Good day! My name is Ellie, and I will be your conference operator for today. At this time, I would like to welcome everyone to the Merus MD investor call. Please note that this call is being recorded. I'd now like to hand the call over to Kathleen Farren, Head of Investor Relations. Please go ahead. Good morning, and thank you for joining our call. This morning, we will be taking you through the interim clinical data of petosemtamab in combination with pembrolizumab or pembro. This will include the data in the abstract, published May 23rd on the American Society of Clinical Oncology, or ASCO, website, as well as a summary of the data included in the presentation, scheduled next Monday, June 3rd, at the Rapid Oral Head and Neck Session at ASCO. This presentation is available on the Investors and Media page of our website. On this call, we will be making certain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These may include statements about our future expectations and plans, and events and circumstances, including about finances, intellectual property, projections about Merus's clinical development for 2024 and beyond, and the timing for plans and for meeting clinical and regulatory anticipated milestones related to petosemtamab and our other Biclonics candidates. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Merus's filings with the United States Securities and Exchange Commission, including its Form 10-Q for the period ended March 31st, 2024, which we filed with the SEC on May 8th, 2024. Merus does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events, or unless otherwise required to do so by law. Leading us through the agenda will be Dr. Bill Lundberg, CEO, Shannon Campbell, Chief Commercial Officer, and Greg Perry, Chief Financial Officer. Good morning from Boston. This is an exciting time for Merus. Today's call will focus on the impressive updated interim data for petosemtamab in combination with pembro as first-line therapy for head and neck cancer. We will discuss both the data from the abstract and the data that will comprise the presentation at ASCO, as well as our go-forward plans. Let me begin by providing a few brief remarks about our company and foundational technology platform that led to the discovery of petosemtamab and our other clinical-stage assets. Merus is an oncology-focused company with four clinical assets of our own and multiple other clinical assets we have developed with our collaborators and licensees. We've been innovators in the field of multispecific antibodies for over a decade, with our proprietary Multiclonics technology platforms that allow us to make bispecific and trispecific antibodies. Like monoclonal antibodies, a single cell produces essentially a single multispecific antibody. This allows us to leverage the decades of experience making medicines from a well-established monoclonal antibody discovery and development paradigm, including high-throughput screens, manufacturability, large-scale production from single-producer cell lines, global availability of contract manufacturing of antibodies. As fully human IgG1, our molecules are designed to have predictable in vivo behavior, low immunogenicity, consistent half-life, and can have all the Fc domain engineering, like ADCC enhancement or stealth silencing for T-cell engagers, as well as compatibility for the generation of selective and potent antibody drug conjugates, or ADCs. This is a powerful technology platform, and while it doesn't guarantee success in the clinic, we believe it gives us a better chance of being successful, as shown in our pipeline. With our three most advanced programs already showing important clinical activity, Zeno, our most advanced asset, is our bispecific antibody in clinical development for NRG-1 fusion cancer. It has received breakthrough therapy designations for both NRG-1 fusion, non-small cell lung cancer, and pancreatic cancer. We have submitted the biologics license application, which the FDA has accepted under priority review. Our first BLA acceptance is a tremendous milestone for Merus, taking our discovery in the laboratory potentially all the way to approval and providing true validation of our Biclonics platform. Zeno has the potential to be the first and only approved medicine targeted specifically for patients with NRG-1 fusion cancer, and we are looking forward to the meaningful benefit it may provide to patients if approved. MCLA-129, our EGFR and c-MET bispecific antibody, was also discovered at Merus by utilizing an empirical biological screen of hundreds of molecules to identify the most potent candidate. We are planning to investigate MCLA-129 in combination with chemotherapy in previously treated EGFR mutant lung cancer and will present a poster at ASCO on interim clinical data on MCLA-129 in patients with c-MET exon 14 skipping lung cancer. We look forward to sharing these data. MCLA-145 is a T-cell engager that targets PD-L1 on the tumor cell and CD137 on activated T-cells. At ASCO 2024, we will present updated interim clinical data on MCLA-145 monotherapy and in combination with pembro in patients with solid tumors, in a rapid oral presentation. Moving to our lead asset, petosemtamab, or MCLA-158. This is our bispecific antibody that targets the well-established cancer antigen EGFR, as well as LGR5, the cancer stem cell antigen in the Wnt pathway, which has been reported to be upregulated in a number of cancer types, including head and neck, colorectal, and other cancers. We discovered Petosemtamab by screening a large library of our bispecific antibodies against an array of tumor antigens. In those assays, we cast the net wide with a large screen to increase our chance of discovering unique antibodies. And the result was selecting Petosemtamab, which has showed the most potent inhibition of tumor growth over normal cell growth, particularly as compared to cetuximab. As shown on the cartoon on the left, petosemtamab has multiple mechanisms of action. As we've shown preclinically, petosemtamab targets EGFR and potently blocks the EGF ligand from binding. The other arm targets LGR5 outside the region where the ligand binds, and as such, this does not block ligand binding. LGR5 normally internalizes and associates with the proteasome degrader complex. When Petosemtamab is bound to LGR5, we've shown preclinically that it too is internalized, along with EGFR bound to the other arm, leading to EGFR degradation. You can see this in the images on the right side of the slide. In the first image, Petosemtamab in red ends up inside the cell, and there's complete disappearance of the green EGFR. This is in contrast to cetuximab, shown on the far right, which targets only EGFR and does not lead to internalization or disappearance of the green EGFR signal. Finally, the gel image on the bottom right shows degradation of EGFR with Petosemtamab, but not with cetuximab. Lastly, petosemtamab is fully ADCC-enhanced, designed to provide full benefit of the patient's own immune system against the cancer. This may be particularly relevant when combined with other immune-mediated mechanisms, such as blocking the PD-1, PD-L1 T-cell checkpoint axis with pembro. Petosemtamab has also shown important efficacy as monotherapy in patients with second-line plus head and neck cancer. We previously shared interim clinical data at AACR 2023, that petosemtamab demonstrated a 37% response with a median duration of survival of 11.5 months, a substantial improvement over the historical efficacy demonstrated by standard of care, single-agent chemotherapy, or cetuximab in this setting. We believe the importance of these results is further reflected by FDA recently granting breakthrough therapy designation to Petosemtamab for treatment of patients with recurrent or metastatic head and neck cancer, whose disease has progressed following treatment with platinum-based chemotherapy and a PD-1 or PD-L1 antibody. As a reminder, the FDA may grant BTD for drugs intended to treat a serious condition, where preliminary evidence indicates the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint. Needless to say, we're excited about the potential for Petosemtamab in head and neck cancer. On this call, we will review our interim clinical data, both the data provided in the abstract released May 23rd, and follow-up data from these patients, which will be presented formally next week at ASCO. We will also discuss our forward-looking development plans for Petosemtamab in first-line head and neck cancer. We're grateful to the clinical trial participants and our investigators, in particular, our lead investigator for the trial, Dr. Jérôme Fayette. We encourage all of you to attend the full ASCO presentation on Monday, June 3rd. The presentation slides will also be available on our website following the session. I will first summarize the data in the abstract that was published on the ASCO website on May 23rd. I refer you to the abstract itself for the full details. This cohort is evaluating petosemtamab, 1,500 milligrams every two weeks, with pembro, 400 milligrams every six weeks, as first-line treatment of recurrent metastatic head and neck cancer. Briefly, as of November 6th, 2023 abstract data cutoff, 26 patients were treated, with 24 continuing therapy as of the cutoff date, and a median follow-up was a little over a month. Median age was 62.5 years, and this was a relatively typical relapsed metastatic head and neck cancer patient population. A median of two cycles of Petosemtamab were administered. Among 10 patients evaluable for efficacy, six patients or 60%, responded, with one confirmed complete response, two confirmed partial responses, and three unconfirmed partial responses, all of whom subsequently confirmed after the data cutoff. In terms of safety, the combination was well tolerated and no significant overlapping toxicities were observed. Treatment-emergent adverse events were reported in all patients, and most were Grade one or two in severity. No Grade four or five were observed. The presentation at ASCO will include updated clinical data on these initial 26 patients as of a March 6th, 2024, data cutoff date. A total of 45 patients have received at least one dose of Petosemtamab with pembro and comprise the safety population. The median age was 64 years. Efficacy is reported for all patients enrolled as of the abstract cutoff date, who had the opportunity for four or more months follow-up and two or more cycles of petosemtamab treatment, with one or more post-baseline tumor assessments, or who discontinued early due to disease progression or death. We are presenting this efficacy population of patients with the opportunity for four or more months follow-up, as it represents a more complete analysis of response rate among the initial cohort described in the abstract. It allows for two or more tumor assessments to capture potential deepening of responses over time. We do note that in our data, several responses were achieved with the second scan, as has been observed across multiple similar studies in this patient population, such as Sacco 2021, Chung 2022, and Gulati 2023. Finally, allowing for four or more months follow-up, more appropriately reflects comparative data sets from registration studies, where longer patient follow-up is generally provided. This efficacy population is 24 patients of the 26 patients described in the abstract. Two patients are not included. One withdrew consent prior to the first tumor assessment, and the other discontinued due to toxicity with less than two cycles of treatment. Neither patient demonstrated disease progression on study. Overall, 67%, or 16 of 24, patients responded. This includes one complete response, 13 partial responses, and three unconfirmed partial responses that all confirmed after the data cutoff date. Responses were observed across HPV status, where three of four patients with HPV-associated cancer responded, and across PD-L1 levels, with similar response rate in the CPS 1-19 and CPS 20 and greater subsets. At the time of data cutoff, 32 patients of the 45 enrolled remained on treatment, including 14 of 16 responders and 18 of the initial 26 patients enrolled. This is an early look at the data, with a median of 3.6 months follow-up, so no median duration of response, progression-free survival, or overall survival is calculated. The safety profile is presented in the overall population of 45 patients who have received at least one dose of petosemtamab with pembro. The combination was well tolerated, and no significant overlapping toxicities were observed. Treatment-emergent adverse events were reported in all patients, and most were Grade one or two in severity. Infusion-related reactions, as a grouped or composite term, were reported in 38% of patients, of which 7% were Grade three, with no Grade four or five, and mainly occurring during the first infusion and all resolved. I'll now turn the call over to Shannon Campbell, Merus Chief Commercial Officer, followed by Greg Perry, our Chief Financial Officer, and then I will discuss our go-forward strategy, including details of our planned registration trial in first-line head and neck cancer. I'll provide our view of the opportunity in head and neck cancer, marketplace considerations, and why we believe that petosemtamab holds the potential to become an important new standard of care in this devastating disease. Head and neck cancer is a deadly disease with high unmet need, with approximately 460,000 deaths worldwide each year, and new cases are expected to increase by 30% to more than 1 million new cases annually by 2030. It's also a very complex disease. Patients diagnosed with an early stage generally receive surgery and radiation therapy, with the addition of systemic chemotherapy for the more advanced disease patients. Following these initial treatments, most head and neck cancers recur, and patients go on to receive systemic therapy for recurrent and metastatic disease. In the G8 countries, first-line patients typically receive pembrolizumab-based regimens, and because only a subset of patients, around 19%, respond to pembro alone, the 67% response rate reported today with petosemtamab and pembrolizumab is striking. Petosemtamab, in combination with pembro, holds significant potential to become a new chemo-free standard of care in the frontline setting. We believe that the breadth of activity observed with important responses across CPS scores and in patients that are HPV negative and positive, make this frontline combination very interesting and differentiated from other agents in development for head and neck cancer. In addition to the robust response rate, petosemtamab plus pembro has demonstrated a favorable safety profile with a convenient dosing schedule for patients and providers alike. The head and neck cancer market represents a substantial opportunity for Merus, with a global market size expected to achieve around $5 billion annually by 2028. We are excited by this strong frontline interim data, especially when compared to currently available therapies. Alongside the robust monotherapy results in the second-line plus setting and the FDA breakthrough designation, this supports our belief that petosemtamab has the potential to become the first and best-in-class treatment for head and neck cancer, and possibly other tumor types. As Chief Commercial Officer, I am super excited for the opportunity to bring this potential new therapy to patients in need. Merus is in a strong financial position. With our successful financing in August of 2023 and our collaboration with Gilead that brought in $81 million, we reported in our Q1 business update, cash and marketable securities totaling $399 million. At the end of Q1, our guidance on runway accounted for our planned petosemtamab registration trial in second-line plus head and neck cancer. It also partly accounted for a second registration trial in frontline head and neck cancer. As is our practice, we accounted for planned spend over the next 12 months and risk-adjusted spend beyond that. As a reminder, our runway projections do not assume major milestone payments from collaborations, nor future licensing or partnerships. We may include more modest, highly likely, near-term preclinical milestones with our licensees and collaborators. We estimate the cost of the second petosemtamab registration trial, specifically petosemtamab with pembro in frontline head and neck cancer, to be similar to the cost of the second-line plus trial, with the addition of the cost of pembro, which we estimate will be in the high tens of $ millions. We expect that there will be synergies to running two clinical trials in the same disease setting at the same time. Merus remains in a very strong financial position. Look, I'm a drug developer at heart, and this is exciting. Petosemtamab with pembro has demonstrated clinically meaningful activity in first-line head and neck cancer, with a 67% response rate overall across tumor PD-L1 expression levels and HPV status in this interim data update. Importantly, the observed safety profile demonstrated no significant overlapping toxicities and a low rate of infusion-related reactions. Thus far, the profile appears to be far more favorable than that observed with chemotherapy-based regimens, and even appears to have less EGFR-related toxicities than observed with cetuximab-based regimens. We believe petosemtamab has the potential to become first and best in class, and a new chemo-free standard of care for patients with head and neck cancer, both as first-line therapy and in the second-line plus setting. We are now moving forward with a planned phase III registrational trial of petosemtamab with pembro as first-line therapy for relapsed or metastatic PD-L1 positive head and neck cancer. That will include both HPV-negative and HPV-positive cancer. We expect this trial to start by the end of 2024. We anticipate the control arm will be pembro alone, with efficacy endpoints that include ORR, PFS, and OS. The trial scope and design will be based on KEYNOTE-048, the trial that led to the approval of pembro in head and neck cancer. Consistent with FDA Project FrontRunner, we believe that there may be an opportunity for accelerated approval based on an early endpoint, such as overall response rate, with overall survival in the same trial, providing confirmation of benefit for regular or traditional approval. All of this will, of course, be subject to important discussions we expect to have with the FDA in the future. We also continue to move forward with our activities for a phase III clinical trial in second-line plus head and neck cancer, and we're planning on initiating an expansion cohort in colorectal cancer later this year. Thank you for joining us today. We are excited to share these important new data on petosemtamab and our plans for development in head and neck cancer. For Merus, creating novel multispecific antibody medicines is our core competency. I'm proud of the progress we are making towards our ambition to close in on cancer. I'll now turn the call back to the operator for questions. We are now opening the floor for question and answer session. If you'd like to ask a question, please press star followed by the number one on your telephone keypad. We will allow one question for each analyst. Our first question comes from Maury Raycroft from Jefferies. Your line is now open. Hi, good morning. Much congrats on the data. Overall response rate looks impressive. Wondering if you can talk about signals of durability and whether you have an update a year for powering for your frontline pivotal? And for the pivotal trial design, when considering the KEYNOTE-048 and the types of patients you expect to enroll, can you talk about expectations for the control arm performance? Yes, good morning, Maury, and thank you for the question. I think you had a couple of questions in there. One is, what's the support for durability so far in our dataset, and how does it help us think about the duration that we might consider for a control arm performance, and you cited KEYNOTE-048. So a couple of things. First is, this is a very early look at the data, and we have, you know, some median follow-up of 3.8 months. So it's really hard to make any substantive or substantial comments about durability at this point. Typically, we provide swimmer plots in presentations, and so that gives the stakeholders in the broader community an opportunity to see how the patients have done on our study to date. Historically, the patient population, which we think is similar to this population, is like KEYNOTE-048. As you know, there have been other clinical trials with perhaps different patient populations, but we do think KEYNOTE-048 is a relative benchmark that we will use in our planning. We also will incorporate some more conservative modeling to ensure that we have appropriate power for a registrational trial. Thank you for the question. Operator, next question, please. Our next question comes from Tara Bancroft from TD Cowen. Your line is now open. Hi, good morning. So I was hoping that you could explain mechanistically why, why you believe that petosemtamab would be more active in HPV positive patients, potentially, relative to other EGFR inhibitors or EGFR bispecifics? And what is your level of confidence that that 75% will hold up when you do include more patients? Thanks. Good morning, Tara. The question is, what's our understanding of why we're seeing such a robust response rate in HPV positive patients? In our dataset, three out of four patients with HPV positive disease did respond. Now, it's a small N, but it's an encouraging start. We do note that EGFR antibodies alone, the traditional Cetuximab or Cetuximab-like drugs, typically don't have any efficacy in cancer that's driven by HPV, and that has to do with the biology about how human papillomavirus causes cancer. It seems to create an insensitivity to simply blocking the EGFR, EGF mechanism. We do also note that pembrolizumab does have activity in both HPV positive and HPV negative diseases. In addition, to... For Petosemtamab, in addition to blocking EGF, EGFR, like a cetuximab-like drug and having this LGR5 associated mechanism, we have commented that our drug is fully ADCC enhanced. And we believe that may be a real mechanism by which this fully ADCC-enhanced antibody can participate more fully and more effectively with essentially pembro, quote, "taking the brakes off," if you will, the patient's immune system. So we think a combination of these factors really do come into play in giving us the really potent clinical activity that we've seen to date. Next question, please. Our next question comes from Michael Schmidt from Guggenheim. Your line is now open. Hey, guys. Good morning, and, yeah, congrats from me as well on the, you know, excellent data here at ASCO. Could you comment a bit more about sort of the response kinetics over time? I know that the data cut was really early in the median follow-up, was just a bit more than three months, but, you know, just curious if you see response deepening, is there opportunity for additional responses to convert over time? And, the other question I had was just on time to respond. I know that some other drugs in the space had seen responses after more than five months of follow-up. I'm just wondering if that's something one would expect for your therapy as well. Thanks so much. Good morning, Michael. Yes, it is something that we've thought a lot about, and as we talked about on the call, we did present the data, allowing all the first 26 patients who have gone through 4 months of follow-up to be able to capture a more, I would say, appropriate or, you know, even assessment of response rate. But there can be responders even beyond this time period with drugs like these and in head and neck cancer. And if you look across a number of trials, we have seen other patients respond beyond four months, five or six months. In this setting, we did note that at the time of data cutoff of the 26 patients enrolled, 18 remain on study. So there is possibility for deepening of responses over time. Operator, next question, please. Question comes from Etzer Darout from BMO Capital Markets. Your line is now open. Great, thanks for taking the question, and congrats on the data update today. Just maybe a quick follow-up, Bill, if you can sort of elaborate on this at all. Just wanted to know if you could comment on maybe the median follow-up time for the responding patients, if you can, knowing obviously that the median follow-up time overall is fairly short. But wanted to. If you could comment on the follow-up time for the patients that have responded to therapy. Good morning, Etzer, and thanks for the question. We haven't shared or disclosed granular detail about individual patients in this call or in the press release this morning. Typically, historically, as I've commented on, we have provided waterfall plots and swimmer plots in particular that will show durability of responses over time, but it's not something we've broken out specifically. But I can provide some general color. You know, in a clinical trial that we started enrolling in April of last year, we have some patients who've been on quite a long time, and when we look across the responders, we do see quite a range of responses within the confines of that, starting enrolling in April and having a data cutoff on March 6th. So we do see a wide range of where patients are in their sort of duration of response to date. We do note that most of these patients are still on study and continuing on therapy. Great. Thank you. Operator, next question, please. Our next question comes from Tazeen Ahmad from Bank of America. Your line is now open. Hi, guys. Good morning, and congrats from me as well on the strong data. I wanted to get a sense of... I know it's still early, and you're still gathering more data, but as you look forward and as we think about pivotal trial design, what proportion of the head and neck population do you think is eligible for this combination? So you talked about the three-fourths of HPV-positive patients responding. Was there anything in particular about the one that didn't? And also, as you start to get more data for CRC over time, is there any read-through that we can get from the data that you've presented so far? Good morning, Tazeen. So in terms of trial design, we are considering a relatively broad trial design for the first line setting, and we look to KEYNOTE-048 as a real benchmark for the metes and bounds of what we might expect from a clinical trial design. It was just an exceptionally well-run clinical trial and led to, obviously, a number of really important positive readouts for Keytruda in this setting. So that's, in general, a really good guide. We believe that clinical trials can incorporate all HPV characteristics, both the patients with HPV-negative disease and those with HPV-positive disease. And, it's too hard to say anything about the characteristics of an N= 1 non-responder, 'cause we don't really know if any of those characteristics are relevant or germane to whether they responded or not. We do think that most of the patients who can be included, those are all the patients with tumors that express some level of PD-L1, sort of the CPS 1 or greater population, which is approximately 80%-85% of all first-line head and neck cancer patients in this setting. And, in terms of CRC read-through, I think it's too early to make any comments about that. Operator, next question, please. Our next question comes from Ami Fadia from Needham. Your line is now open. Hi, good morning. Congrats on the very impressive data. I had two quick questions. It was good to understand sort of your explanation for why we are seeing a higher response rate in the HPV-positive subset. But could you explain why, in the second-line study, we saw a lower response rate in the HPV-positive subgroup? And then just with regards to one of the discontinuations, could you elaborate a little bit about whether the patient discontinuation was considered related to drug or not? The one that had asthenia, diarrhea, and creatinine increase. Thank you. Good morning, Ami. Regarding the higher response rate in HPV-positive disease seen in the combination study, but lower response rate potentially in HPV-positive disease in the monotherapy arm, I think there are a couple of factors into play. First, we did see activity in HPV-positive disease in the second-line-plus setting. And as we've talked about, we are including all of those patients in our second-line-plus study. So we do believe that there is activity for our drug in this population. It's just that in our small data set, the number was a little bit lower. Now, historically, cetuximab and cetuximab-like drugs have had zero response rate in HPV-positive disease. So we were really quite encouraged to see some clinical activity, tumor shrinkage, and response in the second-line-plus setting. We think it's partly these multiple mechanisms of action that allow for activity that's not simply an EGF, EGFR-driven, mechanism of action. And then we move it to the frontline setting, of course, the big difference is pembrolizumab or Keytruda, and in this setting, we know that that takes the brakes off the T-cells. And if you have a fully enhanced antibody binding to tumor cells in the setting of taking off the brakes off the T-cells, we think that combination is actually really quite potent and a substantial explanation for why we're seeing more than additive efficacy from the clinical data we have here as compared to the historical response rate. Now, regarding the discontinuations, we haven't articulated specifically whether, in the slides, whether it was related or not related, but I believe, and I'd have to go back and check, I believe they were considered related grade one, grade two events. Operator, next question, please. Our next question comes from Yigal Nochomovitz from Citigroup. Your line is now open. Hi, Bill and team, and congrats as well on the excellent data. I just wanted to follow up on the powering theme regarding the phase III frontline trial. In addition to KEYNOTE-048, as you know, there's a more recent trial called LEAP-10 from Merck and Eisai, which showed, although the study failed, that the response rate for pembro monotherapy was 25% in that trial. I'm just wondering to what extent that data point is being incorporated into your powering thinking regarding the phase III trial. And then with respect to the timing of the first line and the second line, am I correct that you appear to be shifting priority now to the frontline trial, or will both for frontline and second line trials start concurrently once you get the results from Project Optimus for 1100 versus 1500? Thank you very much. Good morning, Yigal. So your first question had to do with LEAP-10 as a, which had pembro alone as a control arm, and should that be the baseline of what we're looking at? Let me make a couple of comments. First is that the LEAP-10 trial, higher response rate in the control arm of pembro, 25%. Of course, we're incorporating that into sensitivity analysis of how much we have to power the trial to make sure that we have the best shot of winning in this registration trial. Having said that, I think there are a couple of reasons why the response rate in these studies jumped from 19% to 25%. LEAP-10 is a failed trial of Lenvima plus pembro, which is a really toxic regimen, and we know a couple things about the trial. The first is the inclusion criteria for the trial were much more stringent, so that we believe that the inclusion criteria focused on healthier patients. We actually know that that may be true for a couple reasons. One, it took a lot more patients to screen through to find patients eligible for this trial. The screen failure rate getting into the trial was much higher, and two is that the rate of performance status zero, the healthier patients in this clinical trial, was higher in this than in KEYNOTE-048. But nonetheless, it is an important metric for us to consider as we look at sensitivity analysis, making sure that our trial is fully powered adequately for potential outcomes on the control arm. The second line, frontline registration trial question is also an important one. We've guided that we will begin a second line plus registration trial in head and neck cancer of petosemtamab monotherapy by the middle of this year, and we're maintaining that guidance. We've guided that we will start a first-line registration trial of petosemtamab with pembro by the end of the year, and we're maintaining that guidance. So it's, full speed ahead for both programs, because here, time is of the essence, both for us and for a drug that has a lot of promise for patients. We wanna get it to the pharmacy shelf as soon as we can. Operator, next question, please. Our next question comes from Brad Canino from Stifel. Your line is now open. Thank you, and a follow-up question for me. I just wanna know if you can help me understand, was the decision to include HPV positive patients in the frontline phase III just based on these four combination patients you've reported to us here today, or does it include observations of additional combo patients without four months of follow-up or even from the monotherapy dose optimization? Thank you. Good morning, Brad. The decision to include HPV negative and HPV positive patients comes from a number of factors that we've thought through, as you rightly surmised. Predominantly from the data sets that we have, the four patients that we've described really do provide, I think, the strongest evidence of whether our drug can have activity. Now, four is a small number, but it is an important number that we have in terms of these four patients in response. We do have evidence that our drug is active and potentially, alone. Our drug mono, as monotherapy is active and potentially, you know, looks like it's a bit more active than cetuximab alone or cetuximab-like drugs in the second-line plus setting. But also when we model different potential outcomes for where the HPV positive patients are in terms of their responses in a large Phase III clinical trial, we are building a clinical trial that ensures that we have the power to be successful, even with a range of different outcomes of the HPV positive subset. So we wanna make sure that the trial design is as robust as possible for what is a relatively complex clinical setting. But given you know, very early, small numbers, but 75% response rate in this population, boy, that would be a terrific thing to be able to provide for patients with HPV positive disease. Operator, next question, please. ... Question comes from Matt Phipps from William Blair. Your line is now open. Good morning, Bill. Congrats on continued strong data with petosemtamab. Just wondering, based on commentary, if we should go ahead and assume that a Keytruda supply agreement will not be in place for this phase III. And then also, you know, following this data, do you plan to look subsequently in, you know, PD-L1, CPS below one patients, either with just this combination or maybe with some Keytruda or chemo combo? Thank you. Good morning, and thanks for the question. So we have been moving forward under the assumption that we will provide pembro for the disease. You know, head and neck cancer is an increasingly important market in oncology, and it's becoming a substantial area of new drug development and product sales. For example, Evaluate Pharma estimates that almost 10% of pembro sales are in head and neck cancer. We have estimated that the cost of pembro in this clinical trial is in the multiple, multiple tens of millions of dollars, a substantial cost. So it is a consideration. You know, at the same time, we need to be thoughtful about our relationships with companies, especially when it comes to our most important asset. In terms of low PD-L1, it is an area that we are interested in potentially exploring. These are patients who don't fit the CPS-1 or greater category, but whose tumors don't have any PD-L1 expression, where Keytruda isn't--Keytruda monotherapy isn't labeled. It's obviously a substantial number of patients, and if we have a potentially active combination in this setting, it is something we're very interested in understanding what's the best way to bring it forward to patients. Something we're considering internally and with our key opinion leaders and clinicians. Operator, next question, please. Our next question comes from Tony Butler from Rodman & Renshaw. Your line is now open. Bill, good morning. I wanted to ask about this notion of running two trials at the same time, one in first line, one in second line. If you follow the KEYNOTE-048 protocol, roughly, if it's, say, 800 patients and 200 clinical sites, are there a number of clinical sites that are not only enrolling frontline patients, but also enrolling second-line patients? I would love for you to speak a minute about that. And then second to this, based on the Sacco data of 2021, published in 2021, could I ask, what is the second line control arm? Is it simply physician's choice, or is it a specific agent? Thank you very much. Good morning. So with respect to running two trials, the second line plus trial and the frontline trial, just to comment on the KEYNOTE-048 clinical trial done by Dr. Barbara Burtness, that was a three-arm trial, and of course, we anticipate running a two-arm trial here in the registrational setting. So the 800 patients may be a little bit overestimated for us, but the 200 clinical trial sites is, yeah, that's what it takes to get a registrational trial done. And I think you point out something really important, which is that there can be sites for both clinical trials. And importantly, you know, that represents this concept that there can be synergies in running both of these trials together. Now, frontline trials are complex and costly, both the fixed costs of the infrastructure and setting up and the variable per patient costs. There are a number of potential synergies, certainly among the fixed costs, such as the CRO, infrastructure, site management expenses, but also in terms of us being able to be close to the clinical trial sites and close to the investigators and close to the teams at the sites to really ensure the best quality of execution of our clinical trial. So we do think that's an important element of how we're gonna manage both of these registration trials at the same time. The second question you asked had to do with the second line control arm. So we're anticipating starting a second-line plus registrational study mid this year, and it will follow the clinical trial designs that got both Keytruda and Opdivo registered in the second-line setting. And that is comparing the experimental arm, in our case, petosemtamab, to an investigator's choice. And it's the exact same investigator's choice used in both of those trials of monotherapy, chemotherapy, either methotrexate or docetaxel, or cetuximab. The investigator and the clinician can choose one of those three to give to his or her patients. And that clinical trial design has been successful, both in demonstrating the efficacy of those two drugs and demonstrating, you know, successful, successful outcome in terms of a registrational setting. So we think that's a tried and true approach for the second-line, plus, clinical trial design. Operator, next question, please. Our next question comes from Asthika Goonewardene from Truist Securities. Your line is now open. Hey, good morning, guys. Thanks for taking my questions, and I'll also add congratulations on what looks like pretty cool data here. Going back to that data, I was wondering in, you know, you had the impressive response rate and the 24 patients evaluable. You had about another 20 more patients on top of that who were recruited, dosed, but not, didn't have any mature data there. I was wondering, without getting too granular here, maybe can you qualitatively tell me, have you seen unconfirmed responses in those other 20 or so patients who were subsequently recruited? And then, if I can latch on a subquestion here, of the 16 responses that you've had in the first 24, what proportion of that was on first scan versus second or subsequent scan? Thanks. So thanks for the question, Asthika. Of the first 24 patients, the 16 responders, most did respond on the first scan, but there were several where the responses didn't come until a later scan. Historically, if you look across the other clinical trials of the combination of cetuximab with either Keytruda or Opdivo or durvalumab, it's about a similar rate. In those studies, it was about 20% or 25% of patients who did respond, did respond in a scan later than the first scan. In terms of, you know, additional data, we haven't disclosed anything about, from an efficacy standpoint, about the rest of the patients in the cohort. We've talked about the safety profile of all the patients who have been dosed, but we haven't described any further efficacy. We would anticipate providing an update on this clinical trial in the future. Operator, next question, please. The next question comes from Sebastiaan van der Schoot from Van Lanschot Kempen. Your line is now open. Hey, good afternoon, team, and congrats on the strong update. My question is regarding the recruitment rate. If I look at the base number, it looks quite high. Can you maybe comment on how recruitment has been going over the last year? And then maybe also add some comment on how many more clinical trials you or clinical sites you are aiming to add, and what the efforts have been in that department. Thank you. Good afternoon, Sebastian, and thanks for the question. So, you're right. I think we've been really pleased by the excitement this clinical trial has generated, the enthusiasm from the investigators, and continued enthusiasm now, particularly with these data. I think that it's important to note we did start enrolling in April, and we could only enroll a small cohort, and we needed to follow them for safety for a period of time before we could open up enrollment to all the sites. And as with all clinical trials, we were bringing sites up throughout the majority of the second half of last year. So we are really pleased with the sort of enthusiastic level of engagement, the excitement that this clinical trial is generating... has generated, and, you know, the fact that the community is broadly really keen to move forward with petosemtamab, both in the second line plus setting and petosemtamab with pembro in the frontline setting. In terms of how many clinical trial sites, Tony Butler commented around KEYNOTE-048, that it had around 200 clinical trial sites. It takes a lot of clinical trial sites to effectively execute in a timely manner. So yes, we need a lot more clinical trial sites. And, the teams are working really hard and diligently, both to get additional clinical trial sites and also to understand which sites could support potentially both the first-line registrational trial and the second-line plus registrational trial to afford us some synergies, both in cost and in terms of investigator engagement and relationships and execution. So I believe that's all the questions that we're able to take. Thank you for joining us this morning. We are really excited for the potential for petosemtamab, and excited to share these new data on petosemtamab with pembrolizumab, and our plans for development in head and neck cancer. For Merus, creating novel multi-specific antibody medicines is our core competency. I'm really proud of the progress we continue to make towards our ambition to close in on cancer. I'll now turn the call back to the operator. Thank you so much. Thank you, everyone, for attending today's call. We hope you have a wonderful day. You may now disconnect.