Incyte Corporation (INCY) Earnings Call Transcript & Summary

Ladies and gentlemen, welcome to the MorphoSys and Incyte Joint Conference Call. [Operator Instruction] The conference is being recorded. [Operator Instructions] I would like to turn the conference over to Dr. Anja Pomrehn, please go ahead, madam.

Thank you. Ladies and gentlemen, good afternoon, or good morning. My name is Anja Pomrehn, Head of Investor Relations at MorphoSys. It is my pleasure to welcome you to this joint MorphoSys and Incyte conference call and webcast to discuss the unmet needs and global opportunities for tafasitamab in non-Hodgkin's lymphoma. We have the great pleasure to have Professor Gilles Salles opening our call today with a presentation on r/r DLBCL and the frontline DLBCL landscape, followed by speakers from both Incyte and MorphoSys. From MorphoSys, we have Jean-Paul Kress, CEO; Malte Peters, Chief Research and Development Officer; and Roland Wandeler, Chief Operating Officer. Speakers from Incyte will be General Manager North America, Barry Flannelly; and Steven Stein, Incyte's CMO. Also joining for the Q&A session will be Hervé Hoppenot, Incyte's Chairman and CEO; Christiana Stamoulis, Incyte's CFO; as well as Jens Holstein, MorphoSys' CFO. Mike Booth, Head of IR of Incyte will conduct the Q&A session with me. We will have 2 Q&A sessions in today's call. The first one will be after Dr. Salles' talk and the second one at the end of the call. [Operator Instructions] Before we begin, I'd like to remind you that some of the statements made by Incyte and MorphoSys during the call today are forward-looking statements, including statements regarding our expectations for the commercialization of Monjuvi and our development plans and expectations for tafasitamab as well as the development plans of our collaboration partners. These forward-looking statements are subject to a number of risks and uncertainties that may cause our actual results to differ materially, including those described in inside the quarterly report on Form 10-Q for the quarter ended June 30, 2020, MorphoSys 20-F and annual report both for the year ended December 31, 2019, and from time to time to other SEC documents filed by Incyte and MorphoSys. In addition, I would like to caution everyone that the COVID-19 pandemic is an evolving situation, and we may not be able to assess the full effect of governmental, business and social actions and policies and overall economic conditions on our business. Accordingly, it is important to keep in mind that our statements on this webcast speak as of today. And with that, I will hand over to Malte. Malte, please?

Thank you, Anja. Good morning, and good afternoon, everyone, and welcome to our tafasitamab expert event today. We are extremely pleased to have Gilles Salles today with us, and I want to thank him on behalf of MorphoSys and Incyte for his time and for sharing his knowledge and expertise on DLBCL with us. As many of you know, Professor Gilles Salles is not only a well-known expert in the field of lymphoma, but he is also the principal investigator of the L-MIND study, which led to the accelerated FDA approval of Monjuvi in the United States of America. Gilles has recently been appointed as the Chief of the Lymphoma Service at the Memorial Sloan Kettering Cancer Center in New York. He has previously held a position of Professor of Hematology and Medicine at the University of Lyon in France and Head of the Department of Hematology at the Hospital of Lyon Sud also in France. Professor Gilles obtained his doctoral degree in differentiation, genetics and immunology as well as his medical degree from Université Claude Bernard in Lyon. He completed further training in oncology and also served as a researcher at the Dana Farber Cancer Institute at Harvard Medical School in Boston, Massachusetts. During his career, Gilles has been especially interested in the clinical and biological study of lymphoma. The primary focus of his work is on the description and validation of prognostic factors and clinical trials in indolent lymphomas. He has also been involved in the investigation and development of new therapeutic agents such as targeted therapies, new monoclonal antibodies and other immunotherapies in the field. I want to take this opportunity to thank all colleagues at MorphoSys who have worked diligently to successfully develop Monjuvi. Further, I want to take the opportunity to thank all patients, their families as well as investigators and caregivers without whom clinical development would not be possible. But before I hand over to Gilles, I would like to extend my special thanks to our partner Incyte, with whom we have worked very hard together to achieve where we stand today. We at MorphoSys and Incyte will continue to work together as we not only execute joint commercialization of Monjuvi in the U.S. but also to jointly develop tafasitamab beyond the DLBCL patient population. And with that, I want to hand over to Gilles. Gilles, please?

Thank you, Malte, and good morning or good afternoon, everybody. I'm very pleased to be here and discuss with you the current landscape of diffuse large B-cell lymphoma as well as the recent results achieved with the use of Monjuvi/tafasitamab in this field. I will obviously discuss these matters on my personal point of view and not those of my employer. I have been also received financial compensation from different companies involved in drug development and commercialization in the field of lymphoma. So if we consider the epidemiology of non-Hodgkin's lymphoma, I gave you here on this slide the actual number of newly diagnosed B-cell lymphoma in the United States every year. As you can see, there are about 70,000 new patients diagnosed with non-Hodgkin's lymphoma, the B-cell phenotype each year, and the majority of them, 35% to 40%, are diffuse large B-cell lymphoma. Therefore, this entity is the most common one in the field. If we focus on diffuse large B-cell lymphoma on the next slide, we do know that it's the most frequent non-Hodgkin's lymphoma overall, including B and T-cell lymphomas that spontaneously patients present with lymphadenopathy, usually rapidly developing sometimes extra novel disease and alteration of the performance stages and obviously, it's a fatal disease if not treated or if not responsive to treatment. Recent years have allowed us to describe several histological forms of diffuse large B-cell lymphoma. However, we continue to group them together in terms of treatment, especially with immunological agents. And we should also mention that the recent update of the WHO classification of lymphoma have grouped under this term, the coexistence or evolution of indolent lymphoma, which can transform to diffuse large B-cell lymphoma. Finally, there is also a predominance of male which present this disease -- who present this disease as compared to female. On the next slide, you can see that the median age of incidents of diffuse large B-cell lymphoma is between 65 and 70 years. So it's really a disease that occurs in the maturity of our life. This is well described on this slide and the green curve, which is on the top, is a curve with diffuse large B-cell lymphoma. And as you can see, there is a very high incidence in patients after 65, 70, 75. You have to take into consideration also that this is the age of diagnosis, but for patients with relapsed/refractory disease, we may encounter these patients several years later. And that finally, data from several countries indicate that the median age of occurrence of this disease is probably more advanced in women than in men. If we look at the incidence of diffuse large B-cell lymphoma and the trend over the last decade, you can see that the green line again on the top shows that the number of newly diagnosed cases per 100,000 inhabitants has been relatively stable or slowly moving upward. So there have been some discussions that all the subtypes of lymphoma may have had diminished on incidents, we are still facing a frequent disease, again, the most frequent of B-cell lymphoma with a stable incident, especially in the elderly. The diagnosis of diffuse large B-cell lymphoma is made on a biopsy specimen, who shows this features of large cell dispersed in the lymphoid tissues and with diffusing filtration. Several immunohistochemical markers can be used to characterize this disease. And in 99.9% of the cases, DLBCL do express the antigen CD19 and CD20, the other antigen described here being viable. This actually lead us to the classification refinement on the molecular field of diffused large B-cell lymphoma. As you can see on the next slide, we have, in recent years, understood better the underlying biology of this disease. On the left of this slide, you see gene expressions for filing figures that have been developed by the group of the National Cancer Institute and published almost 20 years ago, showing that there were different subtype of diffused large B-cell lymphoma, which evolves from different state of differentiation of the B-cell. This has led to many work in the field, including mutation analysis and other inventory of genetic alterations of this disease. Recently, the same group on the right has actually published an update of the classification based on all the findings that have been developed over these 20 years. What I would like to point is that the molecular classification of DLBCL is an evolving field, that the tools to assess the different subtypes in clinical practice are not ready for use. They are still confined to very specialized high-level technological labs and that the therapeutic changes or targeted therapeutic that may apply to certain of the subtypes will still have to prove their benefit I will discuss later. So let's discuss the treatment of diffuse large B-cell lymphoma. I brought back this slide, which is a little bit old, that showed us that in the '80s, '90s, there was different chemotherapy regimens that were expected to improve the outcome of diffuse large B-cell lymphoma, but that -- unfortunately, none of them were proved to be superior to CHOP could remain really the backbone on which everything has been built so far. And after this curve may be reassuring, we do know that when we prolong this curve at 10 years, only about 35% of the patients are free of disease reoccurrence. This is before the time of monoclonal antibody. And the first monoclonal antibody that was developed and used in diffuse large B-cell lymphoma is rituximab and anti-CD20 antibody that you all know, which has been combined to CHOP in a clinical trial that we led into France with Bertrand Coiffier in patients aged 60 to 80 showing a very early benefit of the addition of rituximab to CHOP in terms of disease-free survival, overall survival, progression-free survival. As you know, this has been a major advance, and the clinical trial results were rapidly confirmed by some other trials and by some real-life data gathered in different countries, including, as shown on the next slide, in Canada, where the examination of patients outcome before or after rituximab showed a marked difference in terms of overall survival. Besides the medical progress that was really achieved with the introduction of this antibody, I think this demonstrates 2 things. First of all that there was a dramatic change and paradigm in moving the field forward with the addition of an immunotherapy, something that was not necessarily believed to be the major way many, many years ago. And that really a single monocline antibodies was really changing the face of this disease. So where are we now? On the next slide, you can see the overall survival of patients with diffuse large B-cell lymphoma treated in the United States. There is some heterogeneity as you can see here and the recent epidemiological data in the U.S. advice for 64% overall survival at 5 years, probably close to 55% at 10 years as shown on this slide. So as you see, despite the progress that we have made from 35% to 55%, there is still an unmet medical need and we need to continue to move forward. So what has been done in recent years to try to move forward. As you can see, this is a long-term follow-up of the R-CHOP study with the red curve on the top, and we wanted to focus on improving the initial treatment of diffuse large B-cell lymphoma. As mentioned earlier, the understanding of the biology of this disease have led to several interventions that were guided by the identification of potential targets for drugs such as bortezomib, ibrutinib or lenalidomide, interfering with some specific pathways in the field of -- in the biology of diffuse large B-cell. Other attempts were made by using maintenance therapy with rituximab, lenalidomide or other agents or by moving out 1 agent to replace by bortezomib, which was replacing vincristine or obinutuzumab, another anti-CD20 antibody to replace rituximab. There were multiple trials and multiple efforts in the last decade in this field, but unfortunately, all of these trials were proved to be negative and we haven't made any major advance in the field since R-CHOP 20 years ago. So what's the current stages of patients' journey or patients' pathway in diffuse large B-cell lymphoma. If we go back to the numbers and an estimate of 30,000 new patients diagnosed in the United States every year based on the numbers I have shown earlier, we will cure about 60% of them with the first-line therapy with R-CHOP. The response rate is higher, but some participations that will respond to therapy will relapse. And we still face 10% to 15% that are -- of patients that are primarily refractory. This lead to this group on the first rectangle of relapsed/refractory DLBCL. About half of them are deemed to be non-eligible for autologous stem cell transplant, while another half are supposed to be eligible for this therapy. If we focus on the left-hand side on this slide, about half, as I said, are eligible for transplant, but we do know from many studies that half of them don't make it to transplant. And again, becoming transplant ineligible because they don't respond to salvage therapy. If they succeed to go to transplant going down on the slide, about 30% to 40% of these patients are cured and do not relapse, but some still relapse in the eligible population. So basically, we face on the right, a population of patients that are non-eligible for transplant, a population that were supposed to be eligible but do not respond and some patients that relapse after transplant, which in comprised roughly 30% of all diffused large B-cell lymphoma diagnosed every year. So if we move on the next slide, we see what are the current standard of treatment for these patients. But first, let me show you the outcome of patient after autologous stem cell transplant. This is a slide done from a large international study in U.S. in Europe, showing that there was about more than half of the patients relapsing after autologous transplant. So even if it's a good intervention that has proved to be efficient, it's not enough. So on the next slide, you will see the different regimens that have been adopted for the patient. Transplant-eligible patients which received intensive chemotherapy based on cytarabine, platinum-derivative, gemcitabine [indiscernible] different regimen using different places. For the patient we'll discuss in more detail today, which are the transplant ineligible patients, the standard of care before the approval of tafasitamab was the following one. We had the use and the usual use of 2 regimens, either a combination of gemcitabine-oxaliplatin plus or minus rituximab or bendamustine plus or minus rituximab, many other regimens could be used, but not being the mainstream used in general. Several compounds have been recently approved in the third-line setting such as Polatuzumab, Vedotin, Polivy in combination with bendamustine-rituximab, the different cell therapies, CAR-Ts and very recently selinexor. But let's review first the results in second line of the current regimens. On the next slide, we will see the results of the rituximab GemOx regimen in relapsed/refractory DLBCL as published many years ago by our group in France. And these results were reproduced everywhere in the world. What I will say is that there is an encouraging response rate, but if you focus on the left-hand side, on the patients that had received prior rituximab, you can see that the overall response rate of these patients is only 32%, the median progression-free survival is 4 months and the median overall survival is 8 months. So let's keep these results in mind. If we move forward and examine the result of the recently approved bendamustine-rituximab plus Polatuzumab-Vedotin combination because this allows us to examine both bendamustine-rituximab, which was the control arm of this trial and this new combination approved in third-line of therapy in the U.S. You can see from these diagraphs that the overall response rate was only 18% for bendamustine-rituximab with a few patients achieving complete remission 18% overall. The complete response -- the overall and complete response rate achieved with the combination of polatuzumab plus BR were respectively of 45% and 40%. So these were quite encouraging results compared to the BR alone or even to the 32% of our GemOx that I mentioned previously. What is important is to know whether these response are durable, and we know from the publication that 7 patients out of 40 had ongoing response after 1.5 years. And this is shown better on this curve which demonstrate that with bendamustine, the response duration was very short in the range to 7 to 8 months. And with the combination, as you can see, it was close to 12 months for those patients that responded to the bendamustin-rituximab. Again, these are duration of response curve. I should also mention that this was a Phase-II randomized trial and that some patients that were responding to treatment, actually these are the [indiscernible] the top of the curve underwent consolidation with transplant. If we move to the progression-free survival of the patients in this trial, you can see on the next curve that the bendamustine-rituximab, a valuable regimen in second line, had very poor results. And that the Polatuzumab-Vedotin improve these result, but still, we have a curve which is rapidly declining and with about 25% to 30% or 30% of the patients remaining progression-free after 18 months. So these are the standard of care for patients which are treated in second line with our GemOx-BR and in third line with Pola-BR. Let me say a word regarding the recent results achieved with CAR-T cells after the clinical trials in real life. And our colleague, Loretta Nastoupil just published recently in the Journal of Clinical Oncology the experience of more than 300 patients treated with axicabtagene ciloleucel on the commercial project. As you can see, the progression-free survival curve and overall survival curve are very encouraging overall. But what this curve also show you is that there is a population of patients that unfortunately have a limited benefit of these CAR-T cells. These are patients with an advanced performance status or patients with high LDH. So patients with low performance status were very few receiving CAR-T, and that's common, I will say, selection bias of CAR-T studies. But with patients with high LDH, which there is a common feature of aggressive lymphoma, as you can see, about half of them had elevated LDH and has clearly a poor outcome than the other one in terms of progression-free survival and overall serval. So again, this was a major advance with CAR-T cell that it has this limitation. And I have tried to summarize here on the next slide, the CAR-T cell advances. For us, as hematologists and hemato-oncology, clearly, CAR-T cell was a major attractive innovation. We love cell therapy, we love immune-based therapy and having this concept of modifying the T-cell of a patient to fight the disease was very attractive. We had the results of the studies with 2 different marketed products and recently with a third one that will be in the market soon of a 50% to 80% response rate, very high CR rate, 40% to 55%, and durable response about 70% to 80% of patients in complete response after CAR-T being durable at 2 years. However, there are several issues. The first one is the logistic complexity. You probably know and understand that to manufacture the CAR-T, you have to make [indiscernible] collect the T-cell of the patient. This is a process that needs to be organized with blood banks or blood centers. This product has to be qualified, has to be shipped to the manufacturing centers. It has been modified by retroviral or lentiviral infections, quality control and send back to the manufacturing place. Overall, this process takes about 3 weeks, sometimes 4 weeks. We have also the time to get the insurance approval. So it's clearly a product that is not readily available when you see a patient with a relapsed disease, which is, again, an aggressive disease. And this leads to clearly patient selections with CAR-T. As you also know, there are specific Grade III/IV adverse event with CAR-T cytokine release syndrome and neurological events, sometimes really difficult to manage. And finally, they are very high cost and difficulty in availability, the use of CAR-T cell is restricted to some centers which are qualified after a long work by all the providers, physician and health care providers involved, and patients sometimes have to travel several hundred miles to get this treatment. So that was data of the available therapy today. And we are happy to have today another potential standard of care, which is tafasitamab-lenalidomide as shown here. And this is approved now in second line of therapy, and I will briefly review with you what were the trials and the results that led to this approval. First of all, tafasitamab is directed against the CD19 antigen. And you will see on this slide that the CD19 antigen is expressed all of the B-cell differentiation from early B-cell to mature B-cell, it's actually wider than CD20 expression that are co-expressed, but completely independent. On the next slide, you will see that tafasitamab is glycoengineered antibody, which has been improved to increase the ability to mobilize the immune cells, macrophages and NK cells to kill the malignant cells recognized by the antigen. So not only the antibody has a direct cytotoxic effect, but it's mobilized natural killer cells and macrophages to engage the function of cytotoxicity. Based on these results, a single agent tafasitamab trial had been run several years ago. And you can see on this slide, the result of this trial as a single agent, this agent was allowing about 1/4 of the patient with diffuse large B-cell lymphoma to respond and a substantial number of patients with other the entities. And some of this responses were very durable as a single agent, I think that 4 patients were alive about more than 2 years with the single-agent study. Based on these results and based on technical data, in vitro and animal models, it was logical to exploit and take advantage of the biological ability of tafasitamab to mobilize ADCC and ADCP and to combine another agent, which we know for some time being commercialized in multiple myeloma and now in follicular lymphoma to increase cytotoxicity, to increase and activate these natural killer cells and to improve ADCC. So it was shown already in vitro that combining lenalidomide plus tafasitamab in experimental models was increasing the activity of tafasitamab. That led to the study L-MIND, which is schematized on this slide and this was the study recruiting relapsed/refractory DLBCL not eligible for autologous stem cell transplant who received tafasitamab and lenalidomide initially at weekly intervals and biweekly and lenalidomide given at a standard dose patients responding to this therapy after 1-year treatment were consolidated with tafasitamab until progression. Actually, all patients with clinical benefits responding all with stable disease. The result -- the population that was recruited in this trial is depicted here. And as you can see, this was a very representative population of patients with relapsed/refractory diffuse large B-cell lymphoma non-eligible for transplant. The median age was 72 years, and you will find very few studies recruiting patients with this median age. There was an equilibrium in this patients according to different risk factors according to the disease. Most patients have advanced enable state disease, a little bit -- less than half of elevated LDH. Many patients have received only one line of therapy or 2 or more lines of therapy, 44% of the patients were refractory to that last prior therapy and a few had been refractory to their first line of therapy. Some patients had relapsed after autologous stem cell transplant. You have probably seen the response rate, which was the primary endpoint of this trial and which is shown here, the overall response rate was assessed in the first cutoff at 60%, with 42.5% of the patients achieving a complete response. The vast majority of these response were confirmed with the current standard of best confirmed assessment. What was important was whether all patients could benefit from this study. And the first plot, which is depicted on this slide. So that eventually all categories of patients actually had similar overall response rate as you can see here. Whether you were older or younger, whether you had a high IPI score or low IPI score, whether you were refractory to rituximab or not, and so on and so forth, all of these categories of patients had very similar response rate ranging from around 60% as you can see. That responding is important, what is more important is the duration of response. And what was probably one of the most striking results of this study besides the 60% response rate, 42.5% CR rate, was the median duration of response which was assessed in this first data cutoff, which was the one we published recently in Onset Oncology at 21.7 months. Moreover, if we break down the duration of response for patients that had only a partial response, they had a median duration of response of 4.4 months, but for those who had reached a complete response, you can see that the duration of response was substantially prolonged and is actually reminiscent of the duration of response we usually see with CAR-T cell. We also looked at the criteria of duration of response at 1 year according to the different patient characteristics. And let's, for discussion, start from the bottom of this graph. As you can see, at 1 year, according to the initial response, very few patient with partial response were still responding. But more than 90% of the patients with CR were still responding. This was also true that patients according to the number of prior lines of therapy were equally benefiting at 1 year of this combination. There was a substantial benefit for these patients that were non-primary refractory, but 44% of the primary refractory, a very difficult-to-treat population, were still in response at 1 year. Equally, patients that were refractory to the last line of therapy or not were responding in 1 year, there was a little difference nonsignificant according to the cell of origin molecular classification of these patients. Patient with adverse prognostic features linked to the disease had a little bit lower 12-month response rate, but this is still 50% of them. So as you can see, we see that at 1 year, many, many patients did benefited from this combination. We looked more specifically at the outcome of the second-line population, which comprised 40 patients. And as you can see, this is really the population of choice for this combination, an overall response rate of 70%, CR rate 52%, median progression-free survival almost 2 years and 87% of them being alive at 1 year. So this could be really a major game-changer in the way we manage patients in second line as compared to the results I discussed earlier with standard chemotherapy. We recently updated the result of this study with is another data point cutoff in fall 2019. And this curve shows the long-term follow-up, which really confirmed what was observed. Again, you see in dark blue, the duration of response, the upper curves are the patients that had the CR, and you can see that after a median time of observation that was close to 2 years, we still have the majority -- vast majority of patients being still responsive and a few patients even with BR still being responsive. We'll see on the next curve the progression-free survival, which shows that the median progression-free survival was 16 months. On previous slide, just as remembering, the median duration of response was 34.6 months. Here, we have a median progression-free survival of 16 months. And on the next slide, you have the median overall survival of this population, which is of 31.6 months. So not -- almost 3 years but not that far from that. So these are very encouraging results that confirmed the early achievement of the first data cutoff. Obviously, when we have a new drug, we care about the side effect and the tolerability of this treatment and this was examined in details in the study. On the left, you have the side effects that are observed during the 1-year combination of tafasitamab and lenalidomide up to 12 cycles. And on the right, you have the side effects observed during tafasitamab monotherapy consolidation after 1 year. As you can see, and these are the dark violet or orange bar, there were a few Grade III/IV events, essentially in neutropenia, which was encountered in about half of the patients, also a few patients with anemia or thrombocytopenia. Most of these side effects were, in fact, asymptomatic, and the number of patients with Grade III or IV febrile neutropenia. So when you have neutropenia lower blood count, what is important is this patient developed infection and not fever. So the number of febrile neutropenia or Grade III/IV were only of 10%. The other side effects were essentially of Grade I and II and eventually Grade III/IV rash. And although that we see most commonly with the use of lenalidomide, either alone or combined with another agent, and they were mostly reversible. If we look at the right graph, you can see that the side effect diminished in frequency and in intensity during the consolidation to tafasitamab, making that a quite tolerable regimen as consolidation. So the conclusion of the L-MIND trial are the following: we have combination of tafasitamab-LEN with is a high overall response rate, high CR rate, durable response; a high activity that is consistently observed in different patient subgroup that overall have limited treatment options and not a good prognosis; very good survival data and a safety profile, which is largely driven by lenalidomide and an expected tafasitamab safety profile from the Phase II study. So this is the result of L-MIND, and I would like to bring that in the context of other therapies being developed in the field of diffuse large B-cell lymphoma and B-cell lymphoma in general. And I have tried to summarize all the different agents being developed. I think that we have some [indiscernible] anti-CD20, but very doubtful that they are very superior to what we have right now with rituximab, obinutuzumab and ofatumumab. We have some antibody drug conjugate, Polatuzumab-Vedotin being one of them. We have bispecific antibodies binding CD3 and CD20 or CD3 and CD19 with some encouraging results and can discuss that later. Immune checkpoint blocker have been very disappointing in the field. IMIDs as a single agent has a limited efficacy that can be combined with antibody. And a few targeted therapy against cell signaling, intracellular trafficking, apoptosis or epigenetic. The results achieved with these novel agents are summarized on this slide. And as you can see, the top line is the results achieved with the combination of tafasitamab-lenalidomide on this consolidated Phase-II result, overall response rate again 60%; complete response rate, 43%. If you look down, you can see that this regimen really is one of the best, if not the best, in the field. There are obviously some antibody drug conjugates that have led to favorable results. We still don't have the duration of response for loncastuximab tesirine. We have the response rate observed with bispecific antibodies is blinatumomab, which is difficult to handle in diffuse large B, but mosunetuzumab or glofitamab, which are now starting to have mature results. And as you can see, the other selected therapy have much lower overall response rate or complete response rate. So we really have here a combination, which seems to be very favorable for these patients. As always, when we discuss diffuse large B-cell lymphoma and have found a combination which led to very satisfactory results in the relapse setting, we tend to see, well, can we now improve the frontline treatment of these patients by using this combination. As seen on this curve and as initially discussed, we still have some progress to make, especially for the patients who have a high IPI score of 3 to 5, this is an index that assess based on disease characteristics and patient characteristic, the probability of outcome of this patient. Recently, when we examined the trials that have come in different -- combined different agent with CHOP or R-CHOP, we can see on the next curve that the ROBUST trial, which was a study where we combined rituximab, CHOP and lenalidomide, trial that has been presented overall, and we expect the publication soon. This was a combination of lenalidomide plus R-CHOP, so-called R-Squared CHOP. And this was selected to some subset of patients. But as you can see, despite the fact that overall the result of the trial were not meeting the primary endpoint, there was a trend for better efficacy of this combination in patient with advanced disease stage or with an advanced IPI score, suggesting that there may be some group that can benefit of this combination. So based on this data, there is a rationale to combine tafasitamab, lenalidomide and R-CHOP in first line of DLBCL. And this is summarized on the slide. There is a synergistic mechanism of action of tafasitamab plus lenalidomide. There's a strong data obtained with the L-MIND regimen. We do know that the exploration pattern of CD20 can change after exposure to R-CHOP, but CD19 expression is more [indiscernible] compared to CD20, and it's preserved in the small number of cases where CD20 disappear or becomes -- start to be faint in staying. So targeting 2 antigens with 2 different antibodies is also a very appealing approach. And finally, we have these high-risk IPI patients that need to be treated. So basically to the -- my last slide, which is the description of the First-MIND study, which is a study that will assess in randomization, the combination of tafasitamab plus R-CHOP or tafasitamab-LEN plus R-CHOP. This is the early stage of the study, the Phase-IB, including patients, non-previously treated. A little bit broader population to assess the safety of this combination tafasitamab-R-CHOP or tafasitamab-LEN-R-CHOP. Obviously, this trial, which will be discussed by colleagues from MorphoSys and Incyte in the next session, has been occuring fast, and we will allow to decide whether we can move forward by integrating tafasitamab plus R-CHOP plus or minus LEN in a large randomized study to establish that as a frontline regimen that could become a standard of care. I hope I wasn't too long, but I'm happy to answer any questions. And I thank you for your attention. Thank you.

Super. Thank you, Gilles, and great insight in the field of DLBCL, non-Hodgkin's lymphoma, summarizing everything that's going on. I hand over to the operator now to maneuver the questions.

[Operator Instructions] The first question received from Geoffrey Porges of SVB Leerink.

Two questions, if I may. First, do you believe that Monjuvi, in any way, affects your ability to offer CD19 CAR-T in later lines? And reverse, do you think that Monjuvi might be active in CAR-T failures? And then could you just talk a little bit about follicular lymphoma? The CD20 bispecific seem to be more active in follicular and CD19 perhaps less active. So could you comment on whether there's a reverse situation some way in follicular compared to DLBCL?

Well, that's not two questions, but that's not the problem. The first one, I think it's an important question and I think investigators as well as the companies are developing results in this field. Obviously, there were a few patients treated so far with the combination of CD19 antibody. There is no data from previous Phase II trial, also with other CD19 directed antibodies that there could be a loss of expression of CD19 or that there could be modification at the molecular level of the CD19 gene or transcript and that the expression will be preserved. Obviously, it's a limited set of data of patients treated with the L-MIND regimen, but there is a communication that will be presented in future meetings, showing that in cases where we had bad biopsy or investigators from [indiscernible] have bad biopsy to examine CD19 expression was still concern. There could be in theory a stereotactic impeachment of CAR-T to bind to CD19 but this theoretical and we have already the case of 2 patients being treated successfully with CAR-T. So yes, I think CAR-T can be as far as we know and with the current data been utilizing patients that receive Monjuvi. Maybe we may have to have a little washout but I think this could be achieved quite easily. On the other side, I think the other sequence, I think we don't have data yet. What we know is that in diffuse large B-cell lymphoma, there is still a relapse setting of CAR-T in about 25% to 35% of the case that may have lost the CD19 antigen based on genetic mechanisms. So this patient won't be eligible for this combination. And finally, I think we have to take -- with precaution the discussion of follicular diffuse large B. The early result of rituximab were achieved in rituximab-naive patients, here we have patients that have been usually pretreated, and this was not a head-to-head comparison, but we don't know yet, and I think there is still some space to explore the activity of this drug in follicular.

The next question received is from Marc Frahm of Cowen.

You mentioned in your talk a couple of trials have been run putting active agents into the front line on top of R-CHOP or in places of agents and failed. Obviously, there are some improvements that can be made with risk factors and things like that. But what type of data are you going to be looking for from First-MIND to kind of really give you confidence that this regimen is going to be the one that finally beats R-CHOP? Is it response rate, 1-year event free survival, is it PET, CR? What's the end point that we shall all be looking at?

Well, I will probably defer the question to the MorphoSys, Incyte colleagues, but my point of view is that we have to look first at safety of this combination. And obviously, the end of treatment CR rate such as by PET as well as some other exploratory endpoints. But maybe colleagues can answer that.

Yes, Gilles, we have a slide in our presentation on the details of the endpoints, maybe we can come back to that question in the second part of the meeting.

Then we take the next question, it's from James Gordon of JPMorgan.

James Gordon from the European Pharma Biotech team at JPMorgan. The question was about combination therapy. So you mentioned some combination approaches that can be used to [indiscernible] with Monjuvi. And there's also a slide talking about some of the monotherapy approaches and one of those in CD3, CD20s. So my question is what's the enthusiasm for combination of Monjuvi with a CD3, CD20 therapy. And if there is high enthusiasm there, would you want to see CD3, CD20s approved as monotherapies before you consider enrolling patient into a combo trial with them? And maybe for the second half of the call, sort of the same question to the company as well really. So latest thinking on doing a combo Monjuvi, CD3, CD20 and when something like that could get going?

Well, I think your question is very interesting. We have here a backbone of an immune intervention, combining an antibody again CD19 plus LEN, which is a drug that activate cytotoxicity [indiscernible] toxicity. So it's a backbone of immunotherapy that can be obviously combined with other agents. It can be combined with single-agent again with CD-20s, such as rituximab, but obviously using another mechanism of actions which activate T-cell, such as bispecific will be interesting. I think we have to see a little bit [indiscernible] the safety profile, we do know that bispecific have some side effects such as cytokine release syndrome. They also have a significant incidence of neutropenia. So obviously, this kind of combination should be very carefully evaluated. I don't think we need to -- personally, I don't think we need to have the drug approved to start investigating this combination. And again, I think tafa-Len is a very nice platform where we can -- that we can use to try to combine with new antibodies and other new immune-based mechanism of action molecules.

And the next one is from Evan Seigerman of Crédit Suisse.

So some recent feedback we've gotten from physicians suggests really favorable view of the tafasitamab in the second-line plus setting. However, there still seems to be some sort of a bias if appropriate to use CAR-T therapy, which you had touched on potentially to cure patients, I used that loosely. So with potential data of T-cell in second-line DLBCL near term, how do we expect Monjuvi and CAR-T therapies to kind of coexist in this line of therapy? And will there be a bias to use CAR-T in more patients to get that cure? Or do you see Monjuvi being used more in these patients?

Well, that's an interesting question. So yes, let's suppose that at some point, our T-Cell and other CAR-T could be approved in second line of therapy, we will have different options for the patient. So there is no comparison head-to-head of these studies. But again, when you look at the complete response rate of second line of the tafa-Len combination, Monjuvi plus lenalidomide, you have a 52.5% CR rate, which is a CR rate which is very close to the CR rate achieved by CAR-T at 3 months at least. And the duration of CR is very good. So I think this is kind of competing approaches. And when we talked about cure, I think that we have obviously now almost 3 years median follow-up for the study a little bit less. But as I have seen, the duration of response for patient in CR are really very favorable curve and I personally believe, from my experience with diffuse large B-cell lymphoma, that when a patient has been in complete remission for 1 year, whether the patient is still under therapy with a monoclonal antibody or not, the likelihood of this patient being cured is very high because especially the relapsed/refractory setting when we relapsed occur, they occur quite rapidly. So I do believe we don't have the proof and we'll have to wait for a longer follow-up that proportion of patients, which are the complete responders and stable complete responders at 1 year of patients treated with tafa-Len are probably cured. Afterwards, I think whether people will prefer one approach over the other, I think we have to, again, see for mature data. We have to balance the side effect, complexity of CAR-T, we have to examine the different populations. As I mentioned, diffuse large B-cell is a disease that occur in the second part of our life. And I think this is a population, which is probably more frail to engage with CAR-T, but I think we can also use tafa-LEM in the 30 years old patients before we go to CAR-T if there is a failure of tafa-LEM in the future. So I think these options are acceptable to my point of view. I think we had some discussion and maybe the companies may comment on that of launching a randomized study of one against the other, but it's pretty challenging given the difference of the 2 arms.

And the next question received is from Graig Suvannavejh of Goldman Sachs.

Doctor, I just wanted to get your view of where do you think Monjuvi is ideally best positioned? Is it really more as a backbone for your treatment of second-line patients? Or do you see it really more -- and obviously, we don't have the data as a potential in a frontline setting. And just to kind of follow-up on the question on second-line use. Given the data that we have thus far, what do you think is in the percent of patients in the second-line setting for the eligible patient population that you could see your use of Monjuvi in combination with lenalidomide?

So the first question is whether it's a drug that is more second line or first line. I think each time we have get a drug that works in the second-line setting and proven to be very beneficial in the second-line setting and that the efficacy safety ratio that was significantly good. We try to move this -- drag in first line because we have more chance to cure a patient in first line than in second line or third line. So I think Monjuvi has prospects of being active and should be tested in first-line because it's definitely an agent that is active. Regarding the proportion of patients in second line that can be candidate for the combination of LEN -- [ CAP ] LEN and Monjuvi, I think I don't see specifically patients that won't be candidate. I think that we've few patients that have -- we have to acknowledge in the trials that we have primary refractory. But as I said, a few of them did respond and benefited for a long time. We know it's a very difficult-to-treat population. And for the other ones, I think the consistency of results according to the different disease characteristics made them pull that majority of them suitable to try this therapy as the second-line therapy with the prospect of achieving a response in more than half of the patients, which will be durable in the vast majority of them.

And the next one is from Ren Benjamin of JMP Securities.

Dr. Salles, in an earlier slide, you talked about 70,000 patients being diagnosed in the U.S. every year. In a subsequent slide, 30,000 are being treated for first line. And so I'm trying to understand, when we look at the market expansion opportunities, is there any way to look at these 40,000 that are not being treated right away? What are their treatment options? And when do they kind of advance? And related to that, the transplant-eligible patient population, what do you think it would take to either move -- tap in line into that population? Or is there some reason why it wouldn't be used in that population?

So let me clarify the numbers. 70,000 patients with B-cell lymphoma, including diffuse large B-cell lymphoma diagnosed every year. About 40% of those are diffuse large B-cell lymphoma will bring us to the 30,000 numbers. So it's not that we have 40,000 patients untreated. It's just that out of the 70,000, 30,000 roughly are diffuse large B-cell. So that, however, and this should be mentioned, a small proportion of patients, actually viable according to different market surveys that do not receive chemotherapy because of age, because of comorbidities, frailties and things like that, even with diffuse large B-cell lymphoma. And I think there are discussions that several investigators are having with the company, whether there could be an attempt to move this Monjuvi-LEN combination as a first-line option for the patients which are not suitable for chemotherapy in the first line. So that's a question of patients for first line and patients not suitable for chemotherapy. Again, it's probably a few thousands in the United States and elsewhere. Discussing the second line for the transplant-eligible population. I think it's always complex to move with standard of care, despite the fact that the standard of care was established almost 40 years ago in a large study that took years to achieve and probably not anymore representative of the population. We do know that right now with the current standard, we have, as I said, about 20 -- between 15% and 25% of patients eligible for transplant that at the end of the day are cured from their disease. So there is a margin for improvement. CAR-T cell has taken the challenge, and we do know that 3 randomized study with CAR-T cell is being performed in this field. I think it goes back to the question we had before, what would we choose is a CAR-T or is a combination of Monjuvi-LEN. I think it's a little bit too early to respond. I think we have to see what the results of the CAR-T trial show, whether it's very marked benefit, whether it's significant but lower benefits. And I think, again, it's 2 different treatments in terms of complexity, in terms of side effect. Maybe there is a way we can sequence them in the future. So I think right now, autologous stem cell transplant is not bad so far. And maybe it could still be used for failure of patients after a CAR-T or after Monjuvi in second line, but it's not unlikely that it will be displaced from the field where -- from where it is now in the next 5 years.

Super. Thank you very much, Gilles, for your expertise again. Thank you for the questions. And we will now move towards the second part of our call. And for this, I would now like to hand over to the commercial team, starting with Ronald.

Thank you, Malte, and good morning, everyone. I'm pleased to have this opportunity to speak with you today. Turning to Slide 54. As we've heard from Dr. Salles, Monjuvi in combination with lenalidomide was granted accelerated FDA approval with both fast track and breakthrough designations on the 31st of July, 1 month ahead of its PDUFA date, as the first second-line treatment for patients with relapsed/refractory DLBCL. Following on Dr. Salles' comments, we believe Monjuvi has seen opportunity to transform the standard of care for patients with DLBCL, the most common type of non-Hodgkin lymphoma, and address unmet need for patients living with relapsed/refractory DLBCL. Today, I will be sharing with you how we are building momentum to address this unmet need since the approval of Monjuvi. Together with our partner Incyte, we have delivered on a rapid speed to market, we were able to adapt and overcome many COVID hurdles to drive engagement with physicians ahead of expectations, and we are encouraged by the early adoption and uptake we see in the marketplace. Moving to Slide 55. Taking a look at the indication, Monjuvi in combination with lenalidomide was approved for the treatment of other patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, including DLBCL arising from lower-grade lymphoma and who are not eligible for autologous stem cell transplant. Speaking to efficacy, Monjuvi produces a meaningful and durable response to treatment. FDA approval was based on data from our L-MIND study, showing a best overall response rate of 55%, a complete response rate of 37% and a median duration of response of 21.7 months, which is remarkable. And as Dr. Salles has outlined, this duration of response is based on the November 2018 L-MIND data, and we heard from him that this duration of response is further extended with our longer-term data. This label translates into a set of important takeaways in our conversations with physicians. One, Monjuvi is the first and only second-line therapy, resulting in a high number of complete and durable responses across subgroups. Two, the combined safety and tolerability profile supports the paradigm shift towards treating patients with progression, potentially allowing for long-term disease control. And three, Monjuvi is accessible to patients in both community care and academic settings as an off-the-shelf product administered by a standard IV infusion that is easy to administer and does not require hospitalization or heavy monitoring. We are hearing consistently from physicians that Monjuvi's accessibility is a strong advantage, especially in community care settings. Please move to Slide 56. When we last spoke to you a few days after Monjuvi's approval, we shared that our teams had anticipated an early approval, and we're well prepared and laser-focused to launch. In fact, we were ready to bring Monjuvi the patients within 1 week of the accelerated FDA approval and made significant traction since then. Our thanks go out to the MorphoSys and Incyte colleagues around the world for their dedication and commitment to bring this new treatment option to patients in dire need. These are just some of the major milestones achieved in the business days following approval. Looking at regulatory, Monjuvi's NDC was listed on day 3. Looking at supply, Monjuvi was ready to ship on day 3 and our specialty distributors were stocked and ready to process customer orders by day 4. My Mission Support, our patient support program, was launched on day 1 to begin helping patients with their access and treatment support needs. And since I've responded to more than 100 customer inquiries for patient support. And looking at customers, we received the first order on day 5. We saw the first account formulary on day 8, and most importantly, the first patient infused with Monjuvi on day 10. Patients were waiting and we were ready. Looking at payers and guidelines. We have provided government and commercial payers with information on the approval of Monjuvi and its labeled indication on business day 1 and saw the first payer confirmation for coverage to label and inclusion in guidelines by week 2. Barry from Incyte will speak in more detail about payer coverage and guidelines in a moment. Now turning to Slide 57. An important focus of the launch was ensuring we effectively adapted to engage customers in the context of the pandemic. Because of the current COVID environment, we have to be thoughtful and flexible in providing launch implementation to our customers in the ways that are most amenable to them. To do this, our teams deployed a combination of individual engagement, peer-to-peer engagement and closed-loop digital engagement tactics. We are extremely pleased to see the traction we built across all channels to create strong awareness and interest from physicians. In terms of individual outreach, our team sends more than 30,000 e-mails since launch with an open rate that is 3x higher than the industry benchmark. Our sales team has made more than 4,400 calls, and our medical teams across the 2 companies had over 1,800 engagements. This was complemented by peer-to-peer engagements. To date, more than 120 speaker programs have been completed or are planned with attendees from top 30 and [ TLA ] healthcare organizations. We are excited about the strong engagement we saw across digital platforms, where digital advertising media was used to create contextually enrich environments. The new Monjuvi patient and physician-focused websites have already received more than 7,000 visits. EMA campaigns have reached more than 75% of the target list, with TLA healthcare providers having the highest rate of engagement. What this tells us is that physicians want to hear about Monjuvi. If you now turn to Slide 58. We saw that this translates from Monjuvi to quickly earn clear leadership and share of voice with greater than 50% SLE and well ahead of other treatment options in this space. This is a testament to the team's ability to get the physicians and to get our message across. Turning to Slide 59. When we look at uptake, we are encouraged by the signals we are seeing only a few weeks in the market. More than 100 key accounts have already ordered. These orders are split 50% between both academic and community care settings. And 50% of the institutions in the NCCN network have already purchased Monjuvi. This speaks to the extra stability of Monjuvi in both the academic and community settings. Note that many top accounts have been using exceptional processes in the first weeks on the market to expedite bringing Monjuvi to patients. But we already have seen over these last weeks, more than 50% of formulary approvals in the top 30 accounts, and we're on track to gain positive formulary decisions in the remaining key accounts. More than 40% of EMR/orders sets were added in top 30 accounts supporting pull-through to enable a broader uptake across the different networks. I'm going to Slide 60. From our first weeks on the market, we are hearing from physicians that they are excited about this important new treatment option on behalf of patients. Specifically, physicians are telling us that they are appreciating the over response rate and the duration of response, the value of the tolerability and safety profile that Monjuvi provides to patients and the appreciated accessibility and ease of use of Monjuvi in community and academic settings. We realize it is still early days, and the team will remain focused on differentiation, adoption accounts, access for patients and using our analytic abilities to quickly learn and adapt on our journey to establish Monjuvi as the standard of care in second-line relapsed/refractory DLBCL. We will be sharing more details on Monjuvi sales with you during our third quarter earnings call. But ahead of that, Barry, my colleague at Incyte, will provide more details around market access and treatment guidelines and our outlook on our medium and long-term potential for Monjuvi and relapsed or refractory DLBCL in the U.S. Barry, please?

I'm good. And uptake has been rapid in certain centers. It is important, of course, that we have smooth distribution and coverage for Monjuvi, and I'm very pleased that we have had to date no unforeseen delays in distribution channel, and the product was available to patients within days of approval and coverage by payers is almost universal. We were also pleased with the speed that Monjuvi was included in the NCCN guidelines, which not only increases awareness within the oncology community, but also drive certain formulary decisions. With our colleagues at MorphoSys, we understand how important it is to support patients through their treatment journeys, and we are committed to help remove barriers to patient care. As part of this commitment, we have launched a robust patient support program called My Mission Support. This program offers numerous services such as benefit investigation, prior authorizations, and claims and billing support, ongoing education and other resources to eligible patients and their caregivers who are prescribed Monjuvi in the United States. Relapsed or refractory diffuse large B-cell lymphoma remains a significant unmet medical need in the United States, as shown on Slide 63. There are approximately 30,000 new diffuse large B-cell lymphoma patients in the United States placed on treatment each year. And first-line standard of care is R-CHOP, which leads to cures in about 60% of patients. For the approximately 40% who progress, a little more than half of these patients may be eligible for autologous stem cell transplant and approximately 5,000 that are ineligible for stem cell transplant are eligible for Monjuvi. Second-line stem cell transplant leads to cures in around 15% to 20% of patients. And therefore, Monjuvi is also an option for the approximately 5,000 patients for whom stem cell transplant is not curative for a total opportunity of approximately 10,000 new patients each year. On Slide 64, we wanted to provide some metrics for consideration as you build and refine your forecast models for Monjuvi in the United States. As I mentioned, we believe that the opportunity for Monjuvi in relapsed or refractory diffuse large B-cell lymphoma is around 10,000 new patients per year and one must not only consider these new patients, but also a potential number of ongoing patients who are on therapy for more than 1 year. Year-on-year, we expect a number of ongoing patients to grow and further out into the launch curve. We believe that in any given year, the revenue from new patients will be matched by the revenue from ongoing patients. Given the patient population and the duration of therapy, we are providing an initial guidance range for the peak potential of Monjuvi in relapsed or refractory diffuse large B-cell lymphoma to be between $500 million and $750 million in the United States. Now we'll move to the clinical sections with Dr. Peters from MorphoSys.

Thank you, Barry. So we have already heard from Gilles, a lot of information about the aggressive nature of DLBCL. Therefore, our mission and ambition at MorphoSys and Incyte is to improve cure rates in DLBCL, not only in front line, but also in the second and later lines of DLBCL and continue the development in other indications and expand it to become a backbone treatment in non-Hodgkin lymphoma. In order to realize this ambition, we are pursuing several steps, as outlined on Slide 66. Today, I will address the first 3 steps. As you have heard from Roland, Monjuvi is the only FDA-approved second-line treatment for patients with relapsed or refractory DLBCL who were not eligible for stem cell transplant. The objective response rate and durability of the responses may make it a preferred option for these patients, and we aim to establish the Monjuvi and lenalidomide combination as standard of care in relapsed and refractory during this year. The clinical data that you have heard from Roland and from Gilles complemented by safety profile, the ability to combine Monjuvi with other anti-cancer treatments, and its ease of use could favor Monjuvi as a preferred option in second-line DLBCL. This encourages us to pursue our goal to develop Monjuvi as a backbone for DLBCL treatment and a combination partner of choice across all lines of therapy. Beyond DLBCL, it is our goal to bring Monjuvi to every hematological cancer indication where CD19 is associated with the mode of action of the disease. Let's move to Slide 67. Let me quickly outline the progress that we have made in our strategy to establish tafasitamab as the potential backbone treatment for patients with DLBCL. Moving from left to right on this slide. With respect to the treatment of DLBCL in frontline, we have complemented enrollment of our Phase Ib/II study First-MIND one month ahead of schedule. This shows the great interest of the community in this potential treatment option. We are well on track regarding our pivotal Phase III study Front MIND, and discussions with EMA and FDA are very advanced. In addition, we will explore novel combinations with Monjuvi, which could lead to chemo-free treatment options in front-line DLBCL. Roland and Barry have already discussed the FDA approval for the Monjuvi lenalidomide combination in second-line DLBCL to achieve our goal of bringing tafasitamab to relapse or refractory DBCL patients. And lastly, we are in discussion with several companies about possible combination strategies of tafasitamab with novel anti-lymphoma treatments to established tafasitamab as the therapy of choice in DLBCL across all lines of treatment. Now let's move to Slide 68. Let me reinforce quickly what Gilles has presented earlier. There's a very high unmet need for DLBCL patients in the first line, especially for high-risk patients. If a patient is newly diagnosed with DLBCL and falls into the category of a high-risk profile with an IPI score of 3 to 5, the chances of cure with [indiscernible] are lower than 50%. These numbers underline the need to provide an alternative and better treatment for these patients with a higher prospect of cure, and we are committed to work on such an alternative for the benefit of patients and their families around the world. On Slide 69, we want to show you, as an illustrative example, a PET scan of a patient with a high IPI risk score of 4, treated in our first-line study with tafasitamab, lenalidomide and R-CHOP. You can see that the patient started treatment with a massive tumor load, which completely disappeared, representing a complete response after only 3 cycles of treatment. This single patient's response in their scans encourage us to continue our development of tafasitamab across all lines of treatment. The scans also show that we can aim for cure for patients suffering from DLBCL and that our aim is not unrealistic. Now speaking about our ambition to cure. In the L-MIND study, as Gilles has presented, 20 patients still benefit from this treatment to date, most of them for approximately 3 years and some even for longer. And just to remind you, all of these patients are now on tafasitamab monotherapy. Moreover, in our earlier NHL monotherapy study, which Gilles has also alluded to, there are now patients who have been treated with tafasitamab for around 6 years and counting. Moving to Slide 70. This slide outlines the design of our pivotal Phase III study in newly diagnosed patients with DLBCL. We are planning to conduct this large randomized study to evaluate the tafasitamab lenalidomide combination in addition to R-CHOP compared to the standard-of-care R-CHOP alone. You may ask what gives us the confidence to develop tafasitamab in frontline after multiple attempts have failed, as Gilles has pointed out. Now we have listened very carefully to leading physicians in the field such as Gilles and we'll also consider learnings from previously unsuccessful studies into our study design in order to maximize the likelihood of success. Key factors include, first, with tafasitamab and lenalidomide, we're adding 2 highly synergistic drugs and not only 1 to R-CHOP. And the 2 have shown compelling results in the relapsed/refractory setting. Second, we are focusing on those patients with the highest unmet needs, meaning those with an IPI score of 3 to 5. And we know from earlier trials that in these patients, lenalidomide is active. Lastly, we aimed for a short time span between diagnosis and start of treatment, which makes sure that those patients are enrolled who may benefit from our treatment most. Of note, this Phase III study, utilizing the synergistic potential of tafasitamab and lenalidomide will be part of the post-marketing requirement as discussed and agreed with FDA. Slide 71 provides some details regarding the time lines. As previously mentioned, the pivotal front-line study is planned to start early next year with the primary completion date in 2024 and the following steps thereafter, as outlined on this slide. At the same time, be mind our randomized Phase III study in patients with relapsed or refractory DLBCL is ongoing and recruiting well and will be part of our post-marketing commitment agreed with FDA. Now let me share a couple of thoughts regarding investigator-initiated studies on Slide 72. Our goal is to realize the full potential of tafasitamab. Together with our partner Incyte, we have a broad development program, but we'll also engage in a comprehensive investigator-initiated trial program. We think that tafasitamab has even more opportunities, reaching beyond what we are currently addressing. That's why MorphoSys and Incyte partnered with the leading academic institutions to address additional opportunities. We have received a very high number of ideas coming from academic centers, which demonstrates the extremely high level of interest in tafasitamab. Currently, we have 30 to 40 proposals under evaluation, and we have already approved more than 10. On top of this, the first IITs are scheduled to start later this year. The IIT program addresses various areas such as additional chemotherapy containing and chemo-free combinations, specific patient populations as well as additional indications such as marginal zone lymphoma, ALL and others. We are highly interested to evaluate tafasitamab in specific settings such as pre and post CAR-T cell treatment, as was discussed earlier in this call. This is supported by preliminary evidence on the persistence of CD19 in patients treated with tafasitamab, and we anticipate to publish data on this later this year. Now I hope you have seen how ambitious we are regarding the future opportunities of Monjuvi and how excited we are to launch all these activities. With that, I would like to pass the call on to Steven, who will provide even further insight into our joint development program in additional indications. Steven?

Thank you, Malte. Turning to Slide 74. In my remarks, I will firstly briefly cover both the status of our application for European approval based on L-MIND before moving on to describe our global development plans for tafasitamab beyond diffuse large B-cell lymphoma. We announced the validation of the MAA in May of this year and continued to expect a decision in the second half of next year. The unmet need in Europe is significant, and we have laid out a summary graphic on the right-hand side of Slide 74. We believe that approximately 40,000 newly diagnosed diffuse large B-cell lymphoma patients are placed on first-line R-CHOP therapy each year, which is curative, as you heard, in approximately 60% of cases. For the remaining 40%, we assume that a little over 50% of patients were eligible for autologous stem cell transplantation and of whom around 15% to 20% were cured. These summary estimates suggest an opportunity for tafasitamab of approximately 14,000 new patients each year in Europe. We also have ongoing and planned development and regulatory discussions in other territories such as Canada, Japan and China as we seek to bring the potential of tafasitamab to all appropriate patients as soon as we are able. Turning to Slide 75. The first indication beyond diffuse large B-cell lymphoma, where we planned in a pivotal program is follicular lymphoma, and we have provided some global epidemiology estimates on this slide. Our pivotal trial will be in the relapsed refractory population, where there are approximately 17,000 treated patients each year across the U.S., Europe and Japan. Preferred regimens for these treatments in second-line are CD20 plus chemotherapy or CD20 plus REVLIMID, commonly referred to as the R-squared regimen. And in the third and later lines, we're starting to see the appearance of PI3 kinase delta inhibitors, which I'll come to shortly. Slide 76 summarizes our proposed pivotal trial to evaluate tafasitamab in combination with R-squared in patients with relapsed or refractory follicular lymphoma. We have received broad endorsement from regulatory authorities, and this is the appropriate study to run on a global basis, and we expect to recruit around 500 patients randomized one to one across the 2 arms. We expect to initiate this study in the early part of next year, and we expect the trial to take 2 to 3 years to complete. Turning to Slide 77. Insight has long been an advocate about the potential utility of PI3 kinase delta inhibition in B-cell malignancies, and we continue to believe that parsaclisib may represent the most potent and the most selective molecule in the class. We have worked diligently to understand the optimum dosing and profile of parsaclisib in a variety of tumor types, including as a single agent in B-cell malignancies, and we are very excited to investigate its potential in combination with the CD19-directed therapy. Turning to Slide 78. Part of the reason for our excitement was the publication at ASH last year of the COSMOS data, showing compelling activity of tafasitamab plus idelalisib, a first-generation delta inhibitor, in 10 out of 11 heavily pretreated CLL patients, all of whom had received prior BTK therapy. On Slide 79, you can see we are finalizing the protocol for the proof-of-concept study of tafasitamab plus parsaclisib now, and this summary design is shown on the slide. We expect to recruit patients across a range of different B-cell malignancies and look forward to sharing the data with you in the future. I will close with a summary of the global development plan for tafasitamab on Slide 80, which I believe illustrates both the depth and the breadth of our ambition as we work diligently to bring this novel medicine to as many patients as we can and as soon as we can. It is now my pleasure to pass the call to Jean-Paul for a few concluding remarks before we open for Q&A. Jean-Paul, over to you.

Thank you, Steven. Today, we discussed the aggressive nature of NHL, specifically DLBCL. And I hope we were able to give you a comprehensive overview of our progress. As we have outlined earlier, there is a substantial unmet need for patients suffering from r/r DLBCL as these patients can unfortunately have a very poor prognosis. The approval and launch of Monjuvi in r/r DLBCL in the U.S. are important milestones, not only for us, but mainly for patients battling this very aggressive disease. Monjuvi provides the potential to transform the treatment of these patients with r/r DLBCL. We already saw good market response and positive customer feedback in the first weeks of the launch since early August. And we estimate the U.S. peak sales potential of Monjuvi in r/r DLBCL in the range of USD 500 million to USD 750 million. We also want to bring a tafasitamab to patients around the world suffering from r/r DLBCL. Obviously, the next important milestone is the anticipated EU decision on approval, which is expected in 2021. Both Incyte and MorphoSys are convinced that tafasitamab offers additional options and opportunities. We aim to improve churn rates in first-line DLBCL, in which every year, approximately 30,000 patients are being diagnosed in the U.S. alone. Furthermore, we plan to develop Monjuvi as backbone therapy in DLBCL in our anchorage given the favorable benefit risk profile, the excellent combinability and ease of use. While Incyte and MorphoSys will continue to build depth in DLBCL, we will also explore adjacencies that will allow us to expand tafasitamab beyond the DLBCL patient population. We started a comprehensive development plan to expand and maximize the potential of tafasitamab into other B-cell malignancies. So in summary, we, at Incyte and MorphoSys, are committed to unlocking tafasitamab's full potential. On that, we can now open the line for questions. Operator, please?

[Operator Instruction] And the first question received is from Tazeen Ahmad of Bank of America.

I wanted to get your thoughts on how long -- and thank you for providing what you think the peak sales of that are going to be. How long do you think it will pay for doctors to adopt Monjuvi? Do you think conducting our own checks -- it does seem like the equipment level is quite high already. And to that point, do you think that the adoption will be on the faster side? Or is your internal estimate a little bit different than ours and indicate more of an even slow of an uptake? That's the first question. And then the second question is about future uses for Monjuvi. I know that you're looking at additional indications beyond non-Hodgkin's lymphomas and CLL. What areas do you think are particularly on your unmet need at the time? And when do you think we would hear about additional indications?

This is Barry. To answer your first part of your question, I think as both Roland and myself said, we think that the excitement, and you said yourself, from hematologist, oncologist throughout the United States for Monjuvi is high. We know that in some centers, in particular, the use -- the uptake has been rapid. We think that this should be a very good launch, and we're excited about the future of this combination and Monjuvi, in general.

And Tazeen, it's Steven. In terms of future uses, we tried to address much of it in our prepared remarks. But as Gilles said upfront, wherever CD19 is expressed in a B-cell malignancy, that's obviously of interest to us across the range of B-cell malignancies. We showed you studies we want to do, for example, in follicular lymphoma, and then there might be potentially other B-cell malignancies like CLL where CD19 is expressed. And then also potentially down the pike where there's relevant B-cell biology, even in autoimmune indications where you want to take care of that pathway in terms of ameliorating the disease. But to begin with it step wise, diffuse B-cell lymphoma, as you've seen, relapsed/refractory currently moving to first-line and follicular lymphoma for the moment. Thanks.

Okay. And then maybe just a quick follow-up. Would you want to pick indications where you would ultimately have a chance of being early line therapy? Or is refractory something that will also be appealing?

I think -- it's Steven again. I think it will be disease by disease where it's relevant, and the biology is important and then the unmet need. Those are the things you'll consider and then follow the science strongly. Obviously, the entire premise is to improve cure rates with the therapy. So ultimately, in many B-cell malignancies you will want to get to earlier lines of therapy.

And the next question received from Jason Butler of JMP Securities.

The first one just on First-MIND. Is there any consideration here or potential for an interim analysis or early stopping for overwhelming Fc to be considered by the [ DMBC ]? And then secondly, just, I guess, part -- modeling part clinical question. When you think about the patients that progress directly from R-CHOP versus those that subsequently progress from a transplant, how should we think about duration of treatment in your assumptions there?