Hello, ladies and gentlemen, and welcome to the Autolus Therapeutics first quarter 2021 financial results 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, Rebecca, good morning or good afternoon, everyone, and thank you for taking part in today's call on the financial results and operational highlights for the first quarter of 2021. I'm Andrew Oakley, the Chief Financial Officer, with me today is Dr. Christian Itin, our Chief Executive 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 4, 2021, 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, May 6, 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 point, the company specifically disclaims any obligation to do so, even if the 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 three, you will see the agenda for today, and it is as follows. Christian will provide a brief introduction, and that will be followed by our operational highlights for the first quarter of 2021. I will next discuss the company's financial results, and then Christian will conclude with upcoming milestones and other concluding comments. Of course, we will welcome your questions following our remarks. With that, I'd like to now turn the call over to Christian. Christian? Thank you, Andrew. Good morning to all of you. Thank you for joining us. I'm pleased to review our progress for the first quarter of 2021. First, before we get to the update on our programs, we're very pleased to see the progress in the U.S., the U.K., and the EU with the COVID vaccinations and seeing gradual decline of the case numbers. This bodes well for the conduct of our clinical trials as we move through 2021 and into 2022. With the expected opening of travel for vaccinated people between the U.S. and Europe, we also expect flight operations to start to gradually normalize, which will relax the pressure on logistics. We continue to work hard with our supply chain and logistics teams, as well as our clinical centers, to ensure timely continental and transatlantic deliveries of leukapheresis, final products, and samples for analysis in order to support our clinical trials and ensure timely data availability and integrity. While we feel optimistic about the developments, we continue to monitor them very carefully with a particular focus on patient safety. In the fourth quarter last year, we provided data updates from the phase I ALLCAR study at ASH. The FELIX study is progressing well and remains on track with data expected in 2022. In Q1, we have received the INN for AUTO1 and can now be referred to as obecabtagene autoleucel for obe-cel. We also announced recently that we have received PRIME designation from the European Medicines Agency, again highlighting the innovative nature of obe-cel. We're also exploring the potential of obe-cel for the treatment of B-cell non-Hodgkin lymphoma. We will have first data at EHA in June. Our next generation program, AUTO1/22, is being evaluated in pediatric patients with data expected for ASH at the end of this year. Phase I enrollment of AUTO4 continues. Importantly, we recently received an ILAP designation for AUTO4 from the U.K. Medicines and Healthcare products Regulatory Agency, the MHRA, which may potentially accelerate regulatory review of the development candidate. Moving on to slide number six to discuss the corporate highlights for the quarter. In January and February, we strengthened our balance sheet with the sale of ADSs under our ATM facility for net proceeds of approximately $15 million. Also a public offering of ADSs, raising approximately $107 million in net proceeds. In January, we highlighted our focus on the AUTO1 program and the conduct of the FELIX study. As part of this outlook, we announced our intention to partner our DLBCL program, AUTO3. We also reviewed our commercial manufacturing strategy and decided to build on our manufacturing set up in the U.K., being able to fully leverage our current manufacturing operations, experience, and skill, resulting in a more economical manufacturing platform while minimizing operational risk. In that process, we have terminated our lease of the U.S. manufacturing facility in Rockville. Moving on to slide number seven. We would like to remind you of the clinical profile of AUTO1 and how it compares to the standard of care. The primary treatment option for patients is blinatumomab, while inotuzumab may typically be used as a bridging therapy. If you look at the event-free survival, we are approximately twice as active as blinatumomab at six months, and even at 12 months, we're at 52% for AUTO1 in terms of event-free survival, which substantially exceeds the six months value for blinatumomab at 31%. When looking at the AUTO1 data, it is important to realize that 70% of the patients had either received prior blinatumomab or inotuzumab and failed on those therapies before entering the AUTO1 trial. Despite the elevated AUTO1 activity compared to blinatumomab, cytokine release syndrome and neurotoxicity are very comparable. Put very simply, with AUTO1, we're looking at a program that has at least twice the level of clinical activity to blinatumomab, which is the current standard of care, with a comparable safety profile. We believe that data is very strong and an excellent foundation to move our product into the registrational study. Moving to slide number eight. Just another quick view on two of the key programs and products that are approved in the space, but from a commercial perspective. We're looking at BLINCYTO or blinatumomab and Besponsa or inotuzumab. As you can see, BLINCYTO reached in 2020 annual sales of $379 million. Typically, patients receive an average of two cycles of the product, which translates to approximately 2,100 patients treated with this commercial product globally. Note that the majority of patients, approximately 1,800, who received the product, are adults. We understand the key driver for sales accelerating into the fourth quarter, which was 29% year-over-year, was the expansion to the community hospital segment in the U.S. beyond the academic transplant centers where the product was initially launched in. While BLINCYTO in ALL is moving to non-academic centers, we also expect the launch of Breyanzi in the DLBCL to establish CAR T experience in those centers. Both developments bode well for a product with the properties of AUTO1. Let's now turn to slide number nine. First off, obviously, the AUTO1 program at this point is in motion in the FELIX phase I-B/II pivotal study. It is a single-arm study with approximately 100 patients with relapsed refractory disease. The primary endpoint is overall complete response rate. Secondary endpoints include molecular responses as well as event-free survival and duration of response. This program is ongoing and will recruit through the course of this year and into early next year. As I have mentioned, we're also conducting some additional studies to explore the activity of AUTO1 beyond the adult ALL population. That includes indolent lymphomas as well as other B-cell non-Hodgkin's lymphomas and chronic lymphoblastic leukemia. As mentioned earlier, we're also exploring the activity in primary CNS lymphoma, which is typically a neglected indication. In December, we also started a next generation version of the AUTO1 program called AUTO1/22 that looks at minimizing the relapse rate in pediatric ALL driven by CD19 antigen loss. The AUTO1/22 program builds on AUTO1 with its unique properties and adds a novel, highly active CD22 chimeric antigen receptor. We are planning to present data on this trial in the fourth quarter of this year. In summary, we believe there's a significant commercial opportunity to build an AUTO1 and a franchise around the AUTO1 program anchored in ALL, both with adult and pediatric patients, and have an opportunity to expand further into the B-cell non-Hodgkin's indications. Moving to slide number 10. AUTO4 is our T-cell lymphoma program currently active in the clinic. We expect to have a clinical update by the end of this year and expect a good understanding by that point of the clinical profile of the product. The sister program, AUTO5, is prepared for an IND towards the end of 2021. The medical need in T-cell lymphoma is high with very limited available treatment options for patients once relapsed after frontline therapy. Moving to slide 11. Always good to remind you all of the technology toolkit we have developed at Autolus, particularly as it relates to the suite of next generation programs, some of which you will recall we showcased at AACR last year. We're looking to move several programs into the clinic through 2021 and into 2022, including our first solid tumor programs, which we're very excited to be progressing. Our cell program modules are designed to provide T cells with a high degree of specificity and activity against cancer cells while strengthening the T cell's resilience to withstand the hostile environment cancer cells create to fend off T cell attack. Slide number 12. As you can see, we have tabulated here the next generation programs alongside the expected phase I start dates. I would like to briefly highlight two of our programs. You will note, as discussed, we started the pediatric ALL clinical trial for AUTO1/22 in December last year and are planning for a data update at the end of this year. We haven't yet mentioned, of course, AUTO6NG, which we expect to start a phase I trial in children with neuroblastoma towards the end of 2021. This program builds on the positive clinical experience with AUTO6, published end of last year in "Science Translational Medicine." All programs will initially be explored clinically in collaboration with our academic partners and will drive clinical news flow in 2022 and beyond. With that, I will turn over the call to Andrew for our first quarter 2021 financial update. Andrew? Thanks, Christian. If we move to slide 14, it's my pleasure to review our financial results for the first quarter of 2021. Starting with our cash position. Cash at March 31, 2021 totaled $239 million as compared to $153.3 million at December 31, 2020. In January of this year, the company sold 1.7 million ADSs under its open market sales agreement, resulting in net proceeds of $15.3 million. In February 2021, the company sold 16.4 million ADSs, representing 16.4 million ordinary shares in a follow-on public offering, including the exercise in full by the underwriters of their option to purchase an additional 2.1 million ADSs at a public offering price of $7 per ADS, yielding net proceeds of $106.9 million. Net total operating expenses for the three months ending March 31, 2021 were $39.9 million. That's net of grant income of $0.3 million. That compares to net operating expenses of $38.6 million, net of grant income of $0.3 million for the same period in 2020. Research and development expenses decreased to $30.7 million for the three months ending March 31, 2021, from $31.3 million for the three months ended March 31, 2020. Cash costs, which exclude depreciation and amortization, as well as share-based compensation, increased to $30.7 million from $25.6 million. This increase in research and development cash costs of $5.1 million consisted primarily of, one, an increase in compensation and employment-related costs, which is net of lower travel costs of $3.5 million due to a combination of an increase in employee headcount to support the advancement of our product candidates in clinical development and severance payments related to the reduction in workforce that began to take place during the quarter. An increase of $2.2 million in facilities costs related to the continued scaling of manufacturing operations. Three, an increase of $0.4 million relating to cell logistics, which is offset by decreases in purchased materials in the amount of $0.6 million and project expenses of $0.4 million. Non-cash R&D costs decreased to $36,000 for the three months ending March 31, from $5.7 million for the corresponding period last year. The decrease is primarily related to share-based compensation expense, which decreased by $6.2 million as a result of forfeitures of incentive share options related to employees affected by the reduction in workforce. This was offset by an increase in depreciation of $0.5 million. General and administrative expenses increased to $8.7 million for the three months ending March 31, 2021, from $7.6 million for the corresponding period last year. Cash costs, which again exclude depreciation as well as share-based compensation, increased to $7.6 million from $ 5.9 million. This increase of $1.7 million is related to an increase, firstly, of GBP 0.4 million in facilities costs. An increase of $0.6 million in legal fees and audit fees. Thirdly, an increase of $0.3 million of expenses related to preparations for becoming a commercial stage company. Lastly, an increase of $0.4 million in compensation and employment-related costs related to an increase in headcount, as well as severance payments related to the reduction in workforce that I mentioned earlier. Non-cash general and administrative costs decreased to $1.1 million for the three months ending March 31, from $1.7 million for the corresponding period last year. The decrease is attributed to share-based compensation expense as a result of the lower fair value of stock options recognized during the period. Loss on disposal of leasehold improvements of $ 0.7 million relates to leasehold improvements no longer being utilized in the facility in White City in London. Interest income decreased by $0.5 million for the three months ending March 31, 2021, due to lower interest rates for cash held on deposit. Other income decreased by $3.7 million for the three months. That compares to other income of $4.5 million in the corresponding period last year. There was a decrease of $5.6 million, primarily due to the weakening of the US dollar relative to the pound during the three months ending March 31, 2021. That compares to the three months ending March 31, 2020, which is offset by gains on lease terminations of $2 million. That's net of any related expenses. Income tax benefit increased to $5.7 million for the quarter, that's up from $3.7 million for the corresponding period last year. This is due to increased research and development credits. As research and development credits grew at a faster rate than our net loss before income tax, this led to a higher effective tax rate. Research and development credits are obtained at a maximum of 33.5% of our qualifying research and development expenses, the increase in the net credit was primarily due to an increase in those eligible expenses. Net loss attributable to ordinary shareholders was $33.3 million for the three months ending March 31, 2021, that compares to a $29.9 million loss for the same period in 2020. The basic and diluted net loss per ordinary share for the three months ending March 31 was $0.53. That compares to a basic and diluted net loss per ordinary share of $0.60 for the three months ending March 31, 2020. Our current cash on hand, which obviously includes the recent financings in January and February, will extend the company's cash runway into the first half of 2023. Now with that, I will hand the call back to Christian to give you a brief outlook on expected milestones. Christian. Thanks, Andrew, let me conclude this part of the management discussion on slide 16 with a recap of the major messages from today's call. The company is in a good position combined with our cash on hand, we feel well-poised for success. We're very excited about the AUTO1 program continue to enroll into the FELIX study in adult patients with ALL expect to report data in 2022. We started the phase I program for the AUTO1/22 product in pediatric ALL patients at the end of last year expect first data to read out in Q4 this year. Additionally, we expect first data from the ALLCAR extensions program at EHA to give us first data on patients with non-Hodgkin's lymphoma. We're also planning to expand AUTO1 into primary CNS lymphoma with a CARLYSLE study, which is actually expected to start imminently. As indicated in our business outlook in January this year, we have enhanced our renewed focus on the AUTO1 program while intending to partner AUTO3 for the treatment of DLBCL patients. We expect phase I data from our AUTO4 program, our program for the treatment of patients with peripheral T-cell lymphoma later in the year, and expect multiple next generation development candidates to enter clinical development over the course of 2021 and in 2022. With our successful recent raise, we are in a position of strength with a cash runway into the first half of 2023. We are now happy to take questions. Operator. At this time, if you would like to ask a question, please press star one on your telephone keypad. Your first question comes from the line of Mara Goldstein. Great. Thanks so much. I'm wondering if, since we're expecting data on both the ALL starting in the fourth quarter of this year and obviously the FELIX in 2022, if you could maybe just sort of wrap some color around what we should be anticipating in terms of number of patients, duration of treatment. Secondarily, on the AUTO8, you're going into a BCMA-directed CAR, and I'm just curious as to what your thoughts are from a competitive landscape perspective, given the development in that space and whether or not AUTO8 may, to some degree, suffer the same fate as AUTO3 in terms of your prioritization and how you think about developing that. Thanks, Mara. Appreciate the question. First, with regards to the work we're doing in the ALLCAR study to sort of explore the activities in the non-Hodgkin's indications as well as the CARLYSLE study for patients with primary CNS lymphoma. Those are exploratory studies. We're basically having part of the ALLCAR extension. We're having cohorts of approximately 10 patients each in each of the sub-indications, and that is what we're expecting to actually report on at the end of the year. Overall, will give us a nice additional set of patients, and I think will give us a good feel for the performance of the product that we're seeing across those various indications. On the pediatric study, with the AUTO1/22 program, obviously that's a classical phase I study as well. We expect the study to be enrolled by the end of this year and data available for all of those patients. In terms of follow-up, obviously the follow-up will be limited because most of these patients are being enrolled and treated during the course of this year. We're looking typically at a few months of follow-up for these patients on average. The third question or area that you were touching on is the AUTO8 program and basically the competitive environment in the multiple myeloma space. Now, obviously with the approval of ide-cel, but also the J&J program actually getting close to market as well. What we're doing with this program, and again, this is a program we're running first to an exploratory phase I study on the academic side, is to actually evaluate whether indeed we can actually induce a high degree of deep responses in patients and whether we do see a good level of persistence of the product. Both, I think we believe are characteristics that are important to actually provide a product that has an opportunity for a differentiated profile. You're absolutely correct in asking the question, what about the profile that you actually need to meet? Clearly, we do set a very high hurdle for a multiple myeloma program, given where the standard of care is, not just from a CAR T perspective, but overall, the standard of care obviously has been moving quite significantly over the last few years, and we clearly would need to actually see a good probability of inducing true long-term remissions in these patients, which has still been a challenge to induce with, frankly, any modality at this point in time. Okay. Thank you. If I could just ask, Andrew, can you remind us on the ATM program, what is left outstanding on that program? Yes, Mara, I can. It's around $80 million. Okay, great. Thank you very much. Thanks, Mara. Your next question comes from the line of Matthew Phipps. Hi, guys. Thanks for taking my question. Christian, I guess at EHA, which I think abstracts are even coming out next week, should we expect some data across all three cohorts from that ALLCAR trial, or is it just mainly going to be indolent kind of updates beyond the four patients at ASH? Thanks for joining, Matt. The update will be focused on the indolent cohort. Okay, thanks. Following up on AUTO8, I guess the UCL posted the trial of a BCMA/CD19 dual CAR for BCMA or for multiple myeloma. I'm just wondering if you're at a point we can talk about this decision to use CD19 here versus maybe some of the newer targets, like bispecifics have shown, such as GPRC5D. The way we're thinking about the AUTO8 program is that the program is anchored through the BCMA CAR. The CAR that we designed there actually has quite a different binder, in terms of properties as well to what has been worked so far in the space, and also uses a different actual design in terms of structural design that we're using for the receptor. It's a significant change to certainly what we've had initially in our AUTO2 product, but also what we're seeing across the current programs that are being moved forward. That's the anchor, basically, and what we're looking to get to is, as indicated, the set of responses, which is really the hurdle that the program needs to take first to be moved forward. The next layer of questions that I think we need to address in the space is to actually get to a long level, an extended level of persistence, which has been actually quite challenging in multiple myeloma when we look at the current programs, the data that has been reported so far. What we're looking to actually add is an element that actually gives us an extended persistence with the program. The third area actually will be to address the quite heterogeneous as well as challenging microenvironment that we find in multiple myeloma. A reason why this is still a disease that is basically we can buy time, but we have a hard time actually getting to a cure. There's still remnants of tumors that we can't get to, and there's situations that were clearly very challenging to sort of actually for immunological and frankly, any other approach to currently crack. Those are the three layers that we're basically working on. In terms of the target antigen that we're using, there is an importance there is to actually drive persistence, which is a key aspect of it, and potentially actually support some of the driving cells that we see in multiple myeloma, being able to actually get at those, which may actually, in part, carry BCMA, but also may be, in part, BCMA negatives. Okay. Yeah, you touched on this, especially with the J&J product, the CR rates are extremely high. Do you think you can meaningfully- Correct. I guess, is there an ability to meaningfully beat that as opposed to just wanting. The real thing here is to drive better persistence to get that improved PFS beyond it, moving it meaningfully beyond a year for PFS. You're right in pointing out that obviously the CR rate per se is very high. I think that the more interesting part of the data is that the depth of the CR rate actually is correlated with the length of outcome. What you need to drive towards are very deep responses with very stringent molecular CRs. That is actually where you start to see differences, also differences between ide-cel and the J&J program. That is the area that you really need to actually drive at. It's actually to look at a very high level of stringency in regards to the molecular CRs that you're actually looking at, and that gives you an early readout. You're right, the next level is very clearly that you need to actually drive for persistence and have ability to actually keep the product active over an extended period of time. The third aspect, as we're seeing within the space, is certainly also related to the overall safety profile that we're seeing as well. Great. Last broader question, given what we've seen with AUTO1 on the level of expansion and persistence and safety, do you keep that in mind as far as using a lentiviral system with this construct and just maybe with different scFvs in programs going forward? How will you manage the different backbones, so to speak, of the programs? I think, in indications where persistence is important to sort of actually get to long-term benefits, we clearly do see a benefit of using the lentiviral backbones. That's obviously what we're using in the context of obviously leukemia, as well as multiple myeloma. You'd also be looking at a lentiviral backbone. Okay. Thanks, Christian. Thanks a lot, Matt. Your next question comes from the line of Gil Blum. Hello, everyone. Good morning. Thanks for taking our questions. With the focus of manufacturing in the U.K., could this offer some logistical issues in treating patients in the U.S.? Well, thanks a lot for joining, Gil. Very good question. Obviously, we actually manufacture for our clinical trials currently out of the U.K., out of the manufacturing site that's located north of London in Stevenage. We've been able to actually serve all the various geographies within the U.S., obviously, as well as across Europe, within the timeframe required to actually ship not only frozen leukapheresis but also fresh leukapheresis. We can actually manage the logistics very well, and we're able to do that even during the most limited flight patterns that we had during the course of last year. We don't think that actually that adds a significant component here, in terms of either time or risk from a logistics perspective. Okay. Thank you. Maybe a little bit about AUTO6NG here. Neuroblastoma in children is a relatively small market. Could you kind of remind us what the specialized features of AUTO6NG and how those might translate across your solid tumor platform and learnings that you could have from a study in a relatively small indication? Right. The AUTO6 program, AUTO6 started out with a chimeric antigen receptor targeting GD2, and was first asking the question, can we actually generate an adequate therapeutic window targeting GD2, understanding that there is a low amount of GD2 also present on pain fibers? That basically, that question was answered through the first trial. That was the publication that we had at the end of last year in "Science Translational Medicine." The next question, however, is then once you have an ability to target, is to actually address the challenges that are derived from the microenvironment that is present in neuroblastoma, and frankly, for that matter, in most solid tumors. What we're doing with the program is actually building quite significant level of resilience into the cells, into the CAR T cells, and we do that in three different ways. On the one hand, we're actually rendering the cells insensitive to checkpoints or checkpoint signals by using an intracellularly available dominant-negative version of SHP2, which is a protein that transmits normally the signal from a checkpoint onto a T cell receptor, a chimeric antigen receptor. The dominant-negative version of it, of SHP2, actually abolishes that signal transduction and with that basically renders the cells insensitive to that negative set of signals coming from checkpoint receptors. The second element is TGF-beta, which is certainly one of the ways in how tumor cell actually defend and fend off T cells and other immune cells over a distance. Here we're rendering the cells insensitive to actually transmit the TGF-beta-induced signal into the interior of the CAR T cell, and we're using, again, the dominant negative version of a receptor sub chain that is part of the TGF-beta receptor. The third element that we're adding is a constitutively active IL-7 signal, actually using a receptor that sort of actually gives you an IL-7-like signal on a constitutive basis. What that does is it actually helps the CAR T cells to keep activated and actually, even if they receive negative signals from the environment, keep overcoming those. IL-7, just as a point of reference, is also what we're inducing when we actually do the conditioning regimen. The chemo stretch up front of any of the CAR T therapies, it's actually to induce IL-7 and IL-15, and obviously with the very same reason to actually help the CAR T cells actually take hold at that point, and also in the case of actually having this signal engineered into the cells to actually keep them going, even if the environment actually is difficult to manage. Now, these three components I just talked through obviously are components that are relevant for any program, we believe, in the solid tumor setting. Hence, actually, the data that we're going to be generating in neuroblastoma will be important not just for neuroblastoma, but across our various programs also that we've been working on towards other tumor entities as well. I think that is sort of the important part. The reason why we're actually exploring these modules in neuroblastoma first is because in neuroblastoma we have a homogeneously expressed target antigen, the case of GD2, which actually takes one of the elements of variability out that you often have with tumor-associated antigens, which often are highly variable in their expression. Think about HER2 or EGFR as an example, which have a wide range of expression across cells within a given tumor sample. That obviously creates a lot of challenges, in fact, if you try to interpret results you actually generate. Here we have a homogeneous background. It's a high medical need setting. It's a pediatric indication. There's obviously a very good fit with the pediatric work we're doing in ALL from a center perspective, from a commercial perspective as well. It also gives us a very good background, a clean background, to actually establish those additional modules and their utility in the solid tumor setting. That was very helpful. Last one on the indolent lymphoma program. Could you remind us how important is having a safer, lower CRS CAR T product in this patient population? Maybe with a look at competitive programs here. Thank you. Thanks, Gil. This is a very important question because obviously, when we look at the CAR T experience so far that we have through the initial programs that reached the commercial stage, is that although we expected the CAR Ts to go very broad in a lot of their indications, DLBCL first, but then also now with approvals in follicular and mantle cell, that we should be able to reach a large proportion of patients. The reality is we haven't been able to do that. The fundamental reason why that didn't happen is that actually managing the CAR T therapy in centers outside of highly specialized transplant centers has been really difficult. It's difficult from a handling perspective, from an infrastructure perspective, from a cost perspective. The adverse event profile and in fact, hematological adverse event profiles of the product actually have significantly limited their commercial use and frankly, have limited their ability to actually reach the majority of the patients in those disease settings. If you go into a disease setting like in a follicular lymphoma, or also mantle cell lymphoma, or CLL for that matter, is that those patients very often are treated much more into the periphery, even more so than what we're seeing in DLBCL as an example. That actually creates a very significant need for an excellent safety profile so that indeed the therapy can be managed outside of the highly specialized academic centers. That's really what is the core and what is needed in terms of the commercial translation of this therapeutic approach to reach a broader range of patients in the respective indications. Your next question comes from the line of Eric Joseph. Hi, good morning. This is Rahul on for Eric. Thanks for taking the questions. Just a couple from us. Firstly, on AUTO1, how do you assess its potential in the earlier line settings in adult ALL? I mean, what kind of response and durability would be seen as clinically meaningful, relative to the existing treatment landscape? Is it safe to say that the initial approval would likely be in the third-line setting, followed by a potential label expansion based on the confirmatory phase III study? Thanks a lot for joining and thanks for the questions. Obviously where we're starting with the development for AUTO1 in ALL is the last line setting. The challenge at that point that the patients have is that they've already experienced an enormous amount of cytotoxic agents. As a consequence of that, are both highly immune suppressed, but also are overall in a rather poor condition because of the high level of cumulative toxicity they've been exposed to. In that sense, it creates actually a very difficult population to deal with, both from a safety perspective, but also from a disease perspective because obviously with every line of therapy, you keep selecting the cells that withstand obviously that particular line breakthrough, and actually at that point, obviously are more difficult to treat. Starting at the last line setting and actually showing a significant level of activity in this last line setting, bodes extremely well in terms of the potential of the product in an earlier line. This was also exemplified very nicely by the experience in adult ALL patients with blinatumomab or BLINCYTO, where the last line or third line data was showing a complete remission rate of approximately 42%. However, in front-line consolidation, in patients who actually have gone through the front-line induction chemotherapy consolidation, cycle 1, and at that point still have minimal residual disease, which was obviously resistant to chemo. In that patient population, BLINCYTO actually showed 78% complete remission rate. In other words, what we're seeing is that as you move up, and this is obviously also T-cell mediated activity, as you move up, we would expect actually that the activity we're seeing and the benefit that we're seeing induced in the third-line patients to substantially improve as we go into an early line of therapy. That is what we would expect to see and clearly, in terms of the settings that you can think about, is similar to what I just said with regards to front-line consolidation of high-risk patients is one setting you might want to go. You could also contemplate a more classical second-line setting, either in patients that are ineligible for transplant or patients that are eligible for transplant. Those are the basic settings that you can choose to actually move the product into an earlier line of ALL therapy. Thanks. Thanks for the color. On AUTO3, can you maybe clarify if the phase I/II ALEXANDER study is in store for additional data readouts and useful in 2021, such as survival follow-up and safety data from the outpatient cohort? Right. On the AUTO3 program, we're in the process actually of writing up the data in a publication. Given that we obviously had four oral presentations of the data last year, we feel it's the right time to actually now show the full picture of the data, which is only possible in a limited way in 10-minute presentations and hence we're moving to a publication, which we're hoping to publish during the course of this year. Great. Thanks for taking the questions. Thanks a lot. Appreciate it. Your next question comes from the line of Kelly Shih. Hey, good morning. Thank you for taking my questions. I have a question regarding AUTO4 in T-cell lymphoma. What kind of patients to enroll on this trial, and what does the competitive landscape look like? Also, for the ASH update at this year-end, should we expect to see meaningful efficacy readout? Thank you. Thanks. Thanks a lot, Kelly, for joining. The patients we're enrolling in the AUTO4 phase I trial are patients with peripheral T-cell lymphoma that have failed, obviously, not just the frontline therapy, but typically three lines of therapy before they actually get onto our trial. These are very advanced patients that we're enrolling into the trial. What we're expecting to see towards the end of the year is obviously we're going through the dose escalation with the program, and we expect data from currently what would assume data from three dose levels, at that point in time, potentially, a bit more than that, but that's sort of the bold part that we're looking at. We're looking at the dose escalation and obviously the readout related to that. In terms of the data that we expect to see is obviously safety data as well as obviously tumor assessments in those patients and pharmacological pharmacodynamic type of data, which should give us a good understanding of the performance of the product in that setting. From a competitive perspective, at this point, obviously, the competitive environment in PTCL late-stage setting is rather limited. There is obviously the subset of patients that are CD30 positive, which are eligible for brentuximab, which is unfortunately only a small portion of the patient population. For the patients that are not eligible for brentuximab, obviously the current opportunities are predominantly actually to participate in clinical trials. In that sense, there is none from a commercial perspective or therapy perspective on the market. There is a very small sort of set of agents that are currently available, predominantly related to high-dose chemotherapy, potential transplant, and if you're CD30 positive, brentuximab. Thank you very much. I also have a follow-up for AUTO6. I'm just wondering, so for the safety switch incorporated into the CAR, at what juncture would a physician be allowed to trigger the safety switch? When we designed the original AUTO6 program, obviously the question that we had was really the question around the safety of the product and whether indeed we could get actually to clinical activity without inducing significant neurological toxicity, in this case, a very major PENS syndrome. Because we couldn't predict whether or not our hypothesis around design actually would be working out, obviously we did put an off switch into the product, which would allow the product to be eliminated should that become a necessity. With the product actually having gone through the initial exploration in phase I in neuroblastoma patients and without actually inducing that type of toxicity, I would expect that it's quite unlikely that a physician would actually want to use the switch, and certainly we didn't have a need to use it. I think, in general, when you actually offer switches, build them into your product, it's really the physician's decision. It's the physician's call in the end whether or not to actually frankly abort the therapy, which is what it is. In this case, you would be providing a dose of rituximab, which would take out the CAR T-cells, at which point you literally abort the therapy. You do that clearly if you have indication of a significant level of toxicity that you have a hard time controlling. This is ultimately the decision of the treating physician, where frankly, that decision has to reside. Thank you very much. Thank you. Your next question comes from the line of Asthika Goonewardene. Hi. Hi, guys. Thanks for taking my question. I have a couple on AUTO8, if I may. Christian, could you talk about the design features of the CAR that could help you get more of those stringent CRs or more patients into MRD negativity? What items in your toolkit are you incorporating that could help AUTO8 overcome some of the suppressive factors in the tumor microenvironment? I have a follow-up on AUTO1. Okay. Well, thanks, Asthika, for joining. What we really were working towards and what the design work that we've done on the receptors actually was geared to, is to get to a very high level of cytotoxic activity of the product against multiple myeloma cells that express very low amounts of BCMA. What we had published earlier is that the range of BCMA expression can vary quite a bit in these patients. It can be as low as 10, 20 receptors per cell, up to in the low thousands of receptors per cell. In general, it's an order of magnitude, two orders of magnitude below of what as an example, CD19 would be. The real challenge is how do you get to these cells that actually express very low amounts, and to still be very active on those cells. That is really the test that we applied, and we did actually test a range of different types of binders as well as designs on the receptor for exactly that ability to give us a very high level of activity against those multiple myeloma cells that express very, very low levels of BCMA, and it still has to work there. That's really the optimization that really was driving the selection for those features on design, et cetera, that would give you exactly that outcome. It was a series of designs tested for that particular outcome, and that is actually how we sort of actually addressed the fundamental question that we believe is at the heart of the improvement that needs to be done. With regards to the toolkit, I think what I just went through with regards to the key elements that we're using as an example for the AUTO6NG program, actually those elements all we believe would be relevant as well in the context of multiple myeloma. The exact composition we haven't disclosed at this point, but I think any of these modules actually would believe are supportive in terms of activity and drive further activity in that setting. Great. Thanks, Christian. Just regarding AUTO1 here. There's data that suggests that deep upfront response may be a driver of durability in DLBCL. Do you think there's data in the public domain that suggests that this also is the case with indolent lymphoma, or is persistence something that's more important in this setting? To put the question another way, I'm trying to figure out how does AUTO1 do better than, let's say, Axi-cel, which also has generated some data in indolent. Right. It is an interesting question actually, in terms of depth of response. I think the best data, and also correlative data with outcome that we have across the B-cell malignancies is actually in ALL, where we have excellent data sets that actually show the impact of molecular responses and the importance of reaching molecular responses to outcomes, whether you're looking at patients who do receive subsequent transplants, or whether you look at in the context, obviously, of other therapeutic modality. Getting to a molecular response is critical for a chance to actually have a long-term outcome. If you don't achieve that, your disease will come back very, very quickly. The data set that we're seeing in multiple myeloma starts to point quite similar way, as we talked about before, and I think it sort of gives us a very similar picture. I think that we're starting to gain more information around non-Hodgkin's lymphoma more broadly. The data sets are probably not quite as strong yet in terms of the correlation between the molecular remission as well as the long-term outcome, it's just data that is still actually being generated. In general, I think there's a sense that getting to very deep responses matters, obviously in a significant way, in these disease settings. With regards to follicular lymphoma, I don't think there is enough data to use it as a guide quite yet. I guess we're looking into the next two or three years, I would expect the field will start generating much more substantive data sets that will give much more conclusive answers around the correlation of molecular remissions and durability of response in those settings as well. Great. Thanks, Christian. Sure. Your next question comes from the line of Robert Burns. Hey, everyone, this is Jake for Rob. My first question is on AUTO8. Thanks for the color on the optimized design. Do you think that would potentially help in eliciting lower CRS than neutropenia than something like JNJ's asset, which showed pretty high rates in its phase I study? Do you think the field has evolved to manage some of these toxicities? In other words, are these a major barrier to adoption? A quick question on AUTO1 allogeneic program. Can you provide an update on when you're potentially going to initiate a study and type of patients or maybe even the target? Thanks. Thanks a lot for joining, Jake. The question related to sort of multiple myeloma and the type of safety signals that we're seeing, I think that what we're obviously having multiple myeloma is a disease that actually is present similar to ALL, it's present in the bone marrow, and it has significant impact on the health of the bone marrow of the patients. That obviously can drive, ultimately has an impact on cytopenias, et cetera, and prolonged cytopenias of course as well. I think we have an element here that's intrinsic to the disease. We're obviously working with therapeutic approaches that actually are highly active and have to be highly active in the marrow, and can drive significant levels of cytokines in these patients in the marrow as well, which can have actually a negative impact on the bone marrow's ability to regenerate. I think what we'll have to see, and we probably need a bit more data on that, though in general in the field is at which point does the marrow actually start to recuperate and sort of actually start to compensate and basically rebuild its ability to properly function. That is something I think that we just need more data on, and I'm not sure there's a good lead at this point that will give you a sense around design premises, et cetera, that you need to actually look at to improve the outcome with regards to these types of toxicities. Second question that you raised was related to the activity that we're doing, having on the allogeneic side, that the program that you're referring to is also one obviously that is in collaboration with our academic partners. We expect that program to actually get going towards the middle of the year, and we'll report at that point in time and give an update on where we're going with the program. There will still be a bit of time here before we're going to start talk about it in more detail. That program is obviously on track to be initiated during the course of this year and on the clinical side. Thanks. Thank you. At this time, there are no further questions. Do you have any closing remarks? First off, thanks a lot for joining. Really appreciate your continued interest and support, and we're looking forward to keeping you updated. Next key update for us will be at EHA. All right. Thank you very much. Have a great day. Thank you for participating. This concludes today's conference call. You may now disconnect.