Xencor Inc (XNCR) 2019 Q4 法說會逐字稿

Good afternoon. And welcome to the Xencor Fourth Quarter and Year-end 2019 Financial Results Conference Call. (Operator Instructions) 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 Yang, 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 for 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 sections 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's 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'll 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 2 or more different therapeutic targets simultaneously. And we've initiated 6 Phase I clinical studies evaluating XmAb bispecific antibodies. Our plug-and-play approach to engineering enables the 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 class is the T cell engagers. These are tumor-targeted bispecific antibodies that contain both the tumor antigen binding domain and the cytotoxic T cell binding domain, specifically a CD3 binding domain. These T cell engagers, which we also call CD3 bispecifics, activate T cells at the site of the tumor in order to potently kill malignant cells. We've expanded this class of bispecifics by developing our XmAb 2+1 bispecific format. It uses the same heterodimeric XmAb acetamin is our other bispecific antibodies and cytokines, but has 2 identical tumor-targeting domains and 1 CD3-targeting domain. This format enables higher selectivity for tumor antigen expressing cells and greater flexibility in tuning the potency and, hence, efficacy and tolerability of the molecule. We're looking forward to presenting preclinical data from several of our internally developed XmAb 2+1 bispecific antibody this year.

The next group of our bispecific antibodies are our tumor microenvironment activators. Rather than directly bridging a cytotoxic T cell to a tumor cell, our TME activators seek to more effectively reactivate tumor reactive T cells in existing therapies. These antibodies simultaneously engage multiple T cell targets, such as checkpoints or agonists. The key feature of our design is to choose individual binding affinities for each T cell target to be suboptimal for binding the T cells, with only 1 of the 2 targets present on the surface but to have high binding when both targets are present. This zipping up when multiple handholds are president is called avidity. Our approach reduces the need for multiple antibodies typically used in combination therapy and also allows for more selective targeting of T cells that have multiple checkpoint expression, which are typically found more in the tumor microenvironment than in the periphery.

Finally, we've developed -- we've been developing a suite of cytokines, which are immune signaling proteins that are built upon the XmAb bispecific Fc domain and incorporate our Xtend technology. Using our Fc domain and tuning the potencies enables more druggable cytokines with potentially superior tolerability, slower receptor-mediated clearance and longer half-life.

Now before we move on to reviewing our portfolio of drug candidates, our ability to develop these XmAb technologies, advance our programs into late-stage clinical development while positioning them for commercialization and to support our ongoing efforts to identify additional partnerships, this is all dependent on the skill sets and experience we have on our team.

Really beginning in late 2018, we started strengthening our senior management team with key appointments in project and alliance management, business development, regulatory affairs, legal and most recently, Dr. Allen Yang joined us as Chief Medical Officer in December. Together, these additions allow us to execute more productively on all of our corporate priorities.

Now I'd like to introduce Allen, who joined us after our previous CMO, Paul Foster, retired. Allen will be leading the strong internal clinical development organization that we've built over the past 5 years to advance our multiple therapeutic candidates. Allen?

Thank you, Bassil. Just briefly to touch on my background since I'm new, I'm an M.D. PhD by training and was a board-certified oncologist practicing as an academic oncologists 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 in 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 on to a brief overview of our internal clinical development portfolio of bispecific antibodies and cytokines. First, XmAb14045 is our CD123 CD3 bispecific antibody that's being developed in collaboration with our partner, Novartis. It's in an open-label Phase I dose escalation study to assess its safety, tolerability and preliminary antitumor activity in patients with relapsed or refractory AML as well as other CD123 expressing hematologic malignancies.

In the second quarter of 2019, we resumed enrollment in the study following the lifting of a partial clinical hold. We continue dose escalation in this study and are planning to initiate additional clinical studies evaluating XmAb14045 this year, pending alignment with our partner, Novartis.

Our second hematology program, XmAb13676, has received a nonproprietary name plamotamab. It's a CD20 CD3 bispecific antibody and is being evaluated in the Phase I study for patients with advanced B-cell malignancies like non-Hodgkin's lymphoma and chronic lymphocytic leukemia.

We presented initial safety data and clinical activity from early dose escalation cohorts at the ASH Annual meeting this past December. These results indicated that in early dosing cohorts, plamotamab was generally well tolerated with safety events being mild to moderate in severity, and it demonstrated encouraging clinical activity. The safety analysis included 53 patients treated with plamotamab. The most common treatment-emergent adverse events are consistent with other bispecifics being used in patients with heme malignancies and were pyrexia, CRS or cytokine release syndrome, and anemia.

The 18 patients with diffuse large B-cell lymphoma who received doses of 80 to 170 micrograms per kilogram were included in the analysis to describe clinical activity. Those doses are about 6 to 12 milligrams flat dose as adjusted per patient body weight. The objective response rate was 39% and the complete response rate was 28%. Responses were apparently dose dependent. Additional complete responses were observed in patients with follicular lymphoma, Waldenström's macroglobulinemia and Richter transformation of chronic lymphocytic leukemia.

Dose escalation and optimization of the dosing schedule, including a priming dose and step-up regimen are ongoing. We plan to initiate additional clinical studies for plamotamab and should be able to provide more detail into those clinical development plans later this year.

Note that initial clinical results for both hematology programs, as presented in ASH 2018 for XmAb14045 and ASH 2019 for plamotamab, are available on our corporate website, xencor.com under Investors on the Events & Presentations page.

XmAb18087 is our third CD3 T cell engager, which targets somatostatin receptor 2 or SSTR2, an antigen highly expressed on some solid tumors. In early 2018, we started dosing patients in Phase I dose escalation study to assess its safety, tolerability and preliminary antitumor activity in patients with neuroendocrine tumors and gastrointestinal stromal tumors, and we expect to present initial data from this study later this year.

Moving on from our CD3 bispecifics. Last year, we started dosing the first patients in our second and third clinical trials evaluating our tumor microenvironment activating bispecific antibodies. These are Phase I dose escalation studies for XmAb22841 and XmAb23104. Along with the first program, a Phase I study of XmAb20717, we are focused on enrolling patients with several advanced solid tumor types into these studies. Using the avidity hypothesis Bassil discussed earlier, our hope with these programs is to be able to drive to stronger antitumor responses with improved tolerability for patients. This year, we anticipate in presenting initial dose escalation of biomarker data from the first of the XmAb20717, a PD-1 CTLA-4 bispecific antibody.

We'll end the review of our internal portfolio with our cytokine programs, our first cytokine program and lead in our collaboration with Genentech, which was announced in February of last year is XmAb24306. It's an IL-15/IL-15 receptor-alpha complex fused with our bispecific Fc domain and targets the expansion and activation of T cells and NK cells. XmAb24306 is intended for the development with a wide range of combination agents. And importantly, we can perform our own clinical trials with both our pipeline assets and non-Genentech agents within this collaboration, subject to some conditions.

We look forward to planning a number of these combination studies pending completion of the initial dose escalation study. Genentech's IND application is open. We would anticipate a first-in-human study to be dosing patients very soon.

Finally, our second cytokine candidate, XmAb27564 is an IL-2 Fc fusion protein that we are planning to develop for patients with autoimmune diseases. Similar to the IL-15 program, our XmAb27564, we reduced the potency of IL-2 and incorporated our Xtend technology in order for the candidate to have more drug-like properties. We are currently conducting preclinical activities and anticipate initiating Phase I study in healthy volunteers in 2021.

With that, I'll hand it back to Bassil.

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 help 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. We have 10 ongoing partnerships for XmAb technology, which resulted in 1 marketed product, 7 clinical stage candidates and more in earlier stages of development. Most advanced of these is Ultomiris, a complement inhibitor with improved half-life using our Xtend technology, which Alexion launched last year and 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 and 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 GS-9722, their first-in-class broadly neutralizing anti-HIV antibody in Phase I clinical development as well as at the 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 licensed from us tafasitamab, which was previously known as MOR208 and as XmAb5574 before that. It's an anti-CD19 antibody that we designed and initially developed, incorporating our cytotoxic Fc domain for high ADCC function. MorphoSys completed their BLA submission to the FDA in late December for treating patients with diffuse large B-cell lymphoma in combination with lenalidomide. We are eligible for additional milestones and royalties on sales in the high single-digit to low double-digit percentages.

As we stated, we shifted our internal development focus toward our emerging bispecific antibodies and cytokines in oncology and have sought partnerships for our XmAb7195 in obexelimab programs. In February 2020, we granted Aimmune Therapeutics an exclusive worldwide license to develop and commercialize XmAb7195, our anti-IgE monoclonal antibody with enhanced binding to the Fc gamma receptor IIb. It's now called AIMab7195, and it's designed to rapidly eliminate IgE, a key mediator of allergic response from circulation and to prevent IgE production. We evaluated it in allergic asthma and other IgE mediated disorders and Aimmune intensive development in food allergy, a therapeutic area that is rapidly developing and needs new agents.

Aimmune is very experienced in food allergy, has demonstrated clinical success and has the capability to advance AIMab7195 with its highly complementary pipeline programs. We received an upfront payment of $5 million in cash and $5 million in Aimmune's stock and are eligible to receive milestones and royalties that range from high single-digit to mid-teen percentages.

We've also entered into research collaborations that include the creation of novel XmAb bispecific antibodies to [advance] by partners. Recently, a Phase I study has been initiated for an undisclosed Novartis XmAb bispecific antibody, and we expect initiation of Phase I soon for Amgen's AMG 509. A STEAP1 x CD3 bispecific antibody for patients with prostate cancer that uses an XmAb 2+1 bispecific format.

With that, I'm going to turn the call over to John Kuch to review our fourth quarter and year-end 2019 financial results.

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 and 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 and 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, while revenues for the same period in 2018 were primary milestone payments received from Alexion.

Research and development expense for the fourth quarter of 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 in the same period in 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 of 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 in 2018. Revenues earned in 2019 reflect collaboration and milestone revenue earned from our Genentech, Astellas, Alexion, Amgen and Novartis partnerships compared to milestone revenue earned from Alexion in 2018.

Research and development expenses were $118.6 million in 2019 compared to $97.5 million in 2018. The increase in R&D expense in 2019 over amounts incurred in 2018 reflects additional spending on our bispecific and cytokine clinical and early-stage candidates and technologies. Note that our reported R&D expenses are net of reimbursements from our partners on their cost-sharing arrangements for programs that are being co-developed.

The total general and administrative expenses were $24.3 million in 2019 compared to $22.5 million in 2018. Additional spending on G&A expenses in 2019 reflects increased facility, staffing and spending on intellectual property.

For the full year 2019, net income was $26.9 million or $0.46 on a fully diluted per share basis compared to a net loss of $70.4 million or $1.31 on a fully diluted per share basis for 2018. Net income reported for 2019 compared to a loss report for 2018 is primarily due to additional collaboration milestone revenue recognized in excess of additional spending in R&D during 2019.

Noncash share-based compensation expense for 2019 was $31.9 million compared to $20.5 million for 2018. Total shares outstanding were 56.9 million as of December 31, 2019, compared to 56.3 million as of December 31, 2018.

Taking a brief look at 2020, as Bassil noted, we started the year with 2 new collaboration agreements with Gilead and Aimmune. And these are providing upfront payments and potential future milestones.

Considering our projected revenue and current spending plans, we expect to have cash to fund research and development programs and operations into 2024 and to end 2020 with between $500 million and $550 million in cash, cash equivalents and marketable securities.

With that, we'd now like to open up the call for your questions. Operator?

And our first question comes from Alethia Young with Cantor Fitzgerald.

Maybe a couple for me. One, I just wanted you to talk about with the CD20 x CD3 and the data you had at ASH. I know there are a lot of kind of assets. They are 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 would be through combinations?

My second question is just administrative is just on 8087 and on the 717, should we expect data in the first half of the year? Or is that -- or should we expect that now to be kind of somewhere over 2020?

And then my last question is just can you talk a little bit about the Gilead 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 let me start off with a housekeeping question, we're expecting, for 717 midyear update along the lines of what we said in our press release, biomarkers and initial Phase I data from dose escalation for 18087, we're guiding towards in the second half. So midyear, second half, for 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 malignancies, specifically lymphoma at first beyond where Rituxan combination therapies have gone. I think you're right, the combination therapy is 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're going to 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 are a lot of B-cell malignancies and what I want to remind everybody is where we're at with our Phase I 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're continuing to -- continue to dose patients in follicular lymphoma, Waldenström's, CLL and so forth. So 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 relapsed/refractory diffuse large B-cell lymphoma space, they've been approved 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 of 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, to focus on that rather than thinking of IL-IL combinations.

To address the Gilead point, so the technology they licensed was our good old Fc engineering technology to extend half-life and to induce ADCC function in this case in antibodies that are broadly neutralizing for HIV. So they stick on to the HIV, one of the proteins in HIV. We can't disclose which one. That's up to them. And there's sort of 2 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 -- 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 to last as long as possible. The use of our Xtend technology is 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 3 months or every 6 months or what have you, depending on what the antibody 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 GS-9722 happens to incorporate both of these approaches in 1 Fc domain and we're very, very happy to have them go forward. Earlier in the year, we announced a partnership for our half-life extension Xtend technology with VirBio, 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.

And our next question comes from Ted Tenthoff with Piper Sandler.

Just sort of breaking up on the PD-1 CTLA-4, when should we be expecting that [primary update] and will -- have you already started dosing that in combination with any other agents? Or is that where you really see the opportunity to dose on a sort of an enhanced checkpoint inhibitor?

Yes. So we'll guide on what kind of next phase strategy, we're contemplating midyear. I guess that the initial development is 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 that's more tolerable by focusing on just T cells that are double checkpoint positive. That's hypothesis. We're excited to see 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 double PD-1 CTLA-4 combination therapy. So 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. Some indications, 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.

Okay. Looking for to the update.

Sorry, what was that, Ted. You're kind of tough to hear.

I said, thanks so much. Looking for the update.

Oh. Thank you so much, Ted. Take care.

And our next question comes from Mara Goldstein with Mizuho.

So I have a question on -- and it's essentially a similar question for 18087 and 20717 and that is really trying to 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 as a deferred revenue item? Or should we anticipate that being booked in the first quarter of the year?

I'll take care of the -- hi, Mara, how are you doing? I'll address the first question with respect to the Novartis payment. That milestone was not in deferred revenue. That's a separate item. It's sitting in receivable, the $10 million was sitting in receivable at December 31. So it's totally separate from any deferred item in that arrangement.

And so again, your question, Mara, on 717 and 087 are PD-1 x CTLA-4 and SSTR2 x CD3 antibodies was around what sort of data you would -- how we're going to assess the data, I guess, and define plans for going forward. Again, these are initial dose escalation data sets. 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, its 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, Bassil?

Yes, sure.

Okay. Going to 087, 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.

Yes. So I'll just -- please go ahead, Mara.

Sorry, Bassil, you go ahead. No, you go ahead first, sorry.

Okay. So just to sort of come back to the sort of strategy around it. For our PD-1 x CTLA-4 molecule XmAb20717, the strategy for the Phase I design was expansion cohorts as we've established a go-forward dose. And those are going to be in the relapsed/refractory setting of post PD-1 exposed patients in PD-1 approved tumors. Things like melanoma, nonsmall cell, et cetera, where the high bar that Allen's referring to is actually a fairly low number in terms of response rate. Now we won't have expansion cohort data by midyear, but we should be well along in those cohorts by then. So that's arm 1 is 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, and we'll be able to guide more later on is, indications where PD-1 therapy alone has not had resounding success, but where the addition of CTLA-4, there's good biological rationale. 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 comment on 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 18087, you've got the rare tumor, neuroendocrine tumor. And you've got other ones like Merkle cell that are rare or small cells that are less rare. So there's -- it's just how do we get from the starting point we've gotten to with our biology to 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 this something that the company is interested in pursuing looking at 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 a response for post CAR T patients as a separate stand-alone strategy. That's not something super high on our list. So we will continue to enroll them and evaluate it as we see enrollment trends and see if there's enough need there.

And our next question comes from Gregory Renza with RBC Capital Markets.

Congrats on the progress. 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?

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, 3, 4 years in advance, and so we want to have the highest likelihood as possible of 1 or more of our programs coming out the other end in the late-phase development, and hopefully, 1 day commercialization by Xencor. So we've 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 late-stage development that ought to be ready in time for 1 of these programs to jump into next year or 2. 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-stage experience and commercial experience into the mix.

And our next question comes from Arlinda Lee with Canaccord.

I guess, maybe just a 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, I have no idea because it depends on the specifics of which programs go forward, whether that's 1 because it requires multiple broad Phase IIIs or whether it's 2 or 3 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 address 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.

Okay. And then -- sorry, go ahead.

Arlinda, this is Allen Yang 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, you know 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 will be a larger program, then we would probably have to commit more of our resources to that. But again, as Bassil alluded to, it will 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.

I guess I was also curious about whether this update was specific to plamotamab? Or might we get some of indication of where you might be going with some of the combinations that you have that are may be perhaps less common in the competitive landscape, like your CTLA x LAG-3 or PD-1 x ICOS or something like that?

We're not anticipating having specific guidance on next phase clinical trials this year outside of plamotamab and XmAb14045, 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, sort of progressing all the programs in parallel.

Yes. But for this year, next phase guidance would be on the 2 that I just mentioned, the heme programs.

And our next question comes from Dane Leone with RJS.

And congrats on a great 2019. I just want you to touch on a couple things. Can you give us a little bit more detail in terms of where you think the clinical hurdle is 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?

So I'll talk, I'll probably go in the 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 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 again, 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 jest and how we position it broadly in the other tumor types that might be benefit from it.

Yes, I would like to add, this is Allen Yang. 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 challenge is, 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, and we're sort of exploring those types of tumors, more recently, Merkle 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, CD123 in my previous company, we actually had a partnership for CD123 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, probably.

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

Oh, yes, sorry, could -- actually, on that note, could you just remind us how the partnership works on 14045 with Novartis? Like how is the decision-making done in the disclosures?

Yes. So it's Xencor has U.S. commercial rights, Novartis has ex-U. S. 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 it means you get full dialogue on things. And on disclosure, both parties have to agree to do with disclosure, which means either one can veto any disclosure. As we said in the past, Novartis is not a company that is into disclosure when it doesn't have to.

And our next question comes from Shanshan Xu.

Hi there. So I have actually 2 questions for Allen. Hi, Allen. Welcome to Xencor earnings call. So for your plamotamab that's your CD20 x CD3 molecule. You are 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 IL-IL 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 x CD3 in combination with Gazyva. So how do you like that strategy, would you consider your CD20 x CD3 in combination with our tafasitamab? And I have 2 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 in 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 with 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 relapsed/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 of 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 into other immunotherapies, antibodies without a payload that seem to have high activity, whether they'd 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 that 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 questions?

Yes, right. Perfect. So [Rohan Genentech] hosted Analyst Day last week and started to talk more about theirs, actually, it's your IL-15 franchise. Given that there are several therapeutic strategy to target IL-15 such as super agonists or a biphasic strategy to dual target PD-L1, IL-15. Can you please provide your perspective just to compare 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 is the basis for our whole IL-15 program. So we attached to our Fc domain, we specifically dialed down the potency of the IL-15 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 IL-15, like I said, attached to our Fc domain and use our extended half-life technology. That was a package that the Genentech found very attractive. So that's a baseline, how to get a broad systemic IL-15 activation.

The next strategy beyond that, which there's no real clarity on whether it's better, worse, nobody knows is to target the IL-15 functionality to specific populations, whether they're NK cells or T cells. So using our bispecific Fc domain, we've developed or rather constructed a number of such molecules that we're working on in collaboration with Genentech. And those are about, again, optimizing therapeutic of index, about steering the functionalities of 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 IL-15 very soon.

Okay. So the last one, I promise. So this year you're actually committed to reading out solid tumor data for our 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 XmAb18087 and also AMG 509 that could potentially prevent that pitfall?

Yes, they were designed differently. XmAb18087 has 1 antigen binding domain and 1 CD3 binding domain. In that case, we were going after a tumor type that's known to be very resistant to having objective responses, neuroendo consumers 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 view them, are significantly less potent than the first-generation BiTE-type structures. In the order of 100 to 500 fold less potent. So there's already been a tuning down, and we'll just see where that lands.

AMG 509 was constructed with 2 binding domains to the antigen STEAP1 and 1 to the CD3, and our partners at Amgen did a lot of work looking at how much potency and affinity they 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 selectivity, that they're all themes being played, and we're going to see those more and more. And every tumor type is going to have its own answer. So we'll see.

Our next question comes from Jonathan Chang with SVB Leerink.

This is John Barrett on for Jonathan. My first one, we noticed that the XmAb24306 clinical trial identifier was posted for our exploration with atezolizumab. Previously, you comment that Genentech wants to move very fast in the 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 they 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 IL-15 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's already approved, and so we'll see where they take that one. As for timing of data, I can't 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 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 versus 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 the mix up 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 again, the vast majority of IgG format is the ability to move these binding domains around and have multiple valencies has given us an enormous pallet to deal with just in the IgG format. So for example, 2+1 IgG formats because you have 2 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 published data showing no detectable cytokine release in vitro from 2+1 formats, tune the right way. So we've got a really broad pallet of tools in the IgG formats, and that's only going to get broader as we look at cytokine fusions, as we look at multiple antibody binding domains with different kinds of proteins attached as well. So that really robust, stable, easy-to-use scaffold gives you an enormous flexibility already. And I think the time will come not that far off that we stop 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.

Our next question comes from Michael Schmidt with Guggenheim.

This is Etzer on for Michael. Thanks for taking my question and the updates here. First, is there an opportunity for an accelerated path for 045 in relapsed/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 CD123 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 in 2020 relative to 2019 to the extent that you can comment.

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 in relapsed/refractory tumors or in any tumor with a high unmet need, but that's too much more detail than we really can offer at this point. And ditto on the specific kinds of indications that will come a little bit later in the year. We're happy to tell you about at 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&D G 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 into further stages. So all we can count at this point, it will be higher. And I think going 20% is a starting point through '18 and '19, somewhere along there, possibly higher.

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.