IQVIA Holdings Inc. (IQV) Earnings Call Transcript & Summary

Hello, everyone. Welcome to today's live webinar from IQVIA, CAR-T cell therapy, exploring dynamic market insights and future challenges. Before we begin, a few important announcements. This webcast is designed to be interactive. We encourage you to ask questions during the event. [Operator Instructions] Slides will automatically advance throughout the event. If you have technical problems viewing or hearing this presentation, please click on the question mark help widget in the doc, at the bottom of your presentation window. I would now like to introduce today's speakers. Dr. Karin Berger, and Dr. Nicole Friedersdorf. Dr. Friedersdorf is currently the Director of Global Oncology Product and Strategy at IQVIA Dr. Friedersdorf's oncology expertise is honed by 11 years of oncology experience within pharmaceutical companies, where she held positions in marketing, consulting, market research, medical affairs and medical communications. She also has oncology research roles in her background, including 5 years as a researcher at renowned facilities, such as the German Cancer Research Center in Heidelberg, Germany. She also holds a diploma in biochemistry and immunology from the Technical University of Darmstadt and a PhD in Molecular Biology from the Technical University of Karlsruhe. Her work has been published in peer-reviewed journals and presented at different conferences. Dr. Karin Berger currently serves as a senior scientist in the oncology and hematology department at the University Hospital and Institute for Medical Informatics, processing, biometry, epidemiology at Ludwig-Maximilians-University. She also leads the outcomes research, health economics and access working group. Her current research focuses on clinical and patient-reported outcomes, treatment pattern analysis, patient flow analysis, health economic evaluations, real-world data applications and HTA assessments. Previously, she spent 7 years as a researcher in the Department of Transfusion Medicine Cell Therapeutics and -- at Ludwig-Maximilians University. In this position, she was involved in national and international outcomes research and health economic analyses on high-cost treatments such as hemophilia. Thank you for joining us today. Dr. Berger, please get us started.

Hello to everybody who dialed in for this webinar, and I'm really honored to have the opportunity to give you an introduction here on lot of the clinical perspective. So please do not be disappointed when you expected to hear more about the news result about CAR-T cell therapy. My focus here today is more how to get this new high innovative breakthrough innovation in the healthcare system that many patients or all patients in need that they could get access to these high innovative therapy. As you heard in the introduction, I am working at an academic teaching hospital in Germany, and one -- we are one hospital here in Germany that is -- or has been one of the first CAR-T cell providers in Europe. And the CAR-T cell program here is leaded and headed by Professor Subklewe. And she is a researcher in that -- well-known researcher in that area and as she has been a pioneer here in our hospital. We were also facing a lot of challenges, especially in the context of our healthcare structures, in the discussions with the payers and as well in the kind of information, the decision-makers around us as well as the providers in the hospital, they were really challenging to all of us here. So -- and this will be also one of my focuses today to give you a brief introduction, what kind of data is needed to convince people around us that this is really such a breakthrough innovation and might bring a huge benefit to patients in real need, but we still have a lot of challenges to collect enough data, to provide the evidence that is requested from the decision-makers around us to get people access in an early -- or in the appropriate disease stage. Here on the right-hand side on that slide, you see, since 5 years, there are a lot of progresses in the implementation, the clinical situation to apply CAR-T cell therapy. And the biggest field is still the hematological field, but as well CAR-T cells are now in clinical studies for solid tumors as well in our centers, we have first patients with solid tumors. We think they might benefit from CAR-T cell therapy. But the more challenging process here on the left-hand side, you see is that we have here a total new supply chain we have to take into consideration, and there is also a new situation that clinicians, health care providers and manufacturers are directly involved in the treatment process. That means we have here a very marketed process that takes also time. And at the same time, patients are unique and they would require fast access to this kind of promising therapy. So that means -- so the first step is that we have to collect the T cells at the host site and that is done with leukapheresis. And also leukapheresis is differently organized in the different settings and in different countries. So that means we are also confronted with CAR-T cell therapy with different health care situations, with the different setting situations. So that has also been taken into consideration in that kind of therapy. Then you see that here on the right-hand side on the top box here. Then we have the step that the CAR-T gene has to be inserted, then it has to be expanded at the manufacturer site in most of the cases. And finally, the CAR-T cell therapy comes back to the hospital or to the centers and the patients will get the infusion. And meanwhile, when the CAR-T cells will be produced, the patients will be pretreated for the CAR-T cell therapy. So this is a really complex process that has to be followed by a lot of quality assurance processes, certification processes and the manufacturer and the provider and the clinicians, they have to work hand in hand and a lot of papers have to be produced at that time. So here is the clinical perspective. And that slide, I don't want to go over here through all the detailed data, but when we look here on the complete remission rates in the 3 boxes, you'll see that we have really promising results, and the first people-related clinical studies and as well on the right-hand side in the multiple myeloma case when we see here the that the Kaplan-Meier curve that the patients who received CAR-T cell therapy, they have a much -- a really higher probability to live longer and to be responsive as compared to patients who were treated with a standard of care therapy. Yes. And I already talked about the challenges in CAR-T cell supply and provision. And one of the most challenging processes when we started with CAR-T cell therapy in the center here was really the whole accreditation process here, together with the manufacturers in the health care provider side here in our center. And also, the close cooperation, yes, with the other parties here has been a new process to us. So also in the past, we had close communication with manufacturers, but not in that way that we were so dependent that all of us have to be certified -- accredited, and we have to get the sign-off from the regulation bodies. And on the other hand, we often are really in time need that we need the CAR-T cell approval from the payers very fast. But on the other hand, we still have to do all that paperwork. We have to justify why this patient has to get this high expensive therapy. So also at that side, it was a very close -- or it has to be a very close cooperation together with the manufacturer and our administrators and the clinicians. And there is also another thing that is really important. This is the communication with patients and families. Because in the case of failure in CAR-T production, it could be really disappointing for the patients, if not -- it could be, it is very disappointing for the patients if the patients and the families are not well prepared before starting this whole process here. So at that point, it is really important that patients are extremely empowered that there are about possibilities that could happen during this whole process and that the expectations are real at their side and their family side. And there is also the point of side effect management. Patients should be really aware about the possible side effects. And the side effect topic is also a topic that is challenging for health care structures in the hospital. So -- and that means that a multidisciplinary team has to be trained, and they have to really provide a huge expertise to handle these side effects in CAR-T cell patients. So -- and there is also a big outreach topic in that area because what we often observe that patients come often in a late-disease stage or with a high disease burden to our center. And it would be much better if they would have been referred to our center in a much earlier phase than their cells are not so damaged and -- or they are still much more fitter and the CAR-T therapy would have a greater chance to give a benefit to these patients. So there is really a big challenge to us to communicate to many doctors outside that they are there to identify eligible patients for CAR-T cell therapy and to send them to the center of expertise that the expert at our center can decide together with the doctors outside if the patient should get -- should recommend a CAR-T cell therapy. Here on the left-hand side, you see that it really makes from a clinical perspective a lot of sense that patients with a high disease burden come to -- at a early time to the center, that they will get access to this high innovative therapy. But as we observe as well here in Germany at our centers that often this does not happen. We are preparing a questioning to office-based physicians and to learn more about the awareness, about innovative therapies on CAR-T cell adoption. And here, you see from a publication, in the U.S. American application that others already did this kind of surveys. And here, you see, for example, they did 2 time points, this questioning, they did it in February 2019 and in November 2019. And here, you also see on the top that logistics is a really important point for doctors that might be a hurdle for prescribing or recommending CAR-T cell therapy. Cost is a big issue, and we will come later on -- as well on that -- again, on that topic because what is really expensive or not expensive, this is often a question of comparison, but this is also something I observed here in Germany that at the beginning of the introduction of CAR-T cell therapy, the costs were really in the center of many, many discussions, but in cost discussion without presenting at the same time, the outcomes of innovative treatment for my half economic perspective, really difficult to run. So -- but as you can see as well here in this survey with American clinicians, the cost topic has been also in the focus. The high toxicity has been also mentioned by a lot of doctors that this is -- this might be a hurdle to them for recommending CAR-T cell therapy as well that there is still not a long-term observational data, but it cannot be there at that point of time of the survey because it was just close to the first launches of CAR-T cell therapy. So I only want to show you with that slide that there are some obvious hurdles we should work on to train and to talk to many, many clinicians to present evidence on these topics, for example, like the cost of therapy topic, that -- we also prescribed many, many other therapies. They are not so expensive at an initial point, but on the long-term run, they are as well expensive. If the patient has to take in the for example, for about 5 years. And here on that slide, you see some other hurdles they mentioned. For example, the slow approval process by payers. This is also something we are facing, too, here in Germany, but not only this slow approval processed by payers we observed, it was -- is also an internal hospital discussion because we have so many processes here in the hospital, which are completely different compared to other drug therapies we provide to patients. And for that reason, we also have to justify internally on the cost of CAR-T cell therapy. And there is another very interesting thing. For example, myself, I live here in Bavaria, and we are a center in the south of Bavaria. And if a patient from north of Bavaria would have a CAR-T cell therapy in south of Bavaria, that would mean that they have to come, the patients would have a 3-hours flight to the center. And we have earlier talked about the side effects. So this might be difficult for patients when they are in a town 3 hours away to handle their side effects on such a distance. So this is also something clinicians see critical if patients who have long distances to the centers that it might be difficult to manage them. But that's what we think in our hospital, these hurdles, we can overcome when we start to work more interdisciplinary that we are looking in the times of digital health care, how to bring outpatient physicians or physicians in other areas together with the clinicians and experts here in our academic teaching center that they can conjointly treat the patient and they share documents, so that everybody see at the same time of what is needed to optimize the therapy for the patient. So for that reason, Professor Subklewe and her team, they developed a nice app that can be used by the experts here in our center. And at the same time, with other physician outside the center, caring for this CAR-T cell patients as this cause my T-cell. And here, you see the doctors can fill in for example, patients -- data patients lap value, and they can have direct communication and here with the expert at the center, and then they can communicate directly together about the eligibility of the patient to the CAR-T cell program or not. So this is something we really do hope will help to overcome the discussion about the long distances and that patients have to be treated in expert centers. So this is a really outreach program we have here with that my T-Cell that we provide to office-based doctors or doctors in our clinics. So here, this is a slide summary of topics that I already talked about. I told you that CAR-T cell therapy is cost-intensive here. But it is not only the CAR-T product by itself. We have a lot of procedures to organize. We have as well leukapheresis. We have the CAR-T cell administration. We have a lot of facility costs, for example, the inpatient stay, the ICU stay, and we shouldn't forget about the intensive training that is needed here for CAR-T cell provision. But at the end, the question is, is it really expensive. So -- and as I already said, we cannot talk about, drugs and if they are expensive when we have not determined the value of innovative treatments. And only value at the end could give decision-makers a good rationale to decide about affordability, adequacy and access. But what do we mean by value? Value is from a health economic's perspective, the ratio between health outcomes and costs. And we always compare in that situation the health outcomes of innovative drugs minus the health outcomes of standard of care therapy and the cost of innovative therapies minus the cost of standard of care therapy. But to determine that value, we try a lot of evidence and a lot of data, and this is our biggest challenge in that area. How to get and where to get this data? But we have a really big hope if we could collect and find and identify that data, we, as well, in Germany or Europe, maybe once we can come up with such kind of publications like this U.S. publication that we can say, yes, CAR-T cell therapy is expensive. This is an investment in a first step. But at the end here, when we provide the value assessment, we see here like in that graph, some publications here on value assessment on CAR-T cell therapy that they already have shown that CAR-T cell therapy the value is acceptable. We started here in our center as well, collecting this kind of data. And look on the time, I cannot go here through all the details and -- but the message here is that it is really important to provide, as well, evidence on the standard of care therapy to put the CAR-T cell therapy in perspective, especially the outcome side. Because that's what we've seen so far on the standard of care side and as well in our own studies, that in the past, this kind of patients had a real high burden on outcomes, especially on mortality, but they were also very often hospitalized and it is not only the hospitalization but also the length of the hospitalization when these patients stay a long time in the hospital, and this is a high burden to the patients and their families. And what we also have seen in our studies that the standard of care in the past was also very resource-intensive and costly. And when -- and that puts finally, the CAR-T cell therapy into perspective, the first investment of CAR-T cell therapy. And our big hope is that, in the future, we will hopefully find more information to run more analytics here in that kind of health value determination. What we also started here in Germany, we started to run a budget impact analysis to provide payers, German statutory health insurance, this information about the budget impact of CAR-T cell therapy. And this puts also the initial huge financial investment into perspective because here on that slide, you see, yes, it's good to see that there are not tons of patients and that will be treated in the future with CAR-T cell therapy. But this is a very significant number of patients they are really in need. And at the end, we calculated here a budget impact in 5 years on the top of EUR 166 million. So -- and when we put this EUR 166 million into perspective to our budget impact analysis for Germany and we identified a budget impact analysis for multiple myeloma, which is very good analysis here. Then you see here for different application forms of multiple myeloma treatment. The budget impact is, in some areas, much higher and multiple myeloma is as well an entity that is not such big. It's a little bit bigger compared to the DLBCL population here. But the final message here is that this budget impact analysis could relativize initial cost of CAR-T cell therapy. And on the right-hand side, you see as well at the end, CAR-T costs in year 1, and we started the calculations here in '21, it's about 1% of the statutory health insurance budget. And in 5 years, we expect that it is 3.1% of the German statutory health insurance expenses on antineoplastic agents. So -- and this is a totally different kind of information. We want to provide to payers to start discussions on the value of CAR-T cell therapy. There are a series of other budget impact analysis actually out in the literature. And most of the other publications came to the same result that they say, okay, there is a huge initial investment. But at the end, the national thresholds were not exceeded in these calculations. So finally, let me sum up. From my perspective, I think besides the clinical studies that are ongoing and there are really good results in clinical routine care at the moment, it is absolutely important to collect additional information to support the translation of CAR-T cell therapies from clinical studies to think here and that we will have an open discussion in the future with decision-makers like payers, like politicians. But this discussion should be based on really hard evidence that is collected in routine care. Thank you very much for your attendance. And now I want to hand over to Nicole Friedersdorf. She will give you as well -- or she will give you more insight in data collected in the market.

Thank you, Karin, and thank you for this very enlightened insight. And thank you for handing over. And -- yes, when Karin and me started to think about what could be the topic for today, when we speak about CAR-T and CAR-T is a huge field. So should we concentrate on the manufacturers, on the products, what should we really do to bring the most value to you? And as you can see, Karin part was a lot about patients, about the physicians, about the HCPs, the referring ones, the centers, about the struggles. Because as therapy and if you think about cost, it's a struggle as well. And if you think about a therapy which needs to reach patients and physicians, then it is important to see, can there be certain barriers? Of course. Or what is really happening here in the market? And if you look at the CAR-T, let's say, history, which we see here, the history of CAR-T is when you think about when it really came to market, not very long. And it had a massive, massive impact, a lot of substances coming in. And here are the proofed ones. If you think about the so-called for homebrew example, there is even more in the market. So CAR-T is a very hot topic. I can see this here also on the attendees. And -- but what is -- what does it help if you have a great product if it doesn't reach the patient or if there is maybe no trust or if there's uncertainty. And this is a question we ask a lot here also in the team and came to the -- yes, let's say, came to the decision to introduce those filings, we had on a recent study we did end of last year, which we are currently resuming in really asking referring HCPs and, of course, accredited centers about their perception, they need referral processes, patient load to really see what's going on in the market. And a few findings I will show you today. And let me start where the patient journey actually starts at the referring HCP, at the local oncologists, for example. So what really happens when a patient shows up at the local oncologists, let's say? And what does the local oncologist really do? And what I will show you now in my talk is sometimes I show you an amalgamation of different countries, sometimes the comparison that you see with it that's on a really global scale and what barriers are there if the patient shows originally up. It's a long time with his or her oncologist and what happens if there may be some eligibility in inside, in closed side. So why are maybe those HCPs not referring to a center like Karin center in Munich? What happens there? And what we could see from a global perspective, no matter with Italy or Japan or the U.S. that the geographic distance plays a major role. This is also what Karin really mentioned. So there are heavily treated patients, very sick and they're told to drive 3.5 to 4 hours to the next center to, first of all, get examined if they're really eligible for a therapy. And if they are, do they have to drive again? So the question is for me from this referring perspective, could it be useful to get all over the world, more operated centers. And the question here is -- the answer is, of course, yes, it should be very helpful for the patient because the referring HCPs, they clearly say, gosh, we cannot send them that way. It's too heavy. It's disruption in their daily life. And on the other hand, what the referring HCPs says why they're not referring maybe eligible patient is knowledge about the therapy. And this is exactly what Karin also said. There are well -- let's say, if -- information is challenging, the HCPs need to know about the different products. They need to go about the process, in parallel tell this the patient to convince the patient and their families to do this step. Because we're not speaking about chemotherapy, which, in general, the empowered patients are very informed of. It's a new thing at speaking from the perspective of the patient, they need to learn about something they need to be acquaintance to. And the third thing is the referral process. Often HCPs on the rural side are not really -- well, they're not just familiar with the referring process. They just send it there, do I need to call. And this is, for example, where also the manufacturers today on the call needs to step in and say, okay, maybe there is information like, maybe we're just visiting just the accredited vendors. Maybe we forgot about the referring HCPs because obviously, all over the world, they're raising this issue. And just to show you an example of Italy for the distance, you can see for MM and for ALL and here for DLBCL, it's even a 4-hour average time to drive for a heavy pretreated and sick patients. Usually, they cannot drive for themselves, but then a relative have to commit, a partner, a child, a brother. They need to get free from their employees. So you see that there's heavy disruption in their lives, which could lead to simply not a referral. From an information perspective, here in Italy, in yellow, you see that the physicians who refer -- the ones who should refer they're saying, well, I could use more information about, in general, CAR-T. And it is all over, as you can see on the bottom, the indication. So no matter the indication means in a way as well, no matter the manufacturer, they need more information. If they don't have the information, they're not referring or they are very hesitant in referring and information is an easy thing. MSL's sales rep concentrate on the referring HCPs because if the patient doesn't reach the accredited side. The product will not have a chance to be applied. And the patient has no chance to get the CAR-T therapy, then maybe the HCPs consider this patient for another clinical trial or for -- yes, in the worst decision, for a hospice, which maybe -- could be not the case because this patient could really be eligible. So information is really key. And as you see here, as a more global view of the barriers is, of course, geographic system, a side effects profile. Side effects profile means that the recurring HCP is unsure if he or she can handle the patient coming back from the accredited center, like Karin said, the cytokine rush, the neurological problems, but the fact is, is an oncologist, which after the original treatment, the patient is referred to really, really in charge of handling that if this one really informed. Italy geographic distance, in Belgium as well as geographic distance. So you see it, it's not the distance, it's really the information, the knowledge around the therapy to be applied. In the U.S., we also asked for statements, U.S. supply is a major constraint and also very interesting to know. On the left side, you see only offered at large centers in big cities. So we have the distance issue again, a 3-hours drive. And typically, with patients regardless and let the center make the final decision is also not an ideal choice because imagine all the oncologists they're referring massively patients to their accredited centers. Because the centers, it is overflown by patients they may not be able to handle this a bit of more information to the referring HCP. And everything is clear, then the HCP can do a pre-evaluation and may not send a patient to an accredited center, patient is not losing time and maybe go into a clinical trial, which makes it, all again, global issue the information. Now we're coming to the positive part, the drivers for referring to accredited centers. And this is really mainly due to patient characteristics. So who refers the one which are informed. So it's about the eco status, the comorbidities, patient desire in Japan, very important. Patients are, in general, more excited about than the family, very empowered patients. So patient empowering is anyhow a big topic that needs to be done. And when we look at the doctor's experience, why they do refer? Well, they have a good relationship with their CAR-T center, and then we come again to Karin's app, which is managing the network between her clinic and the referring oncologist, they feel fine. The referring process feel fine. They have kind of a management, kind of a network with the hospital they refer to, so they know everything is taken care of. And this is also very important when it comes to decision, do I refer a possibly eligible patients to an accredited centers. To sum this up, except in Germany, doctors are still not receiving adequate information. It's their perception. But if a doctor say, well, I don't feel informed -- they don't feel informed no matter what, even if you as a the company think they should be informed. If there aren't, they will not refer. They simply feel unsecured. And if you have to look here at the graph, the blue ones are the ones where physician say, well, it's fine. I have enough information, and this makes sometimes up to just 35% and the rest doesn't feel informed, for example, here in France. You won't get these physicians to refer. So a bit of homework needs to be done. Obviously, communication is key and knowledge is key. This is another, let's say, overview from another angle. Here, we really asked about, when you refer to an accredited center, when you decided to refer, do you mention a brand which you think could be working? Or is a class requested? Or if you just refer the patient? And look at it, in the light blue, it's principle -- well, I just refer the patient, except for the U.K. where obviously a class is recommended. But very seldom the brand is requested. And for me, if the brand is requested, the referring HCP really knows what he or she is doing. Then they know well, we have BLDLC then we have this product, okay, the accredited center, I sent you this patient, and I think this should be applied. The others, well, they just refer. And if it then works or not, that's another question. Here's the another side just proving what Karin really said. So it's about patient education. So in many countries, well, here we ask the accredited centers, do you think that the patient would show up at your site, they're really educated about what's -- what maybe happened now at the site. And the orange one is about not empowered, not informed patients, so the HCP, the referral one, refers the patient and the patient has simply to say very, frankly, no clue what's now happening. And that's very crucial because CAR-T therapy needs the commitment of the family, also the employer and especially of the patient. We're not talking about a chemotherapy, which everyone should know about. We're talking about something completely new. And if the patient is not informed, we have another variable here, the patient, which in the end shall get the therapy, which says I'm not informed. And then maybe this leads to -- well, I'm not doing it, which no one wants, not the patient, not the family, not the physician. So information of the HCP and of the patient here, as a total message from this part, is quite key. But what do the centers say? The accredited centers receiving the patients, how they perceive patients referring HCP. So which should be their partner here in crime, the definitive partner? And how do they perceive the manufacturer, which should be the third partner to come to an end to success, to a successful treatment, to a perfect side effect management? So we asked them as well, and we asked them as well about the treatment per day, how many patients they see. Well, the usual stuff. Patients refer dynamics. Do they have networks? When are patients referred? And how it's external, it's internal? And how do you perceive the manufacturer? Do you see them really as a partner? And the good news in the U.S., no matter the brand, you see brands here on the top. When we asked doctors in accredited centers how they perceive your product, they say innovative, it's effective, it's strong, it's powerful. So from a promotional point of view and from an educational point of view for the physicians in the accredited centers, you did a good job. So keep this momentum. So your product is really recognized as it is. It is strong. It's powerful. It's effective. But this doesn't help if the referring HCP doesn't see it that way. And if the patient maybe, says, no, this is too unsecure for me. I'm not really informed. So why does this then happen that there's so much insecurity and this is definitively there. Well, actually, the referring HCP is not seen critical as part of the treatment team. And this was a question we asked to the accredited center. So the physicians that, well, no, there referring HCPs well, yes, they are not really part of the team. They refer the patient, and that's it, and this is a mistake. This is definitively one mistake, which should be taken really into account. Because in the end, the patient is sometimes referred back to the office-based oncologist or they have kind of a hybrid care about side effects and else. And it's crucial for the outcome of the patient to be monitored perfectly, 120%. So this is also a study here from the U.S. apart. So you can see that no matter the brand, [indiscernible] is happening if we should make this a brand thing or an overall thing. And it's really an overall thing. You see this no matter the brand, if a patient has gotten his or her therapy, nearly 50% are referred back to the referring HCP or have a hybrid follow-up treatment. So this means only 50% up to 60% of the patients stay at the accredited center and are monitored completely there. The others go back and they go back to an HCP, which doesn't feel comfortable in side effect treatment. So this should be definitively changed. So from a CAR-T side perspective, here, I took just Japan, for an example, they're referring patients, they're doing a great job. Yes, they do. But they sometimes underestimate T-cell eligibility and they're sometimes also overestimate a lot. So this again here in Japan, it will simply lead back to not being informed properly. So what is my take-home message here? Please build educated multi-disciplinary teams because this is crucial for patient long-term follow-up and the therapeutic outcome -- and what does it mean? It means that from the HCP to the referred center, from the manufacturer to the patient, you need to be treatment. And the referring HCPs, they shall actively, for example, follow up. You as a manufacturer, you should see that the MSLs, that the sales reps, they see those referring oncologists, maybe more often or, let's say, the material to offer, the trainings to offer, maybe not enough. Go out and ask them why they feel unsecured in referring? Why they feel unsecure in just managing the cytokine rash and receptors. There is -- there was a reason behind, and this is what we see here. We don't see well the real why because whatever in Germany, they might not be able to handle cytokine rush properly or whatever. This is the details. But in principle, we have HCPs here, which are here in Italy, referring HCPs, 90% involved in the treatment decision because if they're referred and then the patient gets the CAR-T treatment. But the accredited centers just see 10% of the HCPs referring as a part of the team. And then this could really never work for a proper follow-up. And as you, for example, again, see here in Japan, which leads me directly to my -- to the last part of my talk, it's about -- well, the interaction with you, with the manufacturers, how is this going on? What do you receive as an accredited center, as an HCP, as a referring one? And you see that for all the plans overall, the MSLs see them very often. There's a time span of 6 months here. So this is fine, or fine the MSLs, they -- they go there, they inform that's well. But the question is well, they see the MSLs but what do they get from the MSLs? And really the critical stuff of education materials and a little bit lower patient education materials. Well, they remember just 33% up to 70%, remember, to have gotten something like this. So obviously, there's also a gap in information, which matches what we have seen before that the HCPs don't feel well informed how they should handle patient questions. On the other hand, the MSLs and the reps and e-mailing support in the companies, this is where you did a very great job. So if [indiscernible] wants to partner with you and wants to be accredited for your product, in Japan, they're 90% happy to do this, they trust the brand to get accredited for, that's fine. And this also matches up what I said before. The accredited centers, they are really taking care of. They're educated, they're seen by the MSL and by the reps. And all this business done very properly. The gap is really where the HCP and the patient education starts. One of my last slides, how reliable and transparent are the processes here from Italy, very reliable, processes are fine, we from the accredited centers. We feel quite safe, easy to work with. We like the transparent process. We like the support center. This is all accredited centers here. And when we look as an example in the U.S. for patient support and coordination, well, it's just 50% to 60%. So long-term side effect monitoring here in the middle, comes up. Obviously, not very well informed. It's just 45% say, well, I'm fine with the monitoring, the others aren't. So help coordinate with referring HCP. So that even the accredited centers see your role as a manufacturer also in liaising, the manufacturer liaising between the referring HCP and the accredited centers. So they really want you to take a stance here in a way because they cannot do it, obviously, by themselves. So as my last slide before the take-home message, please build a strong and supportive relationship. You as a manufacturer with the accredited centers. You do this with e-mailing, with the support staff, with the MSLs. You do this, it's fine. It's working on. The accredited centers, they trust you very much. But to get the therapy to the patients, you need to get the trust and the education of patients, #families and friends with also the referring HCP. Without them, it's fine that the accredited centers trust you and want to partner with you, but they will never receive this amount of patients like they should have and patients will not receive a therapy, which they could have received with a bit more education. So manufacturers, please keep this momentum up here. They're doing a great job, do it even more intense. For the HCPs, multidisciplinary teams are key here. For an end-to-end patient management, especially with the side effect, referring HCPs, accredited centers need to feel as a team, as a whole team, which currently in a center, for example, with this app, they started this, it's a good example. But you can also do without an app. You just can we can say, okay, I've accredited centers. I have these 20 oncologists in my reach, let's form some kind of board. Done. So you can just communicate with all of them and discuss their patients. And the patients, then you can be educated, may it be with some leaflets or with some training or you go into these patient networks. There are a lot of possibilities to do. But please do this. Because these are the 3 important partners when it comes to CAR-T therapy. Again, we need the patients to benefit from and with CAR-T, they really can. We are all pretty sure about this. This is the end of my talk, holding up the flag a bit for patients and for referring HCPs. And for the Q&A now, I refer shortly back to my colleague, Phil, and then we start the session.

Thank you so much, and thank you to Dr. Berger and Dr. Friedersdorf for such an informative presentation. [Operator Instructions]

First of all, lot of questions have come in here, if we share the slides afterwards. Yes, we will share with you the slides. If you're interested, you can, in the end reach -- say that you wanted to be reached out, and we'll be happy to share the share part of the slide. And those of you which questions will now not be answered because I just looked at the time, we have just 5 minutes. Don't worry. We will answer your questions in an e-mail, if you like to. I think most of you have given their e-mail, so I'll just look at the name and then you get an answer by e-mail. So don't worry, it will be answered. So let me look at the first question. I go to the very beginning here. Let me see, yes, there is a question for Karin actually. So what are the key factors which caused the high cost of CAR-T treatment?

There is a series of costs and, especially, yes, first, the CAR-T cell therapy itself. Then if the patients will suffer from side effect especially severe side effects, so that can be that they are not long-lasting, but often these patients have to be transferred to the ICU and it's really cost-intensive, a day on ICU. So this has to be added up. And these patients have, in many cases, do receive as well a very expensive other to handle the side effect. For example, the cytokine rush or neuroleptic side effect. So this is also a need to bring multidisciplinary experts together. So that means that we also have a high cost of human resources in the hospital because really a high qualified expert team has to treat these patients. And the follow-up is as well, the cost, yes. But so far, we still have really a limited number of cost studies that I can say that is really the key cost driver. So I think we have to investigate a little bit more in the close -- near future to learn more about the cost dimensions we have to add up here from different perspectives.

Thank you, Karin. And there is another very interesting question about costs, which is also for you. It's especially about Europe. Do you think that cost is a barrier of prescription in Europe because, I mean, there are different systems in place, but is it also an issue in Europe? The cost...

I can -- yes, it's a clear issue in Europe, and it's also a clear issue here in Germany.

And is it more because of the reimbursement? I mean if it's approved, is it always...

That's what I can say from my experience. Here, we have to take into consideration 2 sides, the payer side, the reimbursement side, and as I said as well, the hospital sides because DRG is not shaped for this kind of high innovative drugs. And for that reason, we started here in German discussions how to optimize the DRG system. Because at the moment, all the hospital costs or the providers costs are maybe not covered by the DRGs. So there is a risk for the hospitals then that they might run in a debt by this kind of therapies. But yes, for that reason, I can say, yes, there is a cost issue here in Europe as well.

Okay. Perfect. And now there is the time for last question, which is a very good one. And so -- and this is also something for you, Karin. Do you have seen any best-in-class project to improve this referring pathway? And I notice you have the app. And are there any update? How it is used? Is referring pathways from the referring HCPs to the accredited centers and back? Is this -- is it a best-in-class project, would you say?

No, I haven't seen one. So this is what I'm struggling for, this is what I meant in my presentation, it is evidenced. I think we all have to come together to collect these kind of information. And what we have seen in one of the slides where I've shown results from the service at 2 time points. I think it's so important to follow up routinely this kind of information because there is a dynamic in that area. So -- and I think we will see transformations in the near future.

Okay. Thank you, Karin. And I look at the time, we are perfectly in time. And I'll back to Phil. All the other questions will be answered via e-mail. No worries.

Thank you so much, Dr. Friedersdorf. Unfortunately, we're out of time, but thank you so much for attending and participating in today's event. We would like to ask everyone in the audience to participate in a brief survey. You can see that survey on the right of your screen. You'll receive an e-mail alerting you when this webcast will be available for replay. We invite you to forward that announcement to your colleagues who may have missed today's live event. Thank you all for joining, and we'll see you next time. Goodbye.