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This session at the Morgan Stanley Global Healthcare Conference, we're very excited to have the team from GENMAB, Jan and Tayi, 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 forward slash research disclosurers. I'm Judah Fromer, one of the SMID biopsych analysts here at Morgan Stanley. Like I said, very excited to have GENMAB here for this session. So I thought we could start out with key updates since we saw you here last year. Maris 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'm 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've three late stage assets, which are all expanding their reach for the coming time. So we have actually announced six new phase three trials this year and more to come and also we will have a lot of data in q4 essentially all of the three lead programs will generate phase three data in Q4 so we're very excited and then of course the financials look very solid they increase the revenue by 25 percent in the first half and operating profit by 18 percent so very solid financials this will allow us to invest actually in further expanding the late states programs and also preparing for commercial launches multiple launches next year assuming the data will be very good and follow the phase two data so it made a lot of progress and delighted to be back in new york here great so maybe starting with with maris and impetus symptomab what what drew you to the asset how is it differentiated from other egfr by specifics in recurrent matter metastatic head and neck cancer and crc maybe just initially kind of what drew to that acquisition yeah i can start Part of it, and I'll let Pai fill in a bit more of the differentiation part, but pitocentrum is a truly differentiated next-generation age of our targeting antibody with great preclinical data, very, very good early clinical data, and had a neck cancer, two breakthrough therapy designations, two phase threes. One of them will read out in Q4, and then the other one, the second line, second, third line, had a head and neck cancer will read it out in the Q1. Immediately thereafter, so very well progressing. Data are really, really good on a numerical basis, really outperform potential competitors there, and also colorectal cancer. We've now announced on August 6th two new Phase III trials, one in front line and second line colorectoral cancer. You will hear the reasons why at ASMO end of the October timeframe where we will actually describe the Phase II data which were originally from MIRAS, where we more or less more than doubled the number of patients and then also follow them up for a much longer period of time. But I'll let Tai speak a bit more on differentiation versus other EGFR targeting antibodies. So pause here. Tai? Yeah, I think this goes back to the thesis that we were formulating when we actually announced that we Were Going After Males. As Jan was saying, my picture is a second generation EGFAR, it's quite specific, second arm is against RGR5. And what we saw and I think what continuously to play out was very early on, which is what triggered our interest, but it appeared to have a differentiation on the efficacy. It's like in cost-effective comparisons are always hyper-problematic, but in every data set that is in the public domain, in monotherapy, in combination with PEMBO and head and neck space, in combination mitophilophoxin front line or second line, there's always like a numerically higher response rate vis-à-vis, for example, amivantamod. And on the other end, and that's probably equally important, it also seems to be differentiated on the safety side. So it doesn't have the degree of skin problems. It doesn't has the scalp skin issues that Amirantama was dealing with, which then is managed with the whole Konkun regimen. It doesn'T seem to have the agree of somatitis and all of these things. And they, in totality, then, and this is kind of like a theme in Gemma, they help patients stay on drug and duration of treatment eventually then also becomes duration of response and these things together higher efficacy, longer duration treatment they tend to drive then this package that we're looking for that really is 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 set some of which are going to be presented at ESMO and so we're really excited about it. We're really excited about the readout that we announced is going to happen in this quarter and so we all look forward to having a conversation about that great and 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 by specific LGR 5 oh LGR 4 yeah no I think like you know the story of LGR 5 is obviously an interesting scientific story it came out the Hubei Institute It was an observation that this is a stem cell target. If you really dig into the history of PETO, it was screened in organelle model. Scientifically, this is super intriguing. And in the end, both Jan and me came out of the lab. We are scientists. But ultimately, it is actual clinical data. And so it becomes very difficult to do attributes, whatever profile you see. But in totality, as it is, as a biospecific with these two targets, it has a certain clinical behavior, and that's what we were attracted for, that's why we were doing the diligence on, and that was what drove the enthusiasm to do really a major transformational step for GEMOP, and this is why we're so excitedly waiting for the first readout, the confirmation of our excitement. Okay, great. And like you said, Jan, we'll get the frontline data in the fourth quarter this year, that's the LIGR-HM1 trial. So that'll 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'm wrong, on primary endpoint and safety. But how are you thinking about the communication around those data? Yeah, definitely, as we do with all our phase 3s, there will be multiple phase 3S, hopefully you're reading out in the 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. So that is what you can expect for the frontline head and neck cancer data for pitocentrum. And then further details will then be presented at a medical conference, hopefully sooner after Judah, with more color, of course, on subsets of patients and on other parameters, secondary readouts, et cetera. Okay, great. And 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, you know, like we've talked before, the timing of when you made that decision is important for investors around the world. I can defer that to Tai for sure because we already made that decision in the summer last year before we actually approached Meris. But Tai, you can give it a bit more color. Yeah, I think that decision, and that's gotten a lot of press, so to speak, was one of the first things that we talked about when we were looking in the diligence, that we wanted to increase the sample size for both lines just to basically capture a sufficient number of patients in this what is, in the end, a heterogeneous disease. And it's, by the way, not only heterogeneous by HPV positivity. It's also locality. And so we did that. And I think there was a debate whether this would have a timing impact on enrollment. And so they both, in what we said from the beginning, It won't have an impact on the enrollment. It didn't. And so, yeah, I don't think getting into the details of why we make these decisions is a little bit too much. Maybe just on that point, maybe help us with unmet need in head and neck, kind of what response rates in OS look like if Prambo is the right benchmark currently and maybe how that helped. Well, so if you look at the current standard, but essentially you are faced with two choices. You have Pembro monotherapy or Pembo chemotherapy. MEDOV, which is really attractive, Pembre has like 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 it's 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 that is 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 for 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. So the promise of the pito-pembro combination is if you take the phase 2 data set, 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. And you essentially now have a regimen that would not have the toxicities of chemotherapy. And 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 lead 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 three, that that would be transformational. And so that's what we're looking for. Okay. That's all. So, like you said, you know, the phase two sort of set a high bar for PETO, right? You know, objective response rate, 63%. I think it was a nine-month medium PFS and 79% 12-month OS, right? But I guess, like You said, given the background You mentioned on standard of care, you know where the ORR and OS need to be to be kind of commercially meaningful as the potential first mover of the next gen by specifics? I guess, what has physician reaction been in terms of, you know, could we see data maybe come down a little bit from the phase two? So, I mean, if it is going to be in the ballpark of what the phase is, it is going to be careful with the words one uses prior to having the data, whether it's going to have a transformation impact on the care of patients with with metastatic local recurrence at neck. That's without a doubt. If you look at the speed by which these trials are involved, that gives you a hint. If you see the sense that is building in the community around waiting for this data, that gives your hint. I think there's a significant amount of anticipation for this later, including in general. 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 a new standard in our KOL 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 we have to believe it we have pretty excited about getting the data in our hands. Okay, great. And then 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? And I guess kind of what's the approach here in terms of HPD status? I think two things can be true at the same time when we say agnostic by the way this is also true for arena we're not meaning that it behaves exactly the same way what we're saying is the combination of petro-pembro 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 pockets behave also differently to the pembro and so that's what we're saying and so 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's not only true for PICA it's true for every EGF antibody and there is biological reason for all of that it's actually more about like the oropharyngeal subtype that seems to then co-exist with HPV negativity. But particularly in the front line, I think we're very comfortable with the idea that the data that we're going to generate, the data we have so far generated, that may have been generated and that we have inherited, points very clearly to the fact that regardless of HPV positivity and negativity, there is a differentiation impact. Okay, great. And like you said, we're 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? And will having OS data on hand support positioning versus maybe an AMI-Benz map or other competition? Well, so the sequence of events is going to be first things first, right? So we're 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 GMO minds around the place and the role that Peter will play in head and neck because that's just the dramatically larger space in terms of patients and opportunities to improve outcomes. the second line monotherapy OS study first of all it is an OS study what Janssen has is an accelerator pool based on response it's a little bit trickier here to benchmark to be honest because there is a lot of different data sets that are sometimes conflicting which is why it's 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, you know, in the totality of benefits, a very normal and comprehensive picture about the role of PETO in head and neck that is, you know frankly, not comparable to like a phase two as, you know, as good as it looked like. And then Janssen's strategy is actually going in combination with chemotherapy, which is also completely different. So we feel very good about the program that we inherited on these two studies. I 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 underwrite what we said from the beginning a position for Pay2 to be the best in class also first in class really in front line second generation EGFR by specific okay great and maybe just before we wrap up the head and neck conversation you know competition in the space and additional assets kind of you know coming down development pipelines is great for patients, but maybe just remind folks, you know, how many centers PETO has been investigated in, kind of level of familiarity for head and neck specialists with PETO at this point in time. So how many sites have been tried on these two trials? I think there's some overlaps, but it's a number that's north of 300 sites. I think, like, essentially every major network in head and back, and be a major investigator in head and neck across the mostly Western world in one way or the other as part of the PITO program. And so kudos to those collaborations to actually drive this program where it is now. Yeah, okay, great. And then maybe we spend a few minutes on CRC, right? I think when you bought Maris, you indicated head and necks 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 files? I'm going to take that question again. I think so. I will take over pretty soon. Okay, good. Well, first things first. So we started two phase threes in frontline and in second- line, as you were pointing out. In front line, I cited RAS wild type, roughly 900 patient study against Folfox or Folfuri 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, Folfax, Fofuri combined with Cetzimab or Bevacizumab. So that's one part, slightly broader in this intended population label. And while we at the time said that the idea was underwritten, I think that's what the wording was. So the idea wasn't written 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. And then the only way you actually get an active study enrolling 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 but okay so we will be from the beginning but we're having our eyes very closely on this data um there's going to be more data coming up sometime soon to also drive this this uh enthusiasm for for everybody to see as i said many times these are small phase two data sets one has to be careful but numerically they look incredibly good in our minds they look very very promising and also in comparison cost comparison to army and again i it's it's not about only efficacy it's also about safety and probability um so we're really excited about this core vector of space now that's opening up and so we'll run these studies as fast as we have on 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 and conceptually of course it is very logical to go for colorectal cancer because LGR5 was originally described as part of the signaling pathway and the bispecific glimeras were screened on organoids from colorextal cancer and that is what this one really differentiated versus hundreds of other bispeastics so I think conceptually it really makes a lot of sense to go for coloectal cancer and yes we were a lot more enthusiastic than we actually displayed publicly because I was worried actually that our deal would be threatened between September last year and December with the party being too enthusiastic about colorectal because when you think it through the potential market size of colorector is like three times bigger than head and neck cancer so this could make this a very sweet deal for GenMob so I'm happy that we have now executed the deal on December the 12th and we are now progressing with two phase 3 trials with colorectoral cancer And that's not all. I can tell you that we will further expand the PETA program and we will third expand the RENA program pretty quickly. That is what we're focusing on right now. So super enthusiastic. Great. And what should we think about in terms of efficacy benchmarks in front-line and second-line plus CRC for clinical trials? 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 biomarkers and approaches, so it's a little bit tricky to estimate this, but if you just think about it, I think the overall response rate right now for people in combination with chemotherapies in the high 80s, there is a lot of space in there between what is currently standard of care with Cytuximab, and then what would be the combination data, so we feel very comfortable about that. In second line, it's even wider, and that also then tells you a story to a degree. I mean, what's true in second line is also true in front line. It's the same biology. And then we're running like a high 60%, 70% response rate. there's like a margin of like 30-40 right almost 50% right so again we feel very excited about this trans you know I forgot to mention this but it was good that you reminded us it was actually a drug that was selected to be a co-directed NSAID drug because of the biology of the wind pathway and so the data will be presented so 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 in all of this, the first document that left the house after the deal was signed, 24 hours after the date was signed was the request for an IND. Got it. Great. Maybe we'll move over to Ip Kimley. 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? You're making significant progress there with a lot of adoption in the community setting, and that is driven by the second line, follicular lymphoma. It's also driven bythe fact that this is one T-cell engager targeting both diffuse RASB-cell lymphoma and follicular lympoma, which is much more straightforward for community health care centers. A very good safety profile. It's easy to give. It's like a two-second injection under the skin. Remember that in front-line and second-line basal cancers, these patients want to be treated close to their homes and not in a cancer hospital, four hours flying from their home or a university hospital. So we see a lot of traction right now. In fact, most of the adoption is now coming from the community centers. So very encouraged by that. Looking forward to the front-land readouts, of course, in Q4 because that is basically the largest part of the market. It's essentially half of the potential target market for Epkinley. So 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, so we are going to expand also in other settings there. And also we have, of course, now also the positive data on the second-land diffuse ASB cell lymphoma in combination with linoleumide, where we're also speaking with multiple regulators at different parts of the world right now. So 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 corner with T-cell engagers targeting CD20. I think we're in good shape and actually the best shape possible possible because we are going to have the front line data probably a year to one and a half years sooner than some of the main competitors and I want to remind everybody that in the original third line plus label in the fuselage piece in the form of Judah we had like a 29 day difference between us and a competitor and we have beaten them quarter by quarter every quarter since so I think time really helps and that is what you should all be aware of for GenMob. GenMop is a new company now what we're focusing on is really truly differentiated molecules and very good execution because execution is what matters what we see not only for epkinley where we knew that we already had a number of competitors we see that peter we just spoke about that at least two key competitors now moving in rena where we hopefully will also spend some time on today because it's such an exciting molecule where we see the big ones the astras the lilies and other companies coming in and also with next-generation folate receptor alpha-ADC. So what it comes down to is very good execution, and we have now set up the organization that we can do this in a very effective way. And I think the acceleration of the RNA-S phase 3 shows that for this year, the very rapid coming to the frontline data and had a neck cancer with the pitocintamab acid, and then we're also super excited about having the frontline diffusor of B-cell lymphoma combination trial with our CHOP, which is the gold standard already for 24 years, and we can beat that. I think we have a good presence also in visa cancer. So I think that all in all brings a very, very exciting picture for the company. Definitely. So maybe just on that frontline DLBCL trial, we'll also get a data card flip in Q4. In terms of a PFS hazard ratio, we're not looking to pin you down on a number, but I guess also a ballpark that experts are thinking about that could really transition Epkinley to standard of care on the front line. The ice is cracking under my feet so I'm going to walk very slow. First off, let's stay with what we communicate. We're going to have a readout this year and that is very exciting and it is going to be based on the interim. We are very confident about that to be able to present that. And so there's a lot of mathematical models out there. A lot of the questions that I have in the past, I've received as well as Archup. Does Archup behave the way that Archup behaves? You know, are all things being true and equal? Polarics, front mind, even other studies, it tends to behave a certain way in a very narrow band. We are looking with excitement at this data. And 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 labor, and there was a significant effort. There was a separate study that was done in the community to show that it can actually be done, At least within the U.S. healthcare system where the community often is also a term that describes distance to tertiary access. And then with the regiments, the stereo regiments 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, and that's where they are going to get treated. And so you're going to not have an impact on the disease unless you have a regimen that can be administered by labor restriction or regardless of labor restriction, but just the practicality of how it's being administered in the committee. And so the whole story about Epkini was always about that. So the sub-Q administration, the ease of route, the control of the CRS. And so in totality, you see this now playing out. I think the current indications also with Cignafolio and Icoforma have allowed us to penetrate the community in the U.S. significantly. And this is creating now confidence and experience in preview of hopefully what will be exciting data on the field such research. I think it doesn't really make sense to speculate where they have PFS. I mean, the only thing I will say is this. It's a disease where a segment of patients get cured. Right. And so one has to take that into mind when one starts to think about PFS because the most positive, if you look at the rituximab study, I think that's maybe like the ceiling, if you think about it. The rituximo study had a hazard ratio of 0.59. Right. Right. Okay. That's helpful. And maybe just last one on here, here, just the need or the potential to show benefit in both GCB and ABC patients. How are you thinking about that? With the cell of origin? Yeah. I don't think there's really a reason to believe, and we've never seen anything, that the cell or origin matters for T-cell redirection. This comes a little bit, I think, partially driven by the Polarix data set. Right. without getting too scientific the essay that you use is probably equally important to the determination of self-origin and the actual data it's a very subjective determination if you look behind it 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. No data that I've seen, neither from what Russia's ever put out in the public domain from their trials, nor what we've seen with Epkiney, with, I don' t know, thousands and thousands of years, doesn' t seem neither do actually other historical prognostic factors. So to a degree, when you have a new mechanism, sometimes what happens is like you reset the whole discussion about risk factors. And I'm quite certain you 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. But that's a discussion for tomorrow. Okay. And I want to make sure we touch on RENAS, like you said. So we'll get a face-to-face review out there in P-ROC. Q4 as well. I guess, how are you thinking about differentiation versus Mervituximab specifically? And then, you know, given activity across folate receptor alpha expression levels, could you avoid a companion diagnostic with RENAS? Yeah, so I want to be polite to my friends at Abbey, but I don't think Mervutuximib is part of this conversation. I honestly don't. I think when the data will come out, we're going to have to phase two data, and then we'll have to phase three data, we'll end up having a conversation about a completely different treatment paradigm and path. What we've seen so far, of course, like the initial strategy is in MRF exposed for those who are 75 and above, and that's a regulatory strategy because it's the easier path. But we've seen so far is that VNIS has a very high response rate somewhere around 50% in totality not always the same by these subgroups and again the same story that I've repeated this many times when we say it has a meaningful impact across the spectrum of four receptor alpha expression we're not saying that it's equal in each one of them but it has meaningful and by the way the inequality comes less through the response but more through the duration that's by the way true for MRF2 if you look at the old MRF files the response rate was not necessarily much lower they have roughly a 30% response rate and 75% and above and 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 3 and then it went back really really really go back in history a long time ago So, for me now, what we've seen, what we continuously communicate, because this is what we believe, this is what we have in our hands, is that foliar receptor alpha expression, the way it is determined, again, what happens is actually that for polymorphisms and foliar receptor alpha, you only measure one with the assay. The way it is determined does not really identify a population that would not benefit. So, we have a benefit across the entire spectrum of foliar of the alpha expression from negative all the way to the very high. We believe the data is going to be transformational. It is incredibly well tolerated. It doesn't have eye toxicity. It doesn�t have neurotoxicity. The duration of treatment is extremely long. In the phase two of the data set, we were talking about the duration of response that in aggregate was exceeding 12 months across the entire spectrum. there's like different segments the discontinuation rate due to a ease was in the low percentage single percentage three percent four percent maybe it's the same story or once you get the control over the neutropenia and you little settle on your on your dose there is really no reason why patient discontinue and so we are very excited about it but this study I think it will be a very important study for Gemma, but also for women with POP, and I don't really think Murph is part of the conversation anymore. Okay, great. I think we will, we could keep going, but I think I think we'll park it there for time. Thank you very much for being here. We appreciate it. Thank you.