Good afternoon. Thank you for standing by and welcome to the Xencor’s Second Quarter 2022 Conference Call. At this time, all participants are in a listen-only mode. After the speakers' 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 your speaker today, Charles Liles, Head of Corporate Communications and Investor Relations.

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. We'll 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, 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 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.

Thanks, Charles. We've used our array of modular approach and engineering tools to create a broad internal development portfolio in oncology and autoimmune disease, which allows us to take multiple simultaneous shots on goal in the clinic. Our intent remains using proof-of-concept data from our early-stage studies to guide which programs we advance, which we terminate in which we partner. So, we use our resources on those programs with the greatest potential for success and make room in our portfolio for the next wave of XmAb bispecifics and engineered cytokines. The plug-and-play nature of our XmAb technologies and our ability to generate biologic drug candidates rapidly and efficiently provides us with many opportunities to generate revenue from strategic licensing and collaboration agreements, which has allowed us to avoid accessing public markets for capital for over four years. Supporting our development work are three royalty-producing marketed products, including ULTOMIRIS, which incorporates our Xtend Fc domain to enhance antibody half-life and allow for longer duration of action, less frequent dosing and reduced patient burden of therapy compared with parental antibody. ULTOMIRIS recently received a positive opinion from CHMP in Europe for generalized myasthenia gravis. AstraZeneca has guided the GMP regulatory decisions in the EU and Japan as well as regulatory submissions for neuromyelitis optica spectrum disorder in the U.S., EU, and Japan, all this year. Now we're looking externally for tools and assets that can expand our technology for creating new drug molecules and complement our pipeline candidates. Yesterday, we and our new partner, Caris Life Sciences announced a target discovery collaboration and license agreement to create XmAb bispecific or multi-specific antibodies directed against up to three novel targets discovered with Caris' human tissue bank and bioinformatic approach for finding addressable tumor markers. Our goal is to use our protein engineering tools to create molecules that tackle hard to address biologies and that we can potentially advance to approval and to market if the data and environment support it. And our two newest programs, our first XmAb 2+1 CD3 bispecific and our first CD28 bispecific T-cell engagers are now advancing the first in human studies. I'll now turn the call over to Allen Yang, our Chief Medical Officer, to update on our clinical portfolio and cover upcoming plan.

Thanks Bassil. Last quarter, we went through our whole clinical portfolio, but today, we will briefly review upcoming plans for our data presentations, our clinical data presentation at ASCO, and some recent and near-term study starts. We plan to present data from three studies through the end of the year. First, we expect to present data from the single ascending dose of healthy volunteer study, XmAb-564, our wholly-owned IL-2-Fc-cytokine fusion, which targets regulatory T cells that we are developing in patients with autoimmune disease. We also plan to initiate in the coming months a multiple ascending dose study in patients. Next, for the CD20 x CD3 bispecific antibody, plamotamab, we will present data from the expansion cohorts in the ongoing Phase I IV monotherapy study in patients with advanced non-Hodgkin's lymphoma. Our plans to introduce subcutaneous dosing into this study are underway. And additionally, our Phase II study of the triple combination with Monjuvi and Revlimid is ongoing. For our PD-1 CTLA-4 bispecific, vudalimab, will also present some early data from the first of our two Phase II studies, the chemotherapy combination in patients with metastatic castrate-resistant prostate cancer and our second Phase II study in patients with clinically defined high-risk metastatic castrate-resistant prostate cancer and certain gynecological malignancies is now dosing patients. This June at ASCO, we reported initial data from the monotherapy escalation portion of the Phase I study of our PD-1 ICOS bispecific antibody, XmAb104, in patients with advanced solid tumors. XmAb104 was well-tolerated and exhibited the distinct safety profile compared to other clinical-stage ICOS programs. We observed antitumor activity and biomarker activity consistent with T cell engagement. We are currently enrolling the expansion portion of our Phase I study in combination with ipilimumab in parallel cords of several different advanced solid tumors. Now, on to our…

Thank you, Allen. Total revenue for the second quarter and the first six months of 2022 was $31 million and $115.6 million, respectively. Revenue for the second quarter and the first half of 2022 was primarily royalty revenue from Vir and Alexion partnerships, related sales of sotrovimab and ULTOMIRIS, respectively. Revenue from these royalty streams and income from other partnerships and collaborations help offset our spending on operations and clinical programs. For the first six months of 2022, the total revenue that we received fully funded our operations and further strengthened our balance sheet. Total cash equivalents, receivables, and marketable debt securities at June 30th totaled $679.7 million, which is approximately $50 million more than the $664.1 million balance reported at the beginning of the year. We are updating our year-end guidance and now estimate they will end 2022 with between $550 million and $575 million in cash, cash equivalents, receivables and micro debt securities, and we continue to guide that we will have sufficient cash to fund our R&D programs and operations through the end of 2025. I refer you to our press release this afternoon and to our SEC filings for further details about our financial results. With that, we'd now like to open up the call for questions. Operator?

Thank you. [Operator Instructions] Our first question comes from Mara Goldstein with Mizuho. Your line is open.

Great. Thanks for taking the question. Two things or three rather. The first is on XmAb808. Can you maybe just talk a little bit about the target there, the B7-H3 target, just given what we've seen in the -- on the competitive landscape on the AE profile perspective. And on vudalimab, can you maybe give a little bit of color on which of the groups you do anticipate having data on and how many patients we should start thinking about for the data disclosure there? And just lastly, on the Caris arrangement, you do have some financial [technical difficulty] obligations, milestones and what not. When should we anticipate that something would be required to be paid from that program?

Thanks. I guess I'll start maybe with the Caris one. There was an upfront payment that is roughly a small percentage of the total disclosed vascular payments. But I think the subsequent ones are going to be driven a little bit later into the collaboration. We're at the start taking these initial information on these targets and starting to validate and through [indiscernible] and lead variations of subs that I think it will be a little while, I think, before we start hitting those obligations. And then maybe, John, do you want to touch on -- I guess you're referring for 808 to both CD28 and B7-H3, both targets, Mara?

Yes, yes more specifically B7-H3 target, just what we've seen over the last few months with competitor set back.

Yes, yes. So first of all, we like B7-H3 as a target. We selected it because it's very bright and very broadly expressed across a lot of different solid tumor histologies. I assume you're referring to some of the AEs that we're seeing disclosed by MacroGenics and the head and neck cancer patients. We don't know how to interpret that. I mean the drug conjugates haven't seen those same kinds of events, either the [indiscernible] or the MacroGenics program. Allen, do you want to add anything to that?

Yes, I mean we don't have any details around where the bleeding events whether the related to the product. I mean they seem to say that head and neck cancer has a lot of bleeding events and in their Phase I, they didn't have that many bleeding events. So, we're not concerned about it at this time.

Right. Great and then just on vudalimab and the different cohorts, what you anticipate you might share?

Right so it's going to be data from the patients that came in, right? So it's all the cohorts recruited at the same time. And note that the great majority of patients are receiving the same therapy, a combination of a platinum plus cabazitaxel with vudalumab, except for the small portion that received based on their genotyping of PARP inhibitor or where there's no chemo and existence. So, the great bulk are going to be the chemo combo. And the real point of this data is that initial look at can we combine a dual checkpoint load, PD-1 with potent chemo. How do we look? What kind of results are we seeing and what's the path forward for trying to get chemo-combo into dual checkout, so there will be a few handfuls of patients, and that's the disclosure we plan. It will be spread across the cohorts. But again, almost all patients are getting the chemo-combo.

Okay. Thanks. I appreciate it. I'll hop back on.

Thank you.

Thank you. Our next question comes from David Dai with SMBC. Your line is now open.

Yes, sorry, can you hear me okay?

Yes.

Great. Thanks for taking my questions. I have a couple of questions. So, first question is around the IL-15, R-15, RaFc program just few of these program. We saw that FDA has accepted a BLA from a competitive program in bladder cancer. How should we think about potential views through to your 306 program. Could you maybe share with us some of your differentiation of your IL-15 assets compared to theirs? And then I have a follow-up after?

Sure I guess I'll address that question. So what we understand, the BLA in question is for super agonist IL-15 receptor alpha fusion in non-muscle invasive bladder cancer. So, that is not a systemic therapy it's a therapy given in combination with BCG through cystoscopy, right, into the bladder. So it's not a systemic therapy. And I think that maybe relates to the different -- fundamental difference in design of the molecules. Ours was engineered XmAb306, our IL-15 as well as our whole family of cytokine therapies was engineered with dramatically reduced affinity to the signaling receptors and reduced potency to smooth out that activity time curve. So you don't have the big spikes of activity early on that can drive toxicity, and you don't have the big think of receptor-mediated clearance, lowering the duration of action. So, that's a fundamental difference to a super agonist design, which is trying to amplify things. But I think we're committed to the systemic route and to being able to be used broadly and widely across many different tumor types, we're not just enrolling in solid tumors with Genentech in the Phase I dose escalation in combo with atezolizumab, a PD-L1 inhibitor. But now we Genentech started the combo with daratumumab in myeloma. We're going to be starting a study of our own. We'll disclose the details of that and the indication in the coming months. And we know Genentech is working on further studies. So, I think systemic versus a local delivery is a pretty fundamental difference. So, I'm not sure how much read through there is IL-15 to IL-15.

Got it. That's really helpful. So, second question is for the IL-2 Fc program 564 program. We know that it's currently a healthy volunteer trial. But any updated thoughts on which other immune indications you're planning to move the program into?

There's a lot of potential indications for a T-reg amplifier. Not a lot of deep clinical data, though, from anybody really about what indications T-reg therapy is going to be able to treat just calibers of information. There was recent information released by a competitor program that seemed to show from a very small cohort of patients, promising data, randomized against placebo in atopic dermatitis. We're certainly exploring derm indications and looking it across the spectrum as information starts to come out from competitors at what to add to the mix, we've done a lot of work. We are going to be disclosing the initial indications we're doing in our multiple ascending dose study in patients that we do expect to start within the next few months so shortly. And so we'll be able to guide a lot more when we have our first data readout this half of the year from the single-ascending dose in healthies, will also guide on the specific indications shortly.

Got it. That’s very helpful. Thanks so much for the color.

Thank you. Our next question comes from Kaveri Pohlman with BTIG. Your line is open.

Yes, good afternoon. Thanks for the update and for taking my question. Maybe just one from me. In terms of format for CD3 T cell engagers, you recently discontinued development of daratumumab. Does that mean 2+1 format are the way to go for solid tumors? And how would you compare it to 2+2 formats in the clinic?

So, I think it's going to be tumor antigen by tumor antigen. I think when you've got one where you want to separate binding from healthy normal -- healthy normal tissue with low expression and high expression on tumor. 2+1 is almost certainly going to be the way to go. Again, you need to do the experiments and look at the details. I think there's going to be cases where that won't be such a cleaner simple situation. We're still learning a lot from it. I think we think there's a lot of promise in 2+1 and so we're certainly pursuing them because in many cases, you do have that high, low expression on tumor versus healthy. As for 2+2 formats, John, I'm not familiar with too many. There have been a few historically tried. I don't know that much clinical data I've seen from those.

Yes and most people avoid having two binders to CD3 because you're worried about now selected T cell activation.

It's definitely not a direction that we're pursuing internally then we were.

Got it. Thank you.

Thank you. Our next question comes from Charles Zhu with Guggenheim Partners. Your line is now open.

Hello, can you hear me?

Yes.

Okay, great. Yes, thanks guys for taking the questions and congrats on the progress. My first one on XmAb819, given that it's a CD3 T cell engager as well as the ongoing buzz around FDA project Optimus. How should we think about progression of dose escalation and exploration, particularly when you compare how you might progress with 819 relative to how historical CD3 T cell engager dose escalation has been conducted previously? Thanks.

Well, I think it's way more informed by the data and the science now that there's data and science to go from. I mean, John, you may be dug into this more than any of us about projects.

Yes, I mean I think the project Optimus, it just puts a little bit more pressure on having enough biomarkers in your study that you can really defend that you pick the optimal dose. But of course, we're still going to provide all fashion standards as well. So what's the maximum tolerated dose, how much CRS is happening at different dose levels.

So, I think the biggest learning is the knowledge about priming doses and step-up doses, the magnitude of priming dose you need and what biomarkers you look at to set that dose. And I think relative to what we thought maybe five years ago, priming doses are lower than you might have thought. And they can be quite a lot lower than your ultimate dose and you can still get there fast. So, I think we all expect to be able to move faster because there's a lot more confidence in these serum biomarkers like IL-6 levels and how can you use step up dose to mitigate CRS. Like I think we've been pretty successful with palmotumab and certainly numerous other programs that our competitors or collaborators have done.

Yes Bassil, maybe I can add something here. So in my experience, what I've observed, and it's still early days on this project Optimus is that usually for CD3, the agency is requiring you to explore two different doses in terms of your efficacy or expansion. I don't know if they'll keep that going, but it seems to be like the MTD and maybe a dose slower and that seems to be efficacious with maybe lower toxicity. I'd just say through the 819 study, we have a lot of learnings from our previous studies. So there's a lot of flexibility. The biomarkers are pretty novel. The design is pretty novel. So, give us a lot of flexibility in terms of understanding our dose when we go into that expansion step.

Got it great, that's really helpful. Thanks for all that color. And maybe just one follow-up question regarding vudalamab I guess with respect to your upcoming data readout; how much will we be able to gain from that data set and given the wide spread of different patient populations characterized by molecular subtype you're enrolling. Will we be able to kind of determine or I guess, I should say, would you be able to determine particularly interesting subsets of patients, either from a clinical or a strategic perspective for a longer term development? Thanks.

Yes, this data readout is going to be too early with too few patients to make any kind of conclusions about the different subtypes. But remember, these are all still metastatic CRPC patients, right? And they've all gone through essentially the same therapies prior. And so there's no need to consider them differently outside of their medical -- outside of the therapy, we're giving them, again, the bulk of them chemo plus vudalimab, you can think of those as a group. And then as we accrue greater numbers, we'll see if any patterns emerge, right? But this initial look will be, I think, too early to make any conclusions about that. And we'll just give us an early look at -- is there an efficacy tolerability match for this initial regimen we've come up with, which is simultaneous maximal, chemo and with vudalimab.

Great. That makes sense. Thanks for taking all my questions and look forward to your upcoming readouts.

Thank you.

Thank you. Our next question comes from Edward Tenthoff with Piper Sandler. Your line is open.

Great. Thank you very much and thanks for taking my question [indiscernible] I wanted to get a sense just with respect to the cytokine work that you're doing. And obviously, this will become a big focus for the company, the partnership with Vir and then the work with IL2.? Maybe you can tell us sort of at a high level how you think XmAb really differentiate in this space because there's a lot of competitors who are looking at masking and other technologies. So, I just want to understand sort of how you see that differentiating -- and ultimately, what you occur to do with maybe some of the other known cytokines?

Yes, I mean I'll start and maybe John, you can jump in, but the insight that our team had that John's team had was that cytokines toxicity and overly fast clearance relative to what you want to drug that is, is caused by their naturally very high potency and that you can dial that potency down and create a completely different pharmacodynamic and pharmacokinetic profile. And then how we use that for making the drugs and the future of the platform, there's a lot of ways to go. But I think that's the key insight and differentiation.

Yes, I mean that's the unifying theme. And what excites me about it is these long-acting lower post cytokines are so much better tolerated than our experience so far that it gives us tremendous combination potential as well. You could think about combining these with our CD3 engagers, finding with checkpoint inhibitors, combining with NK engagers, there's just a ton of potential there.

And I think there's a simplicity there where the challenge of really complex protein engineering efforts like you see with masking approaches, conditional activation approaches. There's a lot of biochemical pieces within the drug mode that have to work exactly right, and it's based on assumptions about the biology going on in the body that are just that assumption. I think a simple sort of universal approach we think is really attractive. And we've already applied it to two cytokines that are in the clinic or third one is coming on behind as well. We have an IL-18 program that's in preclinical. And we're also doing targeting of these with antibody domains fused. So, we think that this general low potency platform with its tolerability and half-life, lets you start thinking about cytokine as a real drug development with us and no longer these esoteric molecules.

Appreciate that. Helpful.

Thank you. Our next question comes from the line of Gregory Renza with RBC.

Hi, this is Xinyu Liu for Greg. Thanks for taking our questions. Maybe two from us. First on 808 just curious on your thoughts on the data from CD28 bispecific at least today and how that reads through to the clinical potential and safety considerations of 808 as well as the combination strategy with pembro? And then secondly, maybe just on 564 for the initial data in healthy volunteers, what are the level of change in Tregs and key factors, you could expect to see to give you confidence in its clinical potential? Thanks.

I'll let John take 808 since our CD28 platform is really something that grew out of the work - he led and his team. But let me answer on 564 really quick. I think we've seen what our competitors have delivered in their initial data disclosures from their single-setting dose studies in a little bit of multiple dose study, you see sort of a little bit north of fivefold increase in T-regs you see it up and decaying after a couple of weeks. And reasonable tolerability of the programs vary a bit in that. I think the bar we set for ourselves is to be at least as good as the best-in-class. So I think north of that kind of amplification of T-regs it's got to be selective, no T effectors and good counterability, and we're hoping that our design gives us a longer half-life.

Yes and on the PSMA x CD28 data that was disclosed today. I mean it's obviously early days, right, a small number of patients, but we're actually pretty excited to see what they're saying about it. I mean they put some wind in our sales in a week, a lot of potential in that class, and it's kind of the first clinical validation that you could really move the needle there.

Yes, we view that as a clear proof of concept that you can improve PD-1 therapy, checkpoint inhibitor therapy with CD28 co-stimulation that's been seen in humans. And I think that's a great step for the field, and we're excited to have an agent that's got an open IND and also have 808, and it's going to be in the clinic in the coming months. So, a great first start.

Great. Thank you very much.

Thank you. Our next question comes from Etzer Darout with BMO. Your line is now open.

Great. Thanks for taking the question. Just one quick one for me for vudalimab data that you'll be disclosing in the second half. Just trying to think about the right comparator for the combination with chemo. Is the right way to think about this is sort of chemo like Jevtana, post-docetaxel in patients with metastatic castrate-resistant prostate cancer? Is that the right way to think about this upcoming data set from an efficacy standpoint?

I know you're asking about the chemo comparator, the right one. Is there something that got garbled in the phone. Can you repeat what you stated was the right reference room?

Jevtana, post-docetaxel?

Jevtana you might go Allen.

Yes so I think you are asking like what to expect and how to benchmark the data that we'll be presenting. So I think comparison with PD-1 in combination with docetaxel is a fair comparator, but not actually accurate 100%. In the sense, that remember from our Phase I data, we found very good tolerability of our PD-1/CTLA-4.And we thought we could combine it with a very aggressive chemo regime, the best chemo regimen for prostate cancer, which is a platinum plus cabitaxel. Docetaxel, I think, is just a single agent chemo and a lot of people use that. In terms of benchmarking it to other therapies, I mean, you may want to compare it to the cabozantinib atezo combo as well. That response rate, I think, was 18% centrally reviewed. So, I wouldn't think about comparing it to those agents directly, but I think that gives you a ballpark of how to develop it in the future without giving out too much detail yes.

Thank you. That’s very helpful. Thank you.

Sure.

Thank you. Our next question comes from Jonathan Chang with SVB Securities. Your line is now open.

Hi, this is Matt [indiscernible] on for Jonathan Chang. Congratulations on the recent progress and thanks for taking my questions. Just a first question. In light of the KEYNOTE-921 data this morning, which is the pembro chemo and MRCP, which missed on OS and radiographic PFS. Do you have any updated thoughts on use of PD-1 targeting agents in this setting?

I think it's clear that the limited activity that PD-1 agents have had in MCRPC has been repeatedly confirmed. I think it shows you that they're not highly active, and I think that's why we feel convinced that our dual checkpoint inhibitor with PD-1 and CTLA-4 blockade simultaneously is a different hypothesis that really merits thorough testing. I think also it shows you the encouraging activity you see with the CD28 specific that we saw disclosed earlier today. And on top of the PD-1 agent, showing a number of responses out of a very small patient cohort so again, very early data I think quite encouraging from a focus standpoint. And note that we have not just our B7-H3 CD28 coming to the clinic soon and B7-H3 is highly expressed in prostate cancer. And so that's obviously a place we're considering looking. That's in combo with pembro -- our partner Janssen has a CD28 against a prostate restricted antigen that is going to be behind us in timeline. We'll be the first in the clinic with our platform that they're also excited about. So I think we're going to see a lot about how we can make checkpoint inhibitors work better, whether it's adding CTLA-4 blockade, adding CD28. I think there's a lot of permits, but with still a high unmet need.

Yes. I would just additional that's correct. I think prostate answer is the landscape is shifting very quickly. It was the CD28 data. Specifically to KEYNOTE-921 data, I don't think it impacts us maybe gives us a little bit more breathing room. Remember, both Merck and BMS decided to move forward with their PD-1 in combination with docetaxel to Phase III, and we have the first readout. The interesting issue is that for PD-1, clearly, KEYTRUDA had a low response rate and it appeared that the BMS data with nivo if seemed to be higher. And that's why we were excited about using our PD-1 CTLA-4 vudalimab. Now, we are later to the game to them and they've always started their Phase IIIs with docetaxel. And so therefore, we tried to sort of do something that would be going to where the puck is, not -- or where the puck will be, not where the puck is. And so we try to do a little bit more aggressive in terms of our chemo regimen. So, I think the fact that the docetaxel didn't work for them gives us similar opportunity if that option is there. But I think Bassil hit the nail on the head. There's a lot of things changing in prostate cancer right now.

Yes, thanks for the color and insights. That's really helpful. And then just another quick one from me if I may just how does the new partnership with Caris aide your target discovery beyond your own in-house capabilities? And do you have any specific targets in mind for the partnership?

Yes, I mean the simple answer is we don't have a lot of in-house capabilities. I mean that's a pretty specialized capability that Caris brought to the table, and it's something that we'd rather spend our resources, making best-in-class modalities to address these kinds of targets. But we have other ways of trying to access other targets. And I'll also remind you, we have our Atrica collaboration, which, again, gives us access to novel class of targets

Yes and I would just add, being a former clinician I'm familiar with Caris my clinical days. Remember, they have mountains and decades' worth of tumor samples that they've collected from patients. But I think that's a huge differentiation. We're good in making antibodies, but we do not have the sample database that the tumor databases that they have.

Great. Thanks for taking my questions.

Thank you. Our next question comes from David Nierengarten with Wedbush. Your line is now open.

Hey thanks for taking the question. Might have been asked, but maybe a follow-up on the B7-H3 toxicity question. Your MacroGenics also in that study combined it with various IO agents. And I was just wondering if there was a concern or potential cause of the added toxicity. I don't know, bringing in immune cells to vasculature that's targeted by B7-H3 or something on like that. But I was just wondering if you had any insights or assay preclinical assays or anything that would show a caution on different IO agents plus B7-H3 targeted agents?

I can't say we had anything. We gave our B7-H3 CD28, which, of course, is an immune target CD28 at very high doses in our nonhuman primate tox studies with no effect -- no ill-effect. So, we don't have any more answers on that data than what is offered earlier. I do know that, that is an antibody [indiscernible] that is an immune [indiscernible] antibody. And so it would be expected to have some direct cytotoxicity of BL3 bearing cells could that be favorable possibly.

Yes. I mean every modality is different. So it's really hard to predict. And the other thing I'll add is that our 808 molecule is a 2+1 that was specifically designed to be more selective for binding the tumor cells, which generally have a lot brighter B78C expression. So there could be other points of differentiation that will help us on the safety side.

Okay. Thanks.

Thank you. Our next question comes from Bill Maughan of Canaccord Genuity. Your line is now open.

Hi, thanks for taking the question. So looking forward to this vudalimab readout, is there -- are there any specific cohorts that you think are more or less key to the success of the program, whether that's due to free through for vudalimab mechanism of action being the most appropriate for these patients or commercial or any specific cohorts that you think are more or less key to the success of the program, whether that's due to read-through for vudalimab's mechanism of action being most appropriate for these patients or commercial unmet need for a specific cohort?

We think that again, it's not really going to be that different in terms of the potential or the insights on the readout from the different cohorts of chemo receiving patients, certainly, the PARP inhibitor receiving patients, those that have DNA damage repair deficiencies are sort of a separate category. So no, it really is, again, those -- all those cohorts together--

-- great majority of patients getting chemo, platinum cabazitaxel combo are going to help read outstanding and aggregate on safety and on activity. So initially from very small patients, right, it gives us this first direction.

So, I don't think there's going to be that much insight gleaned on a narrowing of the program at this early of the stage.

Okay. And then on the 104 data from ASCO, beyond just the efficacy and safety on the poster, were you able to green anything on biomarkers, whether it be expression levels or T cell proportions of different populations that might make a patient more or less likely to respond?

No, not really not really. It was a very cleanly well-tolerated molecule, and we saw activity in different tumor types and some long sustained stable disease for multiple years even, but no biomarkers that really popped up that correlated clearly as much of anything. We are trying a biomarker-driven hypothesis in our expansion cohorts combining with ipilimumab, which is known historically to upregulate IQOS.

Okay and last one, sorry if I missed this, I dropped briefly. But can you give detail on the -- on what drove the increase in guidance for your cash balance at the end of the year?

John, do you want to hop on and take that?

Yes, sure. We did update the guidance. As you pointed out, it actually increased. We expect to have between $550 million, $575 million as of 12/31 based on current plans with runway through the end of 2025.

Okay. And can you -- is there anything explicitly that drove that update?

Primarily, I think the royalty revenue from Vir, we didn't have a lot of clarity into the actual timing and the dollar amounts of that. So it's been a little bit higher than we expected.

Okay. Thank you.

Thank you. And I'm currently showing no further questions at this time. I'd like to turn the call back over to Bassil Dahiyat for closing remarks.

[technical difficulty] everybody for joining us today and we look forward to updating you again soon, and have a wonderful evening.

This concludes today's conference call. Thank you for participating. You may now disconnect.