Thank you guys for joining us for our next fireside chat. I'm happy to be here with Merus CEO, Bill Lundberg. My name is Ben Burnett, biotech analyst here at Wells Fargo, filling in for Eva Fortea-Verdejo. Thank you for being here. Great, thank you, Ben. Great to reconnect with you. We miss Eva today, but excited for her and her family, and really appreciate the relationship we are developing with Wells Fargo. Great. I think maybe just get us started with kind of talk about near-term events that investors should be focused on. Absolutely. First bit of background for those of you who aren't as familiar with Merus. We're an oncology-focused company with a number of clinical assets of our own and a number of clinical assets with our licenses and partners, including Incyte, Loxo, or now Lilly and Gilead, and others. We've been innovators in the field of bispecific antibodies for a number of years, really developing what we believe is a profoundly important platform technology that allows us to develop bispecific and multispecific antibodies like monoclonal antibodies. The reason that's important is because we know how to make really good medicines out of monoclonal antibodies. The fundamental belief we have at Merus is that the more that we can mitigate the risk of each of the individual steps of developing new medicine, the more that we can improve the chances that we can make a really good drug for patients. This includes things like the discovery process using true high-throughput screens or being able to evaluate these drugs as monoclonal antibodies for the developability from the very beginning, not needing to invent new ways for process development, being able to leverage all the well-established CDMO or manufacturing capabilities globally for monoclonal antibodies, and all of the IgG engineering that allows for stealth silencing for T-cell engagers or immune activation such as ADCC to optimally engage the patient's own immune system. Our platform technology, our foundational approach, is compatible with the standard linkers and toxins that are used for antibody drug conjugates. This doesn't guarantee success in the clinic, but what I think we've seen now with certainly three out of four of our clinical stage assets is that it certainly seems to improve the chances substantially and has led us to have molecules like BIZENGRI, which we received approval for last year, and petosemtamab, which is going to be the subject of 99% of the discussion today, which is showing really important activity in head and neck cancer, substantial for other cancers beyond head and neck cancers as well. Okay, fantastic. I think you've generated a lot of data in head and neck cancer with petosemtamab, but I think you have some colorectal cancer data coming up. Is that right? That's right. We've presented in a number of presentations really robust clinical data in head and neck cancer, what I believe to be truly compelling efficacy data and very strong safety data in head and neck cancer. One of the important questions we have for petosemtamab is just how big can this molecule be? How important in medicine can it be for patients with solid tumors beyond head and neck cancer? The cohorts that you're talking about are three different cohorts in genetically wild-type metastatic colorectal cancer. We've been enrolling these now for a number of months, and we've guided a clinical update in the second half of the year on our colorectal cancer program. Oay, fantastic. Maybe with that data coming up, can we talk about the mechanism of action of these two targets and their applicability to colorectal cancer? I guess part of that will depend on the line of therapy, depending on whether or not patients have maybe seen EGFR. How do you think about the mechanism of action in this context? Yes, so petosemtamab is a bispecific antibody that binds on one arm to EGFR, which is a well-established target, the epidermal growth factor receptor, and is the target of well-established and successful medicines such as cetuximab and panitumumab. The other arm we discovered by doing a large-scale screen. Here we take the monoclonal antibody approach of letting the biology really select for us what is a really good partner for an EGFR binding arm. This is where the screens themselves pulled out a series of molecules that bound with the other arm to LGR5, the leucine-rich G protein coupled receptor 5. We didn't set out to make an LGR5 bispecific, but this is what the biology taught us had the best activity in relatively sophisticated screens against organoids that were derived from cancer as compared to normal and the bispecific as compared to the single arm alone. This really allowed us to discover what we believe is a very potent molecule. We've done a series of preclinical studies showing that this molecule has little outsized activity in colorectal cancer models. In addition, over the past number of years, the biology of these LGR5- positive cells has been elucidated by a number of the top academic labs in the world, showing in normal organs such as your colon, the LGR5 cell plays an essential role as being the adult stem cell of the colon. In cancer, it appears to play a similar role where the LGR5- positive cell does appear to be the source of the cells that drive cancer growth and metastases. Really having this LGR5 mechanism that we appear to be targeting is incredibly important. At a molecular level, we think our antibody does three things. One, like cetuximab or panitumumab, it blocks the interaction of the EGF growth signal with EGFR. Two is that because of this linkage with LGR5, we believe that the whole complex gets internalized and EGFR and LGR5 get degraded by the proteasome degrader complex. Three is the enhanced immune-engaging nature of the bispecific. It's fully ADCC enhanced, leading to optimal engagements of the patient's own immune system. We think each of these contributes to what we're seeing today, this really outsized activity in head and neck cancer and what we believe to be a real potential in colorectal cancer and potentially beyond. On that LGR5 piece, is it known what the expression is generally in CRC? How does that compare to head and neck? Yes, LGR5 is believed to be expressed in only a subset of cells within a cancer, just like it's only expressed in a subset of cells within our normal colon. Those cells really are the cells in the case of normal tissue that replace the epithelial lining and maintain organ homeostasis. In the setting of cancers, those really are the cells that drive cancer growth and metastases. The levels of expression appear, to the best of our ability, to be similar in this regard. Okay, excellent. Maybe just in terms of the data that you've generated here in colorectal cancer, could you maybe speak to some of those, the efficacy and safety data? Really on the safety side, what are the adverse events that are sort of characterized here and how are physicians kind of dealing with those adverse events? Those are two parts. First, the safety of petosemtamab, which I'll speak about, and then what was our initial data in colorectal cancer. From a safety standpoint, we have over 120 patients treated with petosemtamab in head and neck cancer alone. That's both monotherapy and in combination with pembrolizumab or KEYTRUDA. We have additional data from other small cohorts that I'll speak to. Generally, petosemtamab is very well tolerated. There is a range of grade 1, grade 2 AEs that you would expect from a drug like this. It also has EGFR-associated safety findings, skin rash, and associated gut toxicity. Numerically, it appears to be a little bit less than the EGFR bispecific cetuximab, panitumumab, but generally very favorable. The one safety event category that we have discussed extensively is that infusing this antibody and other EGFR bispecifics has been associated with infusion-related reactions. These are virtually all first dose. After a patient has gone through the first dose, they're generally fine. Currently, with our premedication and management regimen, this occurs in about a third of the patients with really a single-digit proportion of patients getting grade 3 or greater events. Typically, you slow down or stop the infusion. Every patient who's been restarted has been rechallenged or restarted fine. We believe it's at a place where it is manageable. Okay, excellent. I'll do better about asking one question at a time. Oh, yeah, I was going to comment on the phase 1 data. I forgot the second question. Interestingly enough, this along with having really good basic science rationale, initial preclinical data in colorectal cancer, and if our drug's going to work anywhere, we really would believe colorectal cancer would be the place. We do have early clinical experience in colorectal cancer as well. The first population of patients we chose to evaluate in dose escalation were patients with colorectal cancer. At the top dose levels, 750 mg, 1,100 mg, or 1,500 mg, we saw no responses in those 10 patients. In retrospect, as we look back at that experience, this was a heavily pretreated population of phase 1 center- type patients with either a high degree of mutational burden in the cancers or the patients having received extensive prior EGFR antibody therapy. Unlikely to see a response or a high response rate in that setting. We decided to go back now into colorectal cancer, addressing these issues where the earlier line of therapy, no prior cetuximab for the first and second line, genetically wild-type, is the population we're now studying. What should be the expectations or what do you want to see from these three different cohorts to kind of move this forward? In colorectal cancer, and this is microsatellite-stable or non-mutator phenotype and genetically wild-type metastatic colorectal cancer, so no RAS or RAF mutations, there's a literature on how cetuximab does with chemotherapy in the first line and second line. It's a 5-FU, 5-fluorouracil-based chemotherapy called FOLFOX or FOLFIRI. I can point to how cetuximab does as the benchmark that we will be compared to. Generally, in the first-line setting, the response rates are around 65%. In the second-line setting, response rates are around 30%. This is roughly ± 5% to ± 10%, depending on which study you choose to look at. Those are the benchmark or analog studies for what's currently available for patients today. There's an additional molecule, imivantamab, which is an EGFR bispecific, not with LGR5 on the other arm, but instead with MET, the arm that binds to the HGF or scatter factor receptor. That has shown some very early data that's similar to the EGFR cetuximab numbers that I just cited there. Excellent. Do you have a sense for enrollment timelines and whether or not some of these data, in certain cohorts, could become more mature before the others? We have guided a clinical update the second half of this year. We generally prefer to provide our clinical updates at medical conferences, and we haven't provided any more specificity than that. What I have said is typically our signal-seeking cohorts, like these types of studies, are around 20 patients, the size of the cohorts we aim to enroll. We are actively enrolling all three cohorts. This is a first-line with chemotherapy, a second-line with chemotherapy, and a third-line monotherapy cohort, third-line plus monotherapy cohort. This will be an early look at the data. Two of these cohorts only started around the beginning of the year this year, so not a lot of time to have any duration of follow-up. We believe it's important to share our early signal-seeking data. Okay, great. Maybe just one last question around this program, just in terms of the sort of the next steps, should these data be positive. I guess, would you expect to kind of go through a similar Project FrontRunner style design as what you're doing at head and neck? It's a really interesting question. Just a word on head and neck cancer. Our two phase 3 registration trials, which you may touch on in a minute, are designed such that there's an early efficacy look based on response rate, ORR, overall response rate, and a later endpoint with final ultimate survival. We believe, and this is based on direct conversation with the FDA and public comments the FDA has said, that we have the opportunity to consider accelerated approval for our drug in each of these two trials based on an early endpoint such as ORR. In our case, it is ORR with confirmation coming with survival in the same trial. This is the framework that's called the Project FrontRunner framework. The first drug that got approval under Project FrontRunner was BRAFTOVI, approved just at the end of last year, and received accelerated approval. The question of whether this is possible in colorectal cancer is actually a really interesting one. Historically, colorectal cancer has been a disease where PFS and, more importantly, overall survival has been the endpoint leading to approval. What's interesting about this first Project FrontRunner example is that it actually was in colon cancer. The notion that Project FrontRunner could be possible in colon cancer is quite interesting. I don't have any more specific comments about it other than that. I do think it's worth noting. Okay, great. I want to move to head and neck. Before I do, anyone in the audience have any questions around colorectal cancer? Let's talk about the head and neck program. I think you've kind of given us a little bit of a preview there, but maybe just remind us about the data that you've generated in first and second line. We have provided updates on two different cohorts of patients with head and neck cancer. This is recurrent or metastatic head and neck cancer. The journey of a patient with head and neck cancer is typically they get diagnosed with some local disease. There is a local treatment given for that local disease. Some of those patients are cured. Some of them are not cured. They recur either locally or with metastatic disease. They go on to systemic therapy. That is the population we are talking about, recurrent or metastatic head and neck cancer, which requires systemic therapy. We have provided both first-line treatment data and second-line treatment data. I will talk about both of these. In the first-line setting, standard of care is a pembrolizumab-based regimen that typically provides as monotherapy a 19%- 25% response rate and median overall survival of around 12.3 months- 17.9 months or a 12-month survival rate of around 50%- 59% as a landmark analysis. Patients can also be treated with pembrolizumab plus chemo. The response rate is a bit higher, around 34%. Survival is not much better. It does not really improve survival. In this context, we have tested our drug, petosemtamab, in combination with pembrolizumab in 43 evaluable patients and reported this at ASCO this year. Importantly, what we have seen is very strong efficacy data across a number of different metrics and very good safety data in combination. In terms of efficacy, we saw instead of the 19%- 25% efficacy you might have seen, we have seen an almost tripling of that to 63% response rate and responses across all major subtypes, HPV-driven and HPV-negative cancers, cancers that express high levels of the KEYTRUDA target PD-L1, cancers that express low levels of that. It has really been a very strong data set. In terms of durability, we saw almost 8 out of 10 patients alive at one year. That is an unprecedented number in head and neck cancer. That has never been reported for a population being treated with recurrent metastatic head and neck cancer. It gives us high confidence, both the strength of the data and the consistency across all these metrics, that we really have a drug that has high potential to be meaningful for patients with head and neck cancer. Importantly also, petosemtamab, it is not only us, but the FDA has granted petosemtamab breakthrough therapy designation, both in this first-line setting and in the second-line setting that I will talk about in a minute. From a safety standpoint, again, there was the safety profile that has been reported that I described earlier for petosemtamab monotherapy. There is a safety profile associated with KEYTRUDA. There were not any overlapping amplified toxicities of the combination. It is very well tolerated. That is really what has given us high confidence going into this phase 3 registration trial. In the second-line setting, if I can keep going, if that is okay. Sure. We reported updated data on 75 patients with recurrent metastatic head and neck cancer after they had already progressed on IO agent, typically pembrolizumab or KEYTRUDA, and platinum-based chemotherapy. In this population, typically single-agent chemotherapy or cetuximab alone would give you a single-digit to 13% to mid-teens response rate and a median survival of around six to eight months, roughly. What we saw was not a teens response rate, but almost a tripling of that response rate to 36%, a much longer progression-free survival, and an overall survival in the patients with the longest follow-up of 12.5 months. All of these updates and presentations are available on our website. You don't need to write all these numbers down. You can just go to our website and look at the presentations yourself. Again, a very favorable safety profile. I will comment again on the infusion-related reactions when you can see the data on our website. I believe that is being well managed at this point. Both the strength of the data and the consistency across combination, monotherapy, first line, second line, overall the patient subsets, the different efficacy endpoints, the safety profile across the entire population really give us high confidence in petosemtamab in head and neck cancer. That's really why we've been so interested in exploring the potential beyond head and neck cancer and colorectal cancer. Okay, great. Now, I think the first-line landmark PFS data, OS data, excuse me, that you mentioned, 80% just about, I think that's pretty incredible. What did the data show in terms of the historical data, in terms of how predictive that is of median survival? Is there any data that implies that it might be different based on HPV status? With respect to your first question, how meaningful is 12-month survival rate for median overall survival? The single best predictor of how survival will go in a clinical trial is basically survival. Like, how does it look a year in? When you look at a wide range of head and neck cancer studies, there's a really good correlation. High 12-month survival rates really do correlate with long median overall survival. The delta between 50% to 59% to almost 80%, that's 21%- 29% difference in the 12-month rate. That is a rate that's incredibly high. In other settings that we've been able to find, it has been associated with a substantial prolongation, maybe even potentially doubling or more of the survival rate. We think it gives us high confidence around the overall survival. One of the questions you've now asked has to do with how does survival differ between patients who have cancers driven by smoking, drinking, carcinogens versus head and neck cancers driven by the human papillomavirus or HPV-positive head and neck cancer. There is a limited amount of data available on this topic. Most studies don't break out HPV positive and negative. Retrospective studies, which can be fraught with all sorts of bias, suggest that there may be a bit of a difference between HPV positive and negative data. When we look at our own data and we remove the HPV positive patients from our overall population and ask, how does survival do, survival is actually a little better. We don't see a dramatic difference in survival. Again, our data set is small numbers of patients, so I don't want to read too much into it. It's basically similar in our own data set. Okay, great. You know, another thing is there's a lot of biomarkers here potentially. You have HPV status, obviously PD-L1 status, but also EGFR scores and the like. What's the FDA's view on how do they view, or actually, what is the FDA feedback in terms of how they view head and neck cancer patients? Do they care about these biomarkers and showing activity specifically within subgroups or just overall? This comment that I'm about to make is generic for oncology approvals. When the FDA looks at a data set to take into consideration for approval, they will look across all the different subgroups that they can to look for consistency of your data across the subgroups. It's an important metric for them to have confidence in the results as well. Generally, though, I will say the last five registration trials in head and neck cancer have been for the entire population with the one caveat that KEYTRUDA itself as monotherapy was approved in the population of patients whose cancers expressed the KEYTRUDA target, PD-L1. That's the one wrinkle. In general, it's for all patients regardless of whether it's HPV-driven or carcinogen-driven and whether it's EGFR high or medium or low or any other characteristic like that. Okay, great. Maybe we can talk about the design of your study. What have you said about kind of the stats for the first and second line study around the interim analysis? What we've described is a registration trial that compares our experimental arm. In the first line, it's KEYTRUDA with petosemtamab, our drug. In the second line, it's petosemtamab alone against a standard control arm, which is the standard therapy patients would otherwise receive. In the first line setting, it's KEYTRUDA or pembrolizumab alone. In the second line setting, that control arm is an investigator's choice of cetuximab or single-agent chemotherapy. Both of those trial designs, first line setting and the second, third line setting, follow very closely prior registration trials in head and neck cancer. These trials have historically been around 500 patients each and there are numerous examples of this. Typically, the endpoints for efficacy have included, for example, ORR and ultimate overall survival. Our trial design, as we talked about, follows this Project FrontRunner rubric where the initial efficacy look is based on response rate for potential consideration for accelerated approval and overall survival for ultimate confirmation of benefit or traditional or regular approval. Would you expect EGFR scores, and I don't know if you're capturing this, but LGR5 scores in the pivotal programs or in these later stage programs to be similar to sort of the mix of patients that you enrolled previously? Generally, yes. The proportion or most patients with head and neck cancer, their tumors do express medium or high levels of EGFR. LGR5 is a marker that is much harder to detect. There are not good assays for immunohistochemistry from, say, patient biopsies. Generally, we measure RNA levels. The rates of levels of expression have been consistent in our populations. Excellent. Just a couple of commercial questions. Was there a question? A couple of commercial questions. How big do you see the opportunity in head and neck? Head and neck cancer, we believe today currently is around a $4 billion market globally. I'm not a commercial expert. I would encourage you to go to the commercial slide in our corporate deck for these details and also the citations that support these numbers. We do believe that a new medicine with a substantial greater efficacy, substantial greater durability has an opportunity to make a meaningful impact on the overall market opportunity as well. I think a big part of the commercial opportunity also is just the duration the patients are on therapy. I guess when you think about that $4 billion number, what is sort of the duration you're thinking per patient? We haven't guided a specific duration in terms of our numbers. One can simply look at the average duration of therapy of currently available therapies to get a sense of what they are today. We do believe, given the strength of the data we've seen and the data we presented most recently at ASCO this year, that that does represent a substantial increase in durability compared to what, say, in the first line, KEYTRUDA alone would afford patients. Okay. In terms of, you have a couple of different cohorts here. What have you said about the enrollment timelines? Would you expect the front-line cohort to enroll faster? We have two phase 3 registration trials ongoing in head and neck cancer. One is the first-line trial, the other is the second- and third-line trial. We started them around a year ago, the second- and third-line trial a little bit more than a year ago, the first-line trial just about a year ago. What we've shown is an incredibly rapid acceleration of site activation and country activation. That is the single best predictor of how a clinical trial is going to enroll. Currently, both trials have more than 150 sites active and actively screening and enrolling patients. When you get to this point, this is the point at which enrollment really catalyzes and takes off dramatically. It's incredibly important to get the studies up and running quickly. It's really based on our site activation and country activation that gave us the conviction to guide that we would be substantially enrolled in both trials by the end of this year and that we would expect top-line interim readout of one or both trials next year. We're really pleased by site activation and really pleased by enrollment and the progress of the phase 3 trials. Has Merus said the number of sites that you think could potentially need these studies? We have not said specifically our number of sites. We have pointed to an analog study, KEYNOTE- 048, as a good analog to look at the size and scope of how big these trials need to be. I think last question for me is just talk about your cash position and the catalyst that you think that funds the business through. We have a strong balance sheet with $892 million. That is sufficient to run the business at least into 2028. Importantly, that finances us through top- line readout of both phase 3 registration trials and beyond. It puts us in a really strong position to be able to focus on executing on these phase 3 trials and doing the right thing for giving petosemtamab a best chance to be a medicine in head and neck cancer. In addition, explore additional opportunities such as colorectal cancer, which we think could be very important for the medicine in terms of demonstrating the breadth of potential for petosemtamab. Okay, all right. Great. Thank you so much. Thank you, Ben.