Recording in progress For the safety and convenience of both you, our audience, and our speakers, we have once again gone virtual for this year's R&D update and data review. As always, we have a busy agenda, so let's begin. Please move to slide two. As a reminder, this presentation may contain forward-looking statements and may contain certain risks and uncertainties. Let's move to slide three. Genmab has a science-focused on innovation-based culture, and collaborations and partnerships have always been part of our DNA. During today's presentation, we will reference some of the products being developed under these strategic collaborations, and this slide acknowledges those relationships. Let's move to slide four. We will kick off this year's event with a review of some of the exciting events of the past year, both within our own portfolio and the ways in which our innovation has been applied to programs of partner companies. You will then see an excellent presentation from Janine Schuurman, Genmab Senior Vice President and Head of Antibody Research and Technology. Many of you may already be familiar with Janine, as she has significant expertise in the antibody field and is a key inventor of our DuoBody and HexaBody technologies. Janine will provide you with an overview of our proprietary next generation antibody technology platforms, which are fueling both our own proposed pipeline as well as the pipelines of our partners. Of course, one of the promising product candidates created with the DuoBody technology, epcoritamab, was featured in multiple presentations at ASH. We are pleased to be able to provide you with a prerecorded summary presentation of this data by Martin Hutchings, who unfortunately was not able to join us in person for today's event as he is currently in a plane moving back to Denmark from the conference. We will have a lively Q&A however, and because we are fortunate to have with us today Dr. Kim Linton from the University of Manchester. Dr. Linton is a specialist in the clinical management of lymphoma, and yesterday she presented the preliminary results from the phase I/II study of epcoritamab in relapsed or refractory follicular lymphoma. After this energizing Q&A, we will conclude the event with a discussion of our key priorities for 2022 and provide you with an additional opportunity for Q&A. I'm also happy to share that we have both Judith Klimovsky, our Chief Development Officer, and Tahamtan Ahmadi, our Chief Medical Officer, available for today's Q&A. As a brief housekeeping note regarding today's Q&As, I'm sure that you're all very familiar with Zoom by this time. If you would like to ask a question, please let us know by posting in the chat, and a member of our IR team will then let you know when you can unmute to ask your question. If you would rather submit a written question, please do so, and also to the chat. These questions will then be read out by one of our team members and answered by the fabulous experts we have with us today. Now let's begin with a reminder of some of what Genmab has achieved during this past year and how it positions us perfectly for continued successful growth. Please move on to the next slide. As I stated during our Q3 results call recently, Genmab has never been in a better position to achieve our ambitious vision of transforming cancer treatments. We have a consistent and solid track record of success with now five medicines on the market that were created using Genmab's innovation. We have a world-class team of experienced and dedicated employees driven to make a real difference for cancer patients. One of the results of that drive is our innovative proprietary technologies, which, as I said are fueling our first in class and/or best in class pipeline. Excitingly, now also including our first approved medicine. Our expertise also makes us a partner of choice, as we have a large variety of partnerships with industry leaders across the innovation ecosystem. Importantly, our work is supported by extremely strong financials, which gives us the ability to invest in both our pipeline and our capabilities. Taken together, the solid foundation we have built has allowed us to evolve into a fully integrated biotech innovation powerhouse. Next. The events of the past year moved us solidly forward in this evolution. One of the most exciting developments of 2021 was the FDA accelerated approval for TIVDAK. As the first and only antibody-drug conjugate approved in this indication, TIVDAK may provide a much needed new treatment option for patients with metastatic cervical cancer. For the first time in history, we, in collaboration with our partner on TIVDAK, Seagen, are able to bring our own medicine to patients. With commercial and field teams ready for launch even with an approval three weeks before the PDUFA dates. Our commercialization efforts are just one aspect of our recent growth as we aim to remain at the forefront of innovation in all areas of our business. We will continue to strategically build our capabilities with the eventual goal of bringing our own medicines to patients on our own. We are currently fortunate to partner with industry leaders who share our goal of bringing innovative medicines to patients. This includes broad development plans for both tisotumab vedotin with Seagen and epcoritamab with AbbVie, both of which entered into phase III trials this year. For bispecifics in development biotech, GEN1046 and GEN1042 progressed in development this year with a new phase II study and expansion cohorts added to the existing phase I/II study respectively. New product candidates are also entered the clinic with the first-in-human studies of HexaBody-CD38 or GEN3014 and very soon we anticipate the first patient dose with DuoBody-CD3xB7H4 or GEN1047. In addition to progress in the clinic, we have multiple data presentations at prestigious conferences including, of course, ASH, as well as ASCO, EHA, ESMO, AACR, and SITC, as well as publications including dose escalation data from the EPCORE NHL-1 study of epcoritamab in The Lancet. Looking to the future, we entered into an oncology research and development agreement with Bolt Biotherapeutics, with the goal of discovering and developing next generation immune stimulatory antibody-based conjugate therapeutics for the treatment of cancer. Next slide, please. I would now like to focus on two of our early-stage product candidates. HexaBody-CD38 or GEN3014, and DuoHexaBody-CD37 or GEN3009. This is in development with AbbVie. Both are currently in dose escalation, and so far we are very pleased with the data we have seen. There are early signs of activity for both products with no safety signals. I'm excited about the potential of both products and look forward to providing you with further updates as well as the first clinical data at a future medical conference in 2022. Next slide, please. As I noted earlier, our innovations are not limited to our own pipeline. Starting with progress for previously approved therapies, once again, DARZALEX moved from strength to strength with additional approvals, including becoming the first and only therapy approved for newly diagnosed AL amyloidosis. Kesimpta also received additional approvals in Europe and Japan. Throughout 2021, a variety of data was presented and new studies were announced for clinical-stage programs that either incorporate our expertise or that leverage our technology. These include the first phase III studies of inclacumab, originally created under an agreement with Roche, and now under development with Global Blood Therapeutics. The first phase II study of Lu AF82422, which was invented by Lundbeck in collaboration with Genmab. The announcement on clinicaltrials.gov of the intention of Novo Nordisk to start a phase III study of Mim8, a molecule created using our DuoBody technology. Of key significance was this approval in the U.S., in Europe, and in the U.K. of Janssen's RYBREVANT. The first medicine created using our DuoBody platform to receive regulatory approval. Another of the bispecific products under development with Janssen, Teclistamab, received breakthrough therapy designation from the U.S. FDA and recently moved into phase III. Exciting data from Teclistamab as well as Janssen's Talquetamab was just presented at ASH, including in combination with Daratumumab. We are very encouraged to see the progress over the past year with so many products that incorporate Genmab's innovation and expertise. Next slide, please. It's now my distinct pleasure to hand over to Janine Schuurman, our Senior Vice President and Head of Antibody Research and Technology, who will tell you all about DuoBody and the other exciting innovative technologies developed by our world-class R&D team. Janine, the floor is yours. Thank you very much, Jan, for this nice introduction, and I'm very excited to be here today and take you through our innovative antibody technology platform technologies. At Genmab, we are truly fascinated by antibody molecules, and we are inspired by understanding the basic immunological principles underneath the antibodies down to its smallest molecular details. We translate this knowledge into innovative technologies which we use to create differentiated, knock your socks off antibody products. Products which can have a real impact on the lives of patients with cancer and their families. Here you see rotating in this slide our therapeutic modality of choice, the antibody molecule, and consider the intrinsic attributes of this molecule. Its high specificity for the target and the antigen binding domains of the antibody are indicated in blue, and also the possibilities which gives this molecule with the Fc domain to steer its interaction with immune cells and other components. This Fc domain also gives this molecule its favorable in vivo half-life. Next slide, please. Before we go to our proprietary platform technology suites, the technologies itself, and maybe it's nice to click also to have the right side also. Thank you. I feel it's essential to put some emphasis on our product ideation and discovery philosophy, which is in one word set, biologically outcome-focused. The disease biology, its underlying mechanisms and targets, combined with the antibody format, are all seen as critical components for a transformative product. Our product ideas have very different molecular requirements depending on their application or the biology of the target or the target combination. Having a suite of technologies available is instrumental to our discovery, is instrumental to reach our mission of having a killer pipeline of products. Products which can have a real impact on the lives of patients with cancer. Next slide. What do we have in our platform technology suite? First of all, our DuoBody platform, the platform being used for epcoritamab and other products in the Genmab product pipeline, as well as in the pipelines of others. This is our bispecific antibody platform. We can use that, for instance, for the recruitment of cells like T-cells, effector cells, or can be used to combat tumor heterogeneity. Secondly, we have our HexaBody platform, which is being used, for instance, for HexaBody-CD38. This platform can enhance the potency of a molecule, enhance the potency with respect to complement-dependent cytotoxicity, but also with respect to bringing targets together on the cell surface and forcing outside-in signaling, for instance, enforcing apoptosis. Thirdly, we have our DuoHexaBody platform, which combines the DuoBody, the bispecific platform, with our HexaBody platform and creating therefore bispecific molecules with an enhanced potency. This technology is being used for our DuoHexaBody-CD37 program. Lastly, our newest kid on the block, which is being explored in our discovery processes at the moment, it's HexElect, and it's not the topic of today. With this platform, you make this hexamerization process codependent on two antibodies. By making it codependent, we can unlock the potency, making it more selective to cells which express two targets. This may open a new target space, which has been previously inaccessible. Next slide. Let me first focus on the DuoBody platform. As we are all aware, bispecific antibodies were conceived decades ago, but faced many challenges limiting their application as therapeutics. You may wonder why DuoBody technology results in such a high product hit rate or low attrition rate, or low attrition in the clinical development. I'd like to take a moment to explain more about the principle behind this technology, because this principle explains why this technology is a game changer. Before we go there, what has been the problem? From a protein engineer's point of view, the antibody molecule is quite a complex molecule. It consists of four chains, two heavy and two light chains, which are covalently paired. Due to the structure of this antibody molecule, it was very complex to produce bispecific regular IgG molecules. It needed heavy engineering and/or other tricks to make these materials, to generate bispecific molecules. Sometimes, or most of the technologies also relied on the identification of an identical light chain. Of course, that impacts discovery and subsequent development and manufacturing processes. The DuoBody principle solves these issues I mentioned. For the DuoBody bispecific molecules, we first produce two parental IgG molecules, each carrying a single point mutation. We mix these parental molecules under controlled Fab arm exchange conditions, reducing conditions that allow the exchange of these half molecules into the bispecific molecule. After reoxidation, we have these molecules recovered at, without any further purification efforts, 90% efficiency at ease. This minimal engineering preserves regular IgG structure, stability, and the functional properties, as well as the long half-life, the pharmacokinetics, and it also minimizes the risk of immunogenicity. This controlled Fab-arm exchange process lifts those previously identified complexities from the protein engineer's point of view, which benefits discovery and development processes. Next slide. From the product discovery point of view, this principle of controlled Fab-arm exchange offers great advantages. First of all, it gives us the opportunity that any previously identified or discovered IgG antibody sequence can be used in a DuoBody molecule. Original heavy light chain pairing is preserved by this process, and that enables product lead discovery processes in an unbiased search in its final format, selecting the lead clinical candidate in an unbiased and data-driven, so fully rational manner. You could now say, why is that important? Why is it important to do that in an unbiased and empirical screening? Simply said, we as humans are excelling in taking assumptions, which is counterproductive from a bispecific product discovery point of view. Let's have a look at the left part of this slide, which shows a standard bispecific antibody discovery processes. The antibody with the best characteristics as a monoclonal antibody is then picked and reformatted for the generation of a bispecific lead, which might often not be the most optimal candidate because we then ignore all kind of attributes which do change in the reformatting process and which might have a huge impact on the biological outcome. The DuoBody platform, which you can see on the right part of this slide, enables the generation of large libraries of bispecific molecules, and these large libraries can then be screened in an unbiased and empirical approach in the final format, in a regular architectured IgG molecule. This enables the selection of the best bispecific lead candidate based on functional criteria. We managed to minimize the discovery timelines and are able to maximize the throughput of the candidate screens in this process by a fully automated process that converts panels of parental antibodies into DuoBody libraries, and then we can screen to find this final lead. The winner, you could say. At least we maximize the likelihood of success by not acting assumption driven, but by selecting the lead by a biological outcome. Next slide. A sum up of the advantages from the product discovery point of view is indicated in the left box on this slide. Just to sum up a few, the DuoBody platform is compatible with any previously discovered antibody sequence, any IgG subclass, and it also is compatible with other Fc engineering platforms. It enables the discovery of bispecific lead molecules in an unbiased approach, and as is apparent from our product pipeline, we have identified a CD3 arm, which is being used in T-cell redirection and an inert backbone, which you can use for T-cell redirection, but also, for instance, agonistic applications. On the right part of this slide, you see the perspectives from the development point of view. Over 10 clinical programs are active, and the DuoBody manufacturing process is compatible with the standard unit operations as being used in the industry for IgG1. The exchange process is robust and fully scalable and has been established at multiple contract manufacturing facilities and collaboration partners. Next slide. Let's move on to our HexaBody technology, which is platform for the discovery and development of potentiated IgG antibodies. The HexaBody technology is based upon the natural principle on how effective polyclonal antibody responses act in nature. Effective polyclonal antibody responses act as a team. They form after binding to its target hexamers. We leverage that principle to our HexaBody technology, again by minimal protein engineering, and I have to put emphasis on that. Only after binding to the cellular surface, these HexaBody molecules are more susceptible to assemble into organized teams of six in hexamers. These hexamers can then force target clustering, bringing targets together on the cellular membrane, and so induce outside-in signaling or engage C1 and trigger the complement activation route. HexaBody platform preserves IgG1-like properties, are acting as monomers in solution, decay, stability, and developability are all similar to regular IgG1. By now we have gathered clinical and manufacturing experience during the development of our investigational HexaBody products, and I'd like to again mention HexaBody-CD38. Next slide, please. Depending on our product design criteria, we could also turn to our DuoHexaBody technology, which is a combination of the DuoBody and the HexaBody technology. Bispecific molecules with potentiated properties. DuoHexaBody enables us to combine these effects and then engage target clustering or complement activation. These molecules also again, preserve IgG1-like properties like pharmacokinetic profile and stability. Our DuoHexaBody-CD37 development program provides us with a clinical and manufacturing experience. Next slide. To conclude, Genmab today focuses strongly on antibody product discovery around product ideation, which is biologically focused, so mechanistically focused. The disease biology, its underlying mechanisms and targets, combined with the antibody format, are all seen as critical co-components for a transformative product. Targets and target combinations impose different specific molecular requirements. Our antibody products may have very different molecular needs depending on the application and the biology of the target or of the target combination. It's great to have this playground with this platform technology suite within Genmab, our proprietary platform technologies, because that enables us the discovery and development of transformative products for patients. I'd like to thank you for your attention. Thank you, Janine, for that truly inspirational presentation. Well done. Turning now to epcoritamab at ASH, I would like to introduce a video of Dr. Martin Hutchings. Martin is a hemato-oncologist at Rigshospitalet in Copenhagen, Denmark. He's an expert in the treatment of malignant lymphoma and a key investigator on the first phase I/II study of epcoritamab. Relapsed or refractory B-cell non-Hodgkin lymphoma continues to be an area of unmet medical need for patients. We appreciate Martin being with us once again, now via video, to review this important epcoritamab data. Please start the video. Hello, my name is Martin Hutchings. I'm a senior consultant at the Department of Hematology in the phase I unit at Rigshospitalet in Copenhagen, Denmark. I wish I could be with you in person, but I have to leave back home to take care of my clinic. I'm leaving ASH early, and I've been allowed to record this presentation for you about the data which have been presented here at ASH in Atlanta from different studies of the epcoritamab program. Epcoritamab is a bispecific antibody targeting CD3, which attracts T-cells and CD20 on the malignant B-cells. It is a drug which has been designed for the treatment of CD20 positive B-cell malignancies, including lymphoma and chronic lymphocytic leukemia. By binding to CD20 on the tumor cells and CD3 on the B-cells, we get a close interaction between the cytotoxic T-cells and the tumor cells, meaning that we have activation of the T-cells leading to cytokine-mediated cell kill and also proliferation of T-cells in the immediate microenvironment of the tumors. We've already presented data from the dose-escalation study of single-agent epcoritamab in heavily pre-treated patients with both aggressive and indolent B-cell non-Hodgkin lymphoma, and recently data from that phase I dose escalation and expansion study have been presented in The Lancet. What were the conclusions from that study so far? Well, we've only seen data from the escalation part of that study, but we've certainly seen very promising efficacy data, particularly in aggressive lymphomas, but also in the smaller group of patients with indolent lymphomas. The safety profile so far has been very encouraging with no cytokine release syndrome higher than grade two and no serious neurological adverse events. So far the data coming out of this program has been really promising. What has been presented here at ASH? Well, I'll focus on these three studies which have all been presented as posters. Two of the abstracts came from the same study, which is a multi-arm study called the EPCORE NHL-2 study. It's a multi-arm study where each of the different arms or cohorts combines epcoritamab with different standard treatments in different settings of treatment settings of different kinds or groups of B-cell non-Hodgkin lymphomas. The two abstracts presented at this meeting have been from arm one and arm two. Arm one is a study where epcoritamab is being combined with R-CHOP chemotherapy in newly diagnosed diffuse large B-cell lymphoma patients. Arm two is a study where epcoritamab is being combined with rituximab and lenalidomide, also called R², for the treatment of relapsed refractory follicular lymphoma. The third abstract also presented as a poster is from the EPCORE CLL-1 study, and that is sort of a companion study to the Phase I single-agent study in B-cell non-Hodgkin lymphoma, where single-agent epcoritamab is given for the treatment of relapsed refractory chronic lymphocytic leukemia. We'll start with the first of the three abstract. That is the EPCORE NHL arm one study. Again, this was a combination of R-CHOP with epcoritamab. The idea of combining these is that you have a standard treatment for newly diagnosed diffuse large B-cell lymphoma, which cures the majority of patients, but unfortunately it's a small majority of patients and high-risk subgroups of DLBCL there is still much room for improvement. We have way too many failures, early refractory patients and patients who later relapse. The rationale for combining R-CHOP with epcoritamab are two. First of all, the toxicity profile of epcoritamab, which as I already said is very favorable, is also highly combinable. The dominant side effect of epcoritamab as well as the other bispecifics is cytokine release syndrome. This is a phenomenon which primarily occurs during the first 3-4 weeks of treatment, unlike toxicities of standard chemotherapy and most other anti-lymphoma agents which appear all the way during treatment and in many cases also in a cumulative fashion, occurring more and more frequently and with more and more severity the longer the patient has been treated. Another rationale for combining these drugs is the preclinical demonstration that epcoritamab is active in the presence of what we call naked anti-CD20 antibodies, including rituximab, unlike most of the other CD3/CD20 bispecifics, which are not potent or they don't have enough affinity to compete with rituximab for the CD20 antigens on the tumor cells. This study, the arm one study of the EPCORE NHL-2 study, included newly diagnosed diffuse large B-cell lymphoma patients with high-risk features, and this was defined as the International Prognostic Index of 3-5, which means pretty sick patients. The most easy to treat patients were not included in this study. This is a layout of the study design. Inclusion criteria, like I said, newly diagnosed diffuse large B-cell lymphoma, including the subgroups of high-grade B-cell lymphoma, double or triple-hit DLBCL, and also follicular lymphoma grade 3B, which is treated and has more or less the same prognosis as normal DLBCL. Patients needed to have reasonable organ function and a performance status of 0-2, so relatively frail patients could be enrolled in this study. Patients were first treated in a short escalation part of the study, beginning with a full dose of epcoritamab of 24 mg, and quickly after the enrollment of four patients were with no particular safety signals moving on to the second and final dose level of a full dose of 48 mg. Patients were treated with six cycles of R-CHOP, which is standard chemotherapy with rituximab every three weeks for six cycles. For the first four cycles, so for the first 12 weeks, epcoritamab was given weekly. For the next two cycles or the final two cycles of R-CHOP every three weeks, so along with the chemotherapy and from the end of chemotherapy and onwards until a full year of treatment every four weeks. In the expansion part of the study, all patients were treated with the recommended phase II dose of epcoritamab, 48 milligrams, according to the schedule that I just described. At the data cutoff in mid-September for this presentation, 11 patients have been enrolled into the dose escalation part, and 13 patients have been enrolled into the expansion part, with another 7 patients in the expansion part of the study planned. Here, you're looking at the baseline demographics and characteristics of the patient, median age 65, which is typical for diffuse large B-cell lymphoma, newly diagnosed. You can see that it was really quite a sick patient population with, three out of four patients having performance status one or two, so very few patients in an excellent general condition, and 75% of patients also in stage four disease. The majority of patients were of germinal center B subtype, which is what you expect. Roughly two out of three patients have the GCB subtype. We do not have data on the FISH or on double-hit or triple-hit characteristics in this presentation. Now we're moving on to the key safety data, which is really the primary endpoint objective of this study, to look at safety. To cut it short, we see side effects of R-CHOP, we see side effects of epcoritamab. There doesn't seem to be any added or synergistic effect when it comes to safety. There is all the side effects from R-CHOP that you would expect, and there is cytokine release syndrome. Looking at cytokine release syndrome, this was observed in 38% of patients, which is less than you would perhaps expect if the drug had been given as a single agent, particularly because these patients are newly diagnosed, so they have not been treated with several prior lines of treatment. Patients who have been exposed to a lot of chemotherapy previously perhaps have some T-cells that are not quite so fresh as newly diagnosed patients. So if you give epcoritamab to newly diagnosed patients alone, then you would expect to see more cytokine release syndrome. In this case, we see perhaps less than expected, 38%, with 33 of the 38% being of grade 1-2. That is probably because the disease is well controlled with R-CHOP chemotherapy. Already with the combination of R-CHOP, we see killing of many tumor cells. Also rituximab occupies the CD20 antigen, giving a good extra mitigation of serious cytokine release syndrome. Now we're looking at the swimmer plots on the efficacy data. There were 24 patients all in all treated before the cut for this presentation, but you can see that while the safety population was 24 patients, only 11 patients had reached the first point of assessment. The only 11 patients were really evaluable for efficacy for this presentation. These are very preliminary data, and of course, efficacy is not the primary endpoint of this study. It's quite encouraging to see that all patients responded. You will expect the majority of newly diagnosed DLBCL patients to respond to R-CHOP alone, maybe not 100%, but of course, this does not necessarily show that epcoritamab added anything to the efficacy, but it's certainly encouraging in this respect. It's also encouraging to see that the majority of responses were complete responses, 73 out of the 100%. It's also encouraging to see, which is depicted in the swimmer plot, that the majority of the complete responses, all except one, occurred already at the first assessment of efficacy, which is after six weeks or two cycles of treatment. In conclusion, for this study, which is really preliminary data, the combination of R-CHOP with epcoritamab showed no added or synergistic toxicity, no dose-limiting toxicity for epcoritamab. Generally, safety was manageable. There was no observed events of immune cell-associated neurotoxicity syndrome called ICANS, something which is particularly feared and quite commonly seen with many T-cell engaging immunotherapies. Only one case of tumor lysis syndrome, which is hardly something we can attribute to epcoritamab because it's something that we do see occasionally with R-CHOP chemotherapy alone. Like I said, encouraging responses in 100% of patients. Doesn't mean they are all cured, but it's very encouraging. 73% of the responses were complete, the majority of which occurred already at the first assessment of response after six weeks. I think it's very modest to say that the data support the further exploration of this interesting combination. Now we're moving on to the second poster, the arm two from the NHL2 study. That is a combination of epcoritamab, this time with what we call R², so rituximab and lenalidomide. That is already a standard treatment. It's approved, and it's being used in follicular lymphoma and also in mantle cell lymphoma, where it's highly active. The idea behind this comparison also is just like with the combination with R-CHOP, that the toxicity profiles are virtually non-overlapping. Also there are data to suggest that lenalidomide probably can enhance the T-cell-mediated killing, which is sparked by epcoritamab. This is the general layout of the study. Again, we have a standard R² treatment, which consists of rituximab every four weeks and lenalidomide for 21 days out of 28 days, so four-week cycles. That goes on for a full year, after which the patients can continue with epcoritamab maintenance for another year, so a total of two years of treatment. Again, a dose escalation part of the study with altogether six patients enrolled starting on 24 milligrams as the full dose of epcoritamab moving up to 48, the recommended phase II dose, and that is where the expansion part of the study also was dosed. In the expansion study, the first 23 patients are treated according to the same schedule as in the escalation part. That's three cycles of weekly epcoritamab, then six cycles of bi-weekly epcoritamab, and then moving over to four weeks. In the planned 80 patients in cohort 2-B, which is an added expansion cohort, patients will only receive epcoritamab weekly for two cycles, and then already from cycle three and onwards, move on to treatment every four cycles. This is respecting that many patients will already at that point be in a complete remission, so probably or hopefully without the need for very dense epcoritamab treatment for such a long time. Now we're looking at the baseline characteristics and demographics. Here we can see that the median age, 67 years, very characteristic for a relapsed refractory follicular lymphoma population. And you can also see that this is completely different from patients with newly diagnosed diffuse large B-cell lymphoma. Even though these patients were not particularly heavily pretreated, actually, the median number of prior lines of treatment was just one. You can see that the median time from diagnosis to the first dose was 92 months. This is a disease with a completely different natural history and much longer remissions expected. Moving on to the safety, just like with the combination with R-CHOP, there are side effects to epcoritamab. There are side effects to rituximab and lenalidomide. To cut another long short story short, there is nothing to suggest any synergistic safety signals. We do see cytokine release syndrome. We do see side effects of lenalidomide, but they don't seem to add anything to each other. It's comforting to see less than 50% of patients overall with cytokine release syndrome, 48% out of the total of 29 patients in the safety evaluable cohort. Even more encouraging to see that the vast majority of these had cytokine release syndrome which was grade one or two. Efficacy data are again preliminary. You can see that the patients have generally not been treated for so long, but the swimmer plots will tell you that the vast majority of patients are responding, actually 100%, and most of these patients are still in remission and on treatment at the time of the data cut for this presentation. Overall responses in 100%, including 81% with complete responses. Now some of you might wonder how you would expect R² to perform in this setting. You would expect R² to perform relatively well, maybe response rates of 60-70, at best 75%. No one would expect 100% overall response. Of course, this is my subjective view, but I have no doubt in my mind this is primarily owed to the presence of epcoritamab. In conclusion, again, this combination is promising. It's apparently safe, no added toxicity, no dose-limiting toxicity for epcoritamab, no ICANS, no tumor lysis syndrome, which is something that we sometimes see in the treatment of these lymphomas. Like I just said, response in 100% of patients, including 81% with complete responses, the majority of which were achieved already at the first assessment after just six weeks of treatment. Now I'm moving on to the third poster, which was presented here at ASH, which was from the EPCORE CLL-1 study. As the title says, a study including patients with chronic lymphocytic leukemia. This is a single-agent study. Epcoritamab was first introduced into NHL and second into CLL, and the reason for this is an expected higher rate of toxicity because CLL is a blood-borne disease present in the bone marrow, present in peripheral blood. These are features which mean that you will expect higher rates of cytokine release syndrome. I'll keep you waiting for that, but I can assure you that it's not as bad as some of us perhaps had feared. This is the study design, a more simple one than the ones I've just showed you before. Patients had to have relapsed refractory CLL with at least two prior lines of treatment, including treatment with or intolerance to BTK inhibition. Most of the patients had received ibrutinib, which is an approved BTK inhibitor for CLL in most countries. They also needed measurable disease, either nodal disease or blood-borne disease, and acceptable organ function and general condition with an ECOG performance status of 0- 2. Again, there was a small escalation part of this study moving from 24 as the full dose to 48 milligrams, and then an ongoing expansion part of the study where patients are treated at 48 milligrams, again, the recommended phase II dose. Look here at the demographics and characteristics of the patients. You can see a median age of 63 years. CLL is a disease of the elderly, so this is actually a relatively young CLL population. And it's a population which where probably age is the only favorable prognostic factor, because if you look to the right, you can see that the majority of patients had mutations of TP53, deletion 17p, both of which are adverse prognostic factors, and only 18% had mutated IGHV, which is a favorable prognostic factor. These are really quite adverse factors. You can see, again, all patients, 100%, had been exposed to BTK inhibition, and two out of three patients exposed to and failed venetoclax. Looking at safety, some of us had feared high, not only high frequencies, but also high grades of CRS due to the nature of the disease. I've been comforted here because there are 73% of patients experienced cytokine release syndrome, but all of which stay within grades one and two, and this is indeed something which is very encouraging, that no severe grades of cytokine release syndrome have been observed. Also, no cases of tumor lysis syndrome, which is also a positive surprise. Some of the drugs that have been introduced into the treatment of CLL have had problems with tumor lysis syndrome, which makes it quite laborious to start patients on this treatment. This has not been the case in this study of epcoritamab. Also we've seen no cases of ICANS, none of the serious neurological adverse events which is sometimes seen in the context of the T-cell engagers. Now, very few patients have been treated far enough to be evaluable for response, only nine of those. You can see that with these very preliminary observations, there are signals of activity. Four responders so far, one of whom is a complete responder, one of my patients, and three partial responders so far. Then a number of patients progressing disease and also one patient discontinuing treatment without progression, but in a stable disease based on physician decision. In conclusion, just like with the EPCORE NHL-1 and... Sorry, two studies that I presented before, we've not seen any dose-limiting toxicity to epcoritamab. Generally, again, the toxicity profile has been manageable. Nothing really unexpected, except perhaps in my subjective view, that the grades of CRS have again been restricted to grade one and two, just like we saw in the single agent study of epcoritamab in non-Hodgkin lymphomas. This is really important because many had expected higher grades of CRS in the context of CLL. It's a little bit early to say anything about efficacy, but we do see responses in so far in four out of nine evaluable patients. I think we can all agree that this sparks and encourages further evaluation of this drug, not only alone, but probably also in combination with other drugs in the setting of relapsed, refractory or perhaps with time, even newly diagnosed CLL. With that, I thank you for your attention. I hope I kept to my time, and I hope you all have a good trip back from ASH or wherever you are in front of the screen. Thank you very much. We now have 20 minutes for Q&A. As a reminder, please indicate in the chat if you would like to ask a question and then a member of our IR team, I think Andrew, will let you know when you can unmute your line. You can also type in your question in the chat and then we will actually read it out loud, and then one of the experts will answer. Let's start with the questions. Who wants to ask a question? Please indicate it in the chat. Thank you, Jan. I think we have Kennen MacKay from RBC Capital. Please go ahead. Yes. Hey, how are you doing? This is Sudan Loganathan, one of Kennen's associates from RBC. Thanks again for the really great presentation on epcoritamab. My question is basically on epcoritamab, the CRS levels versus the efficacy. W hen physicians are looking at, you know, choosing epcoritamab, what is the sweet spot in efficacy versus CRS levels that needs to be achieved? Are there physicians that are more willing to take on a, you know, a lower efficacy level for to ensure that they have, you know, a better safety outcome or, you know, or what are you hearing on that aspect? Thanks for the question. I think I will ask Kim Linton, Dr. Linton to start first, and then maybe Tahi can give an extra perspective. Kim, I hand it over to you. Thanks very much for the question. I think the first thing to say is we don't really have a sense that there's a correlation between the degree of CRS and the efficacy signal that we're seeing with epcoritamab, and indeed with the other bispecifics that are being developed. One thing that's very clear, with the bispecific drugs, and epcoritamab is particularly good in this regard, is that, the rates of cytokine release syndrome are really very low. It's a mild toxicity, and it's very much limited to the first cycle of treatment, just the first few weeks of treatment of epcoritamab, predominantly when you give the first full dose. Because it is so m ild and very easy to manage. I mean, most of these patients just get fever. They don't even require any oxygen support or any tocilizumab or any vasopressors. It's so manageable that we don't really take that into consideration when we're thinking about using a drug like epcoritamab. The only thing I think that potentially comes into consideration is the need for a brief need for hospitalization for these patients. But again, as we're gaining more and more experience with these drugs, we're recognizing that we don't necessarily need to admit these patients as we did before. A lready, as we've developed epcoritamab, we've now reduced the requirement for admissions to the first full dose, which is cycle one, day 15. I hope that addresses your question. It's really not a major consideration. Yeah. Thank you. really quick, wanted to squeeze one in. The RP2D at 48 milligrams, is that a dose that will be the you know go forward dose for epcoritamab? Or is there any due to the lower CRS rates and you know getting good efficacy readout, is there a chance for you know evaluating higher doses? Kim, do you want to take that, or should I hand it over to Tahi? I think Tahi might want to take that one. Exactly. I see him already smiling. So, thanks, Kim. Hi. Very good answer. Tahi, the floor is yours. My pleasure taking the question. Yeah. W e actually will in due time publish this. We did a very extensive PK/PD modeling to come up with the appropriate dose of epcoritamab, which is really a function of what we call time of formation, the dose at which you get the optimal engagement of T-cells, the optimal binding to B-cells. This is really where we landed with 48 mg, certainly for lymphomas, I would say. A s we look into CLL, I think in a different disease setting with a completely different kinetics of B-cell tumor burden, there is a possibility we will look at the PK data whether there are other opportunities to optimize. Right now, all we have is what we know, and what we know is that the dose is the optimal dose for all the tumors that we have treated so far. Yeah. Thanks, Tahi. Let's move on to the next question. Andrew, let's see what other questions here. Yeah. The next question is from Jonathan Chang from Leerink Partners. Please go ahead. Jonathan, please go ahead. Hi, guys. Hi. Hi, guys. Thanks for taking my questions, and congrats on the ASH data. First question, which epcoritamab combination strategies are you most excited about? Second question, actually on your partnered programs, how does GPRC5D compare to BCMA as a target for multiple myeloma? What are the implications on how talquetamab compares to teclistamab as a development candidate in multiple myeloma? Thank you. Thanks, Jonathan, for the questions. The first one, we'll definitely hand over to Tahi. The second one, I think it's really a question for J&J, 'cause they are really developing talquetamab and teclistamab. I don't think it's appropriate for us to, Jonathan, to go into too much detail. They both work fine. I mean, you've seen the data. They are working fantastic, and they both work even better when you combine it with daratumumab in multiple myeloma. I probably want to park that question, Jonathan, and you can ask Peter Lebowitz or one of the other colleagues from J&J, and they will be delighted, I think, to get back to you. Tahi, maybe you can handle the first question. What are you most excited about? Or are you excited about everything we do with epcoritamab? Indeed. I would say this, we view Epco and the mechanism of T-cell direction as a fundamental cornerstone of future treatment of B-cell malignancies, both in diffuse large B-cell lymphoma, as well as indolent. The combinations that we are moving are in relation to the treatment paradigms in these different settings. In indolent lymphoma, lenalidomide in combination with rituximab has shown remarkable efficacies. There are biological rationales to believe that lenalidomide can enhance the activity of with the T-cell redirection combination with Epco. The data is remarkable for the small numbers, 100% response with nearly everyone in CR. We're very excited about that. Equally, we believe that if you introduce epcoritamab into a frontline diffuse large B-cell regimen, focus on the patients with high features, highest features such as IPI three and above, that this drug and this mechanism can be really transformational and can increase the cure rate for patients with diffuse large B-cells. I'm equally excited about both of the opportunities. Really looking forward to the start of the phase IIIs in the near future. Jonathan, we haven't even spoken with you about new combinations with other drugs and we are pre-clinically testing novel combinations. We found some really, really good ones, and I am sure that the team will speak about that in the upcoming year. Some of these combinations will definitely go into the clinic as well to be tested in patients. We can hardly sit still, Jonathan. We're very excited. Maybe we can move to the next question, Andrew. Yeah. The next question is from Asthika from Truist. Go ahead, Asthika. Asthika, are you there? Don't be shy. Sorry about that. Can you hear me now? Yes, we can hear you. Please go ahead. Thank you. Thank you for taking my questions, guys. First off, I just wanna think about maybe the data flow that we'll be getting for 2022. I like that we'll be seeing a couple of new assets potentially there. I wanted to check in on GEN1042 and GEN1046 and maybe get an idea as to what we can expect and when. All right, Asthika. I think I will hand over this question to Tahi again. I will in the next slide section, Asthika, after the Q&A, we will say a bit more about what we expect for next years. Maybe, Tahi, you can more specifically talk about ten forty-two and ten forty-six. They're both really important in the new year, and we are very excited about both. Maybe you can see what you're willing to give here to Asthika, Tahi. I'm interested to hear that also. Not much, Asthika. I would say, you know, last time you and I spoke, a lot of these things were not in the public domain. In the meantime, they are actually in the public domain. We have executed, as we said, on our strategy. We now have combinations for 1042 and pembro, both alone or also in combination with chemotherapy, where we're evaluating the safety and then going into expansion cohorts. Similarly, with 1046 in combination with pembro, also exploring a dosing regimen that interrogates the idea of 4-1BB activation, subsequent checkpoint inhibition we call low-high. These things are ongoing, and certainly there will be data somewhere in 2022. I'm sure we'll share some of it, but I cannot give you any view right now of when we'll have this data. We're really excited about generating it right now, and so more to come. Okay. Thanks, Tahi. Thank you, Asthika, for the question. We will stay in touch, huh? Okay, sounds good. Thanks, guys. Thanks. Maybe, Andrew, let's see whether there are more questions for now. Yeah, we have next question from Xian Deng from Berenberg. Please go ahead. Thank you. Thank you for taking my question. Could you hear me all right? Perfect. Absolutely perfect. Welcome to the team. Thank you for covering us now. Thank you. It's a pleasure. I have questions because this year's ASH, we see, for example, POLARIX and also CAR T potentially moving into second line. With this sort of potentially paradigm changing new regimens, I was just wondering, how do you think, especially POLARIX, how should we think about that? Do you think that could potentially impact your future trial designs? Do you think, for example, CAR T into second line could reduce your patient pool to your third line for epcoritamab? Thank you. Thanks for the questions, and they're very good questions. I just looked at the POLARIX data that's presented today, I think at ASH. But perhaps the best thing is to first ask Tahi and then maybe Kim for the perspective how these data could actually impact the further development of epcoritamab. I think, Tahi, why don't you start, and then- Yeah. Let's see what Kim can add to that, huh? Two questions. One is I suspect the CAR T data set that was presented in second-line transplant-eligible. I think the jury is still out there, and I will leave Dr. Kim Linton to comment on to what degree this data with the limitations and some of the challenges on the population is going to convince the community to adopt CAR T therapy and replacement of auto transplant. My personal view is somewhat subdued, but this is my personal view. The other question was on POLARIX. I think congratulations that this is the first phase III in a long period of trials that has had the positive results. Again, the jury will be out there and to what degree this will lead to an adoption. From our point of view, we don't really see either of these two data sets changing our strategy. We have a very clear strategy what we want to do with epcoritamab. You know, we have already generated some safety data with R-CHOP. We have not really shared yet what we are going to do in a transplant-eligible setting, although we have already generated data there as well. We have a very clear plan, and we're gonna execute on that plan. Neither of these data sets has changed our perception of what our strategy is going to be. Thanks. Thanks, Tahi. Kim, do you want to add anything to this? You're on mute, Kim. We cannot hear you. You should be able to hear me now. Yes. Yes. Perfect. Perfect. Yeah. Do you want to add anything to what Tahi already said on POLARIX or CAR T, or it can impact the development of epco in your opinion? Yeah, absolutely. I mean, the POLARIX study was interesting. I mean, it was obviously a very large study done in over 800 patients with mostly high-risk diffuse large B-cell lymphoma. So a similar population, if you like, to the R-CHOP epcoritamab first-line indication, and actually produced, you know, quite similar complete metabolic response rates. But that study didn't show any progression-free survival advantage for POLARIX in combination with R-CHOP compared to R-CHOP alone. I think that being the case with a modest PFS advantage but no overall survival advantage, it seems unlikely that POLARIX is going to take the place of R-CHOP in the first-line setting, in my view. I mean, I think it might be interesting to see whether the survival data matures in time. This is telling a story that we're quite familiar with in first line diffuse large B-cell lymphoma, which is that there's very little that can actually improve upon R-CHOP. I think with regards to the epcoritamab first line combination program, I don't think there's any need for POLARIX to change that trajectory of development in my view. I think it is important, obviously, in due course for epcoritamab R-CHOP to be compared with R-CHOP. If that can show both the progression-free survival and an overall survival advantage, as well as demonstrating the ongoing excellent safety signals that we're already seeing, I think there's a potential chance that epcoritamab R-CHOP could have some legs on it. For the time being, as I say, it doesn't change what we do. With regards to the CAR T data, we saw two interesting presentations, or at least two interesting presentations at ASH. One presenting the ZUMA-7 data and one presenting the BELINDA trial results, both giving completely different outcomes suggesting that in the ZUMA-7, that axicabtagene ciloleucel is better than standard of care, whereas with the tisagenlecleucel that there was no difference. The populations are so very, very different there. The use of bridging therapy in the one study but not in the other would have definitely influenced the selection of those patients. Right now, I'm not sure we've got much evidence that's going to definitively change practice in the second line setting. I think we do need more data on how to better select patients for CAR T therapy. I don't think that is going to impact on the development of certainly the bispecifics in that space. Thank you very much, Kim. I hope that answered your questions, and then, let's move on to the next question, and then we'll go on with the program. Thanks, Kim. Any further questions, Andrew? We have a question from Michael Schmidt from Guggenheim. Yep. Please go ahead. Yeah. Hey, guys. Thanks for taking my questions. I just had one for Jan. I thought I heard you mention in the beginning that you're pleased with the data emerging from the CD37 and CD38 programs. Could you just give us a bit more context, what that means and how we should think about, you know, public disclosures from those trials next year, presumably? Yeah, absolutely, Michael. I will need to be very brief because Tahi and Judith are watching me very closely now. I can tell you that I said, well, basically we see no safety signals. We are very far advanced in the dose escalation for both in multiple myeloma and the other one in B-cell cancers. We see some very clear signs of activity. They're both active. We're very excited about what we see there, Michael. What I already said before is that we will, we plan to show you the data of the complete dose escalation at a conference for both of these molecules. We're already going to test out combinations. Also combination therapies preclinically and next year, hopefully also clinically. More to come next year. Hopefully, we can move one or both of these programs to the next stage in development. Everything we see is pleasing us. That's where we probably should leave it at this time, Michael. Very good. Thank you so much. Thank you for the question. Let's take one more question, Andrew, and then we'll move to the last part of the presentation, and then we have another Q&A so that you can all think about other questions and before we close off today's meeting. Andrew, maybe the next question, and then. Yeah. We move into the program. That is from, Michael Novod from Nordea. Michael, go ahead. Thanks a lot, Andrew. Thanks a lot, Jan. Good to see you. Just one follow-up question to epcoritamab. In CLL, what is the best sequencing strategy? Is it to move ahead with epcoritamab in CLL, where you first debulk with venetoclax and then use epcoritamab? Or is it maybe to use a BTK inhibitor instead and then use epcoritamab? Thanks. Thanks, Michael, for the questions. They're definitely too difficult for me, so I will first move it to Tahi and then ask Kim. Kim, you have a perspective on what you could do in CLL, knowing that we have a safe and effective molecule, essentially from very early preliminary data. Tahi, how can you address this question from Michael? Yeah. It's a good one, I think. I'll try. I would say this. In CLL, we are in a different stage right now than we are already with the B-cell malignancies, with aggressive and transformed large B cells. Martin really nicely handled it, that the first question that we had to ask was, with this regimen of priming, intermediate, and full dose, can we give this drug to CLL patients which have a very different distribution of their disease within the periphery as well as in the marrow, and with a higher concern around cytokine release because of that in a safe manner? I think we're gaining confidence around that. The second question was always from the beginning, whether T-cell redirection is actually a mechanism of action in CLL. CAR-Ts, which are now having generated quite substantial amounts of data in diffuse large B-cell, in follicular lymphoma, now in mantle cell lymphoma, actually despite the initial Carl June paper being three patients with CLL, never really had a foot in CLL, partially because there's an interplay between the disease and the T-cell function. Most T-cells in the refractory setting are actually somewhat dysfunctional. The answer to that question is preliminary indicating it appears we are. We're getting responses, we're getting PRs, we're getting CRs. Like in all the other indications what we have previously shown, we can combine epcoritamab with a variety of other modalities. Obviously, the next step, not far-fetched, is to combine with other modalities, and we are in a partnership, in a fortunate situation with our colleagues at AbbVie, that AbbVie has two exciting and very established drugs in the CLL space, and you mentioned both of them, ibrutinib and venetoclax. I don't think it is unreasonable to imagine that we will explore the combination with either of these two mechanisms, which are, by the way, very different, and also used very different. We can, from there, take the next steps in our development strategy. Thanks, Tahi. Of course, Michael, there's some very good poster data in NIH collaborative study in CLL with very good synergies we see already pre-clinically. I think that's about what we can say at this time. Let me switch to Kim and see, Kim, whether you want to add a perspective for CLL development for epcoritamab. Yeah. I really think it's too early to say about the sequencing of epcoritamab with the other two agents that are well established in the treatment pathways and very active in CLL. Clearly, you know, most patients that have entered this study, or the numbers are very small, have already had a BTK inhibitor and possibly a BCL-2 inhibitor as well. I think other studies could potentially look at changing the order of things. I think it would be difficult to rival a BTK inhibitor with epcoritamab first until we've got more data coming through. Thanks. Thanks, Kim, for that perspective. Thanks, Michael, for the question. Thank you very much. Let's move on to the. Thanks, Michael. Let's move to the next slides. Thank you all for these questions. Let me move to our key priorities for 2022. You will see that we have a lot to look forward to in the coming year. Next slide, please. 2021 was an exceptional year for Genmab as we have envisioned since 2013. We now have our own product on the market and a pipeline of knock-your-socks-off antibodies. As we continue to focus on our core purpose of fundamentally improving the lives of patients, we are preparing for an equally momentous year in 2022. Starting with epcoritamab, you will remember we are developing with AbbVie, and we are very much looking therefore to expanding development with multiple additional phase III studies. Excitingly, the potential for a submission of a BLA, subject of course to supportive feedback from the FDA. If epcoritamab should be approved in the future, it will join TIVDAK as the second Genmab own product on the market. In 2022, we plan to work with our partner Seagen to continue to broaden the clinical development program for TIVDAK and establish it as a clear choice for patients with metastatic cervical cancer, with disease progression on or after chemotherapy. Turning to our product candidates in earlier stages development, and Tai has already spoken about them. We very much look forward to data from the clinical expansion cohorts and progress to next steps for both of the candidates in development with BioNTech, DuoBody-PD-L1x4-1BB or GEN1046, and DuoBody-CD40x4-1BB or GEN1042. We anticipate expanding and advancing our other early-stage programs. We have already spoken about a number of them during today's presentation, including the potential for additional INDs or CTAs in the coming year. Finally, we intend to continue to scale our organization based on our planned portfolio developments and use our solid financial base to support this growth. Taken together, we have a lot to look forward to in the next 12 months. Let's move to the next slide. Thank you for your attention today, and we now can move to a second Q&A session here. Let's see, Andrew, whether there are any questions. We also have here, of course, Judith on board, our Chief Development Officer in addition to Tahi and Janine. Let's see whether there are any further questions from any one of you. Yes, Jan, we have a couple of questions on the chat. Most of them are centered around Epco. A question about why we still believe that we have the best-in-class molecule with Epco and whether or not, you know, we're confident we can file via accelerated approval, and when can we of course see the data that we're going to base our filing upon? Thank you, Andrew, for these questions. Why don't I hand over the question to Judith? Because we haven't heard Judith today. Judith, maybe you can start with why we are still convinced or believe that we have potentially a best-in-class molecule there with epcoritamab. Maybe you can speak a bit to that, and then Tahi can step in and Kim to really see how we can convince the chat person about our belief in this wonderful molecule here. Yeah. I think that there are beliefs and there is the data, and the magic happens when the data confirms the beliefs. I think that this is where we are. I think that this molecule was developed as potential best-in-class based on solid preclinical data. We developed it as subcutaneous to improve convenience for patients and for physicians. As we see the combinability data emerge with these two datasets, it further confirms the whole package, convenience, efficacy, combinability and safety makes potentially as best-in-class. W e expect to share with the medical community and with all of you know, more datasets to keep on building to the set of evidence. I'm still super encouraged by the data and looking forward for the next steps as next months. Thanks. Thanks, Judith. Maybe, Tahi, you can speak a bit about our belief in the potential accelerated approval, of course, based on the positive reception by the FDA of the data. How confident are we that we could potentially move towards that in 2022? Well, I mean, we have always said that we're not going to preempt conversations that we are going to have with the health authorities. We have also been very consistent that we anticipate that if the agency agrees with the fileability of such a that we intend to file in 2022. Nothing has changed in our timelines, so we are on track for everything. In due time, we will share the data that will form the basis for the submission. I think that's probably where we should leave it at, Tahi. I agree, here. Maybe, Andrew, we can move to a next question in the chat or live for one of the participants. Yeah. We have a question with regard to news flow for 2022. What should we expect? Especially when can we expect tisotumab data in solid tumors? I mean, tisotumab data in solid tumors, I can probably take that one. I would say in the first half of next year. I think we've submitted some abstracts to conferences, and we are pretty confident that we will be able to show the data. We're also confident that we will actually move into the further development of tisotumab in one or more solid cancers in 2022. That's probably what I can say about news flow. We will, in time, probably around the February timeframe when we give guidance for 2022, we will give you some better guidance on when to expect data for potentially the HexaBody-CD38 program, the DuoHexaBody-CD37 program, the two BioNTech partner bispecific programs and potentially other studies with our molecules in 2022. It's a bit on the early side, but we'll certainly give you full color and openness on when we expect to see the data in the new year. It will be a very data-rich year, not only for the Genmab proprietary molecules, but also for some of the partner molecules. I'm pretty sure that there will be a lot of data, tumor map data again, and probably more teclistamab and talquetamab data, probably also Mim8 data. This is going to be impactful, we believe, potentially or from Novo Nordisk. 2022 will be a very exciting year. I think we should probably leave it with that, Andrew, at this stage. Excellent. We have James Quigley on the line. James, go ahead. Hello. Thank you for taking my questions. I've got two on frontline DLBCL setting, so maybe one for Dr. Linton, picking up on your comments. It could take a long time for a trial like POLARIX or for epcoritamab in the first-line to show an overall survival benefit. What would you need to see in terms of PFS to sort of start to use a therapy of R-CHOP in the first-line, you know, bearing in mind there's a 27% PFS benefit for POLARIX? Maybe for Tahi, again, on the same sort of line of questioning. With that in mind, in terms of, you know, needing to show survival benefit or at least in order to change treatment patterns, how do you design a first line trial, taking in that consideration? Is there anything clever you can do with endpoints, with biomarkers? Is MRD potentially going to be used in this setting as well? Just love your thoughts on that. Thank you. Thanks, James, for the questions. Maybe I can hand it over to Kim Linton to maybe think a bit about frontline diffuse large B-cell lymphoma. Yeah. In terms of readout for trials, I think obviously progression-free survival is helpful. I think in terms of when you might get an indication that you're improving cure rates, I think if you sustain a plateau in your progression-free survival curve at the sort of two-year and beyond point, you start beginning to think that you're likely to translate into an overall survival benefit for patients with diffuse large B-cell lymphoma. I don't think we have to wait as long as you think necessarily to demonstrate that. You can see an overall survival benefit from sort of two to three years onwards. I think some mature follow-up on POLARIX is gonna be quite important, but for now, the follow-up is just a little bit too short. In terms of what we might look for for surrogate endpoints, I think the PET data and metabolic tumor volume are obviously extremely interesting and looking at your complete metabolic response rates as a surrogate for overall survival, which we know isn't a validated surrogate in diffuse large B-cell lymphoma. Now, we don't have a lot of those data currently for most of the frontline studies in diffuse large B-cell lymphoma. So I think that is something that we can look at a little bit more. I think did you mention MRD? It's not particularly well developed in diffuse large B-cell lymphoma, so less reliable there, and I think probably your PET and your circulating tumor DNA, ctDNA mutational analyses are probably gonna be quite helpful in looking at some endpoints there. Those are the kinds of things I would probably envisage building into further frontline clinical studies to show that there's a benefit. Thanks, Kim. Maybe, Tahi, you can step in here. Are you willing to say a bit about frontline strategies and combinations, or are we going to keep it for ourselves here? No, no. I think what I'm just thinking in principle, I think Dr. Linton mentioned all the key thought processes. I would say and regulatory endpoints are different than endpoints that clinicians might use to get some confidence in understanding the effect size, right? From a regulatory point of view, in diffuse large B-cell, PFS and OS are key critical endpoints, and I don't see a path in a near future where these would change. That doesn't mean that we cannot work on introducing other surrogate datasets to support. But I would say in the foreseeable future, PFS and OS will be the main endpoints for a frontline diffuse large B-cell trial. Dr. Linton already said this actually. I don't think you need to wait that long because of the kinetics of how the behavior of relapse is in diffuse large B-cell, where most of the events happen within the first two years. I think what it actually is focusing the population such that you have the population that has the highest unmet medical need might help. But I think if you look at IPI 2, I'm not so sure that that was helpful in the POLARIX study. And then it's a function of the behavior of the drug. There are two questions, one immediately answerable, the increase in CR rate, and then the second question, not immediately answerable but relevant to the OS question, is the durability of the CRs, and that's why we have to run these trials. Thanks, Tahi and Dr. Linton. I think we should keep it with this, James, thank you for very good questions here. Let's see, Andrew, whether there's one maybe one or two final questions, and then we will close off the session also with respect of all of your time. Andrew? Yep. There are some questions regarding to daratumumab. The questions are centered around when we can expect data readout on the CEPHEUS study. There's also a question with regards to CASSIOPEIA. I think we'll just keep it with the when we expect data readout for the CEPHEUS data for now. Yeah. I think I can take that one. I think it's a Janssen question there. Janssen needs to respond to that. What I'm willing to say is that it's likely going to come in 2022, to our knowledge. But I think Janssen needs to answer the question more precisely, Andrew. 'Cause it's basically their development program. Excellent. There are no further questions, Jan. If anyone feels that we missed a question, please feel free to reach out to me or the team, and send your questions via email, and we will get back to you. Back to you, Jan. Thanks. Thanks, Andrew. Thank you all for the interesting questions and for joining us for this virtual event here. A special word of thanks, and that's really well meant, to the truly exceptional speakers who have joined us here today for the presentations and for the Q&A. From all of us at Genmab, we wish you happy holidays and a healthy, happy, and beautiful 2022. Hope to speak with all of you in the new year. Thank you all. Thank you. Thanks. Thank you, Dr. Linton. This was great. Absolutely great. Looking forward to keeping contact. This is really very highly appreciated. My pleasure. Epcoritamab's a fantastic drug. Thank you. We are super excited also about novel combinations, so we really would like to work with you and all of our colleagues to really position it, to really give us new treatment options for patients, because that's in the end what drives us really strongly, and I'm sure you too. Really nice to meet you, and thank you so much for an excellent contribution here. Likewise. Thank you very much. Take care. Tahi, you were great. Thank you. Bye. Thank you. We'll speak soon, huh? Thank you all. Bye, everyone.