. In terms of CD20 antibody in which CD20 antibody to consider, I think there's overlap with our target. And so scientifically you would be more interested in sort of other targets since we have a CD20 targeted device specific. I don't know if that answers your question.

Right. Perfect. Thanks. So, [indiscernible] Genetic hosted an Analyst Day last week and started to talk more about theirs, actually, it's your IO15 franchise. Given that there are several therapeutic strategy to target all of this teams such as super agonists or advice visit strategy to do a target PD-L1, L15, can you please provide your perspective just to compare it and contrast a little bit regarding those different strategies.

So we think a strategy of having a molecule that maximizes therapeutic window is the best one. That was our goal when we designed XmAb24306 and really was the basis for our IO15 program. So we attached to our Fc domain. We specifically dialed down the potency of the IO15 unit so that you didn't super activate the T-cells, create a pulse of cytokine release and toxicity, and then burn out the T cells have their activity wane and rapidly clear your drug. So we wanted long duration and tolerability. So we tuned down OI15 like I said, attached to our Fc domain and used our extended half-life technology. That was a package that Genentech found very attractive. So that's a baseline how to get broad systemic OI15 activation. The next strategy beyond that, which there is no real clarity on whether it's better, worse, nobody knows, is to target the IO15 functionality to specific populations, whether they're NK cells or T-cells. So using our bispecific Fc domain, we've developed -- a rather constructed a numbers such molecules that we're working on in collaboration with Genentech. And those are about again, optimizing therapeutic index, about steering the functionality to the T cells that you want or the NK cells that you want a lot of unknown biology. But I think the idea of making cytokines much more specific and localized in their function has been a Holy Grail of cytokine engineering for a long time. So we're very happy to have tools to let us target that to T-cells and NK cells and we'll see where that takes us in the next few years. Note that we do expect Genentech to dose the first patient for our non-targeted IO15 very soon.

Okay. So the last one I promise. So this year actually committed to rating out solid tumor data for your CD3 bispecific antibodies. Historically has been challenging to develop a CD3 bispecific in solid tumor given the severity of the CRS, is there anything in the molecular design of tafasitamab 18087 and also AMG509 that could potentially prevent that pitfall? Thank you.

Yes. They were designed differently. XmAb18087 has one antigen binding domain and one CD3 binding domain. In that case we were going after a tumor type that's known to be very resistant to having objective responses, neuroendocrine tumors in particular. And so we went with a fairly potent molecule strategy. Again, there's a lot of unknown here and we need to see what the tolerability looks like, what the kind of activation of immune function looks like. Note of course that these Fc constructed bispecifics as we do them are significantly less potent than the first generation BiTE type structures, on the order of a 100 to 500 fold, less potent. So there's already been a tuning down and we'll just see where that lands. AMG509 was constructed with two binding domains to the antigen STEAP1 and one to the CD3 and our partners at Amgen did a lot of work looking at how much potency and affinity to have on each side of that bispecific to hit the tumor cells they wanted. And so that's an example of using a format that gives you the avidity against your tumor antigen, STEAP1 to steer yourself towards the right cells. So there's all these tools that have come about, the formats themselves and the 2+1 format to give you higher antigen density, selective, the all big themes being played and we're going to see those more and more and every tumor types is going to have its own answer. So we'll see.

Thank you. Your next question comes from Jonathan Chang with SVB Leerink. Please proceed with your question.

Hi guys, this is [John Berry] [ph] for Jonathan. Thanks for taking my questions. My first one, we noticed that the XmAb24306 clinical trial identified was posted for exploration with Atezolizumab. Previously, you commented that Genentech wants to move really fast into combinations with this molecule. Could you comment on what the next combination strategies could be the types of patients you want to recruit for these trials and any opportunity for a rough timeline of when we might see the first data?

Unfortunately, I can't answer any of those questions because those are Genentech's questions to answer. The way this IO15 collaboration is constructed. The Atezolizumab combination is, I think, a fairly obvious one given their franchise there. And we think it's a very good scientific hypothesis. And so I could imagine they're going to have a pretty broad clinical development approach there as we've stated, and that's a variety of different indications that has already approved. And so we'll see where they take that one. As for timing of data, I can say, but I would not expect any this year.

Got it. And we were talking a lot about avidity and affinity recently and there has been some renewed interest in IgM antibodies recently and the engineering of those types of antibodies. Could you just compare and contrast the advantages and disadvantages of engineering IgM verses IgG and how they might compare in the clinic when we get to those data?

Well, I mean, given that there's never really been much in the way of IgM antibodies over the years, I think there's not a lot of data to go on and do the comparison. They've always been very difficult to manage and nobody's really pursued them except for one company and I guess they're in the clinic now. So they've clearly made excellent progress. I think that what you're seeing with antibody -- bispecific antibodies in general, and then again, the vast majority of IgG format is the ability to move these binding domains around and have multiple valence has given us an enormous pallet to deal with just from the IgG format. So, for example, 2+1 IgG formats, because you have two antigen binding domains allows you to tune the potency so broadly because you can do a lot to that potency and still stick selectively to your target. We've published data showing no detectable cytokine release in vitro from 2+1 format tune the right way. So we've got a really broad pallet of tools and the IgG formats, and that's only going to get broader as we look at cytokine fusions as we look at multiple antibiotic binding domains with different kinds of proteins attached as well. So that really robust, stable, easy to use scaffold, it gives you an enormous flexibility already. And I think the time will come not that far off that we stopped worrying about this individual format. We start trying to worry about what format makes sense for this target or that target or the other one.

Thank you. And our next question comes from Michael Schmidt with Guggenheim. Please proceed with your question.

Hi. this is Etzer on for Michael. Thanks for taking my question and the updates here. First, is there an opportunity for an accelerated path, 045 in a relapse refractory AML given historical responses in that setting. And I wondered if you could also provide a little bit more color on plans to evaluate 045 in the broader CD-123 positive indications. And the last question a number of programs in the clinic right now, wondering if you could maybe talk about the pace of R&D spend and 2020 relative to 2019, to the extent that you can comment. Thanks.

So you always roll out all the questions at once so we can't remember what the first one was by the time you get to the last, sorry, I wrote them down. I have a pen. Accelerated approval pathways, we really aren't going to comment on specific regulatory pathways and we haven't even announced what the specific slices of indication are. There's always that potential relapsed refractory tumors or in any tumor with a high unmet need. But that's too much more detailed than we really can offer at this point. It did go on the specific kinds of indications that'll come a little bit later in the year. We're happy to tell you about it all. Then I don't know how much granularity we're giving on the guidance, John, if you want to comment, I don't think we typically go R&DG versus G&A.

The only thing I can comment is R&D spending went up about 20% from '18 to '19. We expect the spending to continue to increase because we've got more programs going the further stages. So all we can count at this point, it will be higher. And I think, going 20% is a starting point from '18 and '19, somewhere along there, possibly higher.

Thank you. And I'm not showing any further questions at this time. I will now turn the call over to Bassil Dahiyat for any further remarks.

Thanks very much operator. And thank everybody very much for joining us today. We look forward to giving further updates on our progress throughout the year. Goodbye.

Ladies and gentlemen, this concludes today's conference. Thank you for participating. You may now disconnect.