Xencor, Inc. (NASDAQ:XNCR) Q2 2023 Earnings Call Transcript

Xencor, Inc. (NASDAQ:XNCR) Q2 2023 Earnings Call Transcript August 6, 2023

Operator: Good afternoon, and thank you for standing by. Welcome to Xencor’s Second Quarter 2023 Conference Call. After the speakers’ presentation there will be a question-and-answer session. [Operator Instructions] Please be advised that this call is going to be recorded at the company’s request. I would now like to turn the call over to your speaker today, Charles Liles, Head of Corporate Communications and Investor Relations. Go ahead, Charles.

Charles Liles: Thank you, and good afternoon. Earlier today, we issued a press release, which outlines the topics we plan to discuss today, available at www.xencor.com. Providing comments on the call is Bassil Dahiyat, President and Chief Executive Officer; and Nancy Valente, Chief Development Officer. Afterwards, we will open up the call for your questions, and we’ll be joined by John Desjarlais, Chief Scientific Officer; and John Kuch, Chief Financial Officer. Before we begin, I would like to remind you that during the course of this conference call, Xencor management may make forward-looking including statements regarding the company’s future financial and operating results, future market conditions, plans and objectives of management, future operations, the company’s partnering efforts, capital requirements, future product offerings and research and development programs.

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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. 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, I’ll pass the call over to Bassil.

Bassil Dahiyat: Thanks, Charles, and good afternoon. We’ll have brief comments and then get to the Q&A because we’ve received positive feedback on having abbreviated comments on our call in the past two quarters. So I think we’ll keep to that. At Xencor, we’re advancing a broad internal development portfolio of antibodies and engineered cytokines in oncology and autoimmune disease that we’ve built with our array of modular continually advancing protein engineering tools by taking multiple simultaneous shots on goal in the clinic, we can let clinical data guide which programs we advance, which we terminate, which we partner, so that we focus our resources on programs with the greatest potential for success and make room in our portfolio for the next wave of innovative biologics.

Now before heading into our pipeline, we’ll cover some updates on partnerships, which provide validation across our suite of XmAb technologies and revenues, which offset our development costs. First, the label on Ultomiris continues to expand in the EU and Japan, where it is now also approved to include neuromyelitis optica spectrum disorder. We earned $11.2 million in royalties in the second quarter, and if Ultomiris sales keep up, we would anticipate earning our remaining sales-based milestone payments of $20 million this year. Notably, we’re enhancing our extended patent coverage and term in multiple global geographies, and we’ve begun to see country-by-country progress in Europe. Our CD28 bispecific collaborations with Janssen Biotech are also progressing well for both the prostate and B-cell targeted CD28 by specific programs, and we anticipate both of them to advance in the clinical testing.

Finally, as noted in the abstract titles for the European Society for Medical Oncology, we anticipate data from Amgen’s study of AMG 509 in prostate cancer at ESMO. AMG 509 or now xaluritamig, that’s with an X as an XmAb or Xencor utilizes our XmAb 2+1 bispecific antibody format that allows for multivalency of targeting demands. And Amgen previously presented very encouraging PSA response data in early 2022. In the case of xaluritamig, 2+1 format allows for higher avidity and tighter binding to a receptor that is barely exposed extracellularly. But we also use this highly versatile format to dial into high expressing tumor cells much more selectively over lower expressing normal cells, like we do with our XmAb819 and XmAb808 programs or to distinguish between nearly identical receptors in the same family like we do with our XmAb541 program.

Now for updates this quarter on our wholly owned clinical portfolio, I’ll turn it over to Nancy Valenti, our Chief Development Officer.

Nancy Valente: Thanks, Bassil. We’ll be starting with vudalimab, our PD-1 CTLA-4 T cell selective checkpoint inhibitor. In light of encouraging competitor data that we saw last fall for PD-1 CTLA-4 bispecific and our own Phase 1 experience, we are moving vudalimab into frontline treatment for patients with locally advanced or metastatic non-squamous non-small cell lung cancer. The first part of the study will randomize patients one to one at two different doses of vudalimab-plus chemotherapy. The second part will take the recommended dose and randomized two to one against pembrolizumab with both arms in combination with chemotherapy with the primary endpoint of PFS. Preparations for initiating sites are ongoing, and we plan to get this study started by the end of the year.

We anticipate having data from our other ongoing Phase II studies in metastatic castrate-resistant prostate cancer in early 2024. Recall 1 study is testing vudalimab monotherapy in clinically defined high-risk prostate cancer and advanced gynecologic malignancies. The other study is taking prostate cancer all comers, and we’re evaluating vudalimab in combination depending on subtype. Moving along to other earlier stage bispecifics, XmAb819, our ENPP3-targeted CD3 bispecific and XmAb808, or B7H3 targeted CD28 bispecific, both have strong enrollment and dose escalation with more interest from investigators than available slots per cohort. These are just two examples of novel XmAb 2+1 bispecifics with unique designs, enabling us to potentially fill a gap in treatment approaches.

We also anticipate submitting our IND for our third internal 2+1 bispecific XmAb541, a CLDN6 targeted CD3 to be developed in ovarian cancer and other solid tumor types later this year and plan to submit an IND for our second internal CD28-bispecific in 2024. In regard to our cytokines, we’ve initiated a Phase 1 study this quarter for XmAb662, our engineered potency reduced IL12 Fc fusion protein in oncology. Now with that, please refer to our press release for financial results, and we’ll open the call to your questions. Operator?

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Q&A Session

Operator: Thank you. We will now conduct our question-and-answer session. [Operator Instructions]. Our first question comes from Mara Goldstein of Mizuho. Your line is open.

Mara Goldstein: Great. Thank you. This is Mara Goldstein. Hey, I wanted to ask just on the [indiscernible] mix. I understand there’s probably limited information that you can share. But given now that the compound has a name and we’re going to see more data, are — I guess the question is, is it fair to assume that this will advance, we’re looking at advancement here? And then the second question I just had is on vudalimab and when you will provide results for the prostate cancer part of the study, can you talk a little bit about what should the expectations there be around the patient numbers and whatnot?

Bassil Dahiyat: Sure. So I’ll take the first one, Mara. So we do know that Amgen has and they publicly disclosed this expanded their Phase 1 study quite substantially to include many different cohorts, both in combination with energy deprivation therapy as well as a subcutaneous dosing format as well as continuing to advance this monotherapy IV. And I think that’s a pretty good sign that, that’s a good commitment to advancement. I think that we should always keep in mind that in today’s day and age, in oncology, people stay in Phase 1 and keep adding patients for quite a long time. So I can’t speak to their specific tactical approach. But we are very encouraged, and we’re watching closely as they keep moving forward. For the results for the prostate cancer that we mentioned we would have in early 2024 from both our monotherapy and combo study, roughly maybe Nancy can give a little bit of rough guidance on that.

Nancy Valente: Yeah. I mean we’re excited. Yeah. So we’re excited about vudalimab in prostate cancer. We previously presented data in Phase 1, where there were a few responses, two responses with long duration of six and 10 months. And then in combination with chemotherapy at last year’s SITC again, with some responses and duration of about 8 months. These studies are enrolling well. It’s hard to say right now, more than that. We’ll have data in early ’24 from the monotherapy cohort and some of the chemo combination cohort. So remember, the combination cohort includes combination both with chemotherapy and a PARP inhibitor. So we hope to have some early data from that as well as longer-term data or more data from the monotherapy cohort.

Mara Goldstein: Okay, thanks. Appreciate it.

Bassil Dahiyat: Thanks, Mara.

Operator: Thank you. One moment for our next question. Our next question comes from the line of Etzer Darout of BMO Capital Markets. Your line is open.

Etzer Darout: Great. I guess the first one, I just wanted to know if you could comment a little bit more on some of the interest that you’re seeing from investigators on XmAb819. Is it just really more around sort of the pace of enrollment that you’re seeing? And then secondly, just wondered if you’ve made constructs of some of the other PD-1 CTLA-4s that are in the clinic. And then maybe specifically about lung cancer, if you see anything differentiating about your molecule and how that may do in non-small cell lung cancer versus what we’ve seen from some of these other PD-1 CTLA-4? Thank you.

Bassil Dahiyat: Sure. Thanks, Etzer. I’ll just say on 819, I think, yes, just to be clear, the interest is from really strong enrollment and strong engagement and maybe the rationale for that and why investigators think this agent has a place. Maybe, Nancy, do you want to comment on that?

Nancy Valente: Yeah, I mean we’ve heard comments that they are really thrilled that someone is developing a product specific for kidney cancer. So typically, kidney cancer is included with other solid tumors studied along with them. But we are really studying the ENPP3 in only kidney cancer because it’s highly expressed there, it makes scientific sense to go there. So — and no one — I guess no one’s ever done that.

Bassil Dahiyat: Yeah. And I think that given the mechanistic rationale and the very strong and specific expression of ENPP3 in renal tumors, I mean it’s a really good fit, a targeted agent against the tumor-specific or tumor-associated antigen in RCC, I think it’s really — is very, very timely. To your question on sort of competitors CTLA-4, PD-1, and lung cancer, I’ll just comment maybe on the structural piece and maybe Nancy can comment on some of the more clinical rationale for why there’s big unmet need. Our PD-1xCTLA-4, vudalimab was designed to really only engage well with target T cells that express both antigens. We really dialed down the affinity on each side, in particular, on the CTLA-4 binding side, so you have to have both targets there to engage or you really don’t get much binding and derepression of the T cell response.

And I think that’s important, really, when we think about how we’re looking at competitor data, in particular, the molecule formerly known as MEDI5752 at AstraZeneca, which was designed with a very similar rationale, and that’s the only one that we’re aware of in the clinic with the same kind of highly selective rationale for the cells that have both PD-1 and CTLA-4. So essentially, your CTLA-4 engagement is conditional on PD-1 being there. The hope is to reduce the scope of cells the T cells that you’re activating that you don’t want. Maybe you want to comment on why frontline lung?

Nancy Valente: Yeah, I’d love to. So when we looked at the MEDI5752 data and really compare the patient populations, what we had previously observed in our Phase I dose escalation and expansion, we thought it would make sense to go into front line lung. Our patients, in particular, are really heavily pretreated. So they have a median of three prior lines of therapy, although one received prior checkpoint inhibitors and 40% actually received two checkpoint inhibitors. So a much different population than the competitor where those patients are checkpoint naive and not as heavily pretreated. So we thought this would be a great place to go. They provided a proof of concept. And maybe we’ll see something really interesting there.

Etzer Darout: Great. Thank you.

Operator: Thank you. One moment for our next question. Our next question comes from the line of Edward Tenthoff from Piper Sandler. Please go ahead.

Edward Tenthoff: Great. Thank you very much. I’m excited about the various updates. This is really cool. So when it comes to lung cancer, again, appreciating that initially, it will be sort of a reasonable size study. Longer term, is this an area where you think you might seek to partner? Or how are you guys thinking about that right now? Thanks.

Bassil Dahiyat: Yeah. I think right now, we want to focus on building value in the program by generating data in this really large population of frontline lung in combo with chemo and demonstrate that we can have the kind of activity that would get us excited. We certainly see AstraZeneca was excited by their initial activity as well as the, hopefully, differentiated safety profile that we have seen so far from PD-1, CTLA-4 combination therapy. I think beyond that initial engagement — sorry, beyond that initial data that we want to see, I think it does make us think about partnering in a different way than when we were focusing on smaller populations in later-line patients. Certainly, the opportunity is huge to try to do better than standard of care therapy because, again, the majority of patients do relapse within — or don’t respond at all within the first two years.

So there’s a lot of opportunity. But it does make us think about how our partnership with the added scope and scale could accelerate things. But we’ll consider that when it would accelerate things, which we don’t think is now at this critical stage of establishing that we have the right efficacy safety profile.

Edward Tenthoff: All right. That make sense. Helpful. Great, thanks for the update.

Operator: Thank you very much. Please standby for our next question. Our next question comes from the line of Brian Chang from JPMorgan. Your line is open.

Brian Chang: Hey, guys. Thanks for taking my question this afternoon. Maybe just one on vudalimab in your new indication in non-small cell lung. Can you give us some color on how you’re thinking about the bar for non-small cell, given the targets that you’re shooting for? I’m interested to see if you have a sense of — especially in the second part where you’re trying to compete against pembro plus chemo. How much delta are you looking for in terms of PFS that you will need to push this program forward? And then I have a follow-up. Thank you.

Bassil Dahiyat: Sure. I think — we don’t want to comment yet on specific deltas we’re targeting for how we powered the study. But we do note that it’s extension of PFS that we saw with the competitor PD-1xCTLA-4 that really seemed to potentially differentiate, and that’s why we made that the primary endpoint. But I don’t think we’re quite ready to comment quantitatively on the Bar success. We will absolutely address that a little bit later.

Brian Chang: Okay. And then maybe just one more on just as a recap on data flow for the near term. Can you remind us, aside from the vudalimab and also the 564 data updates more towards the early part of 2024. What other data catalysts or potential catalysts that investors should look out for?

Bassil Dahiyat: Yeah. So as we’ve sort of been doing this year, we’re not guiding on specific timing of data until we get closer to the events. We want to make sure we can offer certainty and not distraction. But we do expect in next year, we would have updates on our XmAb104 PD-1x ICOS program, which has been enrolling really well in microsatellite stable colorectal cancer. And we are also — that’s expansion cohorts. We would also expect to have next year data from our XmAb19 program which is our ENPP3 targeting CD3 and we are hopeful also we’ll have some things to say about our XmAb 808 program, which is our first CD28 bispecific in the clinic by then as well. So that’s the setup. There’s a lot of flow from these earlier-stage programs for next year.

We’re not going to comment on our partners, which obviously will have their own news flow. So beyond the Vudalimab and 564, those are the things to watch for, and we’ll give specific guidance as we get a little closer to the dates.

Brian Chang: That’s helpful. Thank you.

Operator: Thank you. One moment for our next question. Our next question comes from the line of Alec Stranahan from Bank of America. Your line is open.

Alec Stranahan: Great. Hey, thanks guys. Thanks for taking my questions. Just a couple from us. The first is on the lung cancer study for vudalimab. Any additional thoughts around not including Vudalimab monotherapy cohort in the study? Is this driven more by the standard of care in non-small cell lung? Or is there something from the prostate study that you’re seeing that’s driving this? And then second question is just on expectations around partnership revenues, specifically, any color around what you expect from setrusumab from hear this year given that it was a pretty big contributor last year. Thank you.

Bassil Dahiyat: I’ll take the setrusumab question. We expect none. We reported almost none in the second quarter. Yeah. So we expect strived to be done. Maybe on the lung cancer and why not monotherapy, Nancy can go through the rationale there?

Nancy Valente: Yeah. Most of lung cancer are nonsquamous non-small cell is treated with chemotherapy, even patients, it turns out that should be eligible for just checkpoint inhibitor alone. And so we decided we’d go there. We’re going to look at PD-L1 expression or TPS less than 50%, 49% and lower. So that’s also specifically the chemotherapy part of the non-small cell lung cancer world, like that’s definitely where it’s used. So those are the reasons.

Alec Stranahan: Thank you.

Operator: Thank you. Please standby for our next question. The next question comes from Kaveri Pohlman of BTIG. Your line is open.

Kaveri Pohlman: Good afternoon. And thanks for taking my questions. For 819, I just want to know what makes kidney cancer attractive for this molecule. I know you mentioned ENPP3 has a strong expression, but do you expect T cells to work fairly well after first-line checkpoint inhibitors? And are there any other tumor types where you see opportunities?

Bassil Dahiyat: Yeah. I think I’ll let John Desjarlais, our CSO, take that question. He’s expert in all things the ENPP3.

John Desjarlais: Yeah. Thanks for the question. So I guess maybe the better way to think about it is we like ENPP3 because we’re basically first-in-class for CD3 bysacivic. It is very strongly and essentially uniformly expressed in clear cell renal cell carcinoma. And there’s a few other histologies where there could be high ENPP3 expression, but we wanted to prioritize for renal cell, mostly just to develop a signal once we establish that, then sure with perhaps a companion diagnostic, we could expand into a few other tumor types.

Bassil Dahiyat: And John, maybe the question.

Charles Liles: The other aspect of your questions yeah, with T-cell. Yeah, it’s interesting you asked that it turns out that kidney cancer, if you look at RNA expression levels for T-cell markers, it’s actually one of the highest histologies for having a T-cell presence, kind of consistent with the immune checkpoint inhibitors being very active in renal cell carcinoma. And we don’t think there’s any scientific reason why progression on a checkpoint inhibitor would have much impact on the future effects of it [ph]?

Kaveri Pohlman: Got it. That’s very helpful. Thank you. And maybe one on plamotamab. So you selected a step of dosing to manage CRS. But can you tell us about the safety profile? Do you think with this step-up schedule, you can avoid hospitalization requirement that other bispecifics have?

Bassil Dahiyat: So we’ll address that in the context of the formulation moving forward, our subcu in collaboration with Janssen, which does limit somewhat how much detail we can give. But I mean, I don’t know, Nancy, do you want to take that? Or that’s a goal. I don’t know that we have enough data to say yet.

Nancy Valente: Yeah. Certainly, that’ll be a goal. I think there’s some bispecifics that require a lot of hospitalizations, some that are minimal. Our goal would be to go for the minimal amount that’s appropriate as we look at the safety. And then it’s really about optimizing the step doses to make sure that you have CRS, the patient is primed and not having too much CRS such that it’s dangerous and requires hospitalization or. Yeah. But — so definitely, that’s our goal. And I think a product like Plamo given subcu could probably reach that like having less hospitalizations.

Bassil Dahiyat: We’re not — we don’t have enough information to comment in more detail than we’re hopeful, and we’re making good progress with the subcu, but we haven’t got data to share this moment.

Kaveri Pohlman: Got. Thanks for taking my questions.

Operator: Thank you. One moment for our next question. Our next question comes from the line of Charles Zhu of Guggenheim Securities. Charles?

Charles Zhu: Hey, guys. Thanks for taking the question and for providing progress across your pipeline. I’ll start off with a quick clarifying one on vudalimab. So obviously, an intriguing choice to pursue frontline non-small cell lung cancer. One quick one regarding the chemotherapy backbone. Could you remind us or maybe provide color, is this the standard schedule of 4 cycles in maintenance or maybe or what have you? Or is this something that’s more like a CheckMate 9LA where they stopped at two cycles? Thank you.

Nancy Valente: This is a standard schedule for non-squamous. It’s Pemetrexed and a taxane. I think it’s given four cycles. And yeah, and there is a maintenance component as well.

Charles Zhu: Great. And then maybe another more side —

Nancy Valente: With vudalimab. Sorry, with vudalimab, of course.

Charles Zhu: Great. Thank you. And maybe I just want a bit more. And my second one, maybe a bit more scientific mechanistic one for XmAb564. What’s your view on the potential for a differential expression profile of CD25 as you move from healthy volunteers over to atopic dermatitis and psoriasis patients? And could this potentially impact the clinical profile of your drug? Thank you.

Bassil Dahiyat: I don’t know that there’s any real strong information on CD25 expression levels in those 2 patient populations. Maybe John, do you want to comment on what is known about CD25 expression levels in other populations and how that might change things. I don’t know that we would expect it to have a profound impact but John would know more.

John Desjarlais: Yeah. I mean there is some — when you go into autoimmune diseases, there is some literature suggesting that the Tregs might have slightly lower CD25 expression. And you can also have a deficit of Tregs compared to T effector cells, but of course, that’s exactly why we developed the therapy to expand that deficit of Tregs to catch up to the effector cell population and have a better suppressive capacity. But I don’t think there’s going to be anything prohibitive in terms of CD25 expression for our 564 to actually mobilize those Tregs.

Charles Zhu: Great, thank you.

Operator: Thank you. One moment for our next question. The next question comes from Charles Zhu of Leerink Partners. Johnathan, I apologize.

Matt Kemper: Hey, guys. This is Matt Kemper on for Jonathan Chang. Just one quick one for me. For the 662 study, are there any tumor types that you are — any investigators are particularly keen to evaluate the compound in? Thank you.

Bassil Dahiyat: For 662, the IL12 program, I think we’re just really at this point, exploring a range, making sure we can get a dose where we get the right kind of pharmacodynamics and tolerability data. I don’t know that there’s a particular ones that we’re even most excited about. But I mean, John, do you want to correct me on that?

John Desjarlais: Well, yeah, I mean, we’re sort of going across the board, right, because we’re looking at immune responsive tumors, of course. But on the flip side, we’re also very intrigued to look at 662 in histologists like colorectal cancer, where PD-1s by themselves are known not to do much. And since we’re doing a pembro combination, if we see something, the signal will be more clear. Likewise, for prostate cancer and a few other histologies. So we really want to cast a wide net on this one and see what the signals are.

Matt Kemper: That’s really helpful. Thanks for taking my question guys.

Operator: Thank you. One moment for our next question. Our next question comes from the line of Boris Peaker of TD Cowen. Go ahead.

Boris Peaker: Great, thanks for taking my questions. I have two questions. On vudalimab in lung cancer. Just curious how do you anticipate safety to compare to the competitor by specific, obviously, and also to the combo of KEYTRUDA plus chemo? And on 564, maybe a kind of a broad question, how do you see this drug distinguish in psoriasis and atopic derm given kind of the pretty hot competitive landscape in those indications?

Bassil Dahiyat: Yeah, maybe I’ll touch on the 564 rationale for those indications before I hand it off to Nancy to talk about the vudalimab. Our thinking on safety there, which is pretty early. So for 564, we selected atopic derm and psoriasis as our Phase 1b population because it is a multiple ascending dose study where our key goal is to understand what kind of dosing interval can we treat patients with where we get a long enough duration of T-cell — Treg expansion to cover them throughout the dosing interval and of course, that would be tolerable. We saw dramatically improved duration of T-cell — Treg expansion for 564 relative to what we saw from competitors for single-dose studies. So we’re hoping to exploit that to see if we can exceed the every other week dosing that the competing Treg IL2 programs seem to be at.

So that could be a very important differentiator across the board. So we selected psoriasis in atopic derm because those are populations where there’s a large number of patients, and we felt we could enroll them well. And you can look at the clinical response easily with well-understood endpoints and even get biopsy samples, if you want because it’s in the skin. The tissue is easily accessible. So that was the rationale. I think in particular for psoriasis, that was really mostly the entire rationale. For atopic dermatitis, we were really, really excited by the initial data we had seen out of one of our competitor programs in atopic derm showing strong efficacy in an albeit small population in their Phase Ib, but durability beyond the end of treatment that was perhaps surprising a bit, but maybe even consistent with the mechanism of enhancing Treg function and perhaps tolerance.

So we wanted to chase that down because that could be an exciting area to differentiate in atopic derm. That’s sort of long durability post treatment that we know current agents in AD or every other week or might be getting to monthly soon. Now I’ll let Nancy. Can you restate your question on Vuda Boris because that was pretty long winded there, sorry?

Boris Peaker: Yeah. No, I was just asking in terms of safety. In lung cancer, how do you anticipate it to compare to, obviously, competitor bispecifics as well as just the KEYTRUDA plus chemo combo?

Nancy Valente: Yeah, that’s a bit hard to answer without any data in line of the combination. And that’s why we’re doing — that’s a part 1 and a part 2. So the part 1 allows us to look at two different doses of vudalimab in combination with the standard chemotherapy of pentrexina carbo. And then we’ll see what happens. Like what does that safety look like when you add a bispecific to that chemo versus just a monoclonal PD-1 antibody? And just to clarify, to prior question, it is four cycles of vuda, I’m sorry, we call Vuda vudalimab plus carbo and pemtrexate and then maintenance with vudalimab and pemtrexate. It’s not a limited dosing as mentioned by somebody else. So it’s full cycles.

Boris Peaker: Great. Thanks for taking my question.

Operator: Thank you. One moment for our next question please. Our next question comes from Greg Renza of RBC Capital Markets. Your line is open.

Anish Nikhanj: Yeah. Hi, guys. It’s Anish on for Greg. Congrats on the quarter. I just wanted to ask a couple on sort of your views on positioning of two of your pipeline assets here. So just kind of wanted to see with plamotamab with multiple CD20, CD3 bispecifics approved. How do you believe plamotamab’s combination will position among competitors. And then just on 564, just kind of building on a previous question, not necessarily in terms of differentiation with approved drugs right now. But in terms of lines of care, for example, would you guys see 564 being slotted in for patients with poorly controlled atopic derm or psoriasis that might be being treated with drugs like Sotyktu, Otezla, SKYRIZI, et cetera. Thanks so much for the questions. And congrats again.

Bassil Dahiyat: Yeah. With plamo positioning, we think the crux of this is the same logic that attracted Janssen as a partner for plamo and they are the ones leading the program now taking on the great majority of its cost, 80% of the cost. I think that the key there is the combination with our CD28 could provide that differentiation. And I will say that our competitors in combining with their CD28 bispecifics are really just at the very earliest stages and with plamo, I think, showed competitive efficacy safety profile, IV. We’re moving rapidly on the subcu. The positioning is really in combo to try to leapfrog with better efficacy, the just initially established monotherapy and probably soon to be established hemocombos with the other CD20 CD3s.

And so that’s why we were excited to get a partner like Janssen, which has outstanding capabilities and scale in heme malignancy to help drive this strategy because that’s a strategy that is tough to do alone as a small company. So I think hopefully, that addresses the positioning for Plamo. For 564, I just want to emphasize that we haven’t — we don’t have a final indication study. This is Phase 1b where we want to demonstrate durability of action of Treg enhancement and hopefully tie that to efficacy where it’s easily seen. Certainly, depending on what we see atopic derm could be a go forward. But we are obviously — we are considering other indications and would expect to announce if we propose to advance in any, and there’s a wide range of autoimmune indications where Treg is very likely play a role.

We would expect to announce those later as we’ve nailed down our regimen. So this is not a commitment in Phase 1 to an indication strategy. I will say that this idea of sequencing in AD is going to come up more and more, not just for Treg enhancers, but all of the therapies. And that’s certainly been a place where new additions have had a huge impact in other autoimmune indications, and that we do expect that to happen more and more in skin like it has, say, for example, in arthritis.

Anish Nikhanj: Great. Thanks so much. Really appreciate the color there.

Operator: Thank you very much. One moment for our last question. Our last question comes from Peter Lawson of Barclays. Your line is open.

Unidentified Analyst: This is Alex on for Peter. Thanks for taking our questions. Just one on the ENPP3 program, I was wondering if you could remind us some of the shortcomings of the Astellas ADC going after the same target and what might be the benefits of a bispecific approach. Thank you.

Bassil Dahiyat: Yeah. John, do you want to tackle that one?

John Desjarlais: Yeah. Sure. Yeah. In fact, it was — when we kind of discovered ENPP3 ourselves using a bioinformatic approach looking for selectively expressed tumor-associated antigens. And then we became aware of the Astellas programs once we dug in the literature. I have to say, they had half decent data. I mean they saw responses in Phase 1. Of course, because they had an orstatin payload, they had dose-limiting ocular toxicity. I think that was an interesting time because that was an Agensys program that Astella had acquired Agensys. And from what we know, from folks that have worked there, it was more of a strategic decision to discontinue that program. But we saw it as actually excellent validation for the selectivity of the target and the safety of going after the target.

Operator: Thank you very much. At this time, I would now like to turn the conference back over to Bassil Dahiyat for closing remarks.

Bassil Dahiyat: Okay. Thanks very much, everybody, for joining us this afternoon. Have a great evening, and we look forward to updating you again in the near future.

Operator: This concludes today’s conference call. Thank you for participating. You may now disconnect.