Ladies and gentlemen, welcome to the MorphoSys and Incyte Joint Conference Call. Please note that for the duration of the presentation, all participants will be in a listen-only mode, and the conference is being recorded. After the presentation, there will be an opportunity to ask questions. Please note that we only can take your questions if you are registered by name. Should anyone need assistance during the conference call, they may signal this by pressing star and zero on your telephone. In case you experience issues with your carrier, please use a different dial-in. All contact numbers will also work from outside their respective countries. 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 need and global opportunities for tafasitamab in non-Hodgkin lymphomas. 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 two 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. During the Q&A session, we kindly ask that you limit yourself to one question and, if needed, one follow-up, as this will enable as many of you to ask questions as time allows. 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 Incyte's quarterly report on Form 10-Q for the quarter ended June 30th, 2020, MorphoSys 20-F, an annual report, all for the year ended December 31st, 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 effects 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 the position of Professor of Hematology and Medicine at the University of Lyon in France and Head of the Department of Hematology at the Hôpital Lyon Sud, also in France. Professor Salles 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, he 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 from my personal point of view and not those of my employer. I have 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 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 lymphoma of the B-cell phenotype each year, and the majority of them, 35%-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 lymphoma overall, including B and T-cell lymphomas. That spontaneously, patients present with lymphadenopathy, usually rapidly developing, sometimes extranodal 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 has grouped under this term the coexistence or evolution of indolent lymphomas, which can transform to diffuse large B-cell lymphoma.
Finally, there is also a predominance of males, which presents this disease as compared to females. On the next slide, you can see that the median age of incidence 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 the 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 decades, 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 upwards. So there have been some discussions that all the subtypes of lymphoma may have had diminished incidence. We are still facing a frequent disease, again, the most frequent of B-cell lymphoma, with a stable incidence, especially in the elderly. The diagnosis of diffuse large B-cell lymphoma is made on a biopsy specimen which shows these features of large cells dispersed in the lymphoid tissues and with diffuse infiltration. 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 antigens described here being viable.
This actually leads us to the classification refinement on the molecular field of diffuse 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 expression profiling figures that have been developed by the group of the National Cancer Institute and published almost 20 years ago, showing that there were different subtypes of diffuse large B-cell lymphoma which evolved from different states of differentiation of B-cells. 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 this classification based on all the findings that have been developed over these 20 years.
What I would like to point to is that the molecular classification of DLBCL is an evolving field, that the tools to assess these 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 therapeutics that may apply to certain of these subtypes will still have to prove their benefit, as we'll 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, but showed us that in the 1980s, 1990s, there were 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, which remains really the backbone on which everything has been built so far.
Although this curve may be reassuring, we do know that when we prolong this curve by 10 years, only about 35% of the patients are free of disease recurrence. This is before the time of monoclonal antibodies. The first monoclonal antibody that was developed and used in diffuse large B-cell lymphoma is rituximab, an anti-CD20 antibody that you all know, which has been combined to CHOP in a clinical trial that we led in France with Bertrand Coiffier in patients aged 60-80, 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 realized data gathered in different countries, including, as shown on the next slide, in Canada, where the examination of patients' outcome before and 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 two 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 monoclonal antibody 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. advised for 64% overall survival at five 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 has 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 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 one 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 status 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 patients that will respond to therapy will relapse, and we still face 10%-15% of patients that are primarily refractory. This leads to this group on the first rectangle of relapsed/refractory DLBCL. About half of them are deemed to be ineligible 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 are 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%-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 relapsed after transplant, which comprised roughly 30% of all diffuse large B-cell lymphoma diagnosed every year.
If we move on to the next slide, we see what are the current standard of treatment for this patient. But first, let me show you the outcome of patients after autologous stem cell transplant. This is a slide done from a large international study in the U.S. and Europe, showing that there was about more than half of the patients relapsing after autologous transplant. Even if it's a good intervention that has proved to be efficient, it's not enough. On the next slide, you will see the different regimens that have been adopted for this patient. Transplant-eligible patients receive intensive chemotherapy based on cytarabine, platinum derivative, gemcitabine, ifosfamide etoposide, different regimens used in different places. 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 two regimens. Either a combination of gemcitabine or oxaliplatin plus or minus rituximab, or bendamustine plus or minus rituximab. Many other regimens could be used, but not being the mainstream use in general. Several compounds have been recently approved in the third-line setting, such as polatuzumab vedotin in combination with bendamustine-rituximab, the different cell therapies, CAR-Ts, and very recently selinexor. But let's review first the results in the second line of the current regimens. On the next slide, we will see the results of the rituximab-GMOX regimen in relapsed/refractory DLBCL, as published many years ago by our group in France. These results were reproduced every year in the world.
What I will say is that there is an encouraging response rate that 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 about 32%. Their median progression-free survival is four months, and their median overall survival is eight 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 the third line of therapy in the U.S. You can see from these bar graphs that the overall response rate was only 18% for bendamustine-rituximab, with a few patients achieving complete remission, 18% overall.
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 GMOX that I mentioned previously. What is important is to know whether these responses are durable, and we know from the publication that seven patients out of 40 had ongoing responses after one year and a half. And this is shown better on this curve, which demonstrates that this bendamustine, the response duration was very short in the range to seven to eight months, and with the combination, as you can see, it was close to 12 months for those patients that responded to the bendamustine-rituximab. Again, these are duration of response curves.
I should also mention that this was a phase 2 randomized trial and that some patients that were responding to treatment, actually, these are the tick marks on the top of the curve, underwent consolidation with transplant. If we move to the progression-free survival of these patients in this trial, you can see on the next curve that the bendamustine-rituximab available regimen in the second line had very poor results, and that the polatuzumab vedotin improved these results, but still we have a curve which is rapidly declining and with about 25%-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 the second line with GMOX, BR, and in the third line with polatuzumab BR.
Let me say a word regarding the recent results achieved with CAR-T cell after the clinical trials in real life, and our colleague Loretta Nastupil just published recently in the Journal of Clinical Oncology the experience of more than 300 patients treated with axicabtagene ciloleucel on the commercial product. As you can see, the progression-free survival curve and overall survival curve are very encouraging overall, but what these curves 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 a low performance status, there were very few receiving CAR-T, and that's a common, I will say, selection bias of CAR-T studies.
But with patients with high LDH, which is a common feature of aggressive lymphoma, as you can see, about half of them had elevated LDH and had clearly a poor outcome than the other ones in terms of progression-free survival and overall survival. So again, this was a major advance with CAR-T cell, but it has these limitations. And I have tried to summarize here on the next slide the CAR-T cell advances. For us as hematologists and hemato-oncologists, 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 result of the studies with the two different marketed products and recently with the third one that will be on the market soon, of a 50%-80% response rate, very high CR rate, 40%-55%, and durable response, about 70%-80% of patients in complete response after CAR-T being durable at two years. What were the other issues? The first one is the logistic complexity. You probably know and understand that to manufacture the CAR-T, you have to make an apheresis, 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 insertions, quality control, and sent back to the manufacturing place.
Overall, this process takes about three weeks, sometimes four weeks. You 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 3, 4 adverse events with CAR-T, cytokine release syndrome, and neurological events, sometimes really difficult to manage, and finally, there are very high costs and difficulty in availability. The use of CAR-T cell is restricted to some centers which are qualified after long work by all the providers, physicians, and healthcare providers involved, and patients sometimes have to travel several hundred miles to get this treatment, so that was the data of the available therapy today.
We are happy to have today another potential standard of care, which is tafasitamab lenalidomide as shown here. This is approved on the second line of therapy. 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. You will see on this slide that the CD19 antigen expresses all of the B-cell differentiations from early B-cells to mature B-cells. It's actually wider than CD20 expression. They are co-expressed but completely independent. On the next slide, you will see that tafasitamab is a glyco-engineered 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.
Not only does the antibody have a direct cytotoxic effect, but it mobilizes natural killer cells and macrophages to engage the function of cytotoxicities. Based on these results, a single-agent tafasitamab trial had been run several years ago. You can see on this slide the result of this trial as a single agent. This agent was allowing about one quarter of the patients with diffuse large B-cell lymphoma to respond, and a substantial number of patients with other entities. Some of these responses were very durable as a single agent. I think that four patients were alive for more than two years with the single-agent tafasitamab.
Based on these results and based on 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 with another agent, lenalidomide, being commercialized in multiple myeloma, follicular lymphoma, to increase cytotoxicity, to increase and activate these natural killer cells, and to improve ADCC. So it was shown already in this context that tafasitamab in experimental models was increasing the activity of tafasitamab, which is schematized on this slide. And this was the study recruiting relapsed or refractory that were not eligible for autologous stem cell transplant, who received tafasitamab and lenalidomide initially at weekly intervals, then the lenalidomide given at the standard dose. Patients responding to this therapy after one year of treatment were consolidated with tafasitamab and lenalidomide until progression. Actually, all patients with clinical benefits responding or with stable disease.
The population that was recruited in this trial is depicted here. I can see 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 with patients according to different risk factors according to the disease. Most patients had advanced Ann Arbor stage disease. A little bit less than half had elevated LDH. Many patients had received only one line of therapy or two or more lines of therapy. 44% of the patients were refractory to the last prior therapy, and a few had been refractory to the 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 as 60%, with 42.5% of the patients achieving a complete response. The vast majority of these responses were confirmed with the current standard of best confirmed assessment. What was important was whether all patients could benefit from this study, and the progress plot, which is depicted on this slide, shows that virtually all categories of patients actually had similar overall response rates, 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. Of these categories of patients, they had very similar response rates, ranging from around 60%, as you can see, but responding is important. What is more important is the duration of response.
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 The Oncologist, at 21.7 months. Moreover, if we break down the duration of response for patients that had only a partial response, they had the median duration of response of 4.1 months. But for those who had reached a complete response, you can see that the duration of response was substantially prolonged, and it actually remains the same as the duration of response we usually see with CAR-T cells. We also looked at the criteria of duration of response at one year according to the different patients' characteristics. Let's, for discussion, start from the bottom of this graph.
As you can see, at one year, according to the initial response, very few patients 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 one year of this combination. There was a substantial benefit for these patients that were non-primarily refractory, but 44% of the primarily refractory, very difficult to treat population, were still in response at one year. Equally, patients that were refractory to the last line of therapy or not were responding at one year. There was a little difference, not significant, according to the cell of origin molecular classification of these patients. Patients with adverse prognostic features linked to the disease had a little bit lower 12-month response rate, but this is still 50% of them.
As you can see, we see that at one year, many, many patients did benefit from this combination. We looked more specifically at the outcome of the second line population, which comprised 40 patients. 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 two years, and 87% of them being alive at one year. This could be really a major game changer in the way we manage patients in second line as compared to the result I discussed earlier with standard chemotherapy. We recently updated the result of this study with another data point cutoff in fall 2019. 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 curve are the patients that had the CR. And you can see that after a median time of observation that was close to two years, we still have the vast majority of patients being still responsive, and a few patients even with PR 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 the previous slide, just as a reminder, the median duration of response was 34.6 months. Here we have the median progression-free survival of 16 months. And on the next slide, we have the median overall survival of this population, which is of 31.6 months. So not almost three years, but not that far from that. So these are very encouraging results that confirmed the early achievements of the first data cutoff.
Obviously, when we have a new drug, we care about the side effects and the tolerability of this treatment. This was examined in detail in the study. On the left, you have the side effects that are observed during the one-year combination of tafasitamab and lenalidomide up to 12 cycles. On the right, you have the side effects observed during tafasitamab monotherapy consolidation after one year. As you can see, these are the dark violet or orange bars. There were a few grade 3/4 events, essentially 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. The number of patients with grade 3 or 4 febrile neutropenia, so when you have neutropenia, lower blood counts, what is important is this patient developed infection and had fever.
So the number of febrile neutropenia grade 3, 4 were only 10%. The other side effects were essentially of grade 1 and 2, and eventually grade 3 for rash. And those 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 is the following.
We have a combination of tafasitamab-lenalidomide with a high overall response rate, high CR rate, durable response, a high activity that is consistently observed in different patient subgroups 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 2 study. So these are the results 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 novel 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 we can discuss that later. Immune checkpoint blockers have proven very disappointing in the field. Immune as a single agent has limited efficacy but can be combined with antibody. And a few targeted therapies 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 result achieved with the combination of tafasitamab, lenalidomide on this consolidated phase 2 result, overall response rate again 60%, complete response rate 42%. 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, either being ofatumumab, which is difficult to handle in diffuse large B-cell, but mostly ofatumumab or glofitamab, which have now started to have mature results. And as you can see, the other selected therapies have much lower overall response rate or complete response rate. So we really have here a combination which seems to be very favorable for this patient. 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 three to five. This is an index that assesses based on disease characteristics and patient characteristics, the probability of outcome of this patient. Recently, when we examined the trials that have combined different agents with CHOP or RCHOP, we can see on the next curve that the ROBUST trial, which was a study where we combined rituximab, CHOP, and lenalidomide, a trial that has been presented overall, and we expect the publication soon, this was a combination of lenalidomide plus RCHOP, 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 results of the trial were not meeting the primary endpoint, there was a trend for better efficacy of this combination in patients with advanced disease stage or with an advanced IPI score, suggesting that there may be subgroups that can benefit of this combination. So based on these data, there is a rationale to combine tafasitamab, lenalidomide, and R-CHOP in first line of DLBCL. And this is summarized on this slide. There is a synergistic mechanism of action of tafasitamab plus lenalidomide. There are strong data obtained with the L-MIND regimen. We do know that the expression pattern of CD20 can change after exposure to R-CHOP, but CD19 expression is more homogeneous compared to CD20, and it's preserved in the small number of cases where CD20 disappears or starts to be faint.
So targeting two antigens with two different antibodies is also a very appealing approach. And finally, we have these high-risk IPI patients that need to be treated. So this leads to my last slide, which is a description of the First-MIND study, which is the study that will assess in randomized patients the combination of tafasitamab plus R-CHOP or tafasitamab plus R-CHOP. This is the early phase of the study, the phase 1b, including patients not previously treated, a little bit broader population, to assess the safety of this combination, tafasitamab R-CHOP or tafasitamab and R-CHOP.
Obviously, this trial, which will be discussed by colleagues from MorphoSys and Incyte in the next session, has been accruing fast and will allow us to decide whether we can move forward by integrating tafasitamab plus R-CHOP plus/minus lenalidomide 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, Jte. Great insight in the field of DLBCL, non-Hodgkin's lymphoma, summarizing everything that's going on. I hand it over to the operator now to maneuver the questions.
Ladies and gentlemen, we will now begin the question and answer session. If you'd like to press 0 or 1 on any of these now, you will be advised when you ask a question. If you change your mind and wish to restore your question, please press 0 and 2. Participants are requested to use only handsets while asking a question, and the first question received is from Geoffrey Porges of SVB Leerink. Your line is now open. Please go ahead.
Thank you very much. And Dr. Salles, thank you for the very informative presentation. 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 seemed 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?
That's too difficult a question, but that's not a 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 2 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 would 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 spare biopsy or investigators from Würzburg had spare biopsy to examine CD19 expression, there could be no steric hindrance of CAR-T to bind CD19. But this is already the case of two patients being treated successfully with CAR-T. So yes, I think CAR-T can be, as far as we've utilized in 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 part, 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 2% of patients 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 versus diffuse large B-cell. The early results 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.
Thank you very much.
The next question received is from Mark Frahm of Cowen. Your line is now open, so please go ahead.
Hey, thanks for taking my questions in the great talk earlier. 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 place 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, one-year event-free survival? Is it PET-CR? What's the endpoint that we should all be looking at?
I will probably defer the question to the MorphoSys Incyte colleagues, but my point of view is that we have to look at the safety of this combination and obviously the end-of-treatment CR assessed by PET as well as some other exploratory endpoints. But maybe colleagues can answer that.
Yeah, Jte, 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.
Okay. Then we take the next question. It's from James Gordon of JPMorgan. Your line is now open. Please go ahead.
Hello. Thanks for taking the question. James Gordon from the European Pharma and Biotech Team at JPMorgan. The question was about combination therapy. So you mentioned some combination approaches that could be pursued with Monjuvi. And there's also a slide talking about some of the new monotherapy approaches, and one of those is CD3, CD20s. So my question was the enthusiasm for a combination of Monjuvi with the CD3, CD20 therapy. And if there is high enthusiasm there, would you want to see CD3, CD20s approved as monotherapies before you consider involving a patient into a combo trial with them? And maybe for the second half of the call, sort of the same question to the companies as well, really. So latest thinking on doing a combo of Monjuvi, CD3, CD20, and when something like that could get going. Thanks.
I think your question is very interesting. We have here a backbone of an immune intervention combining an antibody against CD19 plus len, which is a drug that activates cytotoxicity, cellular-based cytotoxicity. So it's a backbone of immunotherapies that can be obviously combined with other agents. It can be combined with single agents against CD20s such as rituximab, but obviously using another mechanism of action which activates T cells such as bispecific will be interesting. I think we have to see a little bit in both beds the safety profile. We do know that bispecific has 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 have the drug approved to start investigating this combination.
Again, I think Tafa-Len is a very nice platform that we can use to try to combine with new antibodies and other new immune-based mechanism of action molecules.
Thank you.
The next one is from Evan Seigerman of Credit Suisse. Your line is now open. Please go ahead.
Hi, all. Thank you so much for taking the question. Thank you very much for the very informative talk this morning. So some recent feedback we've gotten from physicians suggests really favorable views of 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 that use it loosely. So with potential data of Axi-cel and second line DLBCL near term, how do you 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 that get that cure, or do you see Monjuvi being used more in these patients?
That's an interesting question. Yes, let's suppose that at some point axi-cel and other CAR-T could be approved in second line therapy, we will have different options for this patient. 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 tafasitamab + lenalidomide 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 three months at least. The duration of CR is very good. I think this is kind of competing approaches. When we talked about cure, I think that we have obviously now almost three years median follow-up for the study, a little bit less. But as I have seen, the duration of response for patients in CR are really very favorable curves.
I personally believe, from my experience with diffuse large B-cell lymphoma, that when a patient has been in complete remission for one 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 in the relapsed/refractory setting, when relapse occurs, they occur quite rapidly. I do believe we don't have the proof, and we'll have to wait for longer follow-up, that a proportion of patients which are the complete responders and stable complete responders that one year of patients treated with Tafalene 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 occurs in the second part of our lives, and I think this is our population, which is probably more frail to engage with CAR-T, but I think we can also use Tafalene in a 30-year-old patient before we go to CAR-T if there is a failure of Tafalene 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 two arms.
Excellent. Thank you very much for that. I appreciate it.
Yeah, that definitely helps. So thank you very much.
The next question received is from Craig Suvannavejh of Goldman Sachs. Your line is now open. So please go ahead.
Great. Thank you very much. Thanks for taking my question. 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 front line 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 the best in a second line setting for the eligible patient population that you could see your use of Monjuvi in combination with lenalidomide? Thank you.
So the first question is whether it's a drug that I think each time we have get a drug that works in the second line setting and proved beneficial in the second line setting, and the efficacy safety ratio that was significantly good, we try to move this drug 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 a prospect 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 candidates for the combination of Len, Tafalene, Monjuvi, I think I don't see specifically patients that won't be candidates. I think there were few patients that we have to acknowledge in the trials that were 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, for the vast majority of them, suitable to try this therapy as a second line therapy with the prospect of achieving a response in more half of the patients, which will be durable in the vast majority of them.
Okay. Thank you. And the next one is from Reni Benjamin of JMP Securities. Your line is now open. Please go ahead.
Hi, good morning, guys. Thanks for taking the questions. Dr. Sal, 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 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 tafasitamab 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 there are, however, and this should be mentioned, a small proportion of patients, actually variable 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 these patients which are not suitable for chemotherapy in the first line.
That's a question of patients for first line and patients not suitable for chemotherapy. Again, it's probably a few thousand in the United States and elsewhere. Discussing the second line for the transplant-eligible population, I think it's always complex to move a 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. There is a margin for improvement. CAR-T cell has taken the challenge, and we do know there are three randomized studies with CAR-T cell being performed in this field.
I think it goes back to the question we had before. What would we choose? Is it CAR-T or is it 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 trials show, whether it's a very marked benefit, whether it's a significant but lower benefit. And I think, again, it's two different treatments in terms of complexity, in terms of side effects. Maybe there is a way we can sequence them in the future. So I think right now, autologous stem cell transplant is not dead so far. 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 from where it is now in the next five years.
Great. Thanks for the clarification and taking the questions.
Super. Thank you very much, Evel, 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 Roland.
Thank you, Malte, and good morning, everyone. I am pleased to have this opportunity to speak with you today. Turning to slide 54, as we've heard from Dr. Sal, Monjuvi in combination with lenalidomide was granted accelerated FDA approval with both fast track and breakthrough designations on the 31st of July, one month ahead of its PDUFA date as the first second line treatment for patients with relapsed refractory DLBCL. Following on Dr. Sal's comments, we believe Monjuvi has the 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 adult patients with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified, including DLBCL arising from low-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.
Sal 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 a 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 via 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 were well prepared and laser-focused to launch. In fact, we were ready to bring Monjuvi to patients within one 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 three. Looking at supply, Monjuvi was ready to ship on day three and now has specialty distributors for stock and ready to process customer orders by day four.
My MISSION Support, our patient support program, was launched on day one to begin helping patients with their access and treatment support needs, and since have responded to more than 100 customer inquiries for patient support. Looking at customers, we received the first order on day five. We saw the first account formulary on day eight, and most importantly, the first patient infused with Monjuvi on day ten. 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 one and saw the first payer confirmation for coverage to label and inclusion in guidelines by week two. 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 had 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're extremely pleased to see the traction we built across our channels to create strong awareness and interest from physicians. In terms of individual outreach, our team sent more than 30,000 emails since launch with an open rate that is three times higher than the industry benchmark. Our sales team has made more than 4,400 calls, and our medical teams across the two 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 tier A healthcare organizations. We are excited about the strong engagement we saw across digital platforms where digital advertising media was used to create contextually rich environments. New Monjuvi patient and physician-focused websites have already received more than 70,000 visits. Email campaigns have reached more than 75% of the target list, with tier A 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 for Monjuvi to quickly earn clear leadership and share of voice with greater than 50% SOV and well ahead of other treatment options in this space. This is a testament to the team's ability to get to 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 institutions in the NCCN network have already purchased Monjuvi. This speaks to the accessibility of Monjuvi in both the academic and community settings. Note that many top accounts have been using exception processes in the first weeks on market to expedite bringing Monjuvi to patients. But we already have seen over these last weeks more than 50% of formulary approvals in top 30 accounts, and we are on track to gain positive formulary decisions in the remaining key accounts.
More than 40% of EMR order sets were added in top 30 accounts supporting pull-through to enable a broader uptake across the different networks, and 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 overall response rate and the duration of response. They value the tolerability and safety profile that Monjuvi provides to patients, and they appreciate the 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 in 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, would provide more details about market access and treatment guidelines and our outlook on our medium and long-term potential for Monjuvi in relapsed or refractory DLBCL in the US. Barry, please.
Been 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 drives 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. 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. 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% for Monjuvi.
Second line stem cell transplant leads to cures in around 15%-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 the potential number of ongoing patients who are on therapy for more than one year. Year on year, we expect the 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-$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 you 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 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 three steps. As you have heard from Roland, Monjuvi is the only FDA-approved second line treatment for patients with relapsed or refractory DLBCL who are 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 Revlimid combination as standard of care in relapsed and refractory DLBCL. The clinical data that you have heard from Roland and from you, complemented by its 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 a 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 a potential backbone treatment for patients with DLBCL. Moving from left to right on this slide, with respect to the treatment of DLBCL in front line, we have completed enrollment of our phase 1b 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 3 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 and Revlimid combination in second line DLBCL to achieve our goal of bringing tafasitamab to relapsed or refractory DLBCL patients.
And lastly, we are in discussion with several companies about possible combination strategies of tafasitamab with novel anti-lymphoma treatments to establish 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 three to five, the chances of cure with R-CHOP 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 four 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 three cycles of treatment. This single patient's response in the scans encouraged 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 three years and some even for longer.
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 six years and counting. Moving to slide 70, this slide outlines the design of our pivotal phase three 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 front line 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 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 two highly synergistic drugs and not only one to R-CHOP, and the two 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 three to five, and we know from earlier trials that in these patients, lenalidomide is active. Lastly, we aim 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 3 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 timelines. As previously mentioned, the pivotal front line study is planned to start early next year with a primary completion date in 2024 and the following steps thereafter, as outlined on this slide. At the same time, B-MIND, our randomized phase 3 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 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 partner 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 continue 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 four eligible for autologous stem cell transplantation, and of whom around 15%-20% occurred, 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 plan in a pivotal program is follicular lymphoma, and we have provided some global epidemiology estimates on the slide. Our pivotal trial will be in the relapsed or 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. In the third and later lines, we're starting to see the appearance of PI3K 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 that 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 two arms. We expect to initiate the study in the early part of next year, and we expect the trial to take two to three years to complete. Turning to slide 77.
Incyte has long been an advocate about the potential utility of PI3K 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 the 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 a 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 outline earlier there is a substantial unmet need for patients suffering from R/R DLBCL. These patients can unfortunately have a very poor prognosis. The approval and launch of Monjuvi in R/R DLBCL in the US 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 US peak sales potential of Monjuvi in R/R DLBCL in the range of $500 million-$750 million. We also want to bring tafasitamab to patients around the world suffering from R/R DLBCL.
Obviously, our next important milestone is the anticipated EU decision on approval, which occurs in 2021. Both Incyte and MorphoSys are convinced that tafasitamab offers additional options and opportunities. We aim to improve cure 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 and encourage, given the favorable efficacy profile, the excellent combinability and ease of use. While Incyte and MorphoSys will continue to build depth in DLBCL, we will also explore other initiatives 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.
Ladies and gentlemen, we will now begin the question and answer session. If you would like to ask a question, please press zero and one on your telephone keypad now. You will be advised when you ask a question. If you change your mind and wish to withdraw your question, please press zero and two. Participants are requested to use only handsets while asking your question. And the first question received is from Tazeen Ahmad of Bank of America. Your line is now open, madam. Please go ahead.
Good morning. Thanks so much for taking my questions and thanks for hosting this. I wanted to get your thoughts on how long, and thank you for providing what you think the peak sales estimates are going to be. How long do you think it will take for doctors to adopt Monjuvi? We've been conducting our own checks, and it does seem like the excitement 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 slope on 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 lymphomas and CLL, but what areas do you think are particularly under direct need at the time, and when do you think we would hear about additional indications? Thank you.
Hi, Tazeen. 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 hematologists, oncologists throughout the United States for Monjuvi is high. We know that in some centers in particular, 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 and Steven, in terms of future uses, we try to address much of it in our prepared remarks, but as Gil said upfront, wherever CD19 is expressed in a B-cell malignancy, that's obviously of interest to us.
So 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's stepwise. Diffuse large B-cell lymphoma, as you've seen, relapsed or refractory currently, moving to first line, then 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 seeing early line therapy, or is refractory something that would also be appealing?
I think, Steven, again, I think it'll 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'll want to get to early lines of therapy. Thanks.
Thank you.
The next question received is from Jason Butler of JMP Securities. Your line is now open. Please go ahead.
Hi. Thanks for taking the question. First one, just on first-line, is there any consideration here or potential for an interim analysis or early stopping for overwhelming efficacy to be considered by the DMC? 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 the duration of treatment in your assumptions there? Thanks.
It's Malte. Maybe I take the two questions, and Steven can chime in if he has additional comments. On frontline, that's our phase one, phase two study. That study is fully enrolled. The question regarding interim analysis or IDMC look doesn't apply here. For the frontline study, we are still in the final stages of discussing with FDA the statistical design. We're almost finished, but I would prefer at this point not to share any details on the statistical analysis plan. But of course, we will follow study designs which have been used in the past by other companies and by other products so that the study will be very well usable by FDA and EMA for potential approval in frontline DLBCL.
With respect to duration of treatment for patients following R-CHOP or later lines, it's clear that the more advanced you are, particularly between one prior line as opposed to two or more prior lines, the duration of response shortens. That's pretty much normal with all the treatments that you apply. And I would say there's a good confidence based on the results we have seen and based on what Gil has presented, that the Monjuvi lenalidomide combination can really move the needle in second line, but also in third line and higher patients. But maybe, Gil, do you have any additional remarks on this particular topic? You are the expert in the field here on the call.
Sorry, I may not have caught the full question initially.
The question was, is there any significant difference in duration of response in patients second line after R-CHOP as opposed to those in later lines who have been treated with autologous stem cell transplantation?
I think from the L-MIND study, we haven't seen that. I think there was, at one year, equal numbers of patients have durable response depending whether they were in second line or later and depending on their first treatment line. So I think we have similar benefit, I would say.
Okay. Thank you.
The next question received is from Alethia Young of Cantor Fitzgerald. Alethia, please go ahead.
Hey, guys. Thanks for taking my questions, and really appreciate all the information you guys gave out today. Maybe a couple. One, when you're talking about the first front line trial, front line, are you guys stratifying or thinking about any type of subtype like ABC or GCB? And then the second question is, in the Tafa combination with the PI3 kinase, in the initial data, the response is very high, but I guess I was wondering how we might think about maybe either preclinically or what you've seen with what could happen with durability after exposure to BTK. Thanks.
Malte, Steven, if you'll do the front line stratification question, then I'll deal with the second question first. Okay. Alethia, thank you.
PI3K, PI3K- delta combination, as we said, we're extremely interested. Alethia, you know our delta monotherapy data well across B-cell malignancies, but for this audience, we've seen in follicular, mantle, and marginal zone lymphoma very high response rates that are durable with long PFS that we hope to use to submit as a monotherapy indication in the United States next year for those indications. And now, obviously, given the tafasitamab data in COSMOS with idelalisib, albeit a small patient number, but 10 of 11 responders post-BTK, this becomes an extremely interesting combination for us. We do have post-BTK data with monotherapy povorcitinib use and we did see good response rates, a little bit shorter duration. You're right, Alethia, but as the data matures in COSMOS and in combination with tafasitamab, we'll get more precision on that.
We're very, very encouraged by the ability and activity of this combination thus far, and thus we want to pursue this program aggressively. I'll turn it to Malte if he wants to address your stratification question.
Yeah. Thanks, Steven. So for our front line trial, we have not planned to stratify by cell of origin. Particularly encouraged by the data that Gil presented, that was the subgroup analysis where we have not seen a significant difference in patients diagnosed with ABC versus GCB patients. We think that the combination of tafasitamab and lenalidomide is actually helping to alleviate the potential differential activity that has been observed with lenalidomide alone in these two patient populations. The second thought is that more recent data based on prospective trials have not confirmed the big differences that were seen in these earlier retrospective studies.
In the front line setting, we will not stratify for the cell of origin.
The next question received is from Etzer Darout of Guggenheim Securities. Your line is now open. Please go ahead.
Hey, good morning. This is Paul Andreadis. Thanks for the updates and for taking our question. Just a quick one from us. I'm hoping to get some additional comments on script trends for Monjuvi now that we're a couple of weeks into the launch, specifically on how well IQVIA is capturing your volume data, and is that something we can use to gauge uptake? And also any additional color you might be able to provide on launch dynamics. Thanks.
This is Roland. We'll be sharing details on the script trends when we have our earnings call for Q3, but we want to caution you that at this moment for IQVIA, we will not be seeing the actual trends that we see in the marketplace. What we shared today is that we have received orders from more than 100 accounts. We are very pleased and encouraged with the uptake that we see and the momentum that is building as this demand that we see from the accounts is actually driven by patients that have been identified and are receiving continued treatment.
Yeah. Thanks very much.
The next question received is from Vikram Purohit of Morgan Stanley. Your line is now open. Please go ahead.
Hi. Thanks for taking my question. Just one for me. On the sales guidance you provided of $500 million-$750 million, excuse me, for R/R DLBCL, is that only based off the current labeled indication from the L-MIND data, or does that also bake in some form of success from the B-MIND study as well?
It's really just based on L-MIND and the relapsed and refractory patient population, second line plus. That's where the guidance comes from.
Okay. So does that mean that the guidance takes in likely success from that B-MIND setting as well?
B-MIND is relapsed and refractory patient population, obviously a different combination, but nevertheless, we're really just basing it on the success of Monjuvi in the second line plus setting.
Okay. Understood. Thank you.
The next question received is from Suzanne van Voorthuizen of Kempen & Co. Your line is now open, madam. Please go ahead.
Hi, team. This is Suzanne from Kempen. Thanks for taking my question. Just one. You mentioned more convenient formulations such as a subQ as an opportunity for lifecycle management. Can you maybe elaborate on your thoughts there and if you have maybe some preliminary plans to work on a subQ?
Yeah. Thanks. We are at the current stage evaluating multiple opportunities of improving the schedule and the formulation for Monjuvi, particularly for patients who benefit from the treatment for longer terms. That includes evaluation of subcutaneous formulation, but also different schedules and other activities. So it's a bit early for us to really make a sort of conclusive comment of what we will come up with for the future, but we are looking at all standard activities that you normally do in this stage of development.
Got it. And maybe just a follow-up. For the development of a subQ formulation, would you need a different technology to be able to do that, or could you also do that with the antibody assays?
Yeah, so that's an area we are looking into right now. As you know, there are different approaches to tackle subcutaneous formulation. Some involve additional technology, some others don't, and we are in the middle of the evaluation process here, so I can't really give a good guidance at this moment.
Okay. All right. No, perfect. Thanks. Okay.
The next question received is from Jay Olson of Oppenheimer. Your line is now open. Please go ahead.
Hello. Thank you for the presentation, and thank you for taking my questions. I was wondering if, based on the convenient administration and low toxicity advantages for Monjuvi, is it possible that this COVID-19 environment actually favors Monjuvi versus other less convenient and potentially more toxic therapies, and therefore the pandemic could actually accelerate the uptake of Monjuvi? And then, as a related question, could you talk about what novel chemo-free combinations you could use with Monjuvi in the first-line DLBCL setting and describe some of the proposals for investigator-initiated trials that you are receiving and the appetite among doctors and patients to eliminate CHOP from the first-line treatment setting?
Jay, this is Barry. I'll try to tackle your first question and then hand it over to Steven afterwards. But the COVID-19 situation, the pandemic throughout the world is very difficult for everybody. It's certainly difficult for patients with cancer. Maybe what you're alluding to is, would there be less CAR T therapies or less stem cell transplants? It's really hard to say. And sure, Monjuvi is easier to give in the outpatient setting, so there may be some benefit right now, but we really can't see what the—we really can't tell exactly. It's very early days, and if there is a hesitancy to be hospitalized for particular therapies, it's very difficult to say.
Jay, hi. It's Steven. And Malte, I want to add something to what I say. I think Gil said it well. What you do is, so you have an entity where there's a cure rate, and quite a substantial cure rate of 60%. So you've got to be cautious and careful on how you progress there. You can't do any harm to patients in saying the obvious. You can go back to diseases like breast cancer where there have been aspirations for chemotherapy-free type therapies in the adjuvant curative settings that are more biologic-directed. It's the one way of thinking about it. And I think Gil said it well. I think you do things that are potentially biology-directed: CD19, CD20, T-cell redirectors, the bispecifics in combination. Anything that'll do that by the same token, protecting the R-CHOP cure rate and improving on it.
As you heard, it's been a tough two decades to get there, and you'll have to be cautious in terms of doing that. But there's a lot of interest. I mean, you said it well. It's a convenient therapy. There's low toxicity with an impressive efficacy combined. So it lends itself then to thinking about further biologic add-ons to try and improve that. In terms of actual details, I'll disappoint you because until they go up on clinicaltrials.gov, we won't be elucidating them for you, as is our practice. I don't know if, Malte, you want to add anything.
No. I think you summarized it very well. Thanks. Nothing to add from my end.
And the next question, sorry. The next question received is from Craig Suvannavejh of Goldman Sachs. Your line is now open. Please go ahead.
Thank you again for taking the questions. I've got two, if I could. One, just on your success with formularies. And I think there was a number of 57% formulary approvals in your top 30 accounts. Is this just meant to be a reflection of what you've gone through thus far, and it doesn't imply any negative formulary decisions? I just want to get clarity on that and kind of how you're thinking about progress with conversations with payers. And then my second question is just going back to the guidance that had been provided on peak sales in the refractory second line setting. And it's really more about if, directionally, you could give us a sense of how you're thinking about what that opportunity might look like in the first line setting.
As a clarification on the second-line guidance, does that include other combinations that you might be exploring in 2L-plus settings? Thanks.
Hi, Craig. This is Roland. Regarding your first question on formularies, the 57% is really just a reflection of speed that we've seen in those first weeks on the marketplace. So among these top 30 accounts, 57% of formularies have already been cleared, and the rest is well on track to be cleared over the coming weeks. So we do not have sight of any negative formulary decision at this moment in time, and we are confident from what we're hearing in the marketplace that across the large accounts that Monjuvi and lenalidomide will be placed on formulary in accordance with the label that we've received.
Regarding peak sales, your second or your last question on the second-line guidance, as Barry just spoke about, indeed, this is talking about the potential we see for Monjuvi, primarily with lenalidomide at this moment in time, and does not yet include any additional major upside that will be coming from other combinations and looking at first-line, you have heard from Steven and Malte and Dr. Sal a view of the patient population size, and you have also seen the number of patients that have these higher risk scores, IPI 3 to 5. And that gives you a sense of the unmet need and the patient opportunity, at least in these front-line settings, but I leave it here, perhaps for Barry and then Malte and Steven to see whether there's anything to add.
So, Roland, I don't really have anything to add. I think that's fine.
The next question received is from Salveen Richter of Goldman Sachs. Your line is now open. Please go ahead.
Thanks, everyone, for taking the question. This is Andrew on for Salveen. Maybe just as a follow-up to a prior comment that you made, for the centers that haven't seen as rapid of an update to date, what are the gating factors that you've been seeing there, and has there been any variation between the academic and community setting?
Hi, Salveen. Barry, I'll try to answer that question. We actually just think that certain centers have had rapid uptake, and they have had initial orders and repeat orders, and it's really just the ones that have the most experience, I think, with lymphoma patients in general. We have about 50% academic and 50% community at this point. Just the most recent data I saw that the community accounts seem to be really catching up and maybe even will drive the most of the future use. I don't think there's any gating whatsoever for the centers that haven't had as much use yet. It's very early days. But as Roland indicated, every single week we have more new centers, centers that haven't ordered before, and more centers coming back for second, third orders. So we're very encouraged across the nation.
Virtually every state has ordered, and like I said, the accounts go up every single week. So I think we're okay.
Ladies and gentlemen, we just have time for one last question, and it's from Geoffrey Porges of SVB Leerink. Your line is now open again. Please go ahead.
Thank you very much for letting me jump in with one last question. First, I just wonder if you could remind us of the current expectations for your patent exclusivity, assuming some patent term extension in the U.S., and then related somewhat. This is an incremental revenue opportunity for Revlimid. Have you had any discussions with Bristol about whether they might collaborate with you in some way? This is the first labeled indication for Revlimid in DLBCL. Thanks.
Geoffrey, this is Roland. On the first part of the question, the U.S. patent expiration is in 2029, but we estimate it is eligible for and will be granted about four years of patent term extension, thus extending the term to 2033, and that's the date that we actually look at, and in terms of your question regarding to lenalidomide, we do not have a specific collaboration at the company level here, but we are pleased with the access that patients are getting to lenalidomide in general, and we are also very pleased with the feedback that we get from accounts and healthcare professionals in that this combination is one that they can get their hands on.
Great. Thank you.
Ladies and gentlemen, I will now hand back the call over to Dr. Anja Pomrehn to wrap up. Thank you.
Ladies and gentlemen, this concludes. I won't have a Q&A at the conference call today, but the Investor Relations team of both Incyte and MorphoSys will still be available for additional questions. But for now, thank you very much for joining the call today. Have a good day, and bye-bye.
Ladies and gentlemen, the conference is now concluded, and you may disconnect your telephone. Thank you for joining, and have a pleasant day. Good.