Genmab A/S (GMAB) Earnings Call Transcript & Summary

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 have settled a lot of questions in the investor community, but also again in the Gen mines on the place in the world that it will pay 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 -- well, first of all, it is an OS study, right, where the Anson has as an accelerated approval based on the response -- it's a little bit tricky here to benchmark or has to be honest, because there is a lot of different data sets sometimes conflicting. So which is why it's good to have to send a randomized this actually control for that. We are very positive that the pro will also be positive on OS and then you would have in the totality of benefits a very normal and compensive picture about the role of petrol in head and neck that is because it's frankly not comparable to like a Phase II as good as it looked like. And then Janssen strategy is actually going in combination with chemotherapy, right, which is also are completely different. So we feel very good about the program that we inherited on these 2 studies. We feel very good about the data that we have so far seen, and we are very excited about these 2 readouts, which are going to underwrite what we said from the beginning. Position for Peyto to be the best-in-class, also first-in-class really in frontline. AGF second-generation EGFR bispecific.

Okay. Great. And maybe just before we wrap up the head and neck conversation, competition in the space and additional assets kind of coming down development pipelines is great for patients. But maybe just to remind folks how many centers Pito has been investigated in kind of level of familiarity for head and neck specialists with Pito at this point in time.

So how many sites have been these 2 trials. I think there are some overlaps, but it's a number that's north of 300 sites, right. I think like essentially every major network in head and neck, every major investigator of head and neck across the mostly and 1 way or the other is part of the better program. . And so there's kudos to those collaborations. So actually, the last is prolonged was no.

Yes. Okay. Great. And then 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?

I think so I will take over pretty soon. Okay, good -- so Louis started 2 Phase -- is in frontline in the second line colorectal pointing out. In frontline, I cited last wildtype, roughly 900-patient study against FOLFOX offer in combination with cetuximab. In second line, and that's already where that is a little bit slightly smaller study FOLFOX combined with cetuximab or bevacizumab. So that's 1 part that's slightly broader in the antenna population label. And while we, at the time said that the deal was underwritten. I think that's what the wording was. So the deal was underwritten by the head and neck data. We had looked at every single colorectal patients and that 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 closed the deal in January is that you actually started to work on this already value and diligence okay. So we're a bit from the beginning, we were 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 said many times, these are small Phase II data sets in has to be careful. But numerically, they look incredibly good in our mind. They look very promising and also in comparison cost comparison to Army. And 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. And so we're going to run these studies as fast as we have other studies hopefully, we will then be able to catch up on some creative regulatory pathways that exist, but get the data first.

And conceptually, of course, this is very logical to go for colorectal cancer because LTO-5 was originally described as part of the wind signaling pathway and the bispecific gamers was screened on organized from colorectal cancer. . And that is what this one really differentiated versus hundreds of other bispecifics. So I think conceptually, it really makes a lot of sense to go for colorectal cancer. And yes, we have a lot more enthusiastic Durethan we actually displayed publicly because I was worried actually that our deal will be threatened between September last year and December in part being too enthusiastic with colorectal because you think it through potential market size of colorectal is like 3x bigger than head and neck cancer. So this could make this a very sweet deal for Genmab. So I'm happy that we have not executed the deal on December 12 and then are progressing with 2 Phase III trials with colorectal cancer. And that's not all. I can tell you that we will further expand the beta program, and we will further expand Arena 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 frontline and second-line plus CRC for a client.

Well, so again, this is a population now because a lot of the older trials, they have some of the patients in there that are now taking out for biomarker does an approaches. So it's a little bit tricky to estimate this. But if you just think about, I think, like the overall response rate right now for peto in combination chemotherapies in the high 80s. There is a lot of space in there between what is currently standard of care with cetuximab and then what would be the combination data. So we feel very comfortable about that in second line, it's wider and that also then tells you a story to a degree, what's doing the second line is also to frontline, the same priology. And then in we're running like a high 60s, 70s percent response rate. It's like a margin of like 34%, you can be almost 60%. So again, we feel very excited about this trans 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 and work because of the biology of the wind pathway. . And so the data will be presented. And so you have to see it a little bit more a little bit more follow-up, as every step kind of like we confirm this initial enthusiasm, maybe another anecdote and of this, the first document that left the house after the deal was signed 24 hours other deal was signed was a request for an IND.

Great. Right? Maybe we'll move over to Apkimly. 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 and that is driven by the second-line follicular lymphoma. It's also driven by the fact that this is 1 T cell engager targeting both diffuse as cellephoma and for nicelalyphone, which is much more straightforward for community health care centers [Audio Gap] or university hospitals. So we see a lot of traction right now. And in fact, most of the adoption is now coming from the community center. So very encouraged by that. Looking forward to the front line readout, of course, in Q4 because that is basically the largest part of the market. It's essentially half of the potential target market for kindly. So super enthusiastic, but we also see traction in other territories. The second line follicular apharmatetic 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, also the positive data on the second-line diffuse cell B-cell lymphoma. Combination with lenalidomide, 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 the 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 probably 1 year to 1.5 years sooner than some of the main competitors. And I want to remind everybody that in the original third line plus label and the fuselage piece of mature we like a 29-day difference between us and a competitor. 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 or general Galp is a new company now, but we're focusing on is really truly differentiated molecules and very good execution because execution matters. So what we see, not only for Killeen that we already had a number of competitors. We see that Peter, we just spoke about that, these 2 key competitors now moving in Rena, where we hopefully will also spend some time on today because it's such an exciting molecule. And we see the big ones, the Astra, the Lillies and other companies coming in also with next-generation for its offer ADC. So what it comes down to is very good execution. And we have no set up the organization. We can do this in a very effective way. And I think the acceleration of the arena as Phase III shows that for this year, the very rapid coming to the frontline data and had a neck cancer that the pitusentamab asset. And then we're also super excited about having the frontline diffuse B-cell lymphoma combination trial with RCHOP -- this 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, I think, picture for the company.

Definitely. So maybe just on the frontline DLBCL trial that will 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 it, could really transition epti a standard of care in frontline.

Right. Absolute the is cracking under my feet. So I'm going to walk very slow. First off, first, let's stay with what we communicated. So we're 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. And so there's a lot of mathematical models out there. A lot of the questions that I have in the past have received a sort of a sacubehaved the way that sees all things are being true and equal. Polarix frontline. Even other studies, it tends to behave a certain way in a very narrow band. We are looking with the excitement at this data. And then once we have the data, I think we can have a conversation but what it means for the community. One other point maybe to like 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 there was a significant effort. It was a separate study was done in the community to show that it can actually be done in and at least within the U.S. health care system where you -- the community often is also a term that describes distance to tertiary access. And then with the regimen, the steroid regimens that control the CRS, all of this, this was done in preview in anticipation and preplan 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 is can be administered by labor restriction or regardless of labor restrictions, but just the practicality of how it's being administered in the community. And so the whole story about Aptina was always about that. So the subcu administration, the ease of about the control of the CRS. And so in totality, you see this now playing out. I think the current indications also with Tecnopoforma have allowed us to penetrate the community in the U.S. significantly. And this is creating our confidence and experience and hopefully, we will be exciting data on the fuel such I think it doesn't really make sense to speculate the PFS. And 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 1 so thinking about PFS. The most positive if you look at the rituximab study, I think that's maybe like the seating, if you think about it. The rituximab study had a hapato0.59.

Right. Okay. That's helpful. And maybe just last 1 here, just the need or the potential to show benefit in both GCB and ABC patients? How are you thinking about that?

Was the sale of origin?

Yes.

May, I don't think there's really a reason to believe, and we've never seen anything but that the cell-of-origin matters for T cell redirection. This comes a little bit, I think, partially driven by the Polarix data set. And without getting to scientific, right, the assay that you use is probably equally important to the determination of a self origin and the actual data. It's a very subjective determination actually, if you look behind it. Defines is not, but at the overlap. So it was never prespecified to really know what it means. We don't have a reason to believe that it behaves different in any of these subtypes, no data to the public domain from their trials. Now what you've seen with Kinney with, I don't know, 1,000 1,000 doesn't seem -- need to do actually other historical prognostic factors. So to a degree, when you have a new mechanism, sometimes what happens is like we set all discussions about those factors. And I'm quite certainly, well, 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 elevation and others. But that's a discussion for tomorrow.

And I want to make sure we touch on Renas,like you said. So we'll get a pace yes there Q4 as well. I guess how are you thinking about differentiation versus mirvetuximab specifically? And then given activity across folate receptor alpha expression levels, could you avoid a companion diagnostic.

Yes. So I want to be polite to my friends at Abi, but I don't think mirvetuximab as part of this conversation, honestly don't. I think when the data will come ultimately, we'll have the Phase II data and then we will have the Phase III data, we will end up having a conversation about the completely different treatment paradigm on pub. What we've seen so far, of course, like the initial strategy is in Mark 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 Minas has a very high response rate, somewhere around 50% in totality, not always the same by the subgroups. And again, the same story that I have repeated this many times. When we say it has a meaningful impact that cost of spectrometer expression, we're not saying that it's equal in each one of them. It's not but it has a meaningful. By the way, the inquality comes less fully response, but more to the iteration. That's by the way true from F2, if you look at the op side, the response rate was not necessarily much lower. We have roughly a 30% response rate and 75 and above. And then they had like a high 20% response rate and below, it was a duration of response, which basically made it impossible because they actually had a failed Phase III, and then they went back really, really well go back in history a long time ago. So for me now, 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 for the receptor alpha expression, the way it is determined, again, what happens is actually 4 more fines on core 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 fleet of 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 II data set, we were talking about the duration of response that in aggregate was exceeding 12 months across the entire spectrum. So there are different segments. The discontinuation rate due to AEs was in the low percentage, single percentage, 3%, 4%, maybe the same-store, once you get the control of the neutropenia and you settle on your dose, there is really no reason why patients discontinue. And so we are very excited about this study. I think it will be a very important study for GM, but also prevent up. And I don't really think Marvis part of the compensation anymore.

Okay. Great. I think we will probably -- we could keep going, but I think we'll get there for time. Thank you very much for being here. We appreciate it.

Thank you.