All right. Welcome back, everyone, to Day 2 of Citi's Virtual Oncology Leadership Summit. I'm Yigal Nochomovitz, biotech analyst here at Citi. So for Day 2, we're going to kick it off with the CEO of a really interesting oncology company called Merus. We have Bill Lundberg with us virtually. Bill, welcome. Thank you so much for joining. Thank you, Yigal, and thanks to the entire Citi team for the continued support and partnership. Just as a quick housekeeping, if you have questions for Bill, just email me, yigal.nochomovitz@citi.com. Hopefully, I'll see those and then relay over to Bill, so Bill, obviously, very topical to have you on the Zoom today with the news just yesterday. I believe that you got a second breakthrough for petosemtamab and combo with Keytruda. So it'd be great maybe we can just start with that and talk about the significance of that regulatory accolade and what that means for the plans for the phase III, and obviously, that's in addition to the other breakthrough designation you had for the molecule. Yes. Before I get into that, let me just take a minute to talk about Merus for anyone who's unfamiliar with Merus. We're an oncology-focused company with both assets we fully own and those with our partnerships with Incyte, Loxo, Gilead, and others, and we've been innovators in the field of multi-specific antibodies for over a decade. Yes, there are many different bispecific platforms and approaches, but I think what you're seeing from our portfolio and the proprietary Multiclonics technologies we have here at Merus is a number of really interesting and very clinically active molecules. We don't talk much about MCLA-129, but that is clinically active. With Bizengri, our HER2/HER3 bispecific, we got FDA approval in two different indications late last year, and now we'll spend the bulk of our time talking about petosemtamab, our EGFR-LGR5 bispecific, which is very active. Recognition of its clinical activity so far was two breakthrough therapy designations. I believe our success comes from this ability to make bispecific antibodies essentially like monoclonal antibodies, relying as much as we can on already very well-established approaches because we know how to make medicines out of monoclonal antibodies. They give us very, very successful drugs. This includes things like letting the biology drive the selection of our particular antibody that we're going to move forward with through high-throughput screens, using monoclonal antibody manufacturability, global CDMO capabilities, standard process development approaches. Our antibodies are fully human IgG1 antibodies, so we can do all the very well-established engineering for stealth silencing for T-cell engagers or ADCC enhancement, as in petosemtamab. While it doesn't guarantee success in the clinic, I think it increases the chance that we can have molecules that work really well. And we're really seeing that across a number of molecules in our portfolio. Just a word about petosemtamab before we dive all the way into breakthrough therapy designation. This is a bispecific of EGFR with this novel target LGR5. We identified it by performing a large-scale screen to ask, what can we combine with the EGFR family of binders to get greater activity in cancer models? And what we pulled out was this combination, multiple instances of this combination of EGFR and LGR5 on the other side that just appeared to have outsized activity in these preclinical assays against EGFR alone or the other side alone or what we think we normally would have gotten. So we now have compelling clinical data in head and neck cancer, registration trials ongoing in first- and second-, third-line head and neck cancer, and breakthrough therapy designation in both the first-line setting and the second-line plus setting, strong support from KOLs. And this is an area of large unmet medical need. So we think there's a real opportunity to be able to address a relatively large commercial opportunity. I'm sure we'll talk today also about expanding into colorectal cancer and potentially beyond. So that's sort of the background. And we did receive breakthrough therapy designation, the second breakthrough therapy designation on Monday for petosemtamab in combination with pembro in the first-line setting in recurrent metastatic head and neck cancer. Okay, very good. Very good. Thanks for the overview. Appreciate it. How does that, I mean, obviously, just to set the scene, you've got the two phase III trials underway, the front line and the second line, as you pointed out. Given that you're getting the breakthrough now, how will it help given that you're well on your way and you're very late stage, large phase III trials? What will be the additional leverage you may have there? Breakthrough therapy designation is very important because it allows a number of things that you don't normally get with the FDA. The first is the involvement of the most senior reviewers and review teams and senior management within the division, whether it's Oncology Division One, Two, or Three. The second is an ability to engage with the FDA in a very flexible manner. Normally, when you engage with the FDA, it's a very formal process with very concrete and often long timelines. And this allows for flexibility and communication interaction if and as things come up, and they always come up in these complicated programs and projects, and then lastly, it allows the FDA to have regulatory flexibility in its evaluation of programs, so for example, with zenocutuzumab, now Bizengri, we got simultaneous approval in NRG1 fusion pancreatic and NRG1 fusion lung cancer. Our ability to do that was critically dependent on having breakthrough therapy designation for both of those indications, allowing senior review teams and senior reviewers to engage with each other and talk to each other at the FDA. I know it sounds kind of bureaucratic, but at the end of the day, it is an organization that runs with a certain amount of bureaucracy. And so this is a very important step, allowing us these significant benefits. One other point to make about breakthrough therapy designation is that it's almost always for a single molecule in treatment paradigm. So you have your particular molecule in a setting. It's very rare to get breakthrough therapy designation for a combination because the FDA often will ask, how do we know which component of that combination contributes to the outsized activity we're seeing? They don't really know for sure. Maybe the standard drug you're adding to your drug just gave you better efficacy by chance. In this case, getting breakthrough therapy designation for the combination really does speak to the outsized benefit that petosemtamab plus pembro may be able to provide above and beyond currently available therapies. So it's a really important metric, and it really speaks to the belief that this really can provide substantive benefit over currently available therapies. Okay. Okay, so let's get into the, if we could just get into a little more detail then in terms of the data. You had a very interesting ASCO last year and a lot of interest in the combo data last summer. We also did quite a bit of work on it ourselves, as you know, so set the scene as far as what you showed in terms of the combo efficacy versus what would have been expected with Keytruda by itself, and what do you need to achieve in the phase III to hit, to the extent that you can comment? I'm not sure exactly how much detail you provided in terms of powering and this and that, but at a high level, obviously, at least from the phase II, you have a very good cushion. So what do you need to show in that phase III to hit, and how do you believe it will advance the standard of care? So a lot in that one, but. But all important questions. So let's start from the beginning. At ASCO 2024, we showed a clinical data set of 24 patients where we had a response rate for our drug petosemtamab plus pembro of 67%. Now, three of those patients did not respond by the data, sorry, did not confirm their response by the data cutoff date, but were confirmed with scans that occurred after the data cutoff date. And that was across all subsets, whether it was CPS 1- 20, the sort of level of PD-1 expression on the cancer, or whether it was an HPV status, the response rate was virtually identical across p16- positive and negative tumors. And that was a very important data set because when you look at the comparable of Keytruda alone, the response rate in two large phase III studies was 19% and 25%. The data were too early for us to calculate a median progression-free survival or median overall survival, but already most of the patients had passed the four-month mark, and 14 out of the 16 responders were still on study, still on drug and in response. So it was a very early look. Things are continuing to mature, but that compares favorably to the median PFS for Keytruda alone in those two studies, which is three months and roughly three months. So we're already, with the vast majority of patients, well past the median for Keytruda alone. We did not report out any data on overall survival because, of course, it was far too early. And in terms of the breakthrough therapy designation, we did provide the FDA with a later data cut that included updated patient numbers. The total number in the cohort is 45 and provided more mature efficacy, safety, and importantly, durability data in terms of clinical benefit. We haven't gone into the details of exactly what that data is. That's the clinical data that we've guided we would provide in a clinical update, ideally at a medical meeting later this year. Okay, so we will see some, and that update may include PFS as well as an early look at OS, or have you not laid that out at that level of detail? Yeah. I've said the two data points that are the most important first looks is landmark PFS rate at six months. And if you can get to median PFS, that's helpful too. That's important too. And landmark overall survival rate at 12 months. And by way of comparison, the landmark overall survival rate for Keytruda alone, which is a control arm in our study, in these two other studies was 50% and 59%. So that's an important benchmark. 50% and 59% on PFS and. On the 12-month OS landmark, 50% and 59%. Oh, on the two prior trials. Yeah. I see. Okay. All right. Very good. So then as far as timelines, are you able to comment to any extent on when we might see those results? I know the studies have just kicked off, so maybe a little bit hard to predict. In terms of the phase III trials, we haven't provided specific guidance around data readouts. What we have pointed to is the prior trials that have run and said that those are good comparators, so in the first-line setting, these two trials, KEYNOTE- 048 and LEAP-010, they both enrolled in about two years or slightly less than two years, and in the second- and third-line setting, the two comparative trials, KEYNOTE- 040 and CheckMate 141, those both enrolled in under two years, so that gives everyone a sense of how long it takes these trials to enroll. In addition, we have said we've been very pleased with the startup activity in the first number of months, first couple of quarters of these clinical trials. Again, the second-line trial, well, both trials started in the third quarter of last year. Based on the progress we've made already, we've guided to having both trials substantially enrolled by the end of 2025. Okay. And what about in the protocol, are there any interims or any other features of the protocol that could allow for some early identification of a signal that may suggest, yeah, stopping early or something like that? Yes. So both trials are designed where the efficacy endpoints are response rate and overall survival. And based on discussions with the FDA, based on the FDA's public comments about Project Front Runner in policy meetings like Friends of Cancer Research, we do believe that there is a potential for accelerated approval based on an early endpoint such as overall response rate, with confirmation of that benefit for traditional regular approval coming from survival from the same trial. So we believe there is the opportunity for accelerated approval based on overall response rate. Now, a couple of important things to keep in mind. One is that I'm asked, do we need all the patients for overall response rate? And what I've said is if one were to take all the patients for overall response rate, that would be vastly overpowered. Yeah. The second consideration, on the other hand, is that the FDA often wants to know how durable these responses are. Typically, that metric in other settings has been six months. Have they lasted for six months or more? Okay. That's a question that can come up as well. The data that people often provide for accelerated approval based on ORR is the ORR metric plus six months of follow-up. Okay. We're getting flooded with questions here from interested listeners. So I'm just going to rattle through some of those. The one, you've obviously heard this one before, but can you comment at all in terms of the HPV- positive versus negative status? You did have some good data in the HPV- positives. I believe it was three out of four, if I'm not mistaken. But the question is, obviously, how do you see that evolving? It's obviously only four patients. And how do you see that evolving as far as maintaining a strong signal there? And of course, in HPV-negative, you have more data. Right. So in HPV- positive disease, EGFR antibodies, which is half of our antibody, it binds to EGFR, do not work at all. The response rate is zero. Right? It It doesn't matter if the person has a particular history like smoking or anything else. There's no response to cetuximab or an EGFR antibody in head and neck cancer if the patient has HPV-positive disease. We were really surprised to see the fact that we have responses to petosemtamab monotherapy in HPV-positive disease. It's already teaching us that our drug seems to work in HPV-positive disease. Now, as monotherapy, it's not as high a response rate as we see overall or in the HPV-negative population, but it's certainly active in this population, which is fascinating to us. In combination therapy, pembro itself has a response rate in HPV-positive disease. From the best ability to tell from our data, it sure looks like petosemtamab plus pembro is at least as effective, if not more effective, in HPV-positive disease as it is in HPV-negative disease. The numbers you cited, a 75% response rate, it is only three out of four, but it is the number compared to a 67% response rate overall. It's fascinating that our antibody seems to be working in this disease where EGFR-based antibodies don't seem to work. Just to remind everybody that in the phase III, you're enrolling both populations, correct? In the phase III, we're enrolling all patients with head and neck cancer, with recurrent metastatic head and neck cancer. The one distinction here is that these are all patients with tumors that express PD-L1, the target for Keytruda, pembrolizumab. Right. Okay. That sort of brought me to the next. So another question coming in is, I mean, we kind of talked about it already, but maybe to put a finer point on it, everyone is asking me, given that you got the BTD for the combo, is the conclusion that the FDA basically saying, "Look, you're just much better than pembro plus chemo, full stop"? The FDA's comparison is against all other available therapies, and that does include pembro plus chemo. So that's a reasonable conclusion. I think that that's a good interpretation. Okay, and is that statement related to people that have PD-L1 greater than 1%, or that could be broader than that? Right. We're only focusing on the CPS 1 or greater population, PD-L1 1% or greater. We're not talking about PD-L1 negative disease. That is not included in our development plan in this clinical trial, I should say. Okay. So of all available therapies, it means pembro plus chemo, pembro mono, other approaches, cetuximab, right? I mean, it's everything. Is that fair? Yeah. I mean, technically, the FDA will look most rigorously at those who have an approved indication in first-line recurrent metastatic head and neck cancer. But broadly, if there's a regimen that's used commonly, if there's some variation of cetuximab, they'd consider that as well. Now, you okay with the camera? Yeah. Just getting a little bit of light from the screen. Okay. So the screen, you mentioned the early screen, which is fascinating. And you identified a pair that was not obvious, I suppose, to say the least. What is it about? Do we know much about the biology on this? It's this leucine-rich G-protein- coupled. I mean, it gets pretty technical, but is that just because it's expressed, or is it doing something in combo with EGFR that is not obvious? We've talked about three mechanisms of action of our antibody. One is like cetuximab or panitumumab. It's an EGFR antibody. It blocks EGF-binding EGFR. The second is that it appears to, on these LGR5-positive cells, and I'll come back to that in a minute, it appears to drag EGFR off the surface and completely strip EGFR off the surface and degrade it. So it looks like a very potent mechanism. And the third is this enhanced antibody-dependent cellular cytotoxicity characteristic of the antibody, which more potently engages the patient's immune system to help eradicate the cancer, which is interestingly maybe one of the reasons why we're seeing outsized activity together with pembro, which takes the brakes off T- cells. Let me come back to these LGR5-positive cells. This is something that's best worked out in colon cancer. If anyone's interested, all you have to do is google LGR5 in colon cancer, and you'll get 10, 15 papers on this. It turns out that cancers aren't just a homogeneous mass of the same kind of cell. There are some cells that just sort of sit around and don't do much. And there are others that are really the ones that are proliferating, driving cancer growth and seeding metastases. Those are the ones that are critically dependent on this LGR5 function. And there's tumor plasticity, so these cells can interconvert from one to the other. But essentially, the LGR5 population is the key one that drives cancer growth and metastases. Again, this is best worked out in colon cancer models. And it's a fascinating aspect of what's previously been called sort of the cancer stem cell or these cancer driver cells. And it really does look like the LGR5-positive population is critical for this. Even in papers we've published, we've shown that our antibody, petosemtamab, not only blocks growth, but it also can block the metastases to the liver from a colon cancer. And so I think we have good preclinical evidence that our antibody seems to be targeting this mechanism. Just going back quickly to the early look based on the ORR, is that true as well for the second-line monotherapy, or is it just a feature of the front-line one? For both first-line and second, third-line registration trials, we believe accelerated approval has potential to happen based on ORR and early look at ORR. I mean, of course, at this point, you've just started them, and you mentioned they're going well, but nonetheless, a little bit of way to go. At this point, how is it going to work with disclosing these results? Are they going to kind of go neck and neck, no pun intended, in terms of readouts or not? I mean, we haven't guided exactly when, but the enrollment timelines are quite similar. The other advantage I think we have is we're placing both registration trials at similar sites and many of the same sites. So we have a real opportunity to leverage the entire site startup process for the petosemtamab registration trials, whether it's contract and budgeting or familiarity with the process of getting scientific review and ethics or IRB approval, or just getting the site staff up and running with our registration trials. It really does help to have two trials running at many of these sites. A lot of people want to know about crossover. Is that in the protocol, or is it prohibited for crossover on progression? Our registration trials don't allow crossover from one arm to the other. And importantly, the second-line trial doesn't allow enrollment if a patient has previously received an EGFR antibody or participated in a clinical trial with an EGFR-type agent. So we would not enroll a patient in a second-line registration study if that patient had previously been on our petosemtamab trial in the first-line setting or had been on a different regimen or clinical trial in the first-line setting. Yeah. Yeah. That would certainly make sense. And now let's talk a little bit about the colorectal work. Where does that stand? I know it's a little bit earlier. Can you just summarize what we know so far and how that study is being conducted? We have three cohorts in colorectal cancer. Those are a regimen in the first-line setting where we're combining petosemtamab with standard 5-FU chemotherapy, a regimen in the second-line setting where we're combining petosemtamab with the standard second-line 5-FU-based chemotherapy, and a regimen in the third-line setting, which is petosemtamab monotherapy alone. These are all single-arm cohorts, and they're really designed to teach us if there's a signal of activity, which we can use to then plan the rest of clinical development. It's important because we do have prior data in colorectal cancer that I can talk about in a minute, but we see this as a real opportunity. For the reasons I described to you in terms of the mechanism of LGR5, we believe there's a really good chance that our antibody may be able to work in colorectal cancer based on the science, how it was discovered, and the emerging publications from many different academic labs really defining the important role of these LGR5-positive cells. So at this point, what clinical data have you got in CRC at this point, or is this all exploratory at this point? Yeah. So in colorectal cancer, we originally ran dose escalation to define the clinical dose. In colorectal cancer, this was a standard phase I oncology trial where patients with colorectal cancer who'd been heavily pretreated, median four prior lines of therapy, received our drug at escalating doses. And across then some 33 or 35 patients, the top doses enrolled 10 patients who were efficacy evaluable, and we saw no responses. And we were pretty disappointed at the time, and we decided we couldn't further invest in colorectal cancer at that time. Let's evaluate in the other two indications we had previously identified, gastro esophageal and head and neck. As a small company, we just didn't feel like we could continue to invest in colorectal then and there. Looking back at that experiment, every patient, including these 10, had been heavily pretreated with panitumumab or cetuximab, or had a tumor with a RAS mutation where EGFR antibodies don't work, and they were very heavily pretreated, and many of these tumors didn't even express EGFR, so we now look back at that as kind of naive of us to think that we could have seen a response or should have seen a response and see it much more as an uninformative negative. Now, it's just uninformative. We don't know what to make of it, so we really want to do the right experiment now. Okay, and what are the expectations for the daily readouts for those three cohorts you mentioned? We've guided, we've provided clinical update this year on the clinical data in colorectal cancer. We're enrolling as quickly as we can. I can't tell you how many patients we will have enrolled in these different cohorts to constitute the clinical data update. But we're really interested in sharing the data, and we're super excited about the potential in colorectal cancer, which is at least as big as head and neck cancer, if not bigger. People ask me, "Well, what's the benchmark," right? And here, unfortunately, there isn't an easy number that I can just tell investors. It's 32 or 25 or whatever it is because the field has been evolving considerably over the past several years. You have not only first-line and second-line treatment paradigms. These treatment paradigms are with a biologic, either an EGFR antibody, cetuximab or panitumumab, or with Avastin. So that makes a difference. And then more recently, particularly in the first-line setting, there's been an emergence of an understanding that tumors on the left side respond much better to EGFR-targeting drugs, cetuximab, panitumumab, and tumors on the right side appear to respond much better to Avastin or bevacizumab. And then on top of this, the genetic makeup is important because, of course, a RAS or RAF mutation renders EGFR antibodies completely inactive. I was going to ask, so for the RAS, so it's RAS, RAF, wild type, correct? So we are looking specifically at RAS, RAF, wild type, and in the first two lines of setting, no prior EGFR antibody. We really want to get the best chance to see a signal from which to make the best development decisions. This is for the RAS, RAF, wild type restriction. That's for all the second line, for everything, right? First line, second line, third line, is this correct? Yes. And what does that do? What does that mean in terms of, I mean, you said it was at least as big as head and neck. That's under that filter, right? I have to go back and do the math, but roughly that's right. And then you've raised more capital to do the phase IIIs for head and neck, obviously. If these data look good in the colorectal, I mean, we'll get more to the runway later. But just briefly, would you need to do another financing to be able to take this into colorectal in phase III, or that's not in the current budget? Our current balance sheet, and as of the last quarter close, we had $782.9 million. It is important to preserve that for maintaining financing through the head and neck cancer trial, so it doesn't include or contemplate a colorectal registration trial. Before I talk about that further, though, I want to come back to one additional interesting area in colorectal that's not included in these areas we've just talked about. There's been really good data to say that cetuximab does appear to have a role in RAS mutant colorectal cancers when you combine with a RAS inhibitor, and so the potential for the RAS mutant tumors for an antibody like ours with a RAS inhibitor small molecule and the two approved are adagrasib and sotorasib is a really interesting possibility as well. That's not currently included in any of our ongoing activities, but it is an important area as we talk about the whole colorectal cancer landscape. Coming back to the financing, it's very important for us to maintain financial runway through top-line readout of the head and neck cancer registration trials. So that runway doesn't include a phase III registration trial in colorectal cancer, and that would require additional capital. Okay, and this adagrasib, sotorasib, that one, I don't see that yet in your planning in the pipeline. We haven't announced any clinical program in that area. It's more that I wanted to point out a potential strategic approach to the overall colorectal cancer population. Okay. Okay. So that means you could potentially do some sort of supply agreement with Bristol or Amgen? There's an opportunity for broader colorectal cancer development. We're getting another question. So someone's asking, because when I was asking about the crossover, so the question is, what about, okay, you can't cross over to petosemtamab, and you can't enroll someone in the second line that had the petosemtamab in the first, but what about other subsequent therapies? Is there anything that's prohibited? What can they get, any other PD-1? Can you kind of go through that? I know that might get a little technical. Yeah. So one of the questions that we've been asked is in the first-line setting, great, you run your registration trial, but it's a survival trial. Could there be an imbalance between the arms in what patients get subsequently after they come off your trial that could skew things? For example, would more patients on the pembrolizumab arm get cetuximab, get an EGFR antibody than the number of patients coming off the petosemtamab pembrolizumab? It's possible, right? You can't restrict what patients subsequently get unless you're willing to run a pre-specified trial the whole way, which that's not how our trial is designed. But when they come off for progression, I mean, they're not going to know, aren't they not going to know which arm they were in, or they will know? In our trial, it's open label. They will know. It's not blinded, in part because a third of the patients will have some sort of infusion-related reaction, so it's very difficult to blind that. Yeah. And then on the petosemtamab arm, there's a bit of a rash and GI EGFR side effects. Okay. Okay. So that's that one. And then. Let me just make a comment about the potential cetuximab imbalance. First of all, cetuximab in the second- and subsequent-line setting is not available across the globe in many different countries. It's available in the U.S., but many patients won't have that as an option regardless of what arm they're on. Then the second point that's important to make is cetux doesn't work very well. It has a, in the second-line setting, after pembrolizumab or Keytruda, there's a 19%-25% response rate and a median survival of like 6-8.9 months. That's not a lot different from chemotherapy, which is a response rate in the teens and a survival of 5-7.5 months. These are not great drugs. It's not like one is dramatically better than the other. But it's just important to keep these things in mind as you think about the trial dynamics. Okay. So as you mentioned, in second line, cetuximab is not used in most places except the U.S.? It's available in the U.S. and select other countries, I would say, around the globe. In many countries, it's not approved or reimbursed, in part because many other countries require randomized trials for approval and reimbursement, even in the second-line setting. In first line, how does it work geographically with cetuximab? Cetuximab in head and neck cancer has largely been replaced in the first-line setting by Keytruda. The KEYNOTE-048 trial said Keytruda alone or Keytruda chemo is better than cetuximab chemo. Okay. And then in your second-line trial, if they progress, I guess not many people are going to get cetuximab in the third line. Is that right? Right. Right. I mean, there aren't many patients. I mean, sadly, there aren't many patients who can make it to third-line therapy. Those that do, who are more fit, can get maybe a trial of cetuximab, maybe a trial of a different chemotherapy agent, but it's a more difficult setting. Right. Okay. I had a few more, well, this is kind of broader market questions related not just to your pipeline, but just in general. Someone is curious about, I don't know if you can comment on this, like pembrolizumab in head and neck sales today. I think I have an idea what it is, but curious if you could comment on that. We've been told by others that Merck will share that 5%-10% of their $27 billion sales is in head and neck cancer. There's a proportion of patients who do get nivolumab as well, and I don't know what those numbers are. Does that sound right? Yeah. Yeah. That sounds right. I think that's correct. And then cetuximab is probably a lot lower, but. Yeah. Okay, and as far as sort of market share, I guess Keytruda is going to be a major dominating force. I mean, Keytruda is the main therapy in the first-line setting. It's interesting because the clinical data would suggest every patient should get either Keytruda alone or Keytruda chemo. And yet, when we do market research, it looks like the market share isn't 90%, 95%, 100%. Looks like market share now, four or five years after that approval, is around 2/3 of the patients. Okay. Someone is asking another while coming in here. But someone's asking a question just in terms of going back to the comments on potentially filing accelerated on ORR with, as you say, if you go the full distance on the trial, you'll be massively overpowered on ORR. Is there a scenario under which you would get the ORR data and be able to say something sooner than two years from the start of the studies at which point you would have enrolled it based on the LEAP and the other one you mentioned as historical comps? Is there a scenario, for example, like some point in 2026 where we could see something from you saying, "We've done the analysis on a subset on ORR in these studies, and we believe we have an accelerated approval situation"? Yeah. We're very much guided by needing to disclose things that are material, and so we tend to be relatively conservative and want to make sure that we disclose widely anything that's material for the company. The potential for success in the phase III trial is probably a really important data point for our company. Fair point. Fair point. Okay. Let's try to hit some of the other topics. So let's maybe talk about on the next one, but Bizengri, so it's obviously approved. Can you just give us the broad brushstrokes? How big is this market and these NRG1 fusions for the tumors for pancreatic and non-small that you referenced? How is this launch going? What can you say about what expectations should be around sales over this year and beyond? Yeah, so Bizengri, our HER2, HER3 bispecific antibody, formerly zenocutuzumab, was approved in two indications late last year, NRG1 fusion pancreatic cancer and NRG1 fusion lung cancer. It did receive accelerated approval, so there's a post-approval commitment there as well, and importantly, we made the strategic decision to not launch this drug and commercialize it ourselves, and so we've licensed it to Partner Therapeutics for launch and commercialization. The reason we did that is not that it's a potential important source of revenue, but rather the management time focus and attention and the cost of a launch are things that we didn't feel like we could afford to spend given the criticality of making sure that we do everything we can to be successful with petosemtamab, which is clearly the most important asset our company has, and so with Partner Therapeutics, we have a terrific organization. They have boots on the ground, and they have a footprint with commercialization, and they've been moving that forward. The basic broad brushstrokes of the deal are available in our filings, but it is not a significant line item in terms of what we feel like in terms of our potential revenue moving forward. So it's not something that we've been paying a lot of attention to in terms of our quarterly disclosures or others. But just to be clear, it will be, I mean, whatever it is, even if it's a small number, you will disclose it, or it's just not going to be viewed as material to the company? I mean, compared to the potential for petosemtamab, it's modest. We really want to make sure we're aligned with Partner Therapeutics, who we've now licensed the drug to for commercial. Just not too many people are familiar with them. What regions do they operate in? Just so we understand. They're a U.S.-based and international company that have a commercial footprint and have been commercializing oncology products. And so they really represent sort of similar-sized companies, similar philosophy, and importantly, experience in getting this size drug out into the marketplace. Okay. All right. And then the other one, which we just want to touch on, also it's EGFR, but this one is paired with the c-MET. That one's had its ups and downs, I suppose, in terms of the market and how you think about the opportunity. And I think you've indicated that one's sort of open for partnering discussions. Just maybe just remind everyone why the strategic decision to do it that way. Presumably, the answer is fairly obvious in terms of competitive dynamics, but whatever you can comment. And then how are those conversations going? Where does it stand? Right. So MCLA-129 is our drug that is an EGFR x c-MET bispecific. It's very similar to J&J's amivantamab, which is the competitive dynamics that you were referring to. One of the interesting things about MCLA-129 is it's a very active molecule clinically. In EGFR mutant non-small cell lung cancer, we tested it in combination with Tagrisso in the first-line setting, and every patient had tumor shrinkage in that setting. And then, in a different cohort, we took patients who had progressed on Tagrisso alone, and we added MCLA-129 to it, and more than a third of patients got into a true response. So it's a very active drug in lung cancer. Importantly, we did see a safety signal of interstitial lung disease, which is a consideration because hitting EGFR pathway hard multiple different ways can create interstitial lung disease. It's known from other settings that EGFR drugs have that potential liability. It also has significant activity or substantial activity in MET-driven lung cancer that we showed and our partner showed substantial data on this at the most recent ASCO meeting. So it's a really active drug. The challenge for us is twofold. One is we're behind amivantamab and J&J. And so what's the right strategic play and the place for us to invest? And the second major issue we have is that we need to make sure we devote the lion's share of attention and resources to petosemtamab and especially head and neck cancer and other indications because that's really the opportunity to be out front and first with a novel medicine that can really substantially benefit tens of thousands of patients a year. And so we made the strategic decision for us to work on these very focused cohorts, getting data to be able to compare directly to amivantamab in previously treated lung cancer and to also look for a potential partner. And in terms of partnerships, we're continuing conversations and discussions. I don't have any further update on that. Okay. We're not going to hold you to that. So let's talk about now there's a lot going on with these "strategic relationships" in the early, early days, these discovery programs for novel Biclonics and Triclonics. And you've got a number of those. Well, there's Biohaven. There's a few. There's Gilead. I think there may be a few others. So tell us more about those. What are the goals there? How do the economics work? I don't think we know much about targets yet as far as I know. Right. So among the different collaborations, we have more than 17 molecules or programs with our partners and licensees, Gilead, Loxo, Incyte, and one or two others, where we discover and develop preclinically or in a research phase and then transfer to the partner, and then the partner develops further, and if these are successful, we receive milestones and royalties, so there's a substantial number of these opportunities for revenue generation in the future. The most recent deal, well, for these other deals, the disclosures are really up to the partner. They're not ours. What we can disclose is we received a milestone from our Incyte program, or we received a milestone from Gilead or. The most recent program, which is a collaboration with Biohaven to generate bispecific antibodies as ADCs, was a completely different flavor. We decided that it's more interesting for us as the stage of the company that we're in now to have the opportunity to share both the investment and the upside. So these are up to three programs that we share the clinical development and commercialization opportunity with Biohaven. We haven't disclosed the targets, but these are molecules that we're looking to advance relatively quickly. I mean, could it be outside of oncology? Is that fair? Or are we not going to talk to that level of detail right now? I mean, I think we've described these as oncology-focused. Okay. Okay. And so you'll do the antibody side, and the other party will do the payload linker side. Is that right? That's right. And Biohaven isn't commonly thought of as an ADC company, but it turns out they have a suite of linker and toxin technologies that really represents a set of best-in-class resources for us. So our ability to do high-throughput screens, both for bispecifics and then evaluate broadly different linker and toxins, we think is a real advantage in choosing the right drug to bring into the clinic. Now, with this strategy, I mean, do you reserve certain targets for your exclusive internal discovery, or is the early discovery work at Merus focused around these types of partnerships, or do you have your own proprietary early-stage work that's separate? We also have our own proprietary internal pipeline that we've been developing. And obviously, you haven't yet guided to INDs from that perspective. And you've reiterated many times petosemtamab is the clear focus. But is there some cadence of INDs that we could expect from you for new molecules? We haven't provided that guidance. I will say we have had a cadence of INDs even over the past number of years that we've described in terms of the milestones we've received in our partner programs. So there's continued productivity, and there are continued INDs. These have so far been primarily in the partnered programs. We haven't talked about specifically anything in more detail in terms of our own internal work. Okay. So let's maybe just wrap up with what should everyone have on their checklist or calendar for catalysts for 2024-2025? If you could just give us the key ones. I believe you said you're going to have more data to share for the combo, which helped you with the second breakthrough. But beyond that, I'd be curious if there's anything else we need to pay attention to. That's right. I think it's going to be a really busy year for Merus in terms of news and catalysts, so the first and most important for many people on the call is a clinical update of petosemtamab in the first-line setting, and this is the basis for the Breakthrough Therapy Designation that we received from the FDA, and that clinical update will obviously be all the data in the first-line head and neck cancer cohort, and we have enrolled 45 patients. The patients were initially described in the ASCO 2024 presentation, but having more fulsome efficacy, safety, and importantly, durability for those patients, I think, will be very important, and the things that I point to there that are really important are obviously overall response rate. We want to make sure that continues to be strong. The progression-free survival data that'll be really interesting to share. And the overall survival, while we may not have a median, certainly the 12-month landmark overall survival will be important as well. The next major clinical update will be in colorectal cancer and the potential to unlock an entirely new therapeutic area for petosemtamab. And we've guided to a clinical update there this year. And that will include the data on the patients that we've enrolled to date. And I can't tell you now how many patients from which cohort we'll have, but we'll provide the clinical data that we have. And we're looking forward to that because that really will help define both the opportunity and our next steps in colorectal cancer. The other important milestones or pieces of information are really continuing to progress the registration trials and making sure that we remain on track for those registration trials. We've guided substantially enrolled in both trials by the end of 2025, and that's a very important, probably the most important thing that we can do this year is just make sure that we continue to stay head down. We've been executing very effectively as a company, but we need to continue to do that and pay significant attention to execution this year. And then I think we sort of touched on it already, but just as far as the cash runway, you have the funds to prosecute both phase IIIs head and neck. Yeah, I obviously haven't said exactly when they're going to read out, but taking it all together, your runway takes you to when approximately? Into 2028. Into 2028. Okay. All right. So plenty of cushions to see those. I mean, you have sort of implicit in that is that we should get the phase III data by then, I suppose. Although you haven't actually said that, but okay. All right. Great. Well, Bill, it was a pleasure chatting. Thank you so much. Looking forward to a lot of fascinating stuff from you this year and beyond. Always fun to connect. All right. Thank you. All right. Take care. Bye.