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spk11: The conference will begin shortly. To raise your hand during Q&A, you can dial star 1-1.
spk10: Good afternoon. Thank you for standing by.
spk11: And welcome to ZenCorp's second quarter 2022 conference call. At this time, all participants are in the 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 your speaker today, Charles Lyles, Head of Corporate Communications and Investor Relations.
spk16: Thank you, and good afternoon. Earlier today, we issued a press release which outlines the topics we plan to discuss today. Press release is available at www.zencore.com. With me on the call are Basil Dahia, President and Chief Executive Officer, Alan Yang, Chief Medical Officer, John Cush, Chief Financial Officer, and John Desjardins, Chief Scientific Officer. We will 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, Zencore Management may make forward-looking statements, 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 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 describing 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 and quarterly report on Form 10Q.
spk17: Thanks, Charles. We've used our array of modular protein 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, and 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 Altamiris. 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 to its parental antibody. Ultramuris recently received a positive opinion from CHMP in Europe for generalized myasthenia gravis. AstraZeneca has guided to GMG regulatory decisions in the EU and Japan as well as regulatory submissions for neuromyelitis optica spectrum disorder in the US, 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, Keras Life Sciences, announced a target discovery collaboration and license agreement to create XMAP bispecific or multispecific antibodies directed against up to three novel targets discovered with Keras' unique human tissue bank and bioinformatics approach for finding addressable tumor markers. Our goal is to use our protein engineering tool 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 X-Mavich Plus One CD3 bispecific and our first CD28 bispecific G-cell engagers, are now advancing to first in human studies. I'll now turn the call over to Alan Yang, our chief medical officer, to update on our clinical portfolio and cover upcoming plans.
spk04: Thanks, Basil. 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, XMAP564, our wholly-owned IL-2FC 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 by CD3 bispecific antibody, Pomodimab, we will present data from the expansion cohorts in the ongoing phase one 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 two study of the triple combination with Monjuvia and Revlimid is ongoing. For our PD-1 CTLA-4 bispecific, Budalimab, we'll also present some early data from the first of our two phase two studies, the chemotherapy combination in patients with metastatic castrate-resistant prostate cancer, and our second phase two 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 a 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 1 study in combination with ipilimumab in parallel cords of several different advanced solid tumors. Now on to our clinical trial starts. First, we recently initiated and dosed the first patient in a phase 1 study of XMAB819, our ENPP3 by CD3 bispecific antibody in patients with advanced renal cell carcinoma. XMAB819 uses our XMAB2 plus 1, multivalent format for enhanced tumor target selectivity. Preclinically, antibodies built with our 2 plus 1 format, including 819, have shown preferential killing of tumors with high target antigen expression relative to normal cells, which is a particularly exciting tool for developing drug candidates targeted to solid tumors. XMAB 819 is our first 2 plus 1 bispecific to enter the clinic. However, Amgen's similarly engineered SCEP1 targeting bispecific is already advancing through phase one and has shown encouraging early PSA response data. We look forward to following its progress as well. Next, we now have an open IND and are now initiating a phase one study of XMAV808, our B7H3 by CD28 bispecific antibody. Our first CD28 targeting molecule, in combination with pembrolizumab. CD28s are a new class of bispecific engineered to provide conditional co-stimulation of T cells through the CD28 receptor when the molecule is bound to tumor cells, with the goal of enhancing activity of CD3 bispecifics and checkpoint inhibitors. We'll have more to say about this study in the coming months. Now, with that said, I'll hand the call over to John Cush, our CFO, to review our financial highlights.
spk14: Thank you, Alan. Total revenue for the second quarter in the first six months of 2022 was $31 million and $115.6 million, respectively. Revenue for the second quarter in the first half of 2022 was primarily royalty revenue from Lavera and Alexion Partnerships, limited sales of Citroën Mab and Altamiris, 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 and $575 million in cash, cash equivalents, receivables, and marco desk 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?
spk11: Thank you. To ask a question, you will need to press star 11 on your telephone. Please stand by while we compile the Q&A roster.
spk10: Our first question comes from Mara Goldstein with Mizuho.
spk11: Your line is now open.
spk01: Oh, great. Thanks for taking the question. Two things for me, or three rather. The first is on XMAB 818. Can you maybe just talk a little bit about the target there, the B7H3 target, just given what we've seen in the competitive landscape on the AE profile perspective? And on VidelaMap, 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 Paris arrangement, you do have some financial obligations, milestones, and whatnot. When should we anticipate that something would be required to be paid from that program?
spk17: Thanks. I guess I'll start maybe with the Karis one. There was an upfront payment that, you know, the roughly small percentage of the total disclosed basket of 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 them through antibody discovery efforts and lead creation.
spk09: So it's going to be subsequent to that. I think...
spk17: I think it'll be a little while, I think, before we start hitting those obligations. Okay, great. And then maybe, John, do you want to touch on, I guess you're referring for 808 to both CD28 and B7H3, both targets, Mara?
spk01: Yeah, yeah. Most specifically B7H3 target, just what, you know, we've seen over the last few months with competitor setbacks.
spk05: Yeah, thanks. So, you know, first of all, we like B7H3 as a target. You know, 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 were seen disclosed by macrogenics in the head and neck cancer patients. You know, we don't know how to interpret that. I You know, either the or the program. Alan, you want to add anything to that?
spk04: Yeah, I mean, we don't have any details around where the bleeding events were or whether they were related to the product. I mean, they seem to say that cancer has a lot of bleeding events, and in their phase one, they didn't have that many bleeding events. So, we're not concerned about it at this time.
spk01: All right, great. And then, just on the Vidalimab and the different cohorts, what you anticipate you might share?
spk17: 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 Vudalamab, except for the small portion received based on their genotyping a PARP inhibitor or where there's no chemo and it's just a monitor. 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 blockade, PD-1 and TKLA-4, 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 combos into dual checkpoint blockade? So it 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.
spk01: Okay, thanks. I appreciate it. I'll pop back up.
spk17: Thank you.
spk11: Thank you. Our next question comes from David Dye with SMBC. Your line is now open.
spk06: Hi, sorry. David? Yeah, sorry. Can you hear me okay? Yes. Great. Thanks for taking my questions. I have a couple of questions. So the first question is around the IL-15, IL-15 RA FSD program, your 306 program. We saw that FDA has accepted a DLA from a competitive program in bladder cancer. How should we think about potential review through to your 306 program? Could you maybe share with us some of your differentiation of your IL-15 asset compared to theirs? And I have a follow-up after.
spk17: Sure. I guess I'll address that question. So what we understand, the BLA in question is for a 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 fundamental difference in design of the molecules. Ours was engineered, XMAP306, 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 spikes 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 one dose escalation in combo with atezolizumab, a PD-L1 inhibitor. But now Genentech has started the combo with daratumumab and 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.
spk06: That's really helpful. So, the 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 autoimmune indications you're planning to move the program into?
spk17: You know, there's a lot of potential indications for a Treg amplifier. Not a lot of deep clinical data, though, from anybody, really, about what indications a Treg therapy is going to be able to treat. Just glimmers 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 and atopic dermatitis. We're certainly exploring germ indications and looking 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 year from the single ascending dose in healthies. We'll also guide on the specific indications shortly.
spk06: All right, that's really helpful. Thank you so much for the color.
spk11: Thank you. The next question comes from Kavari Pullman with BTIG. Your line is open.
spk08: Yeah, good afternoon. Thanks for the updates and for taking my question. Maybe just one for me. In terms of format for CD3 T cell engagers, you recently discontinued development of to-do-the-maps Does that mean 2 plus 1 formats are the way to go for solid tumors? And how would you compare it to 2 plus 2 formats in the clinic?
spk17: 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 to normal, healthy normal tissue with low expression and high expression on tumor, 2 plus 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 clean or simple situation. You know, we're still learning a lot from it. I think we think there's a lot of promise in 2 plus 1s, 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 plus 2 formats, John, I'm not familiar with too many. There have been a few historically tried. I don't know of that much clinical data I've seen from those.
spk05: Yeah, and most people avoid having two binders to CD3 because you're worried about non-selective T cell activation.
spk17: It's definitely not a direction that we're pursuing internally as NCORP.
spk08: Got it. Thank you.
spk11: Thank you. Our next question comes from Charles Zhu with Guggenheim Partners. Your line is now open.
spk15: Hello, can you hear me?
spk12: Yes.
spk15: Okay, great. Yeah, thanks, guys, for taking the questions, and congrats on the progress. My first one on XMABA819, 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 CE3 T cell engager dose escalation has been conducted previously. Thanks.
spk17: 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've maybe dug into this more than any of us about projects.
spk05: Yeah, I mean, I think the Project Optimist just puts a little bit more pressure on having enough biomarkers in your study, you know, that you can really defend that you pick the optimal dose. But, of course, we're still going to, you know, go by old-fashioned standards as well. So what's the maximum tolerated dose, you know? how much CRS is happening at different dose levels.
spk17: 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 you can use step-up doses to mitigate CRS. Like I think we've been pretty successful out with Pomodimab and certainly numerous other programs that our competitors or collaborators have done.
spk04: Yeah, Basil, maybe I can add something here. So, you know, in my experience, what I've observed, and it's still early days on this Project Optimist, is that usually for CD3s, the agency is requiring you to explore two different doses in terms of your efficacy or expansion. You know, I don't know if they'll keep that going, but it seems to be like the MTE and maybe a dose lower that seems to be efficacious with maybe lower toxicity. I'd just say for 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 it'll give us a lot of flexibility in terms of understanding our dose when we go into that expansion step.
spk15: Got it. Great. That's really helpful. Thanks for all that, Colin. Maybe just one follow-up question regarding Vudalamad. I guess with respect to your upcoming data readout, how much will we be able to glean from that data set? And, you know, given the wide spread of different patient populations characterized by molecular subtype you're enrolling, you know, will we be able to kind of determine, or I guess I should say, would you be able to determine, you know, particularly interesting subsets of patients, either from a clinical or strategic perspective for longer-term development? Thanks.
spk17: At this data readout, it's going to be too early with too few patients to make any kind of conclusions about the different subtypes. 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, rather outside of the therapy we're giving them. Again, the bulk of them chemo plus budalumab. You can think of those as a group. And then as we accrue greater numbers, we'll see if any patterns emerge. 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 matchup for this initial regimen we've come up with, which is simultaneous maximal chemo and budelma?
spk15: Great. That makes sense. Thanks for taking all my questions, and I look forward to your upcoming readouts.
spk06: Thank you.
spk11: Thank you. Our next question comes from Edward Kentoff with Piper Sandler. Your line is open.
spk13: Great. Thank you very much, and thanks for taking my question. It's going to be an exciting back. I wanted to get a sense just with respect to the kind of work that you're doing, and obviously this has become a big focus for the company, the partnership with work for IL-15 and then the work with IL-2. Maybe you can tell us sort of at a high level, how you think xMabs really differentiate in this space? Because there's a lot of competitors who are looking at masking and other technologies. So just want to understand sort of how you see that differentiating and ultimately what you expect to do with maybe some of the other known cytokines.
spk17: Yeah, I mean, I'll start. Maybe, you know, John, you can jump in. But the insight that our team had, that John's team had, was that that cytokines' toxicity and overly fast clearance, relative to what you want a 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 how we use that for making the drugs in the future of the platform, there's a lot of ways to go, but I think that's the key insight in differentiations.
spk05: Yeah, I mean, that's the unifying theme, and what excites me about it is these long-acting lower-pository cytokines are so much better tolerated in our experience so far that it gives us tremendous combination potential as well. You know, you could think about combining these with our CD3 engagers, combining them with checkpoint inhibitors, combining with NK engagers. There's just a ton of potential there.
spk17: And I think there's a simplicity there where, again, The challenge of really complex protein engineering efforts like you see with masking approaches, conditional activation approaches, is there's a lot of biochemical pieces within the drug molecule 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 this simple sort of universal approach we think is really attractive. And, you know, we've already applied it to two cytokines that are in the clinic. Our third one is coming on behind now, IL-12. 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 cytokines as real drug development widgets and no longer these esoteric molecules.
spk13: Cool. Appreciate that. Helpful.
spk11: Thank you. Our next question comes from the line of Gregory Runza with RBC. Your line is now open.
spk07: Hi, this is for Greg. Thanks for taking our questions. Maybe two from us first on 808. Just curious on your thoughts on the data from a city 28 by specific in a state today and how that relates to the clinical potential safety considerations of 808, you know, as well as their combination strategy with Pembroke. And then secondly, maybe just on five, six, four, you know, for the initial data in healthy volunteers, what are the level of change in Tregs and T factors you expect to see to give you confidence in its clinical potential? Thanks.
spk17: You know, I'll let John take 808 since our CD28 platform is really something that grew out of the work that he led in 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 and a little bit of multiple dose study. You see sort of a little bit north of five-fold increase in Tregs. You see it often decaying after a couple of weeks. And, you know, reasonable tolerability of the programs, you know, vary a bit in that. I think the bar we've 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 Tregs, it's got to be selective, no T-effectors, and good tolerability. And we're hoping that our design gives us a longer half-life.
spk05: Yeah, and on the PSMA CD28 data that was disclosed today, I mean, it's obviously early days, right, small number of patients, but we're actually pretty excited to see what they're saying about it. I mean, it puts some wind in our sails on 808. You know, a lot of potential in that class, and it's kind of the first clinical validation that you could really move the needle there.
spk17: Yeah, we view that as 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, our XMA-808, and it's going to be in the clinic in the coming months. So it's a great first start.
spk07: Great. Thank you very much. Thank you.
spk11: Thank you. Our next question comes from Etzer Derout with BMO. Your line is now open.
spk12: Great. Thanks for taking the question. Just one quick one for me. You know, for Videlumab 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, you know, way to think about this is sort of, you know, chemo like Gevtona post-doxetaxel in patients with metastatic cancer-resistant prostate cancer. Is that the right way to think about this upcoming data set from an advocacy standpoint?
spk17: You know, I know you're asking about the chemo comparator, the right one. There's something that got garbled in the phone. Can you repeat what you stated was the right reference frame?
spk12: Oh, Jeftana. Jeftana post-oxytocin.
spk17: Oh, oh, oh, oh. Jeftana, they, um...
spk04: Do you want to go, Alan? Yeah. So I think you're asking, like, what to expect and how to benchmark the data that we'll be presenting. So I think comparison with a PD-1 in combination with dosetaxel is a fair comparator but not actually accurate 100%. Remember, from our Phase I data, we found very good tolerability of our PD-1 CTLA-4. And, you know, we thought we could combine it with a very aggressive chemo regimen, the best chemo regimen for prostate cancer, which is a platinum plus cabotaxel. You know, 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-atizo combo as well. You know, 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.
spk12: Yeah. Thank you. That's very helpful. Thank you. Sure.
spk11: Thank you. Our next question comes from Jonathan Chang with SVB Securities. Your line is now open. Thank you.
spk03: Hi, this is Matt Cowper 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 in MRCP, which missed on OS and radiographic PFS, do you have any updated thoughts on use of PD-1 targeting agents in this setting?
spk17: I think it's clear that the limited activity that PD-1 agents have had in MCRPC has been now 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 benefits activity you see with the CD28 by specific that we saw disclosed earlier today, and on top of a PD-1 agent showing, you know, a number of responses out of a very small patient cohort. So, again, very early data, I think quite encouraging from a process standpoint. And note that we have not just our B783 CD28 coming to the clinic soon, and B783 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, will be the first to the clinic with our platform, but 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 promise, but with still a high unmet need.
spk04: Yeah, I would just add, that was correct. I think prostate cancer is, the landscape is shifting very quickly with the CD28 data. You know, specifically to the Keynote 921 data, I don't think it impacts us. Maybe it gives us a little bit more breathing room. Remember, both Merck and BMS decided to move forward with their PD1s 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 NEVO-IPI seemed to be higher, and that's why we were excited about using our PD-1-CTLA-4, Vudalamab. Now, we were later to the game to them, and they've already started their phase 3s with docetaxel, and so, therefore, we tried to sort of do something that would be going to where the puck is, or where the puck will be and not where the puck is, and so we tried to do a little bit more aggressive in terms of our chemo regimen. So I think the fact that the dose of Paxil didn't work for them gives us some more opportunity, if that option is there. But I think Basil hit the nail on the head. There's a lot of things changing in prostate cancer right now.
spk03: Yeah, thanks for the color and insight there. That's really helpful. And then just another quick one from me, if I may. Just how does the new partnership with Keras aid your target discovery beyond your own in-house capabilities, and do you have any specific targets in mind for the partnership?
spk05: Yeah, 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 CARES brought to the table, and it's something that we'd rather spend our resources, you know, making best-in-class modalities to address these kinds of targets. But, you know, we have other ways of trying to access other targets, and I'll also remind you we have our TRICA collaboration, which, again, gives us access to, you know, novel classes of targets.
spk04: Yeah, and I would just add, being a former clinician, I'm familiar with CARES from my clinical days. Remember, they have mountains and decades' worth of tumor samples that they've collected from patients. I think that's a huge differentiator. We're good at making antibodies, but we do not have the sample database or the tumor databases that they have.
spk03: Great. Thanks for taking my questions.
spk11: Thank you. Our next question comes from David Nearing Garden with Wedbush. Your line is now open.
spk00: Hey, thanks for taking the question. Most might have been asked, but maybe a follow-up on my B7H3 toxicity question. Macrogenics also in that study combined it with various IO agents. And I was just wondering if that was a concern or potential cause of the added toxicity. I don't know, bringing in immune cells to vasculature that's targeted by B7H3 or something like that. But I was just wondering if you had any insights or preclinical assays or anything that would show caution on different IO agents plus B7H3 targeted agents.
spk17: I can't say we've had anything. We gave our B7H3 CD28, which of course is an immune target, CD28, at very high doses in our non-human primate tox studies with no effect, no ill effect. So we don't have any more answers on that data than was offered earlier. I do know that that is an antibody, a B7H3 antibody that is a immune FC gamma receptor component antibody. And so it would be expected to have some direct cytotoxicity on B7H3-bearing cells. Could that be playing a role? Possibly.
spk05: Yeah, I mean, every modality is different, you know, so it's really hard to predict. The other thing I'll add is that our 808 molecule is a 2 plus 1 that was specifically designed to be more selective for binding to tumor cells, which generally have a lot brighter B70C expression. So there could be other points of differentiation that will help us on the safety side.
spk06: Okay. Great.
spk05: Thanks.
spk11: Thank you. Our next question comes from Bill Morgan, Skin Accord Genuity. Your line's now open.
spk02: Hi. Thanks for taking the question. So looking forward to this Vudalamab readout, are there 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 Vudalamab's mechanism of action being most appropriate for these patients, or commercial, you know, unmet. Are there any specific cohorts that you think are more or less key to the success of the program, whether that's due to, you know, read-through for Vidalimab's mechanism of action being the most appropriate for these patients or commercial, you know, unmet need for a specific cohort?
spk17: We think that, again, it's not really going to be that different in terms of the potential or the insights and the readout from the different cohorts of chemo-receiving patients. Certainly the PARP inhibitor-receiving patients, those that have, you know, DNA damage repair deficiencies are sort of a separate category. So, no, it really is, again, all those cohorts together, the great majority of patients getting chemo, you know, platinum, cabazita, calcombo, are going to help us read out sort of an 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 a stage.
spk02: Okay. And then on the 104 data from ASCO, beyond just the efficacy and safety on the poster, Were you able to glean 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?
spk17: Not really. Not really. It was a very cleanly well-tolerated molecule, and we saw activity in different tumor types and some, you know, long, sustained activity. you know, stable disease for multiple years even, but no biomarkers that really popped up that correlated clearly with much of anything. We are trying a biomarker-driven hypothesis in our expansion cohorts, combining it with ipilimumab, which is known historically to upregulate ICOs.
spk02: Okay, and last one. Sorry if I missed this. I dropped briefly. But can you give detail on what drove the increase in guidance for your cash balance at the end of the year?
spk17: John, do you want to hop on and take that?
spk14: Yeah, sure. We did update the guidance. As you pointed out, it actually increased. We expect to have between 550 and 575 million as of 12-31, based on current plans, with runway through the end of 2025. OK.
spk02: And is there anything explicitly that drove that update?
spk14: 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.
spk02: Okay. Thank you.
spk11: Thank you. And I'm currently showing no further questions at this time. I'd like to turn the call back over to Bazil Dahiat for closing remarks. soon and have a wonderful evening everybody for joining us today 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 the conference will begin shortly to raise your hand during q a you can dial star one one
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