Good afternoon, ladies and gentlemen, and thank you for standing by, and welcome to Xencor's first quarter 2022 conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. Please be advised that this call is being recorded at the company's request. Now, I would like to turn the call over to our speaker today, Charles Liles, Head of Corporate Communications and Investor Relations. Please go ahead.
Thank you, and good afternoon. Earlier today, we issued a press release which outlines the topics we plan to discuss today. The press release is available at www.xencor.com. With me on the call are Bassil Dahiyat, President and Chief Executive Officer, Allen Yang, Chief Medical Officer, John Kuch, Chief Financial Officer, and John Desjarlais, Chief Scientific Officer, who will join us when we open up the call for your questions after prepared remarks. 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, future operations, the company's partnering efforts, capital requirements for 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 on information currently available to us. The outcome of the events described in these forward-looking statements are subject to known and unknown risks, uncertainties, and other factors that could cause actual results to differ materially from the results anticipated by these forward-looking statements, including but not limited to those factors contained in the Risk Factors section of our most recently filed annual report on Form 10-K and quarterly report on Form 10-Q. With that, let me pass the call over to Bassil.
Thanks, Charles, and good afternoon, everyone. Continuing with the approach we took last quarter, we're gonna make a few brief comments before spending the majority of today's call on questions. I like to usually open with, we've used our array of modular approach and engineering tools to create a broad internal development portfolio in oncology and autoimmune diseases, which allows us to take multiple simultaneous shots on goal in the clinic. Our intent remains to use proof of concept data from these early-stage studies to guide which programs we advance, which we terminate, and which we partner, so that we're most efficiently using our cash and our employees' time. In a moment, Allen's gonna review our advancing clinical programs and upcoming plans.
First, today we announced our plan to terminate internal development of two phase I programs, XmAb841 and Tidutamab, which focuses our resources on those clinical programs of ours with the greatest potential for success and makes room in our portfolio for the next wave of XmAb bispecifics and engineered cytokines. For Tidutamab, our SSTR2 x CD3 bispecific antibody, and XmAb841, our CTLA-4 x LAG-3 bispecific antibody, after reviewing the data generated to date, we believe that neither program has a competitive enough clinical profile in their respective areas, particularly when compared to the programs we are currently advancing. We're gonna keep supporting patients currently enrolled in the study, including by continuing to provide study drug.
Now, a core piece of our strategy is leveraging our plug-and-play XmAb Fc domain through licensing transactions, especially in therapeutic areas outside of our core focus on oncology and autoimmune disease. We wanted to highlight the recent FDA approval for Alexion, AstraZeneca's Ultomiris for adult patients with generalized myasthenia gravis, its third approval in the U.S. Ultomiris, of course, incorporates our Xtend Fc domain for longer half-life. We also bolstered a cash position with over $70 million in royalty revenue this quarter for the COVID antibody Sotrovimab, which incorporates the same Xtend Fc domain from our partners Vir and GSK. Though, because of the rapidly shifting COVID variants that keep emerging, we expect this revenue to drop very substantially next quarter and beyond.
Now, looking at our partnerships for the XmAb bispecific Fc domain and our T-cell engager toolkit, last quarter we highlighted encouraging early clinical data from Amgen's AMG-509 program in prostate cancer, which in addition to being an XmAb bispecific, uses the XmAb 2+1 multivalent format for T-cell engagement. Now within the past quarter, Astellas' ASP2138, an XmAb claudin 18.2 x CD3 bispecific antibody, has advanced into clinical development for patients with gastric, gastroesophageal, and pancreatic cancers. We look forward to following this program too. Now I'm gonna turn it over to Allen Yang, our Chief Medical Officer, who's gonna briefly review our clinical programs and upcoming plans.
Thanks, Bassil. Starting with our CD3 bispecifics in plamotamab, our CD20 x CD3 bispecific antibody that we are co-developing with Janssen, we announced that the first patient has been dosed in a potentially registration-enabling phase II study, where it is being evaluated in combination with tafasitamab plus lenalidomide in patients with relapse or refractory diffuse large B-cell lymphoma. Note, we are conducting this particular study ourselves, and our partners, MorphoSys and Incyte, are providing tafasitamab. The study has two parts, the first of which is a safety run-in, followed by a planned randomization between the triple combination of tafasitamab, lenalidomide, with or without plamotamab. Later this year, we plan to present data from the expansion cohorts in the ongoing phase Ib monotherapy study. In addition, we also plan to introduce subcutaneous dosing into this study.
Also, for our CD3 platform, soon we anticipate dosing the first patient in a phase I study evaluating our ENPP3-targeting CD3 bispecific antibody XmAb819 in patients with renal cell carcinoma. We're particularly excited about XmAb819, which utilizes the multivalent XmAb 2+1 format. In preclinical studies, we have shown this format preferentially kills tumor cells with high target antigen expression relative to normal cells, which may be of particular benefit against solid tumors. Moving on to our tumor microenvironment activator bispecifics. Our most advanced is vudalimab, which targets PD-1 and CTLA-4 double-positive lymphocytes. We are conducting two phase II studies, the first of which is enrolling patients with metastatic castrate-resistant prostate cancer. In this study, vudalimab is being evaluated as a monotherapy or in combination regimen with standard of care, depending on the tumor's molecular subtype.
We're also initiating a second study in patients with certain gynecological malignancies or clinically defined high risk metastatic castrate-resistant prostate cancer. We're supporting additional signal-seeking investigator-sponsored studies as well. XmAb104, our PD-1 x ICOS bispecific antibody, is our second tumor microenvironment activator and is advancing now in the expansion portion of our phase I study in advanced solid tumors, where we are evaluating it in combination with ipilimumab. We will be presenting a poster with the data of the monotherapy escalation portion of the study at ASCO in a few weeks from now. Moving on to our suite of reduced potency cytokines, all engineered with our bispecific Fc domain and incorporating Xtend technology.
At the recent AACR meeting, we introduced two preclinical stage programs, a decoy-resistant IL-18 and a LAG-3 targeted IL-15, which is biased towards binding and activating LAG-3 positive T cells that are more likely to be tumor associated. Clinically, our most advanced cytokine is XmAb306, a reduced potency long-acting IL-15 SC fusion protein that we are co-developing with Genentech. XmAb306 targets NK and T cells for the treatment of patients with cancer. In the ongoing phase I dose escalation, we observed high levels of sustained NK cell expansion and evidence of peripheral effector T cell proliferation. We announced this last fall. Just recently, Genentech initiated an additional phase I study to evaluate a combination with anti-CD3 antibody, daratumumab, in patients with relapse or refractory multiple myeloma.
We ourselves are planning additional studies with XmAb306 in combination with other therapeutic agents and look forward to providing updates in the near future. Next is our wholly owned XmAb564, reduced potency IL-2-Fc fusion cytokine, which we are developing in autoimmune disease. We're conducting a single ascending dose study, phase I in healthy volunteers, and later this year, we'll present our initial data from this study. In parallel, we plan to initiate a multiple ascending dose study in patients. Our third cytokine to enter the clinic will be the IL-12-Fc XmAb662, for which we anticipate filing an IND near year-end. Finally, one additional exciting program we plan to advance into clinical development this year is our first CD28 bispecific antibody, XmAb808, which targets the broadly expressed tumor antigen B7-H3.
This new class of bispecific is engineered to provide conditional CD28 co-stimulation of T-cells, activating them when bound to tumor cells. Now, with that, I'll hand the call over to John Kuch, our CFO, to review our financial results.
Thank you, Allen. Xencor's broad Fc technologies and the multiple partnerships that we have entered continue to provide us with opportunities to generate cash flows that strengthen our balance sheet and allow us to invest in our pipeline of bispecific antibody and engineered cytokine candidates. In the first quarter, we received $83.7 million of revenue from these partnerships. A breakdown of proceeds includes $78.7 million in royalties and $5 million in expected milestone payments. We'd like to point out that approximately $70 million of the royalty revenue was from our Vir partnership and relates to sales of sotrovimab, and given GSK's recent comments about anticipated sotrovimab sales for the remainder of 2022, we expect that future royalty revenue on net sales sotrovimab will be substantially lower than first quarter amounts. As noted, we continue to maintain a strong balance sheet.
As of March 31st, our cash equivalents, receivables, and marketable securities totaled $683.6 million, which is an increase over December 31st amounts of $664.1 million. We currently estimate ending 2022 with between $500 million and $550 million in cash equivalents, receivables, and marketable debt securities. Based on our current operating plans, we would expect to have cash to fund R&D programs and operations through the end of 2025. I will refer to you to our press release this afternoon and our SEC filing for further review of our financial results. With that, we'd now like to open up the call for your questions. Operator?
Thank you. At this time, I would like to remind everyone, in order to ask a question, please press star then number one. Please press star then number one on your telephone keypad. Your first question comes from the line of Jonathan Chang from SVB Securities. Your line's now open.
Hi, guys. Thanks for taking my questions. First question on XmAb104. Can you help set investor expectations for the upcoming data at ASCO?
Sure. I'll start with that. Thanks for the question on XmAb104. It's gonna cover our dose escalation portion of the study, and the study is currently in expansion. It's gonna go to the dose escalation of that agent where, you know, we're looking to see what kind of safe doses we could achieve. We know that there's been a history of ICOS agents that have had challenges there, and part of the whole goal of our design is by providing selective checkpoint inhibition and co-stimulation, we can provide a different kind of profile. And then, of course, whatever efficacy we can offer. It's in advanced solid tumor patients, as is typical in these studies.
Got it. Second question on tidutamab and XmAb841. Are you able to provide any more color on what you saw or didn't see in those studies, that led to the decision to discontinue those programs?
Yeah, I'll open it, and then I can let Allen jump in. What we really are trying to do with our strategy that we've been executing now for several years is put a number of programs that have promising biology into phase I and use the data to judge which ones could have the characteristics that we could develop and potentially create our own drug with or partner in a way that we think is very valuable. We're always looking at the efficacy versus the competitive landscape, which is always shifting. This was done in the context of that and judging whether our resources could be better spent on other of our programs whose competitive profiles are more attractive. It's about safety and efficacy in a particular context.
I would say I'll pass it over to Allen now, but in general, the efficacy bar for both of those settings is fairly high, and that tended to be what drove our thinking.
Yeah, Jonathan, I'd like to say, you know, predominantly the things to consider were actually outside the program. If you look at XmAb841, Opdualag, the BMS LAG-3 was approved. It was a pretty involved development program just for melanoma. When you look at XmAb841, comparing it to our internal pipeline, we just thought we would deprioritize it. There are better things to invest in in our internal pipeline. Likewise, for tidutamab, I think the key thing that changes Amgen has AMG 757 in small cell lung cancer, which is showing good clinical activity and a good safety profile. Looking at our internal pipeline, again, we just can't compare what we wanna invest in. I think we decided to terminate that program as well.
I'll note that there's investigator-initiated studies that we expect for at least one, if not both of those. We'll certainly support those with drug supply and, you know, see if patients can benefit and if good experiments get done. From an internal investment perspective, it's really about where we get the most bang for the buck.
Understood. Makes sense. Just last question from me. Can you discuss the rationale for the XmAb306 plus daratumumab combination in multiple myeloma?
You know, sure. Why don't we let John Desjarlais, our CSO, take that one? He's calling in remote. John, are you there?
Yeah, happy to take that. Yeah, thanks, Jonathan. You know, I think what it comes down to is, Darzalex, you know, seems to have a pretty strong NK-mediated activity against myeloma. But there's another wrinkle in it, because there's, you know, some a small amount of CD38 on the NK cells, it actually takes a hit on the NK cells as well. The hypothesis is that with our ability with XmAb306 to massively expand the NK cells, there might be additional synergy there on both fronts, right? Just having more NK cells to do the job, but also being able to replenish any of the NK cells that Darzalex takes out.
Understood. Thanks for taking the questions.
Thank you.
Thank you. Your next question comes from the line of Mara Goldstein from Mizuho. Your line is now open.
Hi, This is [audio distortion] for Mara Goldstein. I have a question on the side of the [cytokines] program. Basically, curious to hear your thought on the cis-targeting approach besides therapeutics. Now, they just show the data on [audio distortion], and whether you have enough evidence to say that this approach is changing safer and more effective, and could be incorporated into your clinical program in the near future.
I'll catch you on how we're thinking about it from a development pipeline standpoint. It's in our early development considerations. We're advancing a number of activities we would need, and we have not yet publicly guided on expectations for the time being in the clinic. As to the scientific rationale, i think it's fantasticallty strong, and john can go over that in a second, but really until you're in the clinic with these brands completely, you don't know much.
The basic idea is we started with [audio distortion] XmAb306, which is vastly potentially reduced. [Audio distortion].
If I may just sneak one in. Any additional colors you could provide on background in terms of indications, or potential combianation partners? Any chances you could explore combination with NK or cell therapy? Thank you
Just recall that molecule XmAb306, our engineered potency IL-15 is in a co-development collaboration with Genentech.
You know, it's a 55/45 worldwide split, and both companies have the right to initiate studies. We plan on initiating studies, and we're in the stage of sort of really ramping one up right now to get going, and we'll disclose details about that later. I think both T-cell and NK cell mechanisms are important to explore, and both we fully expect Genentech to expand beyond what they're already doing with the teclistamab combos and now Dara combos, and you'll hear more from Xencor. As for the cell therapies, of course, that's an issue where we and Genentech have to have a basic meeting of the minds on what programs are gonna be advanced by the two companies.
That's one where I think we're gonna have to guide on that later on specifics. I think there's a great potential for these exogenous IL-15 and exogenous cytokine approaches with cell therapy, scientifically. I just don't think we can talk about any kind of concrete plans yet.
Got it. Thank you so much.
Your next question comes from the line of Dane Leone from Raymond James. Your line's now open.
Hi, thank you, and congrats on all the progress. Maybe I will use my question and focus on the expected initial data on vudalimab in the back part of the year. We saw interesting data in MCRPC, I think, last year, if my memory serves me correctly. You know, it seemed like you guys established the premise that for what had been previously tested with, I think PD-1 CTLA-4 in a similar patient population, you're achieving similar results, albeit maybe with less toxicity. What are you going to be looking for from this initial data from the phase II study?
As specific you can get in terms of, like, the scale and scope, of that data set, I think it would be helpful to set expectations. Thank you.
Yeah. I'll before I pass this to Allen, I'll say recall we started this study just very late last year, so by data cutoff for second half. It was last year, SITC, we had the MCRPC data. By data cutoff, we should probably have about, I don't know, seven or eight months of accrual, and so it'll be on the order of a few handfuls of patients that we can show. I think really key here is, like you alluded to, that safety efficacy balance, 'cause recall, this study is in combo with chemo and potentially PARPs based on molecular subtype. Can we start building on this as a backbone?
Yeah. Not much to add. I'll just say that, you know, a lot of our work is sort of based on previous work from pembrolizumab and nivolumab. You know, I think the early data show that there was a benefit combining PD-1 with CTLA-4, but it's challenging to do that. We're very encouraged by our early data, you know, in our phase I, which we report at SITC, where we have a moderate response rate, even though it was a small number of patients. Moving forward, I think the tolerability allowed us to sort of design a really novel study where we look at different molecular subgroups and then combine with the standard of care, right?
You'll see that data with combination of XmAb717 with aggressive chemotherapy or a PARP inhibitor or monotherapy in different subgroups, and that will hopefully bridge us to designing, you know, registration-enabling study.
Yeah, being able to go on top of chemo would, I think, be a big edge here relative to the limitations you might have faced otherwise. It should be with a few handfuls of patients to get a read, start to get a handle on safety, see if there's any acute issues that arise. Of course, we'll show whatever efficacy data we have by that point. I think it'll be a solid but pretty early look. Note we are committed to prostate cancer. We're starting our second study, which is monotherapy in a clinically defined high-risk population as well, along with some gynecologic tumors in a different basket in that same phase II.
Yeah. Just to add a little bit more color on that, remember the BMS program, when they looked at the CheckMate 650 study in combination of Nivo and Yervoy, the combo was better, but in terms of their registration phase III, they're going with Nivo plus chemotherapy, just docetaxel as a single agent without the Yervoy. It sort of speaks to the challenges of combining PD-1 with CTLA-4, and that's what we're looking at. Maybe we can do it better.
Sorry, can I just clarify one thing with you guys? Are all three arms of the study monotherapy plus PARP plus chemo...
No. No.
...that run in parallel?
I'm trying to remember how much we've disclosed on ClinicalTrials.gov, but we'll have a trials in progress poster. There's five arms. I think three of them have chemo, one of them has a PARP inhibitor, and one of them is monotherapy, depending on the arm.
Depending on the molecular subtype that's identified. They're all enrolled in parallel.
They're all enrolled in parallel?
Correct. Yep.
You're expecting a handful of patients from, like, each of the different arms of the study?
Well, one of the arms, which is monotherapy, is the MSI, the microsatellite unstable, that's gonna be pretty rare. I don't know how many patients we'll get in there, but some of the ones that are more easier to enroll in, like the biomarker negative group, it's sort of the ones that don't fit into the other categories should enroll a little bit more aggressively. It depends on the arm and how rare it is.
Okay. Understood. Thank you.
Your next question comes from the line of Charles Zhu from Guggenheim Securities. Your line's open.
Good afternoon, everyone, and thanks for taking my questions. First one as a follow-up to one of the earlier questions that was asked perhaps. With respect to terminating bispecific checkpoint inhibitors due to uncompetitive or early clinical data, have your internal benchmarks for these kinds of go, no-go decisions remained constant, as you've brought these bispecific checkpoints through early-stage studies? By extension, should we expect that the XmAb104 dose escalation data set coming up could be comparable to the sort of readout we saw from, let's say, the initial vudalimab data? Thanks.
Have our metrics remained the same? Well, in the sense that we're always looking at how the competitive landscape is changing, that concept is constant. But as the competitive landscape gets more difficult and as the bar rises, our bar for data is gonna rise. We also look at what indications you might be in and how the drug's gonna be used. Recall that XmAb841, a CTLA-4 LAG-3 bispecific was intended for use in combination with pembro or nivo, intended to use for a combination with PD-1. You're always positioning it as a combo agent, and so it has a different set of comparators, right? You'd be comparing that to Nivo/Ipi, to Nivo/Relatlimab, to Pembro/Chemo as opposed to a monotherapy or a PD-1 containing agent like, say, our XmAb104.
I would say that we have not had expansion cohorts accrue enough to show data at ASCO for XmAb104, so it's gonna have just the escalation portion. Actually, no, I take it back. Our first data look at XmAb717 was just escalation with very little expansion. It's gonna look similar to that, maybe just a smidge less.
Got it. Sounds great.
In terms of the number of patients, the doses, and so therefore how much you'll be able to glean from it.
Got it. Great. Thanks. That makes sense. Maybe just one quick follow-up. Regarding vudalimab in prostate cancer and as a follow-up to another previous question. It sounds like you will have an early look across multiple cohorts, but the study itself will obviously continue to accrue patients and data beyond the near term disclosure. P erhaps can you also provide a little bit more color around your thinking on how much patient data do you generally need to accumulate before making potential go, no-go decisions for registrational studies in prostate cancer? Thanks.
For go, no-go?
I think it depends on how good the data is and what the subgroup is. Remember, like, if you look at what Exelixis did in their I think it's the COSMIC-021 study. You know, they had a couple hundred patients of data, right? They're looking at it as a big group for their cabo combination with the atezo. I think for us, we're sort of breaking it down into sort of molecular subgroups. There's aggressive variants, there's biomarker negative, there's PARP sort of PARP responsive, and the MSI unstable. If we go for a subgroup, we could probably use a lot less data. If we go for a larger study going across all, castration-resistant prostate cancer, we'll probably need more data to be confident and define those.
No, we define each of these subgroups based on what we thought the rarity of the tumor was. The ones that are the aggressive subtypes are 20 patients per arm within this phase II for each subtype, and we think that would be adequate to make a go, no-go.
Got it. Great. Thanks for taking my questions.
Your next question comes from the line of Etzer Darout from BMO Capital Markets. Your line's now open.
Great. Thanks for taking the question. I have another one on XmAb104, I guess, on sort of the early plans here for expansion. If you could speak to any tumor types that look interesting at this point or could potentially be explored. I guess secondly, we're gonna see some data from other PD-1 CTLA-4 agents at ASCO and maybe how we should think about, you know, any molecular differentiation or any potential read-throughs from a mechanistic standpoint that you would be looking to at these data sets. Thank you.
Etzer, just to be clear, you had one question about XmAb104 tumor types that we might or might not be interested in, the other one about molecular differentiation of our PD-1 CTLA-4 versus XmAb717 or vudalimab. Is that right?
That's correct.
Okay, great. On the XmAb104, we really can't comment on the tumor types until after we show our data at ASCO, and there'll be information there that'll make it clear what tumor types we're going after in our expansion cohorts. We will define it.
Yeah. The expansion cohorts will be listed in our presentation.
With rationale. That's coming. As for the other one, molecular differentiation for other PD-1 CTLA-4s at ASCO, our molecule is, I think, one other molecule that we're aware of has a similar design, which is this design to create a molecule that really needs both targets on the T-cell to engage, right? Rather than most of the designs where you've got a bivalent binding to both PD-1 and CTLA-4, you're gonna have high avidity binding to each. Ours are relatively low activity if you only have a PD-1-positive cell, and very little activity with a CTLA-4-positive-only cell. Good activity with both. The only other program we're aware of is AstraZeneca's, which just released some initial data, we recall at AACR.
That molecular differentiation is, we think, at the root of our potentially differentiated safety profile. I think that's how we view our real competition.
Was the question around XmAb717 or XmAb104?
XmAb717
Okay. Sorry.
That's how we view our real competition. Because, again, how are you gonna combine with potentially really toxic chemo regimens like we're exploring in the vudalimab phase I? I think that's the way we're gonna be able to use this kind of agent competitively.
Great. No, thank you. Your next question comes from the line of Gregory Renza from RBC Capital Markets. Your line's now open.
Hi, this is Ning on for Greg. Thank you for taking our questions, and congrats on the progress. Maybe first just a follow-up question on XmAb104 . Could you just expand a little bit on your earlier mention of the historical challenges of ICOS programs where you think XmAb104 could potentially show differentiation?
Sure. Hey, John, did you wanna handle that one, or should we go for it here?
Yeah, I think I need that question repeated, though. I'm sorry.
Yeah, sure. Just wondering if you could expand a little bit on the historical challenges of ICOS-targeting programs where you think XmAb104 could show differentiation?
Oh, yeah. Yeah, no, that's basically. I mean, Bassil alluded to this earlier, right? W e know all the historical challenges of the ICOS programs, and this molecule was kind of magical when we put these two different sites together. This came out of an empirical screen of combining various, you know, PD-1 with various other costimulatory targets. All of our preclinical in vitro assays, the XmAb104 was just the strongest in terms of activation of T-cells, you know, that included in vitro as well as, you know, our in vivo mouse studies, where we just saw raging hot activity on the T-cells. I'll confess, we don't completely understand why this thing is different, but it was intriguing enough that we thought it was worth pursuing clinically.
So it's just a different beast than those other ICOS combinations.
Yes. It's a very different beast, and that also encouraged us that perhaps the central problem that the other ICOS targeting normal mono, monospecific bivalent antibodies have, was toxicity, right? They seem to be pretty toxic, and they were hard to use. The vastly different profile we have with our molecule, for example, it has no effector function in the Fc, so we wouldn't expect it to deplete ICOS-positive cells. We are hopeful that that allows us to have a differentiated profile, that maybe toxicity limited the efficacy, 'cause they couldn't get to enough dose, perhaps, of the historical molecule. Very different design, hopefully can overcome that toxicity limitation and see the activity there. That's what the rationale was for the program.
Great. Thank you. Maybe just another one on plamotamab. When should we expect to see some initial data from the triplet study? Also on the monotherapy, just wondering if we could hear a little bit about your latest thinking around opportunity there and path forward. L astly, just on the subQ formulation, how that will be phased into the expansion study. Thanks.
We're not guiding on our first data from the triplet plamo tafasitamab lenalidomide study. It just started. We'll guide on expectations for first data later. Note that it is a safety run-in at two doses followed by ultimately the randomized phase if we go forward. We will have some interim data, but we'll guide on timing for that at another point. You know, you want to comment on how we're gonna phase in the subQ and what the monotherapy, the rationale for continuing in the expansion is?
Yeah. A couple things. The first thing about the landscape, you know, we are following that very closely, and I think one of the things is that CAR T is definitely moving into second line, right? The data is very strong there. The landscape is changing and, you know, one of the things I wanna point out is that what is considered relapse-refractory diffuse large B-cell lymphoma has changed. What we're noticing in our studies is we're seeing a lot of CAR T refractory patients coming into our studies, especially in diffuse large B-cell lymphoma group, but we're still encouraged by our data.
In terms of subQ, I think everybody suspects that using subQ will sort of change the therapeutic index, offer a better safety profile, allow you to escalate faster and even higher in dose. As we introduce subQ later this year, we're gonna see how good it is and then make decisions on our current studies, which are currently IV. Do we convert them over to subQ? Again, I think we need to see the early data first, but I think everyone is encouraged with that. In terms of our monotherapy data, we're planning to release additional monotherapy data from our IV study in our phase I. That's in diffuse large B-cell lymphoma and follicular lymphoma. This will be IV. I think that data, again, looks good.
The study's designed in a way the data quality is good enough for registration, but would it be worth it since other companies are probably gonna file pivotal sort of single-arm data in the near future.
Yeah, we don't think monotherapy ultimately is the long-term play, or even frankly the medium-term play in CD20/CD3 is trying to get into the B lymphoma landscape. Monotherapy data simply is, I think, not gonna compete against the myriad of combinations that are proceeding, some of which have already shown glimmers of good activity from early studies, whether it's chemo combos. We're very excited by our chemo-free regimen. The monotherapy opportunity, as much as anything, is continuing the studies is not about thinking that there's a great opportunity there, but more about establishing that baseline of data and bringing forward enough data to make sure we can, you know, demonstrate the rationale for our further studies.
Exactly right, Bassil.
That's very helpful. Thank you very much.
Your next question comes from the line of [Zhi Tian Xu] from Berenberg. Your line is now open.
Great. Thank you very much for taking my question. Two from me. First on the discontinuation of tidutamab. I guess the SSTR2 is a de-risk target in neuroendocrine tumors, and you show some activity there. What was the reason for discontinuing in that particular indication? Does it have anything to do with the commercial opportunity, or is it really because you learned something about the T-cell engagement in solid tumors? Second question is a quick one. Can you help us understand the IL-2 program you are developing, with update there and when should we be able to see data? Thanks very much.
On the tidutamab stop in neuroendocrine tumors or NET, I think it was as much as anything, not so much the commercial opportunity per se, but rather the very, very long clinical trials you would have to do to achieve them, where historically in NETs and I think tidutamab would face that as well here, they're long PFS and OS studies that are long to accrue and very long time endpoints, out past two years in many cases. We looked at the timeline for how that might go, and it didn't seem like something that made sense. Even in NETs there's a shifting landscape. That was really the driver for not wanting to pursue NET.
Allen mentioned why the challenge in small cell lung cancer, potentially a great opportunity, didn't make sense anymore based on what we were seeing. Could you repeat your question about our IL-2? I didn't catch that.
Yeah, just kind of, can you update us with the status right now, when should we be able to see the data? Thanks.
The status of the study is we are currently in the phase I single ascending dose study in healthy volunteers, and we expect to have data from that study later this year that is essentially gonna be your trifecta of safety, tolerability, the biomarker data you're looking for regulatory T-cells to go up and for T-effectors to not go up really, and how long that lasts, right? The durability of it. That trio of biomarker data, duration, and tolerability is gonna tell us how really how we stack up, I think, against that same sort of correlated, similar data that was released after SAD studies by some of the competition.
It'll also allow us to really be well set up to start our multiple ascending dose trial, which we're currently in preparation for and will also start this year, and we'll give the details about that later.
Great. Just quick follow-up on the tidutamab, Bassil. Since you mentioned it's sort of long trial duration, are you thinking maybe potentially out-licensing these two programs as you did for some others you discontinued? Thanks very much.
We're always open to finding ways for molecules we make to potentially benefit patients and, you know, accrue value to the company. I would say everything's on the table. I'm not gonna guide to that. I would say it's not a high priority for us for these two programs to find partnerships for. I think we've got other fish to fry, but never say never.
Great. That's helpful. Thank you.
Your next question comes from the line of Peter Lawson from Barclays. Your line is now open.
This is [Gena Wang] for Peter. Thanks for taking the question. Just to follow up a little bit more on the discontinuation. For your CTLA-4 x LAG-3, is there anything in that phase I data that you had developed so far that pointed to you being more negative on the approach of a CTLA-4 x LAG-3? Or do you think it was just more based on the molecule you had and would you want to revisit making another CTLA-4 x LAG-3? Just also a little bit on the vudalimab. Just in light of the discontinuation, what is it that you're actually looking from that second half data that would point to you that you wanna go forward? Further, do you think that this will be a substantial enough update in second half for you to make that decision? Thank you.
First on the vudalimab, it's not gonna be enough data for the go/no-go. It's gonna be an initial look at safety and whatever efficacy we can see from that, you know, few handfuls of patients, you know, across these different molecular subtypes. The tolerability in combination with aggressive chemo is, I think, a very important thing to look at. It really shows the potential. We don't anticipate efficacy go/no-go at in this year's update. We'll have been less than one year into since the study start. Obviously, if safety data can give you a go/no-go at any time, whether you like it or not, but we're optimistic that we can provide an update and fully expect to continue the trial after that update.
It'll give people a read on what is really the potential for this new way of targeting this pair of receptors. Going back to the CTLA-4 by LAG-3, is it the molecule or the target pair? That is essentially what you asked. I will say, I don't know if anybody can address that, given that I think there's only one of these that's ever been in the clinic, and it was ours. I can say that we don't plan on going back and making another one, because as much as anything, I think the landscape of competition has moved, and it's very different from what, we all expected it to be three or four years ago, 'cause you never know what it's gonna be.
We would not plan on making a new one, but I don't think that reads on whether it's the target pair or the specific molecular design choices we made. I wish I could answer that.
Great. Thank you for taking the question. Congrats on the quarter.
Your next question comes from the line of David Dai from SMBC. Your line's now open.
Great. Thanks for taking my questions. One question on vudalimab. We saw in SITC data that there were some modest level of equivalent to rash and pruritus, around 31% or 36%. Could you share with us the physician feedback on the tolerability profile, especially in the context of the combination in various different prostate cancers?
Just to make sure we heard your question right, you were commenting that the most common AE we presented at SITC for vudalimab last year, SITC was rash at around 30%, and you're wondering how that might work. What might happen with chemo in terms of synergistic tox? Is that what you're asking?
That's correct. Yes, that's correct. You know, would you expect to see a sort of higher, you know, tolerability of, or safety issues when you combine with different combinations?
Yeah, let me just sort of generally talk about the tolerability of XmAb717, which we are very impressed with. I mean, remember when you give a PD-1, CTLA-4 combination with the two drugs independent like Nivo and Ipi, you know, a third of patients develop colitis and have to discontinue. Much so that you usually just give the nivo, and then they give the ipi for a short period of time, four courses, I think, is the latest thinking right now. When we looked at our data from SITC, you know, we had a GI sort of diarrhea rate around 10%, which is very tolerable, much lower, and rash was the most common AE. You know, for oncology patients, rash is not a huge. It's not an important toxicity. It's not gonna cause you to discontinue.
Now, whether you would expect to see synergy with chemotherapy for that toxicity profile, probably not. I mean, it's still early. If you think about it, rashes are often treated with low doses of methotrexate, depending on the type of rash. Yeah, for autoimmune diseases and so forth, l ike psoriasis . That's the old days. I don't think we'll see synergy in terms of toxicity, but we don't know. It's still early. I think that was your question, right, David?
That's right. Well, thanks so much for the answer. Then another question on XmAb104. Maybe just help me understand some of your biomarker strategies to identify the responding tumor types for the program.
I think our strategy for identifying the responding tumor types is really about response.
It's about resistant response. I think we have to be stringent about that. We've obviously characterized the biomarkers because understanding the mechanism helps you glean insights into dose selection, the rationale for maybe if you see some kind of activity or toxicity in certain patients. No, it's about the kind of tumor response you see, not really the biomarkers.
Got it. Thank you so much.
Your next question comes from the line of David Nierengarten from Wedbush Securities. Your line's now open.
Hey, thanks for taking the question. Maybe I'll just switch to plamo for a second. Speaking of competitive profiles, it's a pretty competitive space. What do you think you need to hit with the triple combination in terms of a response rate to, consider advancing the program further?
Yeah, I think it's still really hard to say from most of the studies, 'cause I think there's only one study we've seen a significant number reported. It was just top line from the recent AbbVie release, where they had about a 60% OR and a 40% CR rate for that are relapsed/refractory DLBCL population. I think that sort of sets the minimum bar, honestly, for us, 'cause it's a similar population.
How much you can go from there? We know that tafasitamab lenalidomide starts with about a 40% CR rate and about a 60% OR.
Yeah. I think there's a couple things. T he L-MIND study is probably a good benchmark of what we'd expect to see with just tafa len by itself. Granted, the landscape is changing a little bit, but what's nice is remember, we'll have this run-in, so if we think the study may be underpowered, we can adjust the size or change strategy in the second part of the study.
Maybe a quick follow-up. I mean, you know, not to give too many hypotheticals, but, you know, is, you know, pushing those patients to CR more important to you or is it , kind of generally the overall response rate that's more important for you when you assess the prospects?
Yeah, it's a good question. I think that's more of a qualitative answer. I think CR is always important, right?
I think you'll get responses, but when you look at the competitive landscape, I think the power of the CAR T they've been able to push patients into CR that are durable, right? The question is, can bispecifics do something similar to that, right?
Yeah. That's why we think the potential for additive or maybe synergistic activity with a CD19 targeting NK cell recruiting high ADCC antibody is something that just adds another avenue that avoids the tox of chemo that maybe lets us move that needle.
Yeah. Got it.
Thanks.
Thank you. There are no further questions at this time. I would now like to turn the call over back to Bassil Dahiyat.
Thanks very much for joining us today, everybody, and we look forward to updating you again in the near future. Bye-bye.
This concludes today's conference call. You may now disconnect. Thank you.