Hello, and welcome to the Merus Investor Call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session, and if you would like to ask a question, press star one on your telephone keypad. I would now like to turn the conference over to Kathleen Farren, Investor Relations and Corporate Communications. You may begin. Hello. I'm excited to welcome you all to Merus' ESMO Asia Conference Call. This presentation is available on our investors and media page of our website. On this call, we will make 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 commercial opportunities, potential and existing collaborations, finances, intellectual property, projections about Merus' 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' filings with the U.S. Securities and Exchange Commission, including its Form 10-Q for the period ended September 30th, 2024, which we filed with the SEC on October 31st, 2024. Leading us through the agenda will be Dr. Bill Lundberg, President and Chief Executive Officer, Fabian Zohren, Chief Medical Officer, Shannon Campbell, Chief Commercial Officer, and Peter Silverman, Chief Operating Officer. Good morning from Boston, and good evening from Singapore. We're excited to share with you the consistent and impressive interim clinical data on petosemtamab monotherapy in second-line plus recurrent metastatic head and neck cancer, which was presented earlier today by Dr. Christophe Le Tourneau at the ESMO Asia Congress in Singapore. Petosemtamab is our EGFR and LGR5 bispecific antibody in clinical development for head and neck cancer and other indications. We discovered petosemtamab with our proprietary and innovative multi-specific antibody platform we call Multiclonics that allow us to make bispecific and trispecific antibodies just like monoclonal antibodies. This is important because there's a long tradition of making monoclonal antibodies into successful medicines. We can perform large-scale screening, allowing biology to select the best candidate molecules. We can leverage all the advantages of monoclonal antibody development and manufacturing, including well-established process development, grams per liter production from single producer cell lines, and global availability of contract manufacturing. As fully human IgG1, our molecules are designed to be well-behaved in vivo, with low immunogenicity, consistent half-life, and can have all the Fc domain engineering like ADCC enhancement, Fc enhancement, or stealth silencing for T cell engagers, and compatibility with linker toxins for 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 success. We identified 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 that could show differential growth inhibition of tumor-derived as compared to normal tissue-derived organoids. And the result was selecting petosemtamab, a bispecific antibody that targets both EGFR and LGR5. Petosemtamab acts by binding to the well-established cancer antigen EGFR, blocking EGF ligand binding and growth signaling, similar to cetuximab and other EGFR antibodies. Petosemtamab also binds to LGR5, a protein expressed on the subset of cells within a cancer that drive tumor growth and metastases. When petosemtamab binds to both LGR5 and EGFR, the EGFR protein is internalized and degraded, essentially removing it from the cell. Finally, petosemtamab is fully ADCC enhanced, potently engaging the patient's own immune system. This mechanism may be particularly important in combination with the checkpoint inhibitor pembrolizumab, which takes the brakes off the immune system. Targeting LGR5, along with EGFR, is a wholly new approach to cancer therapy and appears to be a robust and potent way to treat cancer. We believe the efficacy of petosemtamab monotherapy in head and neck cancer is substantially greater than that which we've seen historically with other EGFR-based monoclonal and bispecific antibodies in response rate, extent of durability and survival, and in breadth of activity across HPV-related disease and other subgroups. I'd now like to introduce Dr. Fabian Zohren, our new Chief Medical Officer. Fabian is a medical oncologist with extensive experience in Phase III registration trials in solid tumor oncology, encompassing thousands of patients. Fabian will now walk you through the clinical data presented at ESMO Asia earlier today. Thank you very much, Bill. Good morning and good afternoon to everyone. It's an absolute pleasure to be on this call and great to officially meet you all, and of course, to present our updated proof of concept data for single-agent petosemtamab in second-line plus recurrent metastatic head and neck squamous cell cancer from our ongoing Phase II study, MCLA-CL01. MCLA-CL01 is the first-in-human study of petosemtamab that consists of a dose escalation part followed by disease-specific expansion cohort. As discussed by Dr. Le Tourneau during his presentation and outlined here, this update features two interim data sets from two different patient cohorts. The presentation included data from our single-arm cohort in second-line plus recurrent metastatic head and neck cancer, for which interim data were initially presented at AACR 2023. It also included data from a randomized dose optimization cohort designed to compare two doses of petosemtamab, 1500 milligram and 1100 milligram, both given biweekly. The randomized dose comparison cohort was conducted to address the FDA's Project Optimus. Earlier this year, we had a successful Type D meeting with FDA, in which FDA officially accepted the 1500 milligram dose of petosemtamab as the recommended Phase III dose for further development. Following our agreement with FDA, we conducted a pooled analysis of all head and neck cancer patients who were treated in study CL01 with the accepted recommended Phase III dose of 1500 milligram, essentially combining 54 patients from the single-arm cohort with 28 patients from the randomized dose comparison cohort. This pooling strategy provided a robust total of 82 patients treated at the 1500 milligram recommended Phase III dose for this efficacy and safety analysis. As a quick reminder, the data cutoff date for the single-arm cohort presented at AACR 2023 was February 1st, 2023. The new data cutoff date for the pooled analysis is July 5th, 2024, providing an additional 16 months of follow-up for the 54 patients treated in the single-arm cohort. The 28 patients treated at the 1,500 milligram dose level in the dose optimization cohort have a shorter follow-up. Out of the 82 patients enrolled in the study and pooled for this analysis, 75 were evaluable for efficacy. Seven patients were not evaluable for efficacy. These include six patients previously mentioned in the AACR 2023 presentation and one additional patient who experienced an infusion-related reaction during the first infusion and decided to withdraw from the study. 28 patients were treated at the 1,100 milligram dose level, and 27 were evaluable for efficacy. One patient withdrew consent before the first tumor assessment without evidence for disease progression. The baseline and disease characteristics of patients enrolled in the study were typical of advanced head and neck cancer. However, when looking at the two groups presented here, the 1500 milligram pooled cohort and the 1100 milligram cohort that was randomized for dose optimization, I want to highlight that not all prognostic factors were well balanced between these two groups. The majority of patients were male in both groups, 79%, and most patients had an ECOG performance status of 1, 70%-75% across both groups. The median age of participants ranged from 60-64 years in both groups, and the median EGFR H-score measured by immunohistochemistry was high in both groups. The median number of prior systemic therapies was 2 for both groups. However, there was a notable imbalance in the proportion of patients with oropharyngeal cancer and HPV-related cancer between the two cohorts. In the pooled 1,500 milligram group, 21% of patients tested positive for HPV, while only 4% of patients in the 1,100 milligram group were HPV positive. A particular high percentage of HPV-positive patients were enrolled and treated in the 1,500 milligram randomized dose optimization cohort. The reason for discontinuation was generally similar across both dose levels, and the lower rate of discontinuations due to study drug-related adverse events observed at the 1,100 milligram dose level, 0 versus 9%, was attributable to our updated administration regimen that significantly reduced the incidence and severity of infusion-related reactions for both dose levels. Shown here is the summary of treatment-emergent adverse events regardless of causality by grade in all 82 patients that were treated at the 1,500 milligram dose level. Petosemtamab continues to be observed as very well tolerated in this patient population. In particular, skin toxicity such as rash and gastrointestinal side effects continue to appear less frequent and less severe than observed for other EGFR-directed antibody therapies. I believe that our updated administration regimen designed to reduce the incidence and severity of infusion-related reactions has proven effective. As shown on the right, this improved protocol led to a significant decrease in Grade 3 treatment-emergent adverse events associated with infusion-related reactions, reducing the incidence from 24% under the previous dosing instructions to just 9% as of the data cutoff date. I want to highlight that all treatment-emergent adverse events associated with infusion-related reactions continue to occur predominantly during the first infusion of petosemtamab, specifically on cycle one, day one. In conclusion, no new safety signals have been identified for petosemtamab, and we believe the safety profile of petosemtamab at the recommended Phase III dose of 1,500 milligrams given biweekly remains manageable and well tolerated. The primary efficacy endpoint of our study was overall response rate by investigator assessment using RECIST 1.1 criteria, and 75 of the 82 patients with second-line plus recurrent metastatic head and neck squamous cell cancer included in this pooled analysis were evaluable for disease assessment, as previously mentioned. The confirmed overall response rate for petosemtamab monotherapy was 36%. The median time to response was fast at 1.9 months, and the current estimate of the median duration of response is longer than six months. Ten patients were still on treatment at the time of the data cutoff. The observed response rate for patients with HPV-positive cancer was 13%. Two out of 15 patients responded to petosemtamab, and another five patients achieved stable disease. With increased follow-up, we also observed evidence for deepening of the responses with continued petosemtamab treatment. Petosemtamab monotherapy led to four complete responses among the 27 responders. Progression-free survival by investigator assessment and overall survival were secondary efficacy endpoints of our study. The Kaplan-Meier estimates for the pooled 1,500 milligram disease-evaluable population show a median progression-free survival of 4.9 months and a median overall survival of 11.4 months. Importantly, for our most mature data set, the single-arm cohort previously presented at AACR 2023, the median PFS based on the new data cutoff date is now 5.2 months, and the median overall survival is 12.5 months. This analysis is based on 48 disease-evaluable patients, considering the results of this pooled analysis of 75 patients at 1,500 milligrams with a confirmed overall response rate of 36%, a durability of response of more than six months, and an estimated median overall survival between 11.4 to 12.5 months depending on the follow-up and cohort use, we believe that the efficacy observed with petosemtamab compares favorably to historical data and currently available monotherapies. We also believe that these interim data continue to support the FDA Breakthrough Therapy Designation granted to petosemtamab for second-line and later treatment of head and neck squamous cell carcinoma. Overall, we are confident in the design and potential for our registration trials for head and neck cancer. As you can imagine, it's an exciting time to be at Merus. As the Chief Commercial Officer, I'm thrilled by the progress we're making with petosemtamab. From a commercial perspective, I believe petosemtamab has all the attributes one could hope for in a late-stage clinical asset: compelling clinical activity as monotherapy and in combination with pembro, breadth of activity across first-line and second-line plus head and neck cancer, rapid and durable responses across patient subsets, including HPV-positive and negative disease, favorable safety, and patient convenience, all potentially practice-changing, as described by Fabian. Head and neck cancers are complex and devastating diseases requiring a multidisciplinary approach throughout the patient journey. Despite the approval of IO agents, unmet need remains high, and clinicians and patients are looking for more durable responses and improvements in survival. Patients' treatment choice is influenced by the stage of disease. Patients diagnosed with localized head and neck cancer generally receive surgery and radiation therapy with the addition of systemic therapies for the more advanced disease patients. Unfortunately, most head and neck cancers recur after initial treatments, leading patients to receive systemic therapy in the recurrent or metastatic setting, where the most commonly used initial systemic therapy is the pembrolizumab-based regimen. However, only a minority of patients respond to pembro alone or with chemotherapy. In this context, the interim clinical data we presented at ASCO 2024, showing a 67% response rate for petosemtamab in combination with pembro in PD-L1 positive disease, is particularly striking. After patients receive first-line therapy and their cancer does not respond or progresses, they need additional treatment options. There is no preferred standard of care in second-line and third-line plus, especially after pembro and chemo, and oncologists often use cetuximab, docetaxel, or methotrexate alone or in combinations. However, only a fraction of patients typically respond to these treatments. We believe the clinical activity we're seeing with petosemtamab monotherapy demonstrates remarkably high efficacy, including rapid responses and meaningful durability, supporting the potential for petosemtamab to become an important new standard of care in this setting. Turning to the market opportunity, head and neck cancer is a deadly disease with high unmet need, with approximately 930,000 new diagnoses and 467,000 patient deaths each year. In the G7 market, an estimated 55,000 patients each year will present with recurrent or metastatic head and neck cancer requiring first-line systemic therapy, according to epidemiology data from Kantar. There is a need for more effective and tolerable first-line treatments. There is no preferred standard of care in the second-line plus setting, and it represents a significant market opportunity, with more than 22,000 patients each year in the G7 markets receiving treatment in this setting. Currently available options provide only modest benefit, and petosemtamab has the opportunity to become a new standard of care in the second-line plus setting. The head and neck cancer market is a substantial opportunity for Merus, with an estimated market size expected to exceed $5 billion annually by 2028, according to Evaluate Pharma. Of note, the $5 billion plus estimate only reflects the duration of currently available treatments, both in the first-line and second-line plus setting. We believe that whether as monotherapy or in combination with pembro, petosemtamab may significantly transform the head and neck cancer treatment paradigm, with the potential to increase both the number of patients who respond to treatment and their duration of response. We're also expanding our evaluation of petosemtamab into colorectal cancer. Colorectal cancer represents a large opportunity. It's the third most common cancer globally. In 2022, there were an estimated 1.9 million new diagnoses worldwide, and more than 900,000 patients died of this disease, representing the second highest cause of cancer-related mortality. The number of patients affected by colorectal cancer continues to grow every year. Colorectal cancer has a significant patient population and continued unmet need, and we're looking forward to sharing our initial clinical data for petosemtamab in colorectal cancer next year. I hope I've conveyed my enthusiasm for the blockbuster potential of petosemtamab. With two ongoing Phase III studies in head and neck cancer, as well as two Phase II exploratory cohorts in colorectal cancer, petosemtamab represents a significant opportunity across multiple cancer types, and we believe Merus is well positioned to capitalize on these opportunities. Petosemtamab is a highly innovative Multiclonics antibody, the first of its kind targeting the novel combination of EGFR and LGR5. It was generated by Merus based on our own proprietary platform technologies, incorporating our patented heterodimerization technology, novel format with binding domains produced from our patented common light chain transgenic animal MeMo. Of note, we received issuance of the first composition of matter patent this year, which expires not earlier than October 2036, not inclusive of any patent term adjustments, future patent term extensions, or supplementary patent certificates that may be available in Europe. Having developed the molecule internally, we have also filed additional patent applications to protect our franchise asset. We have applications directed to methods of treatment, combination therapy, formulation, and administration of petosemtamab, among other subject matter, with any future patents that may issue from these that could potentially extend exclusivity well beyond 2040. We're quite proud of our history of innovation at Merus. It's through our creative approach to problem-solving that has paved the way for us to execute, not just on the technology front, but in the clinic as well, as we've now embarked on two Phase III trials in head and neck cancer and new Phase II studies in CRC with more to come. In summary, we believe that petosemtamab has true blockbuster potential in head and neck cancer and beyond. Petosemtamab was discovered from our own foundational technology platforms and is supported by strong IP. We believe petosemtamab has the potential to address a large market with significant unmet need: head and neck cancer, with opportunity in colorectal cancer and other indications as well. We now have a large, robust data set of 75 patients treated with petosemtamab alone in second-line plus head and neck cancer, which is demonstrating very strong efficacy, a 36% response rate, and 11.5-month median overall survival. We believe this profile is much stronger than an EGFR antibody therapy such as cetuximab or standard single-agent chemotherapy. We are also seeing robust monotherapy responses deepen over time, now with four complete responses among 27 responders. Our data continue to support the inclusion of HPV-positive disease among HPV-positive cancer. We continue to see tumor responses to petosemtamab in striking contrast to the lack of responses to EGFR inhibition alone with cetuximab across multiple clinical trials, and overall, we believe the clinical profile of petosemtamab in the second-line plus setting strongly supports the potential for best-in-class antibody efficacy, not only in this indication, but potentially in first-line head and neck cancer as well. Our strong data to date also support our view that the combination of LGR5 targeting and EGFR inhibition may be a wholly new way of treating the cells within a cancer that drive tumor growth and metastases. We set very ambitious goals for the company for 2024, and we're on track to achieve them. I am so proud of our company. This has truly been a transformative year for Merus. We are again setting ambitious goals for 2025, including a clinical data update of petosemtamab and pembrolizumab as first-line treatments of PD-L1 positive head and neck cancer. This is the cohort initially presented at ASCO 2024, which we expect will have sufficient follow-up to inform on duration of response and overall survival. We are also planning to expand enrollment in our colorectal cancer program to include both first-line colorectal cancer in combination with standard chemotherapy and third-line plus colorectal cancer as monotherapy, and expect to provide initial interim clinical data in colorectal cancer in 2025. We are continuing to accelerate site activation and patient enrollment in our Phase III registration trials in head and neck cancer, and have set a goal to have both trials substantially enrolled by the end of 2025. We are very excited about the promise of petosemtamab in head and neck cancer and beyond, and look forward to a busy 2025 with multiple data readouts and clinical trial progress. We really appreciate your taking the time today to participate in our call, and we welcome your questions. Operator? Thank you. If you have a question, please press star one on your telephone keypad. We ask that you please limit yourself to one question and rejoin the call if needed. Please ensure your line is not on mute when called upon. Your first question comes from the line of Charles Zhu with LifeSci Capital. Your line is open. Good morning, everyone. Thank you for taking the questions as well as this call, and happy Saturday from San Diego to your teams in Boston and Singapore. But to start off, I'm kind of wondering, is the proportion of HPV positivity in the 1,500 milligram patients that you've reported consistent with what you'd expect in a larger study? And maybe can you also remind us in a similar vein, how have you accounted for HPV-positive patients in your ongoing Phase III study with respect to trial design, sizing, and powering? And can you also remind us if there are potential differences in clinical outcomes in PD-1 clinical outcomes based on patients' HPV status? Thank you. Thank you, Charles. In general, head and neck cancer that is HPV-driven, it tends to respond a little bit less to certain therapies. It doesn't respond at all to cetuximab, but it has a zero response rate to anti-EGFR antibodies or related antibodies. But what's striking is that we've seen responses in our data set really underscoring how petosemtamab is fundamentally different or more than just an EGFR antibody. The proportion across randomized registration trials is around 21%-22%. Anytime you take a small number of patients, you're going to get variance around that. But 21%-22% in registration trials is appropriate. And as you can imagine, we have some assumptions based on to make our Phase III trial, and we've analogged around wide ranges of proportions of HPV-positive to incorporate that. Thank you for your question. The next question is from Maury Raycroft with Jefferies. Your line is open. Hi. Congrats on the update, and thanks for taking my question. I was going to ask about the CR rate, which has improved in this data cut versus your AACR 2023 data cut, and is in line with KEYNOTE- 048, but you're showing this in the second-line plus setting. So for the CRs, can you say what the tumor location was and anything about prior lines of treatment, and then contextualize how the CR data factor into your front line and also the second-line, third-line, Phase III study expectations? Good morning, Maury. It is a really interesting observation. As we've been saying for a long time in solid tumor oncology, you do tend to get a deepening of responses, and that's clearly what we're seeing. Just in solid tumor oncology in general, that's not special, and we're seeing that as well with now multiple CRs that have declared themselves over time. And we do think that this CR rate for patients out of the 27 responders is really important. And again, it underscores how this is clearly doing something substantially more than what cetuximab alone would do. And we haven't shared any further color on the nature of those four CRs. Thank you. The next question is from Michael Schmidt with Guggenheim Securities. Your line is open. Hey, good morning, Bill and team. This is Rosie on for Michael. I will echo everyone's sentiments, congrats on the progress and thanks for taking our questions. Could you maybe elaborate on your strategy for development in CRC, and do you see any read-through to the second-line CRC data next year from the head and neck data presented thus far? And then further, how do you think about the role of LGR5 in head and neck versus CRC and how that might affect the activity in each indication? Thank you. Thank you, Rosie. We know that LGR5 is a marker on certain cells in normal tissues that tend to replenish the normal homeostasis or functioning of epithelial organs in the body, and we know that it plays a critical role, especially well-defined in colorectal cancer, in being really the cells that drive cancer growth and metastases. It's less studied in head and neck cancer, so we just don't know, but we are excited to be looking now not only at second-line colorectal cancer, but expanding our studies into first-line colorectal cancer, again, with standard chemotherapy, and third-line colorectal cancer as monotherapy, and that's important as well. Because as you know from our data, having the ability to show what our drug does alone on a particular indication is very, very important. We do think these data bode well, as I said on the call, for our optimism in the potential success of the front-line program in head and neck cancer. Thank you. Your next question is from Asthika Goonewardene with Truist Securities. Your line is open. Hey, good morning, guys. Thanks for taking my questions, and congrats on the progress as well. Really encouraging to see that in the 48 patients with longer follow-up, that it looks remarkable on the duration of response, PFS, and OS, and that's kind of what was hinted in the abstract as well. I'm just wondering, in the more recently recruited patients, Fabian, you spoke about how there were some slight imbalances between the 1,500 mg and the 1,100 mg. But I'm wondering, in the more recently recruited patients at 1,500 mg, were there any differences in the baseline characteristics compared to those other 48 patients who were enrolled previously? If you can maybe comment on that, that would be helpful. Thank you. I'm not sure I really follow the question, Asthika. What we clearly saw in the dose optimization, randomization between 1,100 and 1,500 was we didn't stratify, meaning making sure that the arms were balanced for certain characteristics like HPV. And what we saw, which can happen with small numbers of patients, was a real imbalance in the number of HPV-positive cancers in the 1,500 being much greater than the number in the 1,100. It's just the law of small numbers. If you look enough at small data sets, you're going to see imbalances in all sorts of different factors. And it really underscores the criticality of making sure you stratify, meaning make sure the arms are balanced for these critical factors when you run the large randomized registration trial. So we think that's really been a consideration in the randomized cohorts. We do think our initial AACR dose expansion data set has the typical characteristics you would expect in the clinical trial that we're currently running, the registration trial that's currently ongoing. Thank you for the question. The next question is from Ami Fadia with Needham & Company. Your line is open. Hi, good morning. Thanks for taking my question, and I'd like to give congratulations on the data. Just as a follow-up to the mix of HPV-positive status, it was about 20% of patients, and we saw all of those patients having tumor in the oropharynx. Could you tell me how reflective is that of the mix of patients in the real-world setting and as well as sort of the location of tumor where you see HPV-positive status? And also, if you could confirm if you tested all the patients in the study for HPV status? And just as a quick follow-up, is there a way to give us the average duration of treatment across the 75 evaluable patient cohort versus the 48 patients with the 1,500 milligram dose? Thank you. Thank you, Ami. We haven't shared the average duration of treatment, I don't think. If it's in the November presentation, it would be shared. Otherwise, we haven't shared it, and I just don't know it off the top of my head. Regarding HPV, human papillomavirus is a sexually transmitted infection that typically infects the oropharynx and doesn't typically infect the other regions that give rise to head and neck cancer, which is why it's typically not tested and almost unheard of to have HPV-driven disease outside of the oropharynx. So while it's sort of 21%-22% overall in a clinical trial, it's a higher proportion in the oropharynx itself in these large randomized registration trials. And we've talked about this previously. It varies significantly over geography. This sexually transmitted infection is much higher in the U.S. The proportion of HPV-driven head and neck cancers is much higher in the U.S. It's sort of medium level in Europe, but it's much lower in Asia. So generally, where you run your clinical trials has an impact over the proportion of HPV, but it tends to be around 21%-22% in virtually all oropharynx head and neck cancer. Thank you. Next question is from Etzer Darout with BMO Capital Markets. Your line is open. Great. Thanks for taking the question. Congrats on the update. Just were curious about the two HPV-positive responders, whether or not they were part of sort of the original 1,500 mg cohort, or were they sort of enrolled later. And is there anything about prior treatments that would make HPV-positive patients resistant to petosemtamab in the second line versus what we've already observed in the front-line setting for petosemtamab? Thank you. Good morning, Etzer. Thank you for asking about the HPV question. So first of all, again, EGFR antibodies like cetuximab or cetuximab-related antibodies have a zero response rate. So the fact that we're seeing two responses and five patients with stable disease in our data set is actually really encouraging and again underscores just how important this medicine is as a substantial step up from currently available therapies. We've looked carefully at these two patients. We did describe one in the initial AACR data set. The second HPV-positive responder did come in the dose randomization experience, and we haven't identified anything about these two or the five stable disease as compared to the other progressive disease patients in terms of patient characteristics or prior therapy or demographics or any other feature that would lend itself readily to an explanation of why we're seeing responders. It does appear that our drug is working in some HPV-positive disease, which is really encouraging. Thank you. Next is Tara Bancroft with TD Cowen. Your line is open. Hi, good morning, and it's great to see the consistency of these data over time and with more patients, so I guess I want to turn more now towards the front-line update next year. Just quickly to confirm, that will be from the dose expansion cohort, right, and not an interim Phase III look? And then what you envision as the bar for durability, and what are you hoping to see there? Thanks. Good morning, Tara. Thank you for the question. Yeah, I will also just underscore your point, which is that we all get excited about small data sets, but when we reach numbers like 75, we can really start to be confident in the response rate, the durability, the survival curves. We really gain a lot of confidence, and particularly with the most mature data having really robust durability of duration of therapy or duration of response, PFS, and OS. It's really encouraging, so super excited to have such robust data. In terms of the front-line update, I can confirm that we are not taking an interim look of the Phase III registration trial. It is an update of the patients, the cohort that was presented, and as you recall, there were 46 patients enrolled, but we had informative data on only about half of that at ASCO. It would be an update that would be much more inclusive, and the durability endpoints are really the critical ones there. In terms of benchmarks, the most important two data points are the pembro alone, backbone therapy in this population gave a 12.3-month median survival in KEYNOTE-048 and a 17.9-month median survival as the control arm of the LEAP-010 trial. So those are really the two benchmarks that we look at that are important to have in mind. Thank you for your question. Next is Richard Law with Goldman Sachs. Your line is open. Hey, Bill and team. Good morning, and congrats on the data as well. Do you guys see a difference in ORRs across the different lines of therapy? So would you expect the ORR for HPV positive and negative to increase in the Phase III trial if you have less prior lines of therapy compared to what you see here? And also, what is the bar for accelerated approval for the HPV positive in the 2L+ setting? For example, is that 13% ORR that you see now, is that good enough for approval if you were to achieve that in the pivotal study? Thanks. Thank you, Rich, for your question. So it's a subtle but actually really important point. We're moving from a second-line plus data set that we've been talking about to a registration trial that's only second, third line. Generally, though, I would say that the second, third line patient population is going to be very similar to the second-line plus cohort that we've provided. While there were some patients who received in the data set Dr. Le Tourneau presented petosemtamab monotherapy in a later line setting, it's generally a second, third line population. So we wouldn't expect a whole lot different. In terms of the bar for approval, we've talked about how we believe that an overall response rate with some durability is an important metric for approval. Project FrontRunner is new, and Dr. Pazdur and others have made comments about Project FrontRunner, this concept of using an early endpoint in a randomized registration trial to seek approval and then have that confirmed by overall survival in the same trial. So we don't have as many precedents to stand on to point to, to say, "This is exactly how it's been done in the past." But in general, we believe that it's the overall population we're evaluating, which includes HPV positive and negative disease in a holistic way, and that overall response rate in the holistic population has to win against the control arm, which, as you know, in this second, third line trial is an investigator's choice of single-agent chemotherapy or cetuximab following KEYNOTE-040 or CheckMate 141 precedent clinical trials. We do think that our results to date compare very favorably, and I'd refer you to those publications of those KEYNOTE-040 and CheckMate 141 trials. We're really very encouraged that especially in a large data set of 75 patients, we really do have robust data to support this. Thank you for your question. Next is David Dai of UBS. Your line is open. Hey, thanks for taking my questions. And again, I want to add my congratulations on the data here. So I just want to talk a little bit more about the safety here. The safety looked overall clean, but we did see a few more cases of dermatitis, a few more cases of blood magnesium decrease. So maybe just help us understand some more color on these patients with grade 3 dermatitis and blood magnesium decrease. And then another patient, it seems like there's one patient that was discontinued due to investigator judgments. Maybe just help me understand some more color on that patient discontinuation. That'd be very helpful. Thank you so much. Thank you. Yeah, in general, as we get to larger numbers, we get to a little bit more precision on the numbers around the safety characteristics. And as you look at the safety profile in Dr. Le Tourneau's presentation, the main thing I want to point out is that this is a very well-tolerated medicine. I'll speak about IRRs in a minute, but outside of IRRs, the rates of grade 3 or greater dermatitis, blood magnesium decreased, rash, they're essentially not different from what we've been showing previously, and they do appear numerically to be much lower than what I might have expected with cetuximab or an anti-EGFR therapy. So I do think the safety profile is very encouraging, both as a monotherapy and in combination. We've seen the safety data in combination with pembro, but it does really open up the opportunity for us to dose our antibody with standard chemotherapy for colorectal cancer and other cancers, for example. So I think it's very encouraging in that regard. And especially when you think about the control arm therapies in the registration trial is single-agent chemotherapy, and that's not easy, right? Or cetuximab, and we just spoke about cetuximab. We have seen IRRs, infusion-related reactions, and as you've seen in Dr. Le Tourneau's presentation, the new dose instructions really have substantially ameliorated the rates of infusion-related reactions. We think it's manageable now at the site. And the one discontinuation due to investigator judgments, I don't at the moment have any further color on that. Next is Sebastiaan van der Schoot with Kempen. Your line is open. Hi Bill and team. Big congrats on the string of great updates over the past week. I wanted to focus on the Phase III registration studies in the head and neck, which maybe provide some color on whether the rate of enrollment has been in line with your internal expectations, and do you think that the historic rates of enrollment for registration studies are a good benchmark for PD-1? And then maybe also, do you notice any differences between the willingness of centers to enroll patients in either the first or the second line study? Thank you. Good morning, Sebastiaan, or good afternoon if you are in Europe. Thank you for the question. We are really excited about our progress on the registration trials, and we've commented on the call about accelerating enrollment. So these trials, we are generating a tremendous amount of enthusiasm coming out of ASCO, the clinical data, and now even early discussions in Singapore with these data have really helped us catalyze a lot of investigator enthusiasm and site enthusiasm for this. We do think that the KEYNOTE- 048 for the front-line trial and KEYNOTE- 040 registration timelines, timeframes, size scope of the clinical trials are good benchmarks for us. They're ambitious. Both of those were run by Merck, which is a very, very good execution oncology company. But I think as you were commenting on earlier, our goal as a company is to be really good at execution, to put our heads down, to make a commitment publicly and within the company, and to really hit that commitment. And we're really proud of having the zenocutuzumab partnership, the zenocutuzumab approval, which is incredibly important for patients, and now continuing to execute effectively on the registration trials. Thank you. Next is Bradley Canino of Stifel. Your line is open. Hey, good morning, and congratulations to the company on the zenocutuzumab approval earlier this week. It's great to see that outcome and the new commercial partner. Going back to the original dose escalation you reported for petosemtamab in 2021, it stated that more than 99% receptor occupancy was achieved for two weeks at doses above 750 milligrams. So can you talk about why the clinical data might have ended up showing such a large difference? You mentioned the steady-state exposure of 1500 is much higher, but why might that have manifested in outcome differences given the original PK predictions were good for both? Thank you. Thank you, Brad, for your question. In terms of the pharmacokinetics, we do see high exposures above 750 milligrams, but we do believe, and I think the early response rate data from 1100 versus 1500 are certainly starting to suggest that fully covering the targets is critically important. And here, not only the mathematical estimate of covering EGFR, but also how we interrogate and interact with LGR5 we think is critically important. And as we've talked about, LGR5 is a dynamic receptor that cycles from the surface into the cell and mediates or facilitates EGFR clearance and degradation off of the cell. It's a complex biology, but we do think the dose and exposure at the higher level, 1500 milligrams, really is important for the full biological effect. What's interesting and a bit ironic is that the response rate at 1900, and again, small number, so I don't want to read into it too much, but the response rate at the 1100 milligram dose is 19%, which is sort of a cetuximab-type response rate in this setting in head and neck cancer. So it certainly does feel like the full 1500 milligram dose of petosemtamab may be needed for both EGFR and LGR5, which is where we think our drug is really working. Thank you. Next is Matt Phipps with William Blair. Your line is open. Hi, great. Thanks for taking the question. This is Madeline on for Matt Phipps. We had one on petosemtamab development in CRC. How are you thinking about competition with other EGFR-targeting therapies like amivantamab and development in the CRC space? Thanks. Good morning, Madeline. We are really excited about the potential for petosemtamab in colorectal cancer because that is where petosemtamab was discovered in models of colorectal cancer, and that's the cancer type in which the LGR5 positive cell driving cancer growth and metastases has been so well defined. We are now currently exploring second-line chemotherapy in colorectal cancer. We've announced today both first-line with chemotherapy plans and third-line monotherapy plans to initiate next year, and we're really excited to be looking broadly in colorectal cancer in these different cohorts. Importantly, we've guided initial interim clinical data expected in 2025. The competition is certainly there. There is competition. I think all of you are aware of the ORIGAMI trial from Johnson & Johnson using amivantamab that has shown some early intriguing single-arm data from a small subset of patients and their plans to move into registration trials in that setting. So that is something we're paying close attention to. But personally, I think if our drug is going to work in an indication beyond head and neck cancer, I really believe that colorectal cancer is the best shot out there. And we're super excited for the opportunity because it's a real opportunity to bring a new medicine to so many patients. Thank you. Next is Tony Butler with Rodman & Renshaw. Your line is open. Bill, I'm curious about how one might think about KEYNOTE-689, which I guess once it finally reads out becomes standard of care, albeit in locally advanced disease, and enrollment and/or the market, at least in second-line PD-1. That's part of the first question. And part B is, if we go back to the HPV positive patient population, do you have any information on whether at least those seven patients that showed stable disease or response were all smokers versus those who may not have been smokers? Because there is a view that maybe EGFR could be upregulated in the smoker population. Thanks very much. Thank you, Tony. Let's take them in reverse order. The question around why are patients with HPV positive disease responding to petosemtamab, and could smoking be a way that they could be responding to EGFR-type antibodies to upregulation of EGFR, is something that's plagued us now for about six months. There's just no basis in factors or cancer biology or clinical data to support that. When you look across all the recent studies using cetuximab alone, the response rate to cetuximab in HPV positive head and neck cancer is zero. Not a single responder. Doesn't matter if they smoke and have elevated EGFR or not. It's just zero. And so this concept that maybe the patients were smokers and could be responding as a result is a lot of smoke and mirrors. It's just not true. The 689 question, let me share with everyone on the call. The KEYNOTE-689 is a study of Keytruda, pembrolizumab in the locally advanced setting where patients get it in the neoadjuvant setting prior to definitive local therapy and then in the adjuvant setting. And that had a dramatic effect on keeping the cancers away for a long time in patients with local disease before they develop recurrent or metastatic disease, which is the population that comes to us in the clinical trials that we've been running. And the question is, would that impact our clinical trials or commercial opportunity? In terms of the clinical trials, we are hoping to be substantially enrolled by the end of 2025. So we think we'll be out in front of this. But if our enrollment were to push out much longer, one might see an effect. Or for other clinical trials in this space where the enrollment might take much longer, it might be impacted by KEYNOTE-689. In terms of the commercial opportunity, we don't yet see any sign that it's increasing the number of cures. It's very hard to cure cancer. So we don't yet see any decrease in the potential commercial opportunity at all. But we would need to see substantially different survival curves for that to be true. So we think there could be some impact down the road in three, four, five years from now in terms of the patient flow, but we have yet to see any other impact in that. I wanted to thank everyone on the call for participating, taking your time this morning to listen to our call and to ask such engaging questions. Thank you. This concludes today's conference call. Thank you for joining. You may now disconnect.