This session at the Morgan Stanley Global Healthcare Conference. We are very excited to have the team from Genmab, Jan and Tahi, with us. Let me just get through a quick disclosure. For important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. I am Judah Frommer, one of the SMID Biotech Analysts here at Morgan Stanley. Like I said, very excited to have Genmab here for this session. I thought we could start out with key updates since we saw you here last year. Merus is, of course, the biggest, but how have the other aspects of your business evolved over the past year from a high level? Thank you, Judah. We are delighted to be here, and I am delighted to update you all on the progress of the company, because we have made a lot of progress. We have now nine medicines that we generate revenue from. We have three late-stage assets, which are all expanding their reach, for the coming time. We have actually announced six new phase III trials this year and more to come. Also, we will have a lot of data in Q4. Essentially, all of the three lead programs will generate phase III data in Q4, so we are very excited. Then of course, the financials look very solid. We increased the revenue by 25% in the first half and operating profit by 18%, so very solid financials. This will allow us to invest actually in further expanding the late-stage programs and also preparing for commercial launches, multiple launches next year, assuming the data will be very good and follow the phase II data. So we have made a lot of progress, and delighted to be back in New York here. Great. So maybe starting with Merus and petosemtamab, what drew you to the asset? How is it differentiated from other EGFR bispecifics in recurrent metastatic head and neck cancer and CRC? Maybe just initially, what drew you to that acquisition? I can start off, and then I will let Tahi fill in a bit more of the differentiation part, but petosemtamab is a truly differentiated next generation EGFR targeting antibody with great preclinical data, very good early clinical data in head and neck cancer, two breakthrough therapy designations, two phase IIIs. One of them will read out in Q4, and then the other one, the second/third line head and neck cancer, will read out in Q1. Immediately thereafter, so very well progressing. Data are really good on a numerical basis, really outperform potential competitors there. Also colorectal cancer, we have now announced on August 6th two new phase III trials, one in frontline and second line colorectal cancer. You will hear the reasons why at ESMO end of the October timeframe, where we will actually describe the phase II data which were originally for Merus. Right. Probably more or less than doubled the number of patients, and then also follow them up for a much longer period of time. But I will let Tahi speak a bit more on differentiation versus other EGFR targeting antibodies. So pause here. Tahi? Yeah, I think this goes back to the thesis that we were formulating when we actually announced that we were going after Merus. As Jan was saying, petosemtamab is a second generation EGFR bispecific. Second arm is against EGFR. What we saw, and I think will continuously to play out, was very early on, which is what triggered our interest, that it appeared to have a differentiation on the efficacy. It is like and cost study comparisons are always hyper problematic, but in every data set that is in the public domain, in monotherapy, in combination with pembrolizumab in the head and neck space, in combination with FOLFIRI or FOLFOX in front line or second line, there's always a numerically higher response rate, vis-à-vis, for example, amivantamab. On the other hand, and that's probably equally important, it also seems to be differentiated on the safety side. It doesn't have the degree of skin problems, it doesn't have the scalp skin issues that amivantamab is dealing with, which then is managed with the whole COCOON regimen. It doesn't seem to have the degree of stomatitis and all of these things. They, in totality then, and this is kind of like a theme in Genmab, they help patients stay on drug. Duration of treatment eventually then also becomes duration of response. These things together, higher efficacy, longer duration treatment, they tend to drive then this package that we're looking for that really is then differentiated for the patients. That's what we saw, and this is what's playing out right now in the long-term follow-up data sets, some of which are going to be presented at ESMO. We're really excited about it. We're really excited about the readout that we announced was going to happen in this quarter. We all look forward to having a conversation about that. Great. Maybe just, we get the question from time to time, was LGR5 on your radar as a target, or was it really the clinical data that stood out and kind of introduced you to the target? The question whether we went after an EGFR bispecific? LGR5. Oh, LGR5. Yeah. No, I think the story of LGR5 is obviously an interesting scientific story. It came out of the Hubrecht Institute. It was an observation that this is a stem cell target. If you really dig into the history of petosemtamab, it was screened in organoid model. Scientifically, this is super intriguing. In the end, both Jan and me came out of the lab. We are scientists. Ultimately, it is actual clinical data. It becomes very difficult to attribute whatever profile you see. But in totality, as it is, as a bispecific with these two targets, it has a certain clinical behavior, and that is what we were attracted for, that is what we were doing the diligence on, and that what drove the enthusiasm to do really a major transformational step for Genmab. This is why we are so excitedly waiting about the first readout, the confirmation of our excitement. Yeah. Okay, great. Like you said, Jan, we will get the frontline data in the fourth quarter of this year, that is the LiGeR-HN1 trial. That will be a top line. I guess, what can you tell us in terms of data communication? What should we expect to be in that press release? You tend to focus, and correct me if I am wrong, on primary endpoint and safety, but how are you thinking about the communication around those data? Yeah, definitely. As we do with other phase III, there will be multiple phase III, hopefully reading out in the- Right. coming time. Top-line results and also a statement on safety, because that is, of course, the second parameter, which is really important for new candidate medicines is that they are not only efficacious but also have a good safety profile, because that in combination will actually predict how successful they can be as a new treatment option. That is what you can expect for the frontline head and neck cancer data for petosemtamab. Okay. Further details will then be presented at a medical conference, hopefully soon after, Judah. Okay. With more color, of course, on subsets of patients and other parameter secondary readouts, et cetera. Okay, great. Maybe just remind us of the timing of the decision to increase enrollment in those LiGeR trials. Any detail you can share around drivers of that decision? I think, like we've talked before, the timing of when you made that decision is important for investors around the world. Yeah. I can refer to Tahi for sure because we already made that decision in the summer last year before we actually approached Merus. But Tahi, you can give it a bit more color. Yeah, I think that decision, and that has gotten a lot of press over this week was one of the first things that we talked about when we were looking in the diligence that we want to increase the sample size for both line just to basically capture sufficient number of patients in this, what is in the end, a heterogeneous disease. It's, by the way, not only heterogeneous by HPV positivity but it's also locality. We did that, and then I think there was a debate whether this would have a timing impact on enrollment. Yeah, they both, and what we said from the beginning, it won't have an impact on the enrollment. It didn't. I don't think getting into the details of why we make these decisions is I mean, a little bit too much. Maybe just on that point, maybe help us with unmet need in head and neck. What response rates and OS look like if pembrolizumab's the right benchmark currently, and maybe how that helped in Well, if you look at the current standard, right? Essentially, you are faced with two choices. You have pembrolizumab monotherapy or pembrolizumab chemotherapy. Neither of which is really attractive. Pembrolizumab has a 19%, depending on what study, somewhere between high teens to low 20% response rate. The PFS then is automatically driven by the non-responders, and the OS is driven by the responders, and this is roughly about a year. Chemotherapy doesn't really actually change much on these dynamics. It is just an option that then gets taken if a patient has a tumor that is in a certain locality that requires a more immediate intervention. Broadly speaking, the response rates are slightly higher. The overall survival is exactly the same. So they are both, to be honest, some of the most dismal outcomes in any frontline indication in cancer, if you really think about this and put this into context, how much progress we have made in other disease areas. The promise of the petosemtamab pembrolizumab combination is if you take the phase II data sets, that you roughly would triple the response rate. You roughly triple the PFS rate, and then that has a significant impact on the overall survival. You essentially now have a regimen that would not have the toxicities of chemotherapy. These patients are really frail. They're beaten up. Their locality is problematic. They are more often also in a bad stage because of the risk factors that leads to the disease. Having essentially a non-toxic or outside of the IRR, relatively well-tolerated regimen that has such a magnitude of improvement in efficacy, disease control, and then durability. I think one could argue if that would actually play out in the phase III, that that would be transformational. Right. That's what we're looking for. Okay. Like you said, the phase II sort of set a high bar for petosemtamab, right? Objective response rate 63%. I think it was a nine-month median PFS and 79% 12-month OS. Right? But I guess, like you said, given the background you mentioned on standard of care, where do ORR and OS need to be to be commercially meaningful as the potential first mover of the next-gen bispecifics? I guess, what has physician reaction been in terms of could we see data maybe come down a little bit from the phase II? So look, if it is going to be in the ballpark what the phase II is, it is going to have to be careful with the words one uses prior to having the data, whether it is going to have a transformational impact on the care of patients with metastatic local recurrent neck. That is without a doubt. If you look at the speed by which these trials enrolled, that gives you a hint. If you see the sense that is building in the community around waiting for this data, that gives you a hint. I think there is a significant amount of anticipation for this data including in Genmab. And if it is going to be somewhere in the ballpark, which we are very confident it will be, then I think there's no question this is the new standard. Yeah. I guess in our conversations in the ballpark is great, but that ballpark is so far away from what standard of care is getting these days that it's one of these instances where investors and doctors maybe have different views on what's good data, but that's good to know. Yeah. Well, to believe it, right? Yeah. We have to see it. Yeah. We are pretty excited about getting the data in our hands. Okay, great. You mentioned just kind of HPV being a driver of some subset of head and neck. Is the goal to be an HPV-agnostic asset? Could we potentially see messaging around efficacy in HPV- negative disease in particular at some point? I guess, what's the approach here in terms of HPV status? Yeah. I think two things can be true at the same time. When we say agnostic, by the way, this is also true for Rina-S. We are not meaning that it behaves exactly the same way. What we are saying is the combination of petosemtamab pembrolizumab in our minds, based on what we know so far, will have a meaningful differentiated impact on the standard of care regardless of which of these two buckets you fall in, because these two buckets behave also differently to petosemtamab. That is what we are saying. The idea is to provide this medicine, this new innovation, if you will, with that hopefully repeated magnitude of efficacy to all patients. Now, there is a difference between HPV- positive and HPV negativity in terms of how they respond to EGFR. That is not only true for petosemtamab, it is true for every EGFR antibody. There is a biological reason for all of that. It is actually more around select the oropharyngeal subtype that seems to then coexist with HPV negativity. Particularly in the frontline, I think we are very comfortable with the idea that the data that we are going to generate, the data that we have so far generated or that Mayo has generated and that we inherited, points very clearly to the fact that regardless of HPV positivity, negativity, there is a differentiation impact. Okay, great. Like you said, we are going to get LiGeR-HN2 data first quarter of next year. I guess, how should we think about level of OS benefit and kind of meaningfulness there? Will having OS data on hand support positioning versus maybe amivantamab or other competition? Well, the sequence of events is going to be first things first, right? We are going to have, hopefully, a positive readout on the frontline study, which I think will settle a lot of questions in the investor community, but also in the Genmab minds around the place and the role that petosemtamab will play in head and neck because that is just the dramatically larger space in terms of patients and opportunities and improve outcomes. The second line monotherapy OS study, well, first of all, it is an OS study. What Janssen has is an accelerated pool based on response. It is a little bit trickier here to benchmark OS, to be honest, because there is a lot of different data sets that are sometimes conflicting, which is why it is good to have this in a randomized trial to actually control for that. We are very positive that this trial will also be positive on OS, and then you would have in the totality of benefits, a very normal and comprehensive picture about the role of petosemtamab in head and neck that is frankly not comparable to a phase II as good as it looked like. The Janssen strategy is actually going combination with chemotherapy which is also completely different. We feel very good about the program that we inherited on these two studies. We feel very good about the data that we have so far seen, and we are very excited about these two readouts, which are going to underlie what we said from the beginning, a position for petosemtamab to be the best in class, also first in class really in frontline EGFR, second generation EGFR bispecific. Okay, great. Maybe just before we wrap up the head and neck conversation, competition in the space and additional assets coming down development pipelines is great for patients, but maybe just remind folks how many centers petosemtamab has been investigated in, kind of level of familiarity for head and neck specialists with petosemtamab at this point in time. How many sites have been- Yeah. part of these two trials? I think there's some overlaps, but it's a number that's north of 300 sites. Right. I think essentially every major network in head and neck, every major investigator in head and neck across the mostly Western world, in one way or the other, is part of the petosemtamab program. Kudos to those collaborations to actually drive this program where it is now. Yeah. Okay, great. Maybe we spend a few minutes on CRC, right? I think when you bought Merus, you indicated head and neck was really the focus for the return on that investment, but you're clearly making progress in colorectal as well. So maybe just briefly describe the planned frontline and second-line plus studies, trial design, arms of those trials, and is there inherent differentiation in design versus competitors' CRC trials? You want to take that question again? I think so. I will take over pretty soon. Okay, good. Well, first things first, right? So Luis started two phase III's in frontline and second-line colorectal, as you were pointing out. In frontline, as cited last fall type, roughly 900-patient study against FOLFOX or FOLFIRI in combination with cetuximab. In second line, and that's already where there's a little bit of a differentiation, same population, slightly smaller study, FOLFOX, FOLFIRI combined with cetuximab or bevacizumab. That's one part, slightly broader in its intended population label. While we at the time said that the deal was underwritten, I think that's what the wording was, the deal was underwritten by the head and neck data. We had looked at every single colorectal patient, and it had, of course, been part of our fantasy and our imagination. The only way you actually get an active study involving patients in September when you close the deal in January is that you actually started to work on this already while you were in diligence. So it's okay. We have been from the beginning having our eyes very closely on this data. There's going to be more data coming up sometime soon to also drive this enthusiasm for everybody to see. As I've said many times, these are small phase II data sets. One has to be careful. Right. Numerically, they look incredibly good in our minds. They look very promising and also in cost comparison to amivantamab. Again, it's not about only efficacy, it's also about safety and tolerability. So we're really excited about this colorectal space now that's opening up. We're going to run these studies as fast as we have run other studies, and hopefully, we'll then be able to catch up on some creative regulatory pathways that exist. But let's get the data first. Conceptually, of course, it is very logical to go for colorectal cancer because LGR5 was originally described as part of the Wnt signaling pathway, and the bispecific by Merus was screened on organoids from colorectal cancer. That is what this one really differentiated versus hundreds of other bispecifics. I think conceptually it really makes a lot of sense to go for colorectal cancer. Yes, we were a lot more enthusiastic during that than we actually displayed publicly. I was worried actually that our deal would be threatened between September last year and December with the party being too enthusiastic about colorectal. Right. Because when you think it through, the potential market size of colorectal is three times bigger than head and neck cancer. This could make this a very sweet deal for Genmab, so I am happy that we have now executed the deal on December 12th, and we are now progressing with two phase III trials with colorectal cancer. I can tell you that we will further expand the petosemtamab program, and we will further expand the Rina-S program pretty quickly. That is what we are focusing on right now. Super enthusiastic. Great. What should we think about in terms of efficacy benchmarks in front line and second line plus CRC for clinical? Well, again, this is a little bit of a tricky population now because a lot of the older trials, they have some of the patients in there that are now taking out for biomarker-driven approaches. So it is a little bit tricky to estimate this, but if you just think about it, I think the overall response rate right now for petosemtamab in combination with chemotherapy is in the high 80s. There is a lot of space in there. Right. Between what is currently standard of care with cetuximab, and then what would be the combination data. We feel very comfortable about that. In second line, it's even wider, and that also then tells you a story to a degree. What's true in second line is also true in front line. It's the same biology. In second line, we're running a high 60%ish, 70%ish response rate with a margin of 30%, 40% almost 50%. Right. Again, we feel very excited about these trials. I forgot to mention this, but it was good that you reminded us. It was actually a drug that was selected to be a colorectal cancer drug because of the biology of the Wnt pathway. The data will be presented, and as you get to see it a little bit more with a little bit more follow-up, has at every step kind of reconfirmed this initial enthusiasm. Maybe another anecdote on all of this, the first document that left the house after the deal was signed 24 hours after the deal was signed was the request for an IND. Got it. Great. Maybe we'll move over to EPKINLY. Maybe just talk about the current growth that's coming from second-line follicular lymphoma versus third-line plus DLBCL. What's the biggest barrier to broader community adoption currently, even though you're making progress there? We're making significant progress there with a lot of adoption in the community setting. That is driven by the second-line follicular lymphoma. It is also driven by the fact that this is one T-cell engager targeting both diffuse large B-cell lymphoma and follicular lymphoma, which is much more straightforward for community healthcare centers. A very good safety profile. It's easy to give. It's a two-second injection under the skin. Remember that in front line and second line B-cell cancers, these patients want to be treated close to their homes and not in a cancer hospital- Right. four hours flying from their home or a university hospital. We see a lot of traction right now, and in fact, most of the adoption is now coming from the community centers. Very encouraged by that. Looking forward to the front line readouts, of course, in Q4. That is basically the largest part of the market. Right. It's essentially half of the potential target market for EPKINLY. Super enthusiastic, but we also see traction now in other territories. The second-line follicular lymphoma setting was approved last year in November in the U.S., and this year in China and Europe. Japan is around the corner, literally. We are going to expand also in other settings there. Also we have, of course, now also the positive data on the second-line diffuse large B-cell lymphoma combination with lenalidomide. There we're also speaking with multiple regulators at different parts of the world right now. I think there's a good momentum now, and you've seen it. I mean, 48% growth year-over-year. I already said it in my introductory remarks. 28% quarter-over-quarter. Going from first quarter to second quarter. Beating competitors quarter after quarter- after- quarter. With T-cell engagers targeting CD20, I think we're in good shape and actually the best shape possible because we are going to have the frontline data- Right. probably a year to 1.5 years sooner than some of the main competitors. I want to remind everybody that in the original third line plus label in diffuse large B-cell lymphoma, Judah, we had a 29-day difference between us and a competitor, and we have beaten them quarter by quarter every quarter since. I think time really helps, and that is what you should all be aware of for Genmab. Genmab is a new company now, but we are focusing on really truly differentiated molecules and very good execution, because execution is what matters. What we see not only for EPKINLY, where we knew that we already had a number of competitors. We see that petosemtamab, we just spoke about that, at least two key competitors now moving in. Rina-S, where we hopefully will also spend some time on today because it's such an exciting molecule. Where we see the big ones, AstraZeneca, Lilly, and other companies coming in, also with next generation folate receptor alpha ADC. What it comes down to is very good execution, and we have now set up the organization. We can do this in a very effective way. I think the acceleration of the Rina-S phase III shows it for this year, the very rapid coming to the frontline data in head and neck cancer with the petosemtamab asset. Then we're also super excited about having the frontline diffuse large B-cell lymphoma combination trial with R-CHOP, which is the gold standard already for 24 years, and we can beat that. I think we have a good presence also on B-cell cancer. I think that all in all brings a very exciting picture for the company. Definitely. Maybe just on that frontline DLBCL trial that we will also get a data card flip in Q4. In terms of a PFS hazard ratio, we are not looking to pin you down on a number, but I guess, also a ballpark that experts are thinking about that could really transition EPKINLY to standard of care on frontline. All right. Yeah. The ice is cracking under my feet, so I am going to walk very slowly. First off, let us stay with what we communicate. We are going to have a readout this year, and that is very exciting, and then it is going to be based on the interim. We are very confident about that, to be able to present that. There is a lot of mathematical models out there. A lot of the questions that I have in the past have received as R-CHOP. Does R-CHOP behave the way that R-CHOP behaves? All things are being true and equal. Polivy, frontline, even other studies, it tends to behave a certain way in a very narrow band. We are looking with excitement at this data. Then once we have the data, I think we can have a conversation about what it means for the community. One other point, maybe to also go back a little bit to the first question. The reason that we were really intensely focused on working with the agencies, particularly the FDA, on getting the hospitalization requirement out of the label, and that was a significant effort. A separate study was done in the community to show that it can actually be done in at least within the U.S. healthcare system, where the community often is also a term that describes distance to tertiary access. With the steroid regimens that control the CRS, all of this was done in preview and in anticipation and pre-planned to be in place by the time we would get the frontline data because there, as Jan was saying, these patients are actually in the community, that is where they are going to get treated. You are going to not have an impact on the disease unless you have a regimen that can be administered by label restriction or regardless of label restriction, just the practicality of how it is being administered in the community. The whole story about EPKINLY was always about that. The sub-Q administration, the ease of route, the control of the CRS. In totality, you see this now playing out. I think the current indications also with [HexaBody-OX40] have allowed us to penetrate the community in the U.S. significantly. This is creating now confidence and experience and preview of hopefully what will be exciting data on the future, as we said. I think it does not really make sense to speculate where the PFS. I mean, the only thing I will say is this, it is a disease where a segment of patients get cured. Right. One has to take that into mind when one starts to think about PFS. The most positive, if you look at the rituximab study, I think that is maybe like the ceiling if you think about it. The rituximab study had a hazard ratio of 0.55. Right. Okay. That is helpful. Maybe just last one on here, just the need or the potential to show benefit in both GCB and ABC patients. How are you thinking about that? Oh, with the cell of origin? Yeah. Yeah, I don't think there's really a reason to believe, and we've never seen anything like that, the cell of origin matters for T-cell redirection. This comes a little bit, I think, partially driven by the Polivy data set. Right. Without getting too scientific, the assay that you use is probably equally important to the determination of a self-origin in the actual data. It's a very subjective determination, actually, if you look behind it. At the fringes it is not, but at the overlap. It was never pre-specified, so I don't really know what it means. We don't have a reason to believe that it behaves differently in any of these subtypes. Okay. No data that I've seen, neither from what Roche has ever put out in the public domain from their trials, nor what we've seen with epcoritamab with, I don't know, thousands there. Doesn't seem, neither do actually other historical prognostic factors. To a degree, when you have a new mechanism, sometimes what happens is like you reset the whole discussion about risk factors. Quite certainly will in the end, hopefully when this trial is positive, have a discussion about completely different physical or clinical attributes that describe a subset of patients that may not necessarily benefit as much from T-cell rejuvenation than others. That's a discussion for tomorrow. Okay. I want to make sure we touch on Rina-S, like you said. We'll get a phase III out there in P-ROC Q4 as well. I guess how are you thinking about differentiation versus mirvetuximab specifically? Given activity across folate receptor alpha expression levels, could you avoid a companion diagnostic with Rina-S? Yeah. I want to be polite to my friends at AbbVie, but I don't think mirvetuximab is part of this conversation. I honestly don't. I think when the data will come out, I mean, we'll have the phase II data, and then we'll have the phase III data, we'll end up having a conversation about a completely different treatment paradigm in part. What we've seen so far, of course, like the initial strategy is in mirvetuximab exposed for those who are 75 and above, and that's a regulatory strategy because it's the easier path. What we've seen so far is that Rina-S has a very high response rate, somewhere around 50% in totality, not always the same by these subgroups. Again, the same story that I've repeated this many times. When we say it has a meaningful impact across the spectrum of folate receptor alpha expression, we're not saying that it's equal in each one of them. It's not. It has a meaningful. By the way, the inequality comes less through the response, but more to the duration. That's, by the way, true for mirvetuximab too. If you look at the old mirvetuximab trials, the response rate was not necessarily much lower. They have like a 30% response rate in 75 and above. Then they had like a high 20% response rate and below. It was the duration of response which basically made it impossible because they actually had a failed phase III, and then they went back. Really go back in history a long time ago. For Rina-S, what we have seen and what we continuously communicate, because this is what we believe, this is what we have in our hands, is that folate receptor alpha expression, the way it is determined, what happens is actually as for polymorphisms on folate receptor alpha, you only measure one with the assay. The way it is determined does not really identify a population that would not benefit. We have a benefit across the entire spectrum of folate receptor alpha expression from negative all the way to the very high. We believe the data is going to be transformational. Right. It is incredibly well-tolerated. It does not have eye toxicity. It does not have neurotoxicity. The duration of treatment is extremely long. In the phase II data set we were talking about a duration of response that in aggregate was exceeding 12 months across the entire spectrum. There is like different segments. The discontinuation rate due to AEs was in the low percentage, single percentage, 3%, 4% maybe. It is the same story all over. Once you get control over the neutropenia and you settle on your dose, there is really no reason why patients discontinue. We are very excited about this study. I think it will be a very important study for Genmab, but also for [Renlevu Park]. I do not really think mirvetuximab is part of the conversation anymore. Okay, great. I think we will park it there for time. Thank you very much for being here. We appreciate it. Thank you.