Conference Transcript - GMAB 2026-09-09

Speaker 2

Okay, so we're ready for our next panel. I have here with me today Judith, CEO of GenMap. Thanks so much for joining us.

Speaker 3

Thank you for having me.

Speaker 2

Perfect. So maybe we can start with, you know, kind of introductory question, you know, give us the lay of the land, how's GenMap, you know, past 12 months, next 6 to 12 months. Obviously, it's a huge year for the pipeline.

Speaker 1

Yeah, so we are in a great point in our journey with a very nice full development pipeline encompassed with our three major phase three assets, Epcoritamab, RINA-S, and Pitocentamab. And we are very excited because we just guided in Q2 that three big phase threes will be disclosed in next quarter. So super excited.

Speaker 2

Great. So maybe we can, you know, lots to discuss today. Maybe we can start with Epcoritamab. We got, you know, in the past few months, we got the Epcor-DLBCL4 data. so reduced risk of progression by 60%, death by 56% versus RGMOX. So what does this data mean for EPCOR's market opportunity? And is there any read-through to the upcoming, you know, EPCOR DLBCL2 readout?

Speaker 1

And this is a great question. So as you said, you know, DLBCL4 tested EPCORN versus RGMOX. interrelapse refractory second line plus setting and the study we disclose great PFS 040 or 044. Now what I would say is talk about the versatility of EPCO in terms of being able to combine with LEN. Now DLBCL2 is a different hypothesis, a different combination, and a different line. So basically there is not a read-through, but the fact that all over and over again we saw, because the LBCL4 is based on NHL5 arm one, so we see how the phase two translates into solid phase three behavior we expect the same for NHL two or one Fauci with the DLBCL 02 but there are separate designs hypotheses and that to be treated independently.

Speaker 2

Got it and in terms of market opportunity how does this fit to you know EPCOR's potential?

Speaker 1

Yeah so the potential the big potential is for the first line opportunity in combination with our job, the study that will be read, we have the approval of the LBCL in phase three plus. So again, everything adds on, but the big commercial opportunity is the LBCL O2.

Speaker 2

Got it. So let's talk about this first line study that's going to read out in the fourth quarter, as you mentioned. So the primary analysis is conducted for the IPI 3 to 5 population, but you do include about, what, 30% of patients that are IPI 2. And so, you know, what's the benchmark for these different patient populations and how should we be thinking about this readout?

Speaker 1

Yeah, so the primary is for the 3 to 5 INS hierarchical testing. So if we pass the boundary for the 3 to 5, then we will test 2 to 5. So the study has statistical assumptions. So to be positive, it has to cross the boundary for efficacy as the statistical assumptions. Now, if you ask me what is the hazard ratio to be an option chosen by physicians or patients, this is a different story and it's a more nuanced because it's not just a hazard ratio but how the subsets will behave or what convenience means to patients in terms of subcutaneous or so it's I cannot establish a threshold but what I would say that if the study is positive and based on what we know from the phase two it will be able to offer a tangible benefit for patients and physicians to consider as a good

Speaker 2

option got it and the primary endpoint it's for pfs and it's unlikely for us to see mature os at any time soon so i guess like is pfs alone sufficient to drive meaningful adoption in the first line or from your diligence does it feel like physicians want to see survival benefit yeah so from a regulatory perspective pfs is an endpoint validated for first line dlbcl we know from polarics we know from front mind as well that were approved based on pfs

Speaker 1

With Polarix, five years, OS is still 0.89, or for FrontMind is 0.85, but it's immature. So PFS is a regulatory well endpoint. From a clinical perspective, it's the totality of the data, and we will see what is the maturity of OS, but it's not expected to be mature enough to be statistically significant with this short-term follow-up got it just just to give us a sense what's the median OS expected for the control arm so for the control arm what we know is that the PFS, two years PFS, is around 65% give and take. And for OS, I would say at two years would be like 70, 75%.

Speaker 2

Very helpful. And maybe just a little bit on the, you know, treatment duration and cycles. It seems like the phase three has, it employs a shorter treatment duration for Epco than what we saw with the phase two. Do you foresee any impact?

Speaker 1

So thank you for the question. And we were asked this question before. So the phase two has 12 cycles of Epco. When we discussed the design with the health authorities in order to mimic the duration on both arms, we were asked to limit to eight cycles. We don't think that this will have any meaningful impact on efficacy because from the phase two data, we know that responses comes early and MRD negativity come early. And it's pretty standard in aggressive diseases that you treat short and hard. So we don't expect any efficacy compromise. Got it.

Speaker 2

And how important are complete responses and MRD negativity?

Speaker 1

It's very important because there is a correlation between CR and duration. So patients who are in CR are more likely to have sustained and non-progress than patients that are on PR. Although PR is still relevant, CR has a better correlation with duration.

Speaker 2

Got it. Very helpful. Mary, maybe in terms of, you know, have you disclosed whether the planned analysis for this first line, pivotal study, will be interim or is it the final read-up? Can you repeat that? Have you discussed if this analysis is an interim analysis or it's the final read-up?

Speaker 1

It's interim analysis.

Speaker 2

Got it. Okay. And maybe just following the March label update, eliminating the 25-hour mandatory hospitalization in the third line, What impact have you seen in the community uptake, and do you expect this impact to continue?

Speaker 1

Yeah, so we have seen an acceleration on the uptake on the community sites, given by the removal of the hospitalization, as well as the approval of the FL2, second-line FL. Brad mentioned at Q2 that most of the new sites are community sites, and 91% of our key customers are two-plus sites, which are this big conglomerate of sites. So we are very happy that Epco, different than other C320s, it doesn't need hospitalization because it makes it much more easier on patients and the health system.

Speaker 2

Got it. And you mentioned this second quarter growth was both because of the label and the FL.

Speaker 1

So would you say that it's been mostly the FL inclusion or it's been more of the, you know, I think that it's very hard to quantify is the combination of everything and even it's very hard on these later stages to dissect the particular indication. So we see that both the LBCL are contributing and we see a cross-pollination. So, you know, new sites that start prescribing on FL, then they go to LBCL and the other way around. This is a very important strategic value of having the double indication. Got it. Very helpful.

Speaker 2

Maybe just moving on to pitocentumab. We have the first-line readout in the fourth quarter this year. Maybe just, you know, we've discussed before how you increase the enrollment in the first-line study to improve the probability of success. Given the studies were already well-powered for response rate, is this more of an OS kind of play? And how should we be thinking about the heterogeneity expected for the control arm?

Speaker 1

So we increased the enrollment to ensure that we have robustness of different subsets, pre-specified under study, and because enrollment was so ahead of schedule that putting more patients didn't impact timelines. On the contrary, accelerated the potential to have OS sooner because the curve is like this. So if we enroll more, we get more events, okay? So in terms of the control arm, so the primary is dual. The interim will be based on ORR and duration of response. So what is expected for the control is 19% ORR with 12 months median overall survival. This is based on Pembro alone, Keynote 048. As you well know, in the phase two proof of concept, Pito-Pembro led to 63% ORR tripling, and 12 mounds, 79% OS, where Pembro alone is 51% OS. so it's major difference from the phase two comparing to benchmark and control got it and last year from our conversations uh on pio centimab it seemed like for a you know project front runner it seemed like just doubling the response rate from pembro was enough is that still your understanding with regulators for project front runner or are there any changes in the way you view the requirements there yeah so the the plan is you know we will have the results next quarter we will disclose we will get engaged with the health authorities and we will align on the strategy for filing and submission including front runner got it and in terms of the patient population enrolled in the study?

Speaker 2

I mean, you included both HPV positive patients and HPV negative. Is there any cap to the HPV positive patients? And can you remind us of the efficacy we've seen for the pedo-Pembroke combination there? And mechanistically, why would it make sense to include this patient population?

Speaker 1

So we didn't cap. What we do is we stratify for HPV to ensure that we have balance between the two arms. And the reason is more than one. So biologically, you know, there is no reason for Pembro IO to work on HPV positive or negative. So, you know, Keynote didn't differentiate HPV positive or HPV negative. neither extreme so the study that led to cetuximab approval showed benefit of cetuximab which is an eGFR in HPV positive on HPV negative this is external data most importantly in pitopembro eight percent eight patients not 30 percent eight patients which is around 20 percent of 43 were HPV positive and the response there was 50 percent five zero which is much more better than 19 so there was no reason for us to exclude those patients that can derive benefit but we are stratifying to ensure balance and given the sample size 700 patients we expect the percentage of HPV positive to align with the epidemiology of the disease, which is around 20, 25%.

Speaker 2

Got it. Very helpful. Maybe just touching upon the phase two data that you showed for this first line opportunity. And it's been a while, right? But the overall survival was still in progress. We didn't have enough data. Are you planning on sharing any of this data before the phase three? And how should we be thinking about this?

Speaker 1

Yeah, so, you know, for that study, we will share, like, more translational data at ESMO. But the reason we think that 12 months is a very good indicator is because of the IEO curve, where after 12 months, for example, for 048, the OS at 12 months is 51%. At three years, it's 25%. At five years, it's 18%. And this is the tail effect. So 12 months, 79%, we are very confident that it will be carried to provide potentially a very sustained overall survival benefit long-term because IEO is in both arms. So we expect the shape of the curve to be an IO curve. So this is why and because, you know, the phase three will come imminently. There is no reason that, again, the 79% of 12 months overall survival first is best in class, you know, above Fisera, above Amivantamab.

Speaker 2

And it's a very, very good predictor of long-term survival benefit. effort got it and maybe for the first the second line opportunity um i mean you also recently changed the study now primary endpoint is overall survival can you just like remind us does that mean you're not pursuing accelerated approval and you're just going to pursue a full approval there and how does how do you envision pito's market opportunity in first line versus the second line Yeah, so you just hit the nail on the head.

Speaker 1

When we assessed the time advantage of filing frontrunner for second line vis-a-vis OS, there was minimal or no time advantage. So there was no reason to have two filings one month apart. So I decided to allocate all the alpha to OS and have a study that can support full approval in a global manner rather than do two cuts. You know, to gain three weeks didn't make any difference. And, of course, the huge unmet medical need and the larger opportunity is the first line. The second line commercially is a much less opportunity. Still, we could benefit patients, and the data is strong, but the data from the phase two of pitopembra could transform the landscape of head and neck treatment.

Speaker 2

Got it, very helpful. Maybe just in terms of how are we going to see this data, and how should we be thinking about the top-line readout for the first line, more importantly, but also the second line. Should we expect, you know, any patient subpopulation information? Or is it more going to be like, oh, the study is positive, primary endpoint, and that's that?

Speaker 1

So, you know, we will operate according to standard in industry, which is, you know, we will have the data we will share with, because it's material, top-line data. we will engage with health authorities and in parallel we will plan for a full disclosure at the medical congress and this is pretty standard should we be expecting the full disclosure before the overall survival we haven't guided yet on when overall survival could come because we don't have these projections firm enough to communicate so as soon as we have this we will communicate so i cannot say because we don't have a firm projection got it maybe just touching upon the locally advanced opportunity i mean how do you see that opportunity for pito in head and neck and you know how does it compare given competitive landscape in head and neck head and neck so we think that Peter will have not only time advantage in being you know first in line for the first line but has the opportunity is will be best in class as well so based on, again, cross-study comparison are never very clean, but when we see the data of Pitopembro versus Amipembro or Physera Pembro in terms of efficacy, you know, overall survival, safety, convenience, we see as a very, very attractive value proposition potentially, you know, for first-line patients with head and neck.

Speaker 2

And maybe just touching upon the competitive landscape, does the potential approval of amivantamab in later stage, head and neck, impact your strategy for PETO at all?

Speaker 1

On the contrary, I think that, so we know that J&J filed and we get priority review, but this will be accelerated approval on the second line plus, second, third line. Whether, you know, the phase three for the first line will provide the approval on the first line. So it's something will straighten the hypothesis of, you know, EGFR by specifics, but they are not in direct competition. And we have a very important time advantage vis-a-vis Origami 5, which could potentially will lead to the approval of AMI in first line. In addition, it's a separate strategy. We chose to go with the chemo-free because of the depth of response and the superiority of this combination vis-a-vis chemo or chemopembro. So it's different and we will be like two years ahead. it is massive got it and and maybe just based on your diligence with physicians what percentage of patients get treated with right now in first line with like pembrolone versus pembrolone chemo is there any specific patients or population that yeah it's it's it's a great question so we there is a flat iron real world evidence published around three years ago and this is after keynote of 48, both arms were approved six years ago, that showed two to one Pembro alone, two Pembro versus one Pembro chemo. Of course, you know, this is published three years ago based on the U.S. Flatiron data. But when we talk to sites or investigators, it's very individualized based on CPS, frailty or comorbidities of the patient, tumor size or speed of tumor growth. And for example, if the patient is CPS above 20, more likely PEMBRO alone than PEMBRO chemo. If the patient is frail or elderly, more likely, many patients are tobacco consumers or alcohol that have more comorbidities. So for those patients, same thing, more likely they won't get exposed to chemo. Although if the patient is young and has a rapid proliferative, we'll take Pembrokemo. But it's a very individualized patient and physician decision.

Speaker 2

Got it. Do you feel like the diligence give similar data or provide similar data in the U.S. versus the EU in this sense?

Speaker 1

I haven't seen the data for the EU, but when we talk with sites, they all say the same is individualized. And just remember, the chemo in combination with Pembro is carbo-5U, 5U is IV, weekly. It's not very friendly. on patients so there is a yeah it's an individualized patient by patient but as per published data is two to one pembro single agent versus pembro chemo got it very helpful maybe just moving on to crc we're going to see some data at esmo and you presented also some data towards the end of last year can you just remind us what's pito's opportunity there and how you're thinking about the development strategy given that amivanta map is ahead yeah so we we think it's the data that in the middle show in the ERTC NCI meeting is very strong with an order of 80 percent in first line independent validating by an order of 62% in the second line which is unprecedented and doubles everything published and with a very solid biological foundation. PITO was discovered through a library of colorectal organoids and shown in every preclinical model to overcome you know to be superior than cetuximab so very strong data. Amivantamab is earlier but we will present more data that is more that position the PITO combination as potentially best-in-class. Not just in terms of efficacy but also safety.

Speaker 2

Got it and you just initiated the phase three. Two phase threes.

Speaker 1

Two phase threes. Can you just remind us which patient populations are you targeting? So for the first line we are combining with Folfox or Folfiti in the KRAS-V-RAF-WILD left side patients and for second line same thing you know KRAS-V-RAF-WILD both sides in combination with Folfox and Folfiti but the comparator will be Bevazuzumab plus Folfox or Folfiti or toximab plus for folks or for feeding.

Speaker 2

Got it, and in terms of, you know, the LGR5 part of PDO, I guess like, what's the rationale on CRC, I mean, this is where, as you mentioned, the molecule was discovered, right, for this indication, what gets you confident that this is not only like a cetoximab-like molecule?

Speaker 1

No, I mean, so if you look at this paper from Edward Battles, it's clear that LGR5 plays a central role. So mechanistically, I mean, two very important things. First, the binding to LGR promotes internalization and degradation of EGFR. And in addition, in the context of treatment with PETO, LGR is overexpressed. and the binding of the biospecifics on LGR strengthens the ADCC and ADCP properties. And it's so beautifully demonstrated on those papers where in organoids, when they treat the organoids, patient-derived organoids from colorectal cancer with PETO, more organoids are stopped So the LGR is related to stem cells, so it stops growth and metastasis. So very strong preclinical and biological foundation that LGR is key for the activity of PETA. Now the problem with LGR is the plasticity. So only a few labs can measure it accurately, but it's no question that LGR and PETO was discovered among 500 other bispecifics that were tested, same organoid panel of colorectal cancer versus normal cells, and PETO was the winner, killing 100 more times two more cells than normal cells. one-handed so it's it's clear that lgr is the one to drive again the problem with lgr is that not every lab can measure because of the plasticity of the cells got it maybe just last question on crc how are you thinking about the commercial opportunity relative to head and neck it's much more bigger so in terms of population and i don't know on the top of my mind but i would say it's at least double the commercial opportunity than head and neck.

Speaker 2

Got it. Okay, that makes sense. Maybe just, you know, with the last few minutes, just switching gears to your folate receptor alpha ADC, Rina S, I mean, you are going to read out the phase three in the fourth quarter. I guess maybe to start just, we've seen a little bit of data in the phase two, not a lot in terms of follow-up. I mean, how should we be thinking? Are we just going to get the phase three, also the phase two? How are we going to see this readout and how much information are we going to get?

Speaker 1

Yeah, so what we message is that we will have both ARM-C, which is the phase two with around 100 patients, and the phase three in Q4 this year. So a lot of data sets coming like boom, boom, boom. But again, we are very confident on the data that Dr. Lee presented in terms of, you know, what are duration, safety, convenience. So we are looking forward and very enthusiastic about the potential of RINA in Prague. And there is the time advantage because potentially RINA-S will become the first, second generation ADC to show positive data for patients with PROC.

Speaker 2

Got it. And maybe just touching upon the study design, I mean, based on our calculations, it seems like the study is well-powered to detect like around 1.5 months. And PFS, if we assume control arm around four months, that would put it on par with Ella here. However, in your view, how much better than Ella here would RINA-S need to be?

Speaker 1

So, you know, so when you design a study of your power, you establish your hazard ratio based on the control. Now, it doesn't mean that the data will behave that way, but you need to power to be statistically positive. we know based on the data from Dr. Lee by 12 months a single patient progress that we expect to be much more better than the minimal assumptions but again the statistically you know and the clinical the actual data you know we expect that we will be the data will be better than in terms of PFS duration of response differentiation on safety with no ocular toxicity or the burden on patients to have these visual tests and potentially the double indication in the future for endometrial and non-selective for folate receptor so we expect to be really differentiated and superior.

Speaker 2

Got it and in terms of like the folate receptor high versus low patients based on the data we have so far are there any signs of difference in efficacy?

Speaker 1

So what we showed is that in the 20 patients for ovarian in the high the response rate was five out of six versus five out of ten in the low but still 50% is very good with consistent durability across the board so this is why we don't believe there is a need to enrich or to have a test that pose another burden on patients so the strategy is in all cameras because the efficacy does support it and given that Ella here is approaching you know blockbusters that is how should we be thinking about RINA-S's commercial opportunity given we've seen you know so much better efficacy in the phase two now so thank you Eva for the question so today you know our estimates for RINA-S is two billion peak sale and the two billions include all the Gainong opportunities Piroc, SOC and endometrial yeah so but we expect to serve a very so today's like 27,000 patients in the US with Piroc but again and this is the number that we estimate for now got it and based on you know the early data you have in endometrial and what we've seen you know for other for the receptor alpha disease and psoc like how should we be thinking about indication expansion and you know rena s's progression once we get the p-rock data so i think that the breadth of the clinical development plan is so we started with p-rock and endometrial O3 which is after PD-1 and chemo failure we expanded to PISOC in second line maintenance and replacement and we plan to expand even farther in both indications ovarian and endometrial to cover every setting where Rina can help and to position as the ABC of choice.

Speaker 2

Excellent well this was incredibly helpful. Thanks so much for joining us today. Thank you, Eva, thank you.