Study Update

Jun 11, 2021

Hello, ladies and gentlemen, and welcome to the Autolus Therapeutics' EHA Data Update Conference Call. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Mr. Andrew Oakley, the company's Chief Financial Officer. Please go ahead. Thank you, Kevin, and good morning or good afternoon, everyone, and thank you for taking part in today's EHA data Update Call. I am Andrew Oakley, the Chief Financial Officer. With me today is Doctor. Christian Eitan, our Chief Executive Officer and Doctor. Martin Coulee, our Chief Scientific Officer. Before we begin, I would like to remind you that during today's call, our discussion will contain forward looking statements. All statements other than statements of historical facts on this call are forward looking statements. Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the section titled Risk Factors in our annual report on Form 20 F filed with the Securities and Exchange Commission on March 3, 2020, which can be accessed on the EDGAR database at www.sec.gov and in subsequent filings we make with the SEC from time to time. The forward looking statements on this call reflect the company's views as of today, June 11, 2021, regarding future events and should not be relied upon as representing the speakers' or the company's views as of any subsequent date. While the company may elect to update these forward looking statements at some future point, the company specifically disclaims any obligation to do so even if company's views change. These forward looking statements should not be relied upon as representing the company's views as of any date subsequent to today. Please be advised that today's call is being recorded and webcast. On Slide 3, you will see the agenda for today and is as follows: Christian will provide a brief introduction, and that will be followed by Martin summarizing the INHL data presented at EHA today. After which, Christian will give an update on the adult ALL durability data that was also presented. Christian will then conclude with upcoming milestones and other concluding comments. And of course, we will welcome your questions following our remarks. So with that, I'd now like to turn the call over to Christian. Christian? Thanks, Andrew, and welcome everybody to our EHA update. We've been looking forward to obviously sharing with you our newest data on AUTO1 or OBL cell. As you know, we've been obviously very active working in the field of ALL, particularly, obviously, driving the Felix study. But we're also, obviously, continued to observe the data coming from the OLCAR-nineteen study, and I'll be sharing with you some additional update after Martin's presentation. We're also active in addition within the OILCAR study in additional indications, including a set of non Hodgkin's indications and CLL. And this is where we're going to be focusing on in the first part of the presentation or the first experience that we have in patients with indolent lymphoma. In addition, we're also actually active in patients that have primary CNS lymphoma in the so called CAROUSEL study and were active in an extension of the CAR PAL study with the next generation program called AUTO-one hundred and twenty two that is designed to address the antigen driven relapses that we've seen in the original CARCOL study with AUTO-one. So with that, we're moving to Slide number 6. I just would like to remind you of kind of some of the key features that we have seen with OV Cell in ALL in particular. Today's data is coming from a data cutoff that was on May 17 this year. Now what we have seen obviously across the study is a high level of sustained complete remissions that were achieved without subsequent stem cell transplant. The durability that we're seeing is highly encouraging, and we're obviously providing an update today that actually extends to 24 months. And we do see that indeed the event free survival actually is at or slightly above 50%, and it is stabilized at 24 months. What we also do obviously know from the program and we shared with you in the past is that the program has a very good safety profile with no patients experiencing high grade cytokine relief syndrome, which is grade 3 or higher. And only a small proportion of patients, total of 20%, had experienced ICANS or neurological adverse events of any grade. And all of those events swiftly resolves with the administration of steroids. We have a pivotal study ongoing called the Felix study and expect full data during the course of next year. And finally, I'd just like to remind you of the opportunity in ALL, which is very significant. It's a market that's significantly underserved, and we'll talk briefly about that in a later slide. But it's important that it's a market that is addressable with a very focused commercial footprint. With that, I would like to actually hand over to Maarten to give us the update on the indolent non Hodgkin's lymphoma experience. Maarten? Thank you very much, Christian. Hello, everybody. And Julia, could you please go to Slide 8? So on Slide 8 then, we're just really describing what we've done with the ORILCAR19 study. So Christian briefly mentioned the ORILCAR19 study and many of you will be familiar with it. This is our Phase 1 study testing, OB cell and relapsedrefractory B ALL. We initially aimed to recruit 20 patients to this study, to treat 20 patients in the study, which we did do by the end of last year. And because the data was so encouraging and we amended this study to turn it into a kind of a basket study. So and this is described here. So with a cohort B where we would treat some 10 DLBCL patients, cohort C where we would treat 10 BCL patients and cohort D where we would treat some BNHL patients. And the aim of this was to see if the same safety profile and high levels of long term engraftments of obicel was the same across all these different subtypes. We've initially focused on Cohort D because for many reasons, this should be quite interesting and this is really what I'm going to talk about next. So, Julia, if you can go to Slide 9, please. So here we're so here is an update on that cohort, on the endurance BNHL cohorts and we've treated 9 patients. 7 of these patients are deflected lymphoma and pseudo mantle cell lymphoma. And in terms of the patient characteristics, they're pretty much what we would expect for relapsedrefractory indolent and BNHL with a median of 3 previous lines of treatment, 4 out of 9 had a previous autologous hematopoietic stem cell transplant and 1 had a previous allogeneic hematopoietic stem cell transplant. All of the patients were either Stage 3 or 4 by PETCT. So that's the patient characteristics. So if you remember, there are 2 main characteristics of OV Cell due to the design of the receptor having a fast off rate interacting with its targets. So, we hope that we'll get less exhaustion and hence better engraftments and persistence. And then at the same time, because each interaction with the targets that will result in less inflammation, we hope to see low levels of toxicity. So we know this is what we get in pediatric and adult ALL. So is this what we get in endurance BNHL? So on the top right of this slide, you can see the marketing levels done by flow. And you can see indeed we do see very nice high levels of expansion of CAR T cells in most patients in a nice plateau. So this is really very similar to what we see in B ALL. And then do we see the same low levels of toxicity? And I think you can see that indeed we do. We have seen CRS of any grade in 5 out of 9 patients. However, only one of these was grade 2 CRS and we did not see any grade 3 CRS in any of these patients. So that is really quite a promising safety profile. In terms of co mediated neurotoxicity, we have not seen that in any of these patients. So I think that's very nice to see that we have really now the same safety profile in indolent BNHL as we do in pediatric and adult BNHL. So what happened to these patients with response slides? So Judith, you can go to Slide 10. So this is just a swim plot of all these patients. So all of these patients, so all 9 patients went into a metabolic remission by PETCT and 8 out of 9 are disease free at the last follow-up. Sadly, we lost one patient due to COVID infection and one patient relapsed with small volume subcutaneous CD19 positive disease that was salvaged with localized radiotherapy. All right. So as we go on to Slide 11, these are small patient numbers. Obviously, this is really just to get our feedback, just to see what the performance of our receptor was in this setting. But we've just put a slide together here just comparing OVYCELL with TAKARTA's and KRYA just really for your information to get a sense of how our receptor our product compares with the competition. And as you can see, we have in this very small group of patients, 100% metabolic CR. And we have no severe CRS and we have no neurotoxicity. And I think this compares favorably with both Tecartis and Kymriah. And then if we go on to Slide 12, really, which is my summary. So this initial obicel efficacy data in indolent NHL is really quite encouraging. It's very nice to see the same consistent safety profile across increasing numbers of indications. And it's also nice to see the engraftments and persistence profile also reproduced in another disease subgroup. And we're adding these additional we're exploring the additional cohorts as explored and further data we should have by Q4 of this year. And Christian mentioned the CAROUSEL study, which is actually separate to the ALLCAR study. So it's not part of the ALLCAR-nineteen basket study. There's a separate study in primary CNS lymphoma, which is now currently open. We hope to have some initial data at the end of this year. And as Christian also mentioned, the 1922 version of OBL, is now open and recruiting patients in pediatric ALL, again, with data expected at the end of this year. So with that, I'd like to hand back over to Christian. Thank you very much for your attention. Thanks a lot, Martin. And we're moving to the update on the ALL side on Slide 14. As you remember, the medical need in ALL, particularly adult ALL remains very high. We start the therapy once the patients are diagnosed with a high dose combination chemotherapy regimen. We get about 90% of the patients in complete remissions. However, only between 30% 40% have a chance of long term remissions. When we look at the median overall survival of the relapsed refractory part of the population, it is less than 1 year. And at this point, obviously, we do not have an approved CAR T therapy in this space. The only redirected T cell therapy that is on the market is blinatumomab. Now we do know from the original experiences in the space, obviously, that CAR T therapies can be highly active, but obviously often had challenges either on durability or on safety. When we look in terms of the opportunity more broadly, we believe that in addition to the last line setting, there are significant opportunities for the products to move up the line and into the earlier settings. Ovisel has been granted orphan drug designation by the FDA for ALL and we also received earlier this year a PRIME designation by EMA for adult patients with ALL. Next slide. What we're looking at on Slide 15 is really the updated SWIM plot of our patients. And this is one of those cases where actually no change is good news. In fact, we have no event between the data cut that we had for ASH at the end of last year and the data cut now on May 17 this year. All the patients that were in remission continue in remission, which is obviously very good news. I'm just pointing out that we have now patients that without any subsequent therapies have crossed 30 months in molecular complete remission. Slide 16. What we're looking at here is the updated event free survival curve, which is really kind of the most sensitive way of looking at how the patients are faring. In blue, we're looking at the morphological EFS curve. Remember, the way we're assessing responses in ALL is by actually measuring the number of blasts in the marrow. If the patient has less than 5% blasts in the marrow, the patient is in morphological complete remission. But then we also measure with a much more sensitive methodology, either by flow or by PCR, whether it's actually presence of much lower levels of leukemic cells in the marrow and that is usually referred to as mineral residual disease at that state where that disease is measurable with those methodologies. And what we also put on here is in the light green curve is actually the molecular EFS curve. In other words, all of the patients that are still in molecular complete remission. It has no sign whatsoever of any disease in the marrow. You see the curves are slightly apart. There is one patient difference and this is literally a patient that was in had an MRD relapse, but was still in morphological CR and was then moved on to a stem cell transplant and that's the difference between the two curves. The important part, however, is that as you're looking from 12 months onward, that both curves are going horizontal. So, when we look at the molecular the morphological EFS at 12 months and at 24 months, we do see that we get to 50.2%, which is sustained over time. Now as we go on Slide 17, what we are looking at here is actually our experience in the OLD CAR19 study, and we're also including, as a point of reference, the now published Phase II data from ZUMA-three. This is the TECARTIS data in adult ALL that was published in Lancet and also presented literally a week ago at ASCO. I think when we look at the baseline characteristics of the patients, we see that they're overall very comparable. On the old CAR side, we have some patients that have an ECOG status too, which is obviously patients that do a bit worse. And we also seem to have a higher number of patients that have gone through a stem cell transplant and failed after the stem cell transplant. Overall, however, the patient populations are very comparable. Going to Slide number 18. When we look at the key markers for the activity, we can see that the we're having with OBSell, obviously, a very robust complete remission rate and molecular complete remission rate at 85 percent, which obviously are numerically higher than what was reported for ZUMA-three in the Phase II study, which were reported around 71% 69%, respectively. When we look at the event free survival and we look at the median, which was not reached obviously for Olchar, but then look at 12 months, 18 months and 24 months, obviously the numbers are all 50.2%. They're identical. However, what we're seeing with Tecartis in SUMA-three is that while at 12 months that number was still around 45%, it dropped to 25% at around 18 months and there was no data reported for a 24 months time point. So while the activity, obviously, as we see on OV Cell is consistent high level of complete remission and a stabilization of the responses after 12 months. Going to Slide 19. What we're looking at, at Slide 19 on the top is obviously again the morphological free survival curve for ovicell. And we have plotted at the bottom with the same time axis the corresponding data from the Lancet paper with Tecargus from ZUMA-three. And as you can see, clearly, the data for Tecartis continues to fall and does not stabilize and clearly highlights that difference, fundamental difference in terms of the longer term outlook that the 2 therapies appear to be offering to patients. When we go on Slide 20, when we look at the actual behavior of the CAR T cells themselves, there seems to be quite a stark difference. I'd like to point out that what we're looking at here on the y axis is a logarithmic scale. And what you can see is actually that in terms of the peak expansion, the maximal amount of CAR T cells formed in the patients, we see about a tenfold increase or higher number of CAR T cells with OD cell compared to TECARTIS. We then see, obviously, as we go to 3 months, that difference going to about 1,000 fold, a very few cells, CAR T cells left in circulation with Vicartis, and they're all gone by month 6. On the other hand, with OV Cell, you see that persisting CAR T cells are stabilizing and they're stabilizing throughout the full 24 months observation period that we now have with these patients. So it's a stark difference in terms of behavior of the product, both in terms of maximal activity in the sense of actually available CAR T cells at peak, which is tenfold, but then obviously a massive difference in terms of the presence continued presence of the CAR T cells. So when we then look on the safety side on Slide 21, obviously, you do remember that we have overall a very good safety profile with no high grade CRS, limited neurotoxicity compared to obviously the published data for Tecartis. I think what is quite telling is we actually look at the treatment for CRS or ICANS, which obviously gives you a very good view of the intensity of patient management required to actually ensure that it can keep the patient safe during the therapy. As you can see, for obicel, there is limited use of tocilizumab and steroids and there is no vasopressis that were required, which is indicative, in fact, of none of the patients having required access to intensive care. Now if you compare that to also the data from ZUMA-three, you see extensive use of tocilizumab, extensive use of steroids. But still, although this extensive use was put in place, 40% of the patients received laser pressers, which tell you that those patients had required intensive care. So there's a stark difference, obviously, in terms of the safety profile between the food products as well. So we believe that we have a potentially differentiated product on efficacy, on durability and on safety. We obviously have seen a very high level of molecular CRs, of MRD negative CRs at a level of 85%. We've seen stabilization of morphological EFS at around 50 percent. We have seen exceptional long term CAR T persistence, which clearly correlate with long term benefit. And we have seen a favorable safety profile with the product in these difficult to treat patients. So with that, I'd like to actually summarize kind of where we are with the program, and we're going to Slide 24. Obviously, building on the positive experience that we're having both in the adult as well as the pediatric ALL population, we're obviously conducting now the pivotal study in adult patients, the FEELIX study. But we're also, as Martin pointed out and walked you through, are exploring and evaluating the activity in the broader range of non Hodgkin's indications as well as taking the next generation program, AUTO-one hundred and twenty two, into pediatric patients. And for all of those sub indications, we expect data by the end of this year. So with that, I would like to actually close the formal part of the presentation and we'd be happy to take questions. Our first question comes from Gil Blum with Needham and Company. Good morning, everyone, and congratulations on the impressive data update. So maybe one for Martin. It looks like patients with indolent lymphoma when treated with cellular therapeutics appear to have lower rates of immunological toxicity. We saw that with other CAR Ts and some of these allogeneic cell programs. Is there any underlying biology that might be explaining this? Hi. Thanks for the question. Well, I mean, I think what causes immunotoxicity is really the amount of antigen that a T cell has encountered over a period of time. I'm not sure that it's been formally studied, but I would suspect that these indolent cells are probably a little bit smaller. They probably have a little bit less antigen and probably also they're slightly less inflammatory. And so overall, the amount of sort of signal CAR T signal you get over a short period of time might be a little bit smaller than from, say, something like ALL. I mean, having said that, TAKARTA is the TAKARTA study, mantle cell lymphoma did show fair amounts of toxicity. I mean, it wasn't really that well tolerated. So that illustrates that it depends on the primary antigen receptor you're using as well and the type of co stimulatory signal that transmits. All right. Maybe kind of veering to the ALL program, we've seen really long term responses here. Is there a historical measure or length of time in which we can see that patients have achieved a cure? I mean, another program in the past 2 years, for example, do these usually last like up to 5? Thank you. So, Gail, it's an excellent question. And typically, what you would look at is you like in many actually, lymphomas and then also potentially other leukemias, you look typically at a 5 year time window. As a sort of a point of reference, the work that was done with BLINCYTO in the early line setting actually did show still although the data looked reasonably positive at 3 years, actually there was a continued drop to 5 years in some of those patients. So typically, a 5 year time window is what you would look at to sort of believe that the patient is kind of out of the woods. But I think getting to a place where the event free survival actually starts to stabilize, as we see now, I think is obviously very good news and indicative of a high chance of a long term benefit. Okay. And kind of a last one. Are there any drawbacks to having long term B cell aphasia? It looks like these C cells are the T cells are very, very persistent out to 2 years. That is correct. So one of the things that obviously you need we need to keep in mind is that the first thing that we have to do in a disease setting like acute leukemia is survive. We shouldn't kid ourselves. All of these patients that are in the relapsed refractory setting are going to die based on the current standard of care. So the first order of business is survival. And I think what we do see is there's a clear correlation between the persistence and the durability of effect. Now obviously, if you have long term activity of the CAR T cells, you will also have an impact on your overall B cell compartment and you certainly will have a B cell compartment that is going to be suppressed for that period of time. What we do know from the experience obviously in NHL patients who've been exposed to rituximab for years is that that actually can be well compensated in many of these patients by other parts of the immune system. Obviously, one of the things we have here is an improvement in terms of the performance also of the T cell compartment. So, I think there is good proxies with regards to, obviously, the experience on rituximab, that indeed we have an ability to compensate from an immune system perspective, but there's certainly for as long as they're active CAR T cells in the patient, there will be a suppression of the B cell compartment. All right. Yes. I mean, it's Matthew here. I mean, if I can add a tiny bit to that. I mean, so for things like ALL, CLL, follicular and mantle, it's going to be very likely you're going to need long term persistence. We need to keep these patients in remission. So I think that's the long term B cell aclase is very likely the price you have to pay for continuing remission in these patients. Remember, the bone marrow resident plasma cells aren't killed off because they don't express CD9 GCAR. So many patients are still able to make antibodies against pathogens they've encountered in the past. And then for the relatively rare patients that run into recurrent respiratory infection, there is a mitigation which is proved in immunoglobulin, which is a reasonable mitigation, so you can get other people's antibodies. This is very similar, as Christian said, to the problem with patients with long term rituximab maintenance, for example, in cancer. So you're right, it is a clinical problem. It's a price we're paying for patients who have a clinical problem with it. There is a relatively simple mitigation set. If it makes sense for deep seated diseases like ALL that's deep in the bone marrow that you would need very long term monitoring of the T cells. And I think the data from Blinopenna points in that direction as well. So thank you for taking our questions and congratulations on the positive update. Thanks, Gil. Thanks for joining. Our next question comes from Mara Goldstein with Mizuho. Great. Thanks so much for taking the question. In the indolent Hodgkin's non Hodgkin's lymphoma study, you had that one patient that relapsed just before the 6 month mark and then was rescued with radiotherapy. And I'm curious as to what you think is going on there to see that patient respond to radiotherapy? And then secondarily, if you could just talk a little bit about the update for later this year and what we can anticipate in that update and if you also have any thoughts on timing around pivotal data in the Felix study for next year sort of early, late or mid-twenty 22 that would be great? It's Martin here. Actually, thanks, Mara. Maybe Martin you take the Yes, exactly. I'm going to hand on to you, Prashu Yang, sorry. Okay. I mean, again, it's a very small study, so it's really difficult to make any conclusions. So in terms of the skin relapse, it is actually very interesting. There are some sanctuary sites that the disease can relapse in and that's ocular subcutaneous and in some cases CNS. And it's interesting that CAR Ts are actually very good at if you have a patient for example with skin and lymphoma and you give CAR T cells, it's actually quite a good treatment for that. But interestingly, when after the initial peak of CAR T expansion and then you sort of enter into kind of low level persistence, You do sometimes see patients breaking through in those sort of sanctuary areas. So presumably that's what happened in this patient. Actually the nice thing about skin diseases, you can give quite specialized radiotherapy that doesn't penetrate very deeply like electron beam radiotherapy. So it's something that we do see these kind of sanctuary site relapses. And I guess it's since you can give very localized radiotherapy, it's not really surprising that the patient responded. But sort of more than that, with just this one patient, I can't really say anymore. But just out of curiosity, do you know if that patient experienced CD19 loss of expression or? No, no. When we did this skin biopsy, there was still CD19 positive. Okay. Thank you. The second part of the question sorry, we still have the second part of that question of the questions and that was the update at the data update at the end of the year. So obviously, key focus of the data update at the end of the year will be the additional cohorts that Martin was talking about. So we're obviously longer term follow-up on the cohort we just discussed on indolent lymphoma, but we're also expecting updates from the cohorts in the additional non Hodgkin subsets as well as the first view of the data with the primary on the patients with primary CNS lymphoma as well as an update on the Phase I experience with the AUTO1 hundred and twenty two in pediatric ALL as well. So that's sort of for the end of the year and we obviously will keep on updating kind of the durability information on ALL from the old car population as well. As we're going into next year, the key update with regards to the Felix study, we expect to be able to report on the primary endpoint in the middle of the year and then towards the end of next year also update provide the durability information on the trial. Okay. And Christian, just as it relates to Alcar, obviously, we have a little bit of data at this point from on the indolent NHL. But what is the, I suppose, threshold to continue to expect to continue? I mean, clearly, the results so far are particularly enticing. And have you thought about how to expand that program? So what we want to see is really how the product performs across these various non Hodgkin sub indications. And really based on the profile we're seeing, actually pick the indication sets that will push forward into the next stage of development. So, we want to see kind of the performance across and the level of differentiation that we're picking up. And as Martin pointed out, one of the important elements, certainly, on the follicular side is durability of effect and want to see continued maintenance of the remissions that we've been able to induce. Okay. Thank you. Thank you. Our next question comes from Asnika Gunewarden with Truro Securities. Hi, guys. Congrats on the update and the positive data here. I guess most of mine have been already answered, but maybe on the broader topic of persistence, I want to ask Martin this. I know the CAT-nineteen helps greatly with this, but I know you guys have done some long follow-up work in patients that you treated with AUTO1. So I'm wondering how long are the CAR positive TN and TSCM cells present in patients and how much things that's differentiated from, the asset sale? Guys, did you get my question? Are we still on? It's Mehdi, I missed the very last compared to I just missed the very last sentence. Your line went very fuzzy. So could you just repeat the last bit of your question? Yes. Sorry, Marty. And I was wondering, and how does that the long term persistence with the CAR positive TN and PSCMs, how does that compare with AUTO1? How does that compare to AXISEL? Yes. I mean, it's a good question. I mean, we're in a very fortunate situation with this product in that patients who have CAR T cells detected by PCR, we can still detect them by So I mean, some patients do lose their engraftments over time, but most patients still have CAR T cells by flow. Now I actually saw, like your Escarta is a 28 VITA CAR, right? And there, I mean, you've seen from Christian's slide with markings that actually that disappears very, very quickly. So there's not really a comparison, I don't think, between OTO-one and AXISL. You lose your CAR T cell market with 28 data very, very quickly. I mean, the one thing that we're able to see with AUTO1 that nearly nobody else is able to is actually do flow in their long term persistent cells. And there, you can pick up still stem cell memory cells and T stem cell memory cells. We published a paper in Nature Genetics where we studied the insertion site profile and the differentiation of also 1C cells in peripheral blood up to a couple of years in our initial pediatric cohort. So, I'll direct you to that for further reading. Excellent. Thank you very much for taking my question. Our next question comes from Ingrid Sotto with Kedrong. Ingrid, your line is open. You can ask your question. All right. Thank you. Sorry, I was on mute for a while there. Can you just remind us if the ZUMA-three trial used any preemptive safety management or perhaps any other approach they might have used for risk mitigation? And I was wondering, do you think that this drop in CAR T persistence that they observe here can be related to this widespread use of steroids? Or do you think that's probably mostly related the use of CD28 as a quick multi domain? Right. So first off, with regards to the general profile that we've seen in terms of persistence for Tecartis or Descarta is predominantly driven by the construct itself and the actual CD28 signaling, we believe, as the predominant driver of that behavior. With regards to the safety management, the safety management was evaluated in the Phase I part of the SUMMAR-three trial and published in blood earlier this year. The authors did indicate a more aggressive intervention with steroids and tocilizumab to be used in Phase II. The Phase II publication, The Lancet in the supplemental section would suggest that there may not have been a consistent use of pre medication or early medication of the patients. It suggests that it was similar to what was used elsewhere. However, it was not really specified in any way, shape or form in that in the document. So I don't think we can comment on what was actually used. What we do know is the totality of steroid use and the totality of TOCI use as well as vasopressor use, which was actually disclosed in the actual publication, but not the timing of which. All right. That's very clear, Christian. Thank you very much. Thank you, Andrea. Our next question comes from Eric Joseph with JPMorgan. Eric, your line is open. You can ask your question. If your line is muted, could you please unmute the line? Did you want to just go ahead and move on to the next question? Let's do that. Our next question comes from Kelly Shi with Jefferies. This is Dave on for Kelly Shi from Jefferies. My question is just following on the earlier question. What will be the bar for starting the pivotal trial for each of these indications? Thank you. Thanks for joining. And as we have indicated, obviously, first of all, we want to understand the actual profile that we have in the various sub indications. I think when you look at the bar, you can look actually in particular with follicular mantle cell DLBCL on the approved products, which give you a very clear level of the bar that you have to hit. But we haven't actually specified beyond the specifics of where we actually need to hit for us to take the program forward that is premature at this point. Thank you. And I'm not showing any further questions at this time. All right. And well, thank you all for joining for this update from the ER conference. And we're looking forward to keeping updated on the additional progress. And wish you all a great day. Thank you. Ladies and gentlemen, this does conclude today's presentation. You may now disconnect, and have a wonderful day.