Great. Thanks, everyone, for continuing to join us here at the Stifel Healthcare Conference. Happy to have Merus on stage with us for the next fireside chat. CEO Bill Lundberg here. Thanks, Bill, for joining us. Thank you, Brad, and thanks to the entire Stifel team. It's a great partnership, and I really appreciate the continued support from you and the entire team. Okay. We'll start with the intro question for introducing Merus and the status of the portfolio. So for those of you who haven't heard me share this yet, Merus is an oncology-focused company with four clinical assets of our own and multiple others with our partners and licensees. We develop multi-specific antibodies based on a technology that allows us to develop them essentially like monoclonal antibodies. And that is important because we fundamentally know how to make medicines out of monoclonal antibodies. We've been doing it for decades. And our view is that the more we can identify tried-and-true methods, the more we can mitigate and discharge risk and avoid taking on additional risk, the better chance we have of getting a drug. So, for example, we use biology to drive the selection of our ultimate clinical candidates using biological assays in true high-throughput screens. We rely on process development to manufacturing capabilities that are for monoclonal antibodies. We can do all the Fc engineering to make these stealth silencing for T-cell engager applications or ADCC- enhanced, as we'll talk about for petosemtamab. And while none of this doesn't guarantee success in the clinic, we think it improves the odds. And if you look across our portfolio now, we'll talk about the really strong clinical data we have for petosemtamab in head and neck cancer, but I'd also point to zenocutuzumab as having really important clinical data in these NRG1 lung and pancreatic cancers, and MCLA-129 is also having strong data. These represent opportunities that really come from our own foundational pipeline platform technologies and really represent the opportunity for Merus going forward. Okay. Now, let's kick off discussion around petosemtamab. You know, obviously, great news this year to see that move into pivotal studies. Can we talk about the frontline trial in head and neck cancer, and can you discuss some of the key design elements for that trial that investors should be aware of? Yes. petosemtamab is our bispecific that targets on one side EGFR and on our other side LGR5, a relatively novel protein in cancer biology. We didn't set out to make that combination. Instead, we ran a screen asking what can we combine with EGFR to get greater activity in a variety of different settings, the screen pulled out LGR5, which is a molecule expressed on the cells within a cancer that really drives cancer growth and metastases. We've taken this through head and neck cancer studies. We have second-line data, front-line data that have driven us to move into registration trials both in the second and third-line setting and in the front-line setting, coming down specifically to the frontline registrational trial, the standard therapy there is pembrolizumab or Keytruda, which itself can give a 19% response rate and a survival of 12.3 months. More recently, a clinical trial had an arm with Keytruda that had a survival of 17.9 months. Now, this 12.3-month or 17.9-month dataset is what we use as the baseline assumption, and we make sure we design and power a trial that has a chance to win regardless of the range of outcomes within that range of how the control arm will do. Okay, and now, is it still your base case that in the frontline setting there can be an accelerated regulatory submission based initially on the ORR and DOR from the randomized trial? Yes. The FDA Project FrontRunner is a relatively new initiative where Dr. Pazdur and the teams want to encourage sponsors like us to seek earlier approvals from randomized trials. And this is using an early endpoint such as ORR to be able to support accelerated approval because, of course, the FDA will get the receipts. They'll get the ultimate survival from that same trial so they can get confidence in the ultimate output. Based on our conversations with the FDA, based on public comments the FDA has made, we do believe that an early endpoint such as confirmed ORR will potentially support accelerated approval in the frontline setting. Now, I'll add two additional things. One is the FDA often talks about durable confirmed ORR, a response that lasts for some five to six months minimum. So that's important. The second thing that Pazdur has commented about is that oftentimes, well, in this setting, they may want to get a sense that the survival is trending in the right direction at the time they may grant potential accelerated approval based on ORR. Now, do you have a good sense yet for the degree of durability maturity that will be required either from a duration of follow-up on responses or on survival endpoints? So on survival endpoint, it's clearly not stat-sig because if you hit stat-sig on survival on your registration trial, game over, you win, right? So it would be a trend in the right direction. On the durability, we don't have precedents for Project FrontRunner that have gone through and been successful yet, but historically, the FDA has talked about durable ORR with ranges of duration from about 5.5 to six months minimum. Okay. And now you mentioned the Keytruda control arm or active arm, depending on the study you're looking at, can historically be anywhere from 12-17 months. And the question that emerges for me from that is, how might patient enrollment be influenced and then the baseline characteristics impacted by the choice of not having a chemotherapy arm in your study? I think we have heard from some physicians that some patients prefer the rapid response from chemo to alleviate the symptoms. Yeah. So in the frontline setting, the standard of care is either Keytruda alone or Keytruda chemo. Those two were not compared formally in the trial from which the data come. But when you look across the two figures in the publication, the survival curves are similar. You get a higher response rate initially with chemotherapy, so more tumor shrinkage initially, but the survival varies between 12.3 and 13 months. So among the various debates we've had with our clinicians, investigators, and KOLs is the debate about whether Keytruda alone or Keytruda chemotherapy represents the standard. Some feel passionately that chemotherapy has to be added because you want as much response as you can get. Others feel passionately that you should not expose your patients to cytotoxic chemotherapy if you're not improving survival. So in the absence of compelling data, the debates can get really quite vigorous. We believe that the early data we're seeing with petosemtamab with pembro already shows a much more substantial early response rate of 67% compared to Keytruda chemo of around 35%. So that we believe a petosemtamab, pembro, or Keytruda regimen could really address both this need for early responses and potentially greater efficacy longer term. Okay, so you see less patient editing perhaps in this trial than maybe we've seen from something like the lenvatinib/pembro trial? In terms of the trial itself, we're just getting up and running, but we certainly see an opportunity for really meaningful clinical benefit. Yeah. Okay. Now, how do you think about the post-protocol therapies potentially influencing the OS when an anti-EGFR mechanism, cetuximab, is available for second-line patients in this setting? So the important thing to keep in mind in head and neck cancer is all the second and subsequent line therapies are really poor in terms of the efficacy they provide. In the second and subsequent line, cetuximab has a 13%-19% response rate and median survival ranging from six to 8.9 months. So, you know, it's possible that there could be an imbalance in the therapies that patients receive subsequently, but they really don't offer much. We do see more cetuximab use in the second and subsequent line in the U.S. and more use of other therapies outside the U.S. We know this because we're also running a second, third-line registration trial. We have data on this. There could be a little bit of imbalance, but these are pretty poorly effective therapies that we don't think will influence the overall outcomes much. Okay. Now, one of the competitive differentiations in this trial is you are enrolling an all-comer population with PD-L1-positive, which means HPV status is not being cut in this trial. What is the sum of evidence that petosemtamab with Keytruda can be more active for patients with HPV-positive disease when cetuximab and other emerging EGFR bispecifics have not shown that? This is an important point, and there's been a lot of discussion about HPV-positive disease, so human papillomavirus is a common human pathogen, and subtypes 16 and 18, and to some extent 33, are associated with not just the formation of papillomas, but the formation of cancer. These are really cancer-causing viruses, and the biology of the HPV-driven head and neck cancers tends to be a little bit different. The response rate, as you alluded to, in these HPV-positive cancers to cetuximab or cetuximab-like drugs or bispecifics is zero. It's not a little tiny bit. It's cold zero. When we started to see responses in tumor shrinkage to petosemtamab, to our drug, we were seeing something fundamentally different than an EGFR antibody, and that's one of the earliest data points that said that this is a really intriguing molecule mechanistically. The fact that we've seen higher response rates than cetuximab would give as monotherapy in combination, in second line, in front line, in responses in HPV-positive patients, you know, all of that really, all of those many different data points speak to this notion that we think that petosemtamab really has something that is substantial and important, well above and beyond EGFR or other EGFR-directed bispecifics. Okay. Now, when do you expect to next potentially update the phase 1B combination with Keytruda in frontline patients? And what maturity of data or elements do you need at that time to ensure that it's interpretable and the right time to cut that dataset again? Yeah. So we're obviously hopeful that Keytruda plus petosemtamab provides a lot of benefit, but the only thing we know so far really is the response rate was very robust with a 67% response rate at ASCO compared to what pembro or Keytruda would do alone, which is a 19% response rate. The time to event or PFS or OS data was really immature at that time point. The two earlier markers that we've talked about, one is a landmark PFS rate at six months, how many patients have not yet progressed or have progressed at six months, and a landmark OS rate at 12 months. Keytruda alone or pembrolizumab alone gives around 52%-59% survival rate at one year. So that's just a metric that we can get from the other comparator trials. Seeing where our data is when we get to that point will be very important. We haven't guided to when our next updates will be, but we know that this is a really important metric in terms of how big could potentially the benefit of our combination be. Okay, and as we look forward to those frontline updates, what are some of the key parameters that need to be considered as we go to cross-trial compare to the emerging competitors in the head and neck space? There are four registration-directed programs in the frontline setting in head and neck cancer right now. Three of them for all-comers, which are already actively enrolling registration trials. That's our program, petosemtamab. It's the Exelixis zanza program, and it's the Akeso molecule ivonescimab, which is in combination with the CD47 drug. Those are all actively enrolling in the overall frontline population, PD-L1 positive population. There's a fourth program, which is Bicara's BCA101, which is targeting an HPV-negative population that has not started yet and still needs to complete a Project Optimus dose comparison before they can even begin their registration-directed component of the randomized registration trial. When you look across these, the most important elements that you'll want to think about, one is what's the inherent population? What are the proportion of patients who are healthier, performance status zero, and other characteristics? You want to look at in the overall population, the relative proportion of HPV-positive disease versus HPV-negative disease. And then in terms of the efficacy side of the house, you'll want to look at the responses, but not just any responses, responses that are confirmed. So so-called confirmed ORR as opposed to unconfirmed is an important component. And then, of course, the durability data, as you can see from, you know, potentially swimmer plots to understand how the durability transpires over time. One of the most important elements is going to be the 12-month landmark overall survival because that will be the earliest time that you can start to see how survival performs in these cohorts of patients. Okay. Now, there has been some investor debate on the convenience of the different competitors, including you. Yeah, I think the common thought is you might have a bit longer infusion time. Some of the competitors might have more frequent infusions. How do you think about this in terms of what is going to be, in your mind, the preferable profile for head and neck cancer patients? I mean, my own opinion is weekly infusion is a problem. It's something that requires patients to be at the clinic every week, week after week, month after month after month. And I'm talking about this both as a medical oncologist who's treated patients at Dana-Farber and as a family member when I would bring my dad to Dana-Farber for treatment. It matters for patients how often they have to be in the clinic or, frankly, how often they don't have to be in the clinic. And when you're talking about a substantial fraction of patients who on pembro or Keytruda alone are on drug for two years or longer, week after week after week, month after month after month, it's, in my own opinion, a substantial issue. I do think that, you know, people have commented on the infusion time for the first dose for petosemtamab, and we've commented about this as well. We've seen infusion-related reactions, which we've described in our presentations, and the ways in which we manage the infusion-related reactions is with a pre-medication regimen that can take time to infuse. Then when we see symptoms, if we see symptoms, which we're seeing in about a third of the patients now, we slow down the infusion to or stop the infusion briefly to ameliorate the symptoms and then restart. It is a long day on day one, but, you know, if you've been a family member taking a patient to an oncology clinic, you know that these are long days. This is really a first-dose phenomenon in terms of the infusion-related reactions. Virtually all of these are first-dose phenomenon, and the other infusions, which is, you know, less than weekly, are standard infusion duration. Okay. Now, moving back to second line, there has been ongoing phase I work, both as additional follow-up to the original data you presented and dose optimization work. Describe the scope of what data elements we expect to receive in an upcoming medical meeting in December, and what would you really focus investors on as the new learnings at this update relative to what we've seen before? At ESMO Asia, petosemtamab monotherapy in the second-line setting will be presented as a mini-oral presentation on December 7th. And the data in that is second-line plus treatment of patients with recurrent metastatic head and neck cancer. There are really two components to that. And the underlying question for all of us is really, how does this help our confidence that this is a real drug compared to the control therapies? So we've already presented an initial look at the expansion cohort in this setting at AACR 2023. Response rate data 37% was pretty mature. The time to event endpoint, PFS OS, was not as mature. It was moderately mature. The first question is, for the patients treated a while ago, how robust with a much longer follow-up is the PFS and particularly OS, and how does that compare to the potential control arm, which would be a blended overall survival of between 5.5 and 8.9 months? The second question is relating to the additional data we'll be presenting, which is our Project Optimus work comparing 1,500- 1,100, about 20 patients in each arm of that study with the additional around 20 patients at 1,500. How does that improve our confidence in the response rates that we've been seeing? The initial data showed a 37% response rate compared to what these control arm drugs would do between about a 5%-19% response rate. Are we able to really converge on a much narrower confidence interval around that point estimate of response rate? Those are the two main questions. I think investors will be interested in seeing, do we have additional data on HPV-driven cancers and with more patients? We hope to have more patients in each different subset. And lastly, how did we negotiate the Project Optimus pathway with the FDA so effectively that we addressed and really aligned with the FDA on 1,500 mg? This is in the rearview mirror, but I think that would be of interest to investors as well. Yeah, and so it sounds like these patients will be stained for the protein p16 as a surrogate for HPV-positive. Are they coming from a lot of the same sites that were from the original phase I, or are these patients that are also coming from different sites? Because I think there is some debate around the heterogeneity of that activity across the globe in HPV-positive patients. That's right, so in the same protocol, the same inclusion-exclusion criteria, generally the same sites, the same parts of the globe. Okay. Got it. Now, how do you think about having the second-line pivotal trial for petosemtamab in terms of what it might add for future competitive positioning for the drug if some of these other frontline trials that you mentioned end up working as well? I think anytime you've got a combination therapy with a single-arm dataset, you don't really know the contribution of components of how much the experimental arm is adding to pembro or Keytruda. Having an independent monotherapy petosemtamab alone dataset that says that we're really seeing 37% response rate in a later-line setting adds a lot of conviction to, hey, in that combination, pembro or Keytruda with petosemtamab, that really does have legs because petosemtamab is really adding something. We're not just getting lucky with the pembro or Keytruda arm randomly being higher than we might expect, so it's a really important dataset giving us a lot of confidence in what we're seeing in our program overall. We do have breakthrough therapy designation for petosemtamab monotherapy in the second-line setting, and breakthrough therapy allows us to have much more frequent engagement with the regulatory authorities. So it really bolsters the regulatory engagement. And then ultimately, an independent second, third-line dataset that shows efficacy and superior efficacy at appropriate safety is something that substantially bolsters the potential for approval in the frontline setting as well. Okay. And then how do you see the relative safety profile of petosemtamab versus some of the other EGFR-based and VEGF-based combinations? Yeah, we're surprised to see lower rates of EGFR-type skin and gut tox with our EGFR LGR5 bispecific. We would have thought that this would behave like cetuximab, and we're seeing numerically lower. Again, independent datasets, smaller numbers, but, you know, we're continuing to see lower rates of EGFR skin and gut-type toxicity. I have to tell you, we don't really understand why. It may be epitope. It may be this particular binder. It may be something to do with this particular molecule. But, you know, we're encouraged by that because we're seeing it in the context of much higher efficacy against these EGFR-expressing tumors. And so we do think both the efficacy and the safety are important components of helping to define what I think is the best molecule out there, both as monotherapy and in combination with Keytruda or pembrolizumab in head and neck cancer. Okay. And now that the head and neck plans have been finalized and it's focused execution on those trials now, you're taking a second shot at CRC, colorectal cancer, with a new study. Can you frame how this trial is designed differently from the first one you ran to help you potentially find a role for peto in this disease? Yes, so we originally did the dose escalation work with petosemtamab in colorectal cancer. Typically, you do it in all tumor types, but we chose to do it in colorectal cancer, and we didn't see any responses, and we were disappointed, but in retrospect, among the around 10 patients at the highest dose cohorts, it's a small number, and what we, looking back now, appreciate is these were very heavily pretreated patients. Median fifth-line therapy is how petosemtamab was given. All the patients had seen a lot of cetuximab or panitumumab, EGFR antibodies, or their tumors expressed RAS mutations to make them resistant to EGFR antibodies, and the level of EGFR on these tumors in this cohort was low, so in retrospect, we think that was kind of an uninformative negative. We're currently enrolling a cohort of patients with colorectal cancer looking at earlier line of therapy, a second line in combination with 5-FU-based chemotherapy, which is a standard chemotherapy, and we're doing it in a patient population that is RAS/RAF wild type, so we're really trying to optimize this cohort for the best possible potential chance that petosemtamab can have activity. We're also quite bolstered by recent data from a different EGFR bispecific, amivantamab or Rybrevant, the OrigAMI study that was just released at ESMO last month, September, about a month ago, that showed that that bispecific really does have legs, and, you know, in a mixed frontline, second-line population, the data looked quite good for that EGFR bispecific, so we are hopeful that this approach really can show the much broader potential for petosemtamab in solid tumor oncology. Okay. And now Merus has obviously become a very petosemtamab-centric story for good reasons, a very unique profile for a drug. But how should investors think about the potential opportunities for the other clinical stage drugs, zenocutuzumab and MCLA-129, today? The two other molecules, zenocutuzumab and MCLA-129, also both have very strong clinical activity. For zenocutuzumab in a setting of previously treated lung cancer or pancreatic cancer, the response rates in these NRG1 fusion cancers are substantially greater than control therapies. We have a BLA under review with the FDA currently for potential approval in that setting. We have talked about the importance of us having a partner commercialize it for reasons we could discuss, because we just think we need to focus on petosemtamab as the real value creation opportunity for Merus. And 129 also has very strong activity both in EGFR-mutant cancers and in MET-driven lung cancers. But again, here too, we only have limited management focus and balance sheet that we can invest in this. With MCLA-129, we do have a partner, Betta, in China who is developing the same molecule for the greater China market, and they are continuing to develop in a number of indications as well. So there's potential there. But again, we really have to focus our resources to make sure we can succeed with petosemtamab. We are open to partnering '129 to help leverage this opportunity. Okay. Now, I guess, how active are efforts to produce new bispecifics? And in what therapeutic areas will you focus on? Are you still going to stay exclusive to cancer? We continue to have a robust pipeline in development. We have talked about some of these in the context of the partnerships we have, making molecules together with Lilly or Incyte or Gilead, and those are programs that continue to move forward. We have announced milestone payments as they progress into IND or into the clinic, those are important. We do have one program in collaboration with our partner, Ono, that is outside of oncology, we do appreciate there is a potential beyond oncology for bispecifics and multispecifics as well. Okay. And then maybe just last question around the cash runway and what that provides in terms of prosecution of the peto phase III trials. Yes. As of the last quarter close, we have $782.9 million in cash, which is a robust balance sheet. So we're fortunate enough to have cash to take us through multiple corporate milestones. Importantly, we need to continue to focus on maintaining our strong financial position to ensure we can fully prosecute the head and neck cancer registrational trials. Okay. Always great to sit down and discuss, Merus, with you. Thanks so much, Bill. Thanks, everyone, for attending. Thank you for your support.