Right. Good afternoon, everyone. Day one of the Leerink Partners Healthcare Conference in sunny Miami. For everyone listening on the webcast, I'm sorry you're not here joining us. Maybe next year. It's beautiful outside. We're very excited to have Merus with us. We have Bill Lundberg, the CEO. I'm Andy Berens, Senior Biotech Analyst here at Leerink Partners. This will be really a forum for you guys to ask questions. Just raise your hand, and I'm glad to let you ask your questions. I have my own. Why don't we get started, Bill, give an overview of Merus for those who may not be familiar with your company? Sure. Happy to. Let me start by saying thanks, Andy, for the longstanding partnership and continued support. Really appreciate it from not only you, but your entire team and Leerink as an institution. We really do appreciate it as a company. I should also say that I may be making forward-looking statements. There is a disclaimer slide on our corporate deck. I would refer you to that for reference. Merus is an oncology-focused company. We have multiple clinical assets of our own in clinical development and a number of assets with our partners and licensees. This is all based on our particular multispecific antibody technology. While there are many different multispecific and bispecific technologies and approaches out there, we think ours is particularly unique in that we really strive to make bispecific antibodies just like monoclonal antibodies. The reason that matters to all of you is because we, as an industry, know how to make really good, successful medicines out of monoclonal antibodies. We've been doing it for years or decades. The more that we, Merus, as a company, can rely on well-established approaches and processes and procedures to make good medicines, the better we think we'll be at actually getting a drug that has meaningful activity. For example, we can make our bispecific antibodies in a single cell, essentially like a monoclonal antibody, which allows us to stand on all of the tricks of making monoclonal antibody drugs with high-throughput screens, letting the biology select the best candidate molecule to take into the clinic. These are fully human IgG1 molecules. All of the Fc domain engineering that you can do with an IgG1 molecule, stealth silencing for T-cell engager approaches, or ADCC enhancement, these are all very well-established, as are process development and manufacturing approaches with global availability of monoclonal antibody manufacturing to allow us to have multiple redundancies to ensure the best approaches for process development and manufacturing. This is a really powerful approach to make our drugs just like monoclonal antibodies. While it does not guarantee success in the clinic, we think it improves the chances that the drugs that we make will actually be meaningful. If you look across the five drugs we brought into the clinic, three have already shown really striking clinical activity. Our drug, MCLA-129, an EGFR-MET bispecific, is just like J&J's Rybrevant. It has shown really important activity in non-small cell lung cancer in a couple of different settings. The challenge there is just we're behind Rybrevant. Zenocutuzumab, now trademarked Bizengri, has gotten approved. We've gotten this drug approved in NRG1 fusion cancers with really striking clinical activity in that indication. Where we'll spend most of the time, petosemtamab, our EGFR x LGR5 bispecific, really outsized activity in head and neck cancer. This is the basis of the company. Again, we have a fundamental belief that the more we can do to risk mitigate our approaches, the more we can do to stand on tried-and-true approaches to make medicines, the better off we'll be in bringing things to the clinic and ultimately to approval. Great. Thank you, Bill. Why don't we talk about head and neck and peto, and then we'll probably migrate into colorectal cancer with the data coming at the year-end. Just remind everyone, if there's any questions, please raise your hand, and we'll let you ask the question. Peto, you've already shown us some combination. That's obviously important to the frontline strategy. Can you remind us what data sets, what data you've shown that you presented, and then what's coming this year? I know you haven't disclosed the meeting, but I think it's coming up in the next few months. Petosemtamab is our bispecific antibody. One side is an EGFR binder. The other one binds to this molecule, LGR5. We didn't set out with the brilliant insight LGR5 is the thing to target. We asked the question, what can we add to an EGFR family binder on one side that will give us outsized activity, much better than EGFR alone, and much better activity in tumor models as opposed to normal tissue models? Specifically, the development was done in colon cancer. What we pulled out was multiple instances of this binder to LGR5. It turns out it has pretty unique activity when in combination, LGR5 and EGFR, it appears to completely strip EGFR off of these cells and lead to EGFR degradation. A really potent ability to target these particular cells. Had outsized activity in a variety of preclinical models, we can get into the mechanism in a minute. We showed initial data both in the second-line setting, where our drug had outsized clinical activity with a response rate of 36% in 75 patients with really good durability and time-to-event endpoints, as compared to cetuximab alone, which has a 13% historical response rate in the label. More recently, what you were getting at was at ASCO 2024, we presented data of our drug, petosemtamab, in combination with standard therapy, pembro, where pembro has a 19%-25% response rate. We showed a 67% response rate. A dramatic increase in first-line head and neck cancer. What we've guided is to provide a clinical update on these data at a medical conference in the first half of this year. The overall population size is 45 patients. We described that in the demographics and patient description in our ASCO 2024 presentation. You could look at those characteristics. We'll have the larger patient population. We'll have updated efficacy data, safety data, and importantly, durability data at that presentation. That's our intention. OK. When you say larger, you mean more than the 45 or still? 45 is the number of patients enrolled. OK. We've subsequently started a phase III registration trial, which is really our priority for enrolling that trial. OK. When did the frontline patients start enrollment? Of this phase II cohort? Yes. It was a good number of years ago. We showed seven patients' data in AACR 2023, I think it was. You can look at the presentations on our website to get the earliest data set. Actually, it was a second half of the year 2023 presentation of the initial cohort of patients, I think. You'd have to go back and look at the numbers. We showed an initial 37% cohort at AACR. We showed 75 patients as monotherapy in ESMO Asia in December of this year. Importantly, let's go back to the ASCO 2024 presentation for the combination of petosemtamab with pembro. That cohort, data cutoff date was March 6. All the patients had been dosed by that date to give you a sense of what the follow-up will be. OK. When we think about OS, and OS is important, I think, because some people are still concerned that maybe PFS and ORR do not always translate to an OS benefit. We saw that with a combination strategy, the LEAP-10 trial. We would have, it sounds like, a fair number of these patients. Maybe all of them would be at 12 months at that point of dosing. We have not guided to a specific medical conference in the first half. I do not want to give too granular a sense here. All the patients had been dosed, had received at least one dose by the March 6, 2024 data cutoff date. OK. It'd be good follow-up. OK. Because we'll be comparing it to Keytruda eventually in the frontline trial, the pivotal trial, what would be Keytruda's performance at 12 months? How many patients would be alive? Yeah. This is something I point to. People do try to extrapolate from response rate or PFS to OS. My first response to this is, if we want to talk about OS, let's look at the OS data as the best predictor of how OS will behave. Importantly, with Keytruda alone in the two recent studies, KEYNOTE- 048 or LEAP-10, Keytruda alone has a rate of survival, a 12-month landmark OS percentage of 50% and 59%. That's an important statistic for people to pay attention to as you evaluate our data and think about how promising it is in terms of performance for the ultimate endpoint in a phase III trial. Ultimately, all these drugs have to win on overall survival in order to get approval. OK. 50% and 59% are the hypothetical bar. While we didn't go into great detail about discussions of the clinical data we presented at ASCO 2024, I will note that the data provided had a median follow-up, an average follow-up of 3.6 months. In other survival curves from KEYNOTE- 048 or LEAP-10 in this population, typically, even at three, three and a half months, you already see a decrease in the survival curve of around 15%. In our disposition table, we described only one of the 45 patients who had died and two who were discontinued and were lost to follow-up or, I should say, withdrew consent, actually, is the right term. While it's early days, we're reading tea leaves at the bottom of the cup, the little data that we had at that presentation was already quite encouraging. The curve for Keytruda, the OS curve, I would assume, obviously, it's only about a fifth of the patients respond. It's really driven by the median numbers driven by patients that are non-responders. Is that a fair assumption? That's right. The difference between the Keytruda historical data is that only about 19%-25% respond across these two studies. The majority of patients that make up the curve are non-responders. What we've shown in our early look at our data was 67 patients responding. The median, the middle patient, where the medians will be, by definition, will have been a responder in our data set, which makes a really big difference. Right. OK. Sounds encouraging. We look forward to the data somewhere in the first half of this year, maybe Chicago. We'll see. In terms of the competitive environment, we obviously have Bicara. We have some small molecules other than Lenvima that are being tested. What do you see as the main competition for peto eventually when it's approved? In the second-line setting, we're running a phase III registration trial. We don't see any significant competition. In the first-line setting of pembro plus petosemtamab, we're running our phase III trial in that setting. There are a number of competitors for people to pay attention to. There are three programs in the first-line setting taking all the patients. This is us, zanzalintinib from Exelixis, which is a similar trial design of pembro plus zanza versus pembro alone in about 500 patients. There is an Akeso program in China that's likely to only be relevant for the China market and not relevant for the U.S. market. There is a fourth program only in the subset of patients with HPV-negative head and neck cancer. This is Bicara's BCA101. Generally, I think in the overall population, we'll see zanza's initial phase II component of their phase II-III approach. The drug itself is a multikinase inhibitor. It's a drug that has no prior data in head and neck cancer. We don't really know how that's going to turn out. Historically, these multikinase inhibitors have had difficulty with tox issues, have been difficult for patients to take, particularly swallowing a pill in head and neck cancer can be difficult. We don't have any data. It feels like an unknown. In the smaller subset of HPV-negative cancers, BCA101 is pursuing an approach in HPV-negative head and neck cancer. What they've taken is an all-comer phase II trial and retrospectively, or in a post-hoc way, looked at and identified the patients that performed the best retrospectively in a post-hoc way in this combination therapy. They're moving forward with that retrospective subset into a phase III registration trial. We do not know prospectively how the data will perform. Retrospectively, you can always identify the best performers and choose those patients to move forward with. Moving forward, we do not know if that outsized effect was really the drug that they are interested in, BCA101, or it was the backbone therapy it was given with pembrolizumab or Keytruda because there is no control arm in that data set. We do know that BCA101 has no activity as monotherapy in head and neck cancer. This is an important point because drugs that have no activity as monotherapy in head and neck cancer have generally not done well when provided in combination in development. This is the world of IDO or TIGIT, which has really had challenges. Nonetheless, there is a phase III registration trial in this setting moving forward. We will have to see what the data show. A couple of questions on that for 101. We do not cover Bicara. I am just curious, are there other criteria that they used other than HPV status that you are referring to to select the patients that respond better? Yeah. Why do we not start with that? All of these populations in the first-line setting look at the PD-L1 positive tumors because the control arm is Keytruda. That is the labeled population for Keytruda. As a control arm, you cannot go beyond what the label is of the control arm. All of us already look at the PD-L1 positive population, about 80% of the overall recurrent metastatic head and neck cancer population. That and HPV negative are the main? Yeah. Just to provide some perspective here, historically, head and neck cancer drug development in the past five registration trials, phase three registration trials, has been all-comers. It has not been subset out by HPV positive or negative. Even in our breakthrough therapy designations, both in the second line and in the first line, that has been all-comers. There was not any question with the regulatory authorities about whether there should be concern about HPV positive or negative. The questions that come up about HPV really only come up in the context of now there is a new company trying this new approach of splitting out HPV negative subset. It is not a thing that has been an issue with the regulatory authorities up until or even conversation around these registration trials up until today. OK. You highlight the lack of monotherapy activity. That always seems strange to me because you would think that just having Erbitux as part of the activity should provide some monotherapy activity. Yeah. I mean, I think you might be looking at a lot of small numbers, which we all have to deal with with all of these data sets. It is just worth noting because we've all been in this space before of a single-arm combination therapy data set where the monotherapy activity didn't perform. You do wonder about. OK. In terms of the HPV status, which you highlighted, you guys have seen activity. I know there's been some question from some of the competing companies about how reproducible that is and whether that was driven by another factor of smoking versus non-smoking in the region. How confident are you based on, I guess, the data that you've seen so far showing peto activity in HPV positive setting? How confident are you that that's going to be reproducible in the phase III? This is the value of having a large monotherapy data set. In 75 patients, we have a subset of patients with HPV positive disease with a 13% response rate to monotherapy petosemtamab in HPV positive disease. In the combination therapy data set, we only have four patients, petosemtamab, pembro, but three out of four, 75% responded. We really do believe our drug works in HPV positive disease, not as well as in HPV negative disease. Let's be clear, this is strikingly different from cetuximab alone. In cetuximab treatment of HPV positive head and neck cancer, the response rate is zero. There has been a discussion of whether or not smokers might be able to respond to cetuximab. The answer is an absolute unqualified no. It does not exist. Despite the continued debate and discussion by one particular KOL, it is just not true. HPV positive head and neck cancer doesn't respond to cetuximab. It doesn't matter if you're a smoker or not. You can look at the Interlink trial or the control arm of the afatinib trial or the control arm of the MET inhibitor trial or the ficlatuzumab cetuximab trial. All of these arms, hundreds and hundreds and hundreds of patients have zero responses to cetuximab. Yet it continues to take up some of the conversation. It's just not true. What about Keytruda? How does that work in HPV positive patients? Keytruda monotherapy overall has a 19%-25% response rate. That response rate is also present both in HPV negative and HPV positive patients. We do not have large data sets to be able to give a precise number of exactly how that breaks out. It is pretty clear when you look at the way it is shown in the Harrington 2022 paper, with a forest plot with HPV that spans across the midline. We do know that there is activity in both HPV positive and negative populations in that setting. OK. In terms of the percentage that you might end up enrolling in your pivotal trial, I'm assuming it should reflect the rate and the prevalence, which would be about 20%. Is there any cap on the number? Like what if investigators decide, hey, this is the only drug right now that's shown activity, obviously the competitors eliminating them, could you guys end up with more than the 20% in your trial? Historically, the head and neck cancer phase III registration trials have been all-comers, not subsetted by HPV negative status. In these all-comer trials, the HPV positive rate in the first-line setting has been 21%-22%. In the second-line plus setting, it's been 25%. It's really geographically driven. It's much higher a rate in the U.S., medium in Europe, and lower in Asia, and driven by where your enrollment comes in the clinical trials. We expect around those ranges of HPV positivity. It's an important factor as we look at the ongoing enrollment of our trial from a demographics standpoint. Importantly, HPV is stratified across both arms. An impact of HPV on the control arm would be similar to an impact of HPV in terms of numbers on the experimental arm. We think we're well covered from clinical trial impacts. For these large registration trials, the HPV rate has been remarkably stable over time. OK. What can you tell us about the statistical plan for the pivotal trial? We have not disclosed a lot of details about our stats plan. We have pointed to KEYNOTE- 048 as a really good precedent. Our clinical trial design is quite similar to the zanzalintinib phase III trial design and patient number. The only difference there is they have an initial early primary endpoint of PFS, where we have an initial early primary endpoint of overall response rate. The trial is designed to have two efficacy endpoints: overall response rate, which we believe may have the potential to support accelerated approval. We could talk about that some. The second endpoint, which all these clinical trials ultimately have to hit, is survival. The alpha or the significance is split between these two endpoints. It is important for us, obviously, if we want to be able to get accelerated approval to win on the ORR endpoint. We have a lot of confidence in this because what we've already shown is a 67% response rate compared to 19%-25% in the historical comparators, as well as overall survival. Is there a prospective analysis in just the HPV negative population that could support an approval in that subgroup? Again, across registration trial after trial after trial over the past six years, the HPV positive negative has not been an issue. In our discussions with the agency, it has not been an issue. In our breakthrough therapy designations, HPV positive versus negative isn't something that came up as an issue. It's not an issue in head and neck cancer development. It only becomes part of the dialogue as a competitor is choosing to pursue an HPV negative subset. Our population we're studying is the overall population of recurrent metastatic head and neck cancer. In the first-line setting, it is these tumors with PD-L1 expression, which is a Keytruda monotherapy labeled population. In the second-line setting, it's overall. Can you remind us how quickly the patients tend to respond to PDO? I recall it's not quite as fast as like a small molecule or chemotherapy. You do start to get delayed. Certainly your competitor, I think that you've mentioned a few times, saw some responses after five months, I believe. Is that correct? Let me focus on our data. The median time to response is 1.9 months in the first-line setting at ASCO 2024. Basically, physicians evaluate their patients by scanning them every two months on our clinical study, every six weeks, I think, on a competitor clinical study. That's probably something that's worth paying attention to. We have seen many of these responses at initial scan. We've also seen a couple of patients who have had stable disease initially, where that stable disease has continued to evolve to a response over time. That's generally what you see in solid tumor oncology studies. It's not unique to head and neck cancer. Patients don't have their best response the first time you look at them. Many patients can continue to derive benefit over time of the drugs. You mentioned there's an accelerated approval. It could be response rate. It sounds like that could be relatively quick. The FDA will also want to see the durations of response. How do you think about how long you have to follow these patients before you can have that readout for the accelerated endpoint? We do believe there's a potential for early accelerated approval based on endpoints such as overall response rate with confirmation in the same trial coming from overall survival. This is Project FrontR unner. This is something the FDA is really interested in. I've said that if we were to take all the patients in the registration trials, then overall response rate endpoint would be vastly overpowered. Actually, in December, the Breakwater trial of Braftovi got approved in this model of Project FrontR unner. It's not only FDA suggesting this is possible, but showing that it's possible. This was a trial of Braftovi that started out as three arms and then converted to two arms. It's around 500 patients in those two arms. You guys can look at the FDA press release from December on this approval, where it notes that 110 patients from each arm was the number of patients on which the overall response rate approval was granted. That is one example that we have. In that case, the response rate difference was around 40% in the control group and 60% in the experimental group. What we've also shared is that responses, as you were alluding to, the FDA often talks about durable responses. They want to know the responses last. All of us in the room and in the community talk about around six months. The FDA has never put a number on that themselves. We all generally think about durable responses. Let's see how they do for at least six months, so six months follow-up of that initial patient population. The third piece that the FDA has talked about in the context of Project FrontR unner is they kind of want to know that survival is trending in the right way. It doesn't have to hit stat sig, or maybe it's not inverted and going the wrong way. There's something about a time to event point like survival that's helpful to bolster the support for accelerated approval. Because remember, the FDA is making a decision on a bunch of endpoints that aren't true clinical benefit endpoints. They're reasonably likely to predict clinical benefit. The FDA wants to have confidence in that assessment. We only have a little over a minute left. We have not touched on colorectal cancer. It is not in our model, but it is certainly one we are paying attention to. Can you tell us about the program? I think you just recently expanded it to include the front line. What made that decision? We're really interested. We started second line middle of last year in second line colorectal cancer in a single arm cohort. We expanded it just recently to first line and third line colorectal cancer. We think that there's a really interesting and important potential for our drug in colorectal cancer. We discovered the drug in colorectal cancer models, the mechanism of LGR5. I would urge you just to Google LGR5 and colorectal cancer, and you'll get 20 academic papers for why it's a really important and underappreciated target. Our initial dose escalation in colorectal cancer showed no responses. In retrospect, we think that was pretty naive of us to imagine we might see responses because it was a median fifth line phase one population of very heavily pretreated patients where the tumors themselves didn't have high EGFR expression. Most of them had RAS or RAF mutations. Those 10 patients at the highest dose levels, probably not the right population to study. We view that as uninformative. We are really hopeful for this population of second line, first line, and third line monotherapy. We have provided clinical update on these data second half of this year. The decision to expand into the front line, was that something that the investigators requested or the company just hypothetically decided that you wanted to go early line too? There were a number of different factors that led to us expanding. All of those seem to really strongly support this is the right thing to do. OK. Thank you, Bill. Appreciate all the color. Great. Thanks, everyone, for joining us. Thank you.