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spk02: Ladies and gentlemen, thank you for standing by and welcome to the Autoless Therapeutics First Quarter 2022 Financial Results Conference Call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. If you require any further assistance, please press star 0. Thank you. I would now like to end the conference with your speaker today, Olivia Manser, Director of Investor Relations. Please go ahead, ma'am. Thank you, Wren.
spk04: Good morning or good afternoon, everyone, and thank you for joining us to take part in today's call on the operational highlights and financial results for the first quarter of 2022. I'm Olivia Manser, Director of Investor Relations, and with me today are Dr. Christian Eiten, our Chief Executive Officer, and Dr. Lucinda Crabtree, our Chief Financial Officer. Before we begin, I would like to remind you that during today's call, our discussion will contain forward-looking statements. Please make sure you're familiar with our disclaimer, which is on slide two of the presentation. On slide three, you'll see the agenda for today, which is as follows. Christian will provide an overview of our operational highlights for the first quarter of 2022. Lucinda will then discuss the company's financial results before Christian will conclude with upcoming milestones and any other concluding comments. Finally, of course, we will welcome your questions.
spk10: Thank you, Olivia, and good morning to you all. Thank you for joining us. It's my pleasure to review our progress for the first quarter of 2022. Please move to slide four. For those of you who are new to Otelus and as a fresher for those who know as well, we're building a fully integrated CAR T company. Building on our broad platform of cell programming technologies, we're generating CAR-T products that are tailored to the specific tumor setting. Illustrating this approach are OviCell, with its focus on physiological engagement of leukemic cells, maximizing potency while improving safety and persistence, Auto4-5, with a unique targeting approach for T-cell lymphomas, and Auto6NG, a CAR-T product candidate building on a clinically validated CAR-2GD2, and adding programming modules to render the CAR-T cells insensitive to checkpoint and TGF beta inhibition while increasing CAR-T cell persistence. For manufacturing, we're using a common platform. We're using common platform and process design principles to generate products that are highly active and persisting in patients. Our current operations for clinical trial supply is working in four shifts, seven days a week, in what we are anticipating to be very close to our commercial manufacturing model. The commercial manufacturing facility designed for 2,000 products per year is under construction in the UK, about a mile away from our clinical trial manufacturing site, and expected to be ready for GMP supply by middle of 2023. Moving to slide five. We had a successful quarter with OVCell clearing the pre-planned futility analysis in the Felix trial and enrollment continuing to plan. In addition to the primary morphological cohort in the FELIX trial, we are expanding the MRD or minimal residual disease cohort to up to 50 patients. In clinical practice, patients get evaluated on a regular basis for recurrence of disease, typically using flow analysis of their bone marrow. Indication of MRD levels or minimal residual disease levels of leukemia triggers treatment of the patients rather than waiting for full-blown relapse before starting treatment. This additional cohort does not impact our client filing timelines as the primary data will be based on the data from the morphological cohort. With obtaining RMAT from the FDA, we have received preferred regulatory access for OB-Cell in all our key territories, the US, EU, and UK. In addition, the EU granted also orphan drug designation for OB-Cell, adding to the same designation we have received previously from the FDA. In the second quarter, we're looking forward to updates at EHA from our evaluation of OB-cell in non-Hodgkin's lymphoma and primary CNS lymphoma, and two oral presentations covering our initial evaluation of the dual-targeting OTO-1-22 in children with ALL who are ineligible for chemo therapy, and our dose escalation experience for OTO-4 in T-cell lymphoma. In addition, the clinical phase one evaluation for OTO-8 in relapsed refractory multiple myeloma started, and we are on track for Auto6NG to start a phase one in the second half of the year. Turning to slide six, here is a snapshot of our operational progress. As indicated, our new manufacturing facility in Stevenage is progressing well. During the quarter, Dr. Lucinda Crafty was appointed as chief financial officer of the retirement of Andrew Oakley, and as we prepare for the potential launch of OBSEL, Brent Rice was promoted to senior vice president and chief commercial officer. As well as clinical progress, we continue to innovate with our cell programming platform, and earlier this week, Otilus announced the online publication of three abstracts submitted to the American Society of Gene and Cell Therapy, ASGCT, to be held May 16 to 19 in Washington, D.C. The three abstracts focus on Otilus' modular approach to CAR-T cell programming. The abstracts involve, first, enhancing CAR-T cell persistence using a constitutively active cytokine receptor, Second, engineering of CAR T cells to express a fast CD40 protein to increase its persistence and antitumor activity. And three, developing a minocycling-mediated protein-protein displacement platform to make cell therapies untunable with a commercially available and safe small molecule in a dose-dependent and reversible manner. Slide seven, we're jumping over and go directly to slide number eight. The focus is here on OB cell. And just to remind you, OB cell has a unique mechanism of action built on a highly specific engagement of CD19 coupled with a fast release from CD19 once the kill of the leukemic cell has been initiated. This fastest engagement is based on the fast off rate of the cat binder and drives three key properties of OB cell. Very high clinical activity paired with minimal toxicity and excellent persistence. Moving to slide nine. There still remains a very high unmet medical need for adult ALL patients, with approximately 3,000 patients reaching the relapsed refractory stage of the disease that are residing in the U.S. and in the EU. While frontline high-dose combination chemotherapy enables about 90% of the adult patients to achieve complete remissions, only about 30% to 40% will achieve long-term remissions. Once patients are relapsed, they have a median overall survival of less than a year. The insight has become the standard of care for relapsed and refractory patients. However, most patients progress rapidly. More recently, the CARDS has been approved, showing a higher level of clinical activity, but also a significant increase in toxicity. When we look at slide number 10, this slide summarizes the key data we have shown to date for OB-CELL in ALL, which suggests that OB-CELL could be potentially a transformational therapy for adult patients with ALL. In the initial Felix Phase 1b data presented at ASH at the end of last year, OB-CELL showed a favorable safety and efficacy profile consistent with the data we have collected prior in the OLCAR19 study in the same patient population. We saw a high overall response rate, and the duration of response from the OLCAR19 study remained highly encouraging with morphological event-free survival for OB-cell of 46% at 24 months with a median follow-up of 29.3 months, and patients approaching up to 42 months of durability. We continue to see sustained OB-cell persistence in those patients as well. And to remind you, Obicel has been granted orphan drug designation by the FDA for ALL, prime designation by EMA, ILAC designation by NHRA, and most recently, RMAT designation by the FDA, and as well as orphan drug designation by EMA as well. Moving to slide 11, we're conducting the FELIX study with 100 patients in a morphological cohort, treating those patients at sites in the US, UK, and in Spain. We expect to be fully roamed as we go through the course of this year, and as mentioned, expect to have initial data starting in the second half of this year with full data in the first half of next year. Switching gears and moving to slide number 13. OB-cell's unique profile means it could be applicable to a broad range of B-cell malignancies. We are evaluating the product outside of ALL in mild Hodgkin's, B-cell lymphomas, including the typical follicular, DLD-CL, mantle cell, and CLL indications, and expect multiple clinical readouts during the course of 2022. The first clinical updates will be in June at EHA, where we have readouts from a Phase I study, an extension of the old CAR study in the non-Hodgkin's indications, as well as from a separate study, the so-called carousel study, in patients with primary CNS lymphoma. On slide 14, on the right-hand table, we provide a quick summary of the basic experience that we had to date with OB-cell in pediatric ALL patients in the so-called CARPAL study. The fundamental finding was that we have excellent activity without high-rate cytokine release syndrome, but we did see about half of the patients relapse due to antigen loss of CD19. That is why we went back and built on this favorable profile of OB-cell that we have seen in kids adding a highly potent CD22 CAR to create a product called OTA1-22. We will have an oral presentation at EHA of the Phase I data for OTA1-22 in pediatric ALL patients that were ineligible for chemorhyotherapy. Moving to slide 16 to talk more broadly about our technology base. Otolith has a wide range of technology covering mostly cell programming modules and product candidates. With over 100 patent families on the prosecution, we have a very significant technology treasure chest that we're building on. Three new cell programming approaches will be presented at ASGCT, the annual meeting in May, which showcase our industry-leading T-cell programming technologies. Key areas covered by our cell program model cover selective targeting of cancers, controlling CAR T-cell activity, shielding CAR T-cells from the cancer microenvironment as well as the patient's immune system, and enhancing CAR T-cell persistence as well as attracting the support of the patient's own immune system in the fight against the cancer. Moving to slide 17. Here we have tabulated next-generation programs alongside the progress in the clinic. Most advanced is Order 4, our program to address T-cell lymphomas. Order 5 is the sister program to Order 4 and following Order 4 into clinical development. Both programs are run internally. In collaboration with our academic partner, UCL, we have moved Auto-8 into the clinic in a phase one clinical study in multiple myeloma patients. And we're working on Auto-6-NG to get into the clinic second half of this year, targeting neuroblastoma, a solid tumor in children. Turning to slide 18, I'll give you further information about Auto-4. We're actively exploring T-cell lymphoma, which is an aggressive disease with very poor prognosis for patients. primary challenge has been to find a structure or target on the surface of T cells that would allow you to target the T cell lymphoma without at the same time targeting all T cells together. And of course, what that means is that you need to have a target that allows you to get the lymphoma, leaving the T cells behind and with that preserving immunity in these patients. Auto4 is targeting a structure called TRBC1, and it's just a program Auto4, a structure TRBC2. Both structures are related. They're part of the constant domain of the T cell receptor beta chain and are coming basically available in T cells in either one or the other isoform. Both targets are novel, and we obviously are planning to show first data in an oral presentation at EHA for Auto4 from our dose escalation experience in phase one. With that, I'd like to actually hand over into the financial section and hand over to Lucy, who's moving to slide number 20.
spk01: Thanks, Christian, and good morning or good afternoon to everyone. So moving to slide 20, it's my pleasure to review our financial results for the first quarter to March 31st, 2022. On the journey to transitioning Allsalus into a fully integrated CAR-T company, we continued in the first quarter of 2022 to focus our research and development efforts on our lead product, OBSEL, and our pipeline assets addressing cancers with limited treatment options. So starting with R&D expense, for the three months ended March 31st, 2022, research and development expenses increased to $34 million from $30.7 million for the three months ended March 31st, 2021. Cash costs, being the biggest component of our R&D expense, were relatively flat at $30.6 million this quarter from $30.7 million for the quarter ended March 31, 2021. The small decrease in research and development cash costs to the tune of $0.1 million consisted primarily of a $2.8 million decrease in compensation and employment-related costs, which was due to a combination of low retention, severance payments, and the timing of salary mix of new employee hires. A $0.9 million decrease in facilities costs related to the termination and exit of our U.S. manufacturing facility in the prior year and shift in our manufacturing strategy. And a $0.2 million decrease in research and development costs related to cell logistics. These decreases in R&D cash costs were offset by an increase of $2.9 million in clinical costs and manufacturing costs primarily related to our OU cell clinical products. $0.8 million increase in legal fees and professional consulting fees in relation to our research and development activities, and a $0.1 million increase related to information technology infrastructure and support for information systems related to the conduct of clinical trials and manufacturing operations. Non-cash costs increased to $3.4 million for the three months ended March 31, 2022, from $36,000, dollars for the three months ended march 31st 2021 the increase is primarily attributable to an increase of 3.1 million dollars in share-based compensation expense included in r&d expenses as a result of the retention employees post the reduction of workforce that was implemented during the three months ended march 31st 2021 in addition depreciation and an amortization expense increased by 0.3 million dollars Just touching on the G&A side, expenses decreased by $0.7 million to $8 million for the three months ended March 31, 2022, from $8.7 million for the three months in the first quarter of the prior year, of which G&A cash costs, which exclude depreciation and amortization, as well as share-based compensation, decreased by $0.6 million to $7 million. All in all, including grant income and net total other expense, with the largest component being the interest expense of $1.8 million, which corresponds to the liability related to sales of future royalties and sales milestones, which arose upon entering into the Blackstone Strategic Collaboration, we ended the first quarter 2022 with a net loss on a pre-tax basis at $42.7 million versus $39 million in Q1 2021. Although income tax benefits related to qualifying research and development expenditures continue to play a role as a source of additional cash, and the tax credit for the three months ended March 31, 2022 amounted to $5.6 million versus $5.7 million in the prior year quarter. All in all, this resulted in net loss attributable to ordinary shareholders of $37.1 million for the three months ended March 31, 2022, versus 33.3 million dollars in the prior year quarter this in turn gave a basic and diluted net loss per ordinary share for the three months ended march 31st 2022 totaling 41 cents compared to a basic and diluted net loss per ordinary share of 53 cents for the three months ended march 31st 21 finally we ended the quarter with a cash position at 268.6 million dollars and consistent with prior guidance, point to a corresponding cash runway into 2024, assuming receipt of Blackstone milestones. And now let me turn back to Christian to give you an overview of the pipeline and brief outlook on expected milestones. Christian.
spk10: Thanks, Lucy. Moving to the final slide, number 22. Finally, next steps. We believe we have an exciting year ahead of us with OB-Cell running through the pivotal study in adult ALL, delivering initial clinical data from this pivotal study later this year and full data expected in the first half of 2023. We plan to provide clinical updates from four of our programs at EHA this June, and this is in addition to progress across the pipeline that we alluded to as well as we went through the presentation, in particular with obviously also looking at all the 6NG expecting to enter the clinic in the second half of this year. Finally, as a result of our collaboration with Blackstone, we're in a strong financial position with Cash Runway, including project financing payments from Blackstone into 2024. With that, we're happy to take questions.
spk02: As a reminder, to ask a question, you will need to press star one on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. Once again, that's star one on your touchtone telephone. Your first question comes from the line of Matt Phipps from William Blair. Your line is open.
spk06: Good morning, Christian. Well, I think it's not morning anymore there, but thanks for the call. I was wondering, Christian, if you could maybe help us set the stage a little bit for the auto four results. We've seen other CAR targets against T cell malignancies such as CD5, CD7. Do see some responses. A lot of patients maybe go to transplant. But I guess you know, are you expecting a lot of patients in the auto four trials to go on to transplant if they do achieve a complete response? And then I assume also looking at things like viral infections will be another key data point for this program in the first update.
spk10: Good morning, Matt. Thanks for joining. Very good question. So as you pointed out, obviously, T cell lymphoma is a very tough disease to go after. There are a number of approaches that have been tried. What you refer to programs like CD5 or CD7 have sort of a limited application. CD7 is mostly present on acute leukemia, T cell acute leukemia, rather than T cell lymphoma. It's only a very small subset of T cell lymphomas that carry CD7. When you look at CD5, that's a general activation marker for T cells. So any T cell that gets activated, including our CAR T cells, would actually become CD5 positives, which obviously creates a number of challenges. And if you go after more general targets like CD4, as an example, you run the risk that you're actually eliminating the compartment as you're trying to attack and trying to tackle the disease itself with consequences for the patient's ability to actually maintain a healthy T cell mediated immune response. So what we're looking to do with auto four and then also with the sister program auto five is really targeting a subset on the one hand, the disease itself, but then also only a subset of healthy T cells so that at least half of the remaining T cells in theory would not be targetable with the CAR-T and with that sustained T-cell mediated response over time. What we're looking to do and what we've been doing in the trial that we're going to be updating on is obviously dose escalation. It's a wide range of doses starting at very low levels to elevated levels. And what we're looking to see are several points. Number one, we want to understand the safety profile. Number two, obviously, do we have an ability to induce complete remissions in these patients? And number three, do we see any evidence that we're impacting the broader T cell compartment in these patients, which obviously would be a concern from an overall safety perspective. As we're in a dose escalation, we have varying degrees of follow up and we'll need to see and gain more experience to see whether indeed some of these patients may need to receive transplant in the future. or whether the therapy on its own will be sufficient to sustain long-term remissions. That is too early to tell, but I think we're going to get a very good understanding. It's a novel target. It's a novel approach. It's first-in-man experience, and I think it will give us a very good initial experience and understanding of the potential of this approach.
spk06: Thanks, Christian. And if I got one additional question, the recent data from Stanford Group at ACR with a GD2 car, you know, showed some encouraging results in a tough glioma setting, but also did use ICV infusions. I'm wondering if that's something you would look at, any kind of intracranial infusions with the Auto6 program.
spk10: Right, so the specific indication that the Stanford group went after is a form of glioma, which is obviously a cancer that is localized in the brain And there are various ways in how we can think about accessing that, whether you access the brain through an infusion of CAR T cells into the bloodstream and then have the CAR T cells migrate across the blood-brain barrier into the brain and then have an ability to target the glioma. That's one approach you can take. What the SAMHSA team has done is take the ultimate approach, which is literally going directly into the brain and, frankly, delivering product directly onto the lesion in those patients. Obviously, that's an approach that's workable. As we're seeing, obviously, and we'll obviously have data for OV cell in primary CNS lymphoma, where we also do approach the dosing from the systemic side, so from the blood side. And I think we can start to see, you know, I think that both rights are possible and are usable. For our own GD2 CAR program, we would envisage a normal systemic approach because the disease we're treating, neuroblastoma, is a kidney-associated tumor that we can actually very well access just through the standard administration into the bloodstream.
spk09: Thanks, Matt.
spk02: Your next question comes from the line of Nick Abbott from Wells Fargo. Your line is open.
spk11: Oh, good morning. Thanks for taking my question. And, yes, lots of things going on here, team. And I apologize that I had to join the call late, but the first question is on what we might expect as a benchmark for primary CNS lymphoma. The MGH group just published in Blood some experience with AxaCell, I think what was quite surprising to me, at least, was low-grade ICANNs, grade 1, grade 2, grade 1 CRS, and they reported a 60% response rate, 50% CR, with three of those complete responses showing significant durability of, you know, greater than six months at least. So I'm wondering, you know, what we should be expecting for primary CNS lymphoma and, you know, whether you think this is a good benchmark.
spk10: So first of all, thanks for joining, Nick. On primary CNS lymphoma, what we're planning to do is provide initial information on the early patients that we have in the trial. Obviously, that gives us a view, an initial view. I don't think we're at the point where we're going to be, I think, where we can easily benchmark given the number of patients that we're able to report on at this point. I think in general, seeing, you know, a give or take 50% CR rate in these patients, I think is very encouraging. And I think it certainly would be a good outcome for patients with this disease, considering also, frankly, the lack of any suitable other options.
spk11: Okay. Thanks, Christian. And then I noticed that you mentioned that, you know, auto aid has been initiated now, do you think you'll have, when do you think you'll be able to present some initial data from that trial?
spk10: I would assume this is a phase one clinical trial, and I would assume that we'll have to look at the second half of next year for early clinical data.
spk11: Okay, great. Thanks a lot, Christian. Thanks a lot, Nick. Appreciate it.
spk02: Your next question comes from the line of Mara Goldstein from Mizuho. Your line is open.
spk03: Great. Thanks so much for taking the question. I wanted to ask just on the Auto4 program, I think the upper dose limit has been raised there to 900 million cells. Can you talk a little bit about that and that dynamic? And then lastly, just on Obitel, and the new MRD cohort. Maybe you can talk a little bit about what are the challenges in that cohort and why OBIS-L may be appropriate there.
spk10: Yes, happy to do that, Mara. Thanks for joining. So first, with regards to auto four, as I indicated, auto four, we ran through a dose escalation, started at relatively low levels. The initial dose that we had in, I think, highlighting clinicaltrial.gov was 225 million cells. And we created an opportunity to go further than that. We will obviously provide an update on kind of the upper dose range that we went to. We didn't go all the way to 900. And you'll see, obviously, overall kind of the efficacy and safety profile that we're starting to achieve at the higher dose levels. With regards to the MRD cohort for Obicel, I think the importance of the MRD cohort is several-fold. First off, we do have a bit of a discrepancy between the regulatory data package that we need to get to an approval versus the data and the treatment that we actually, treatment algorithm that we do see taking hold at clinical centers. Most clinical centers, also based on the experience with Blincytok, in patients with mineral residual disease are preferring to start treating patients when they have a first inkling of the disease coming back. And what normally happens with these patients is that you actually take, you know, at periodic intervals, you take bone marrow biopsies, you run those bone marrow biopsies typically on flow, and you look for the presence of leukemic cells. The sensitivity of that methodology gives you some of the range of 10 to the minus 4, 10 to the minus 3, resolution very reliably, and that compares to a 5% level that you would have to cross the boundary to become a morphological patient. So you do discover and you actually look at that in the clinic for these patients, and you look for these low levels of disease in these patients. Now, when you find that the patient actually does have low-level disease, typically you would not want to wait for that patient to progress to full-blown disease before you start treating because there are two things that happen. On the one hand, you have obviously a lot more tumor burden, which means you have a higher, typically when you intervene with any kind of therapy, a higher amount of toxicity, but you also have a lower probability of actually inducing a lower-term benefit in these patients. So it's both the safety from a safety and a efficacy side not desirable from a physician's perspective to wait. And so what we're doing with the MRD cohort is really alongside the data set that we need to have in place to support the regulatory approval of the product. We're also looking to generate data that actually support and basically characterize the profile of the product against patients and patients with lower disease burden, which is closer to what actually we're seeing in many clinical practices, both in the U.S. and in Europe, the physicians moving to. So that's sort of the backdrop to what we're doing in the work with the MRD cohort.
spk03: All right, thanks so much.
spk10: Thank you.
spk02: Your next question comes from the line of Gil Blum from Needham. Your line is open.
spk12: Good morning, everyone, and thanks for taking our questions. Maybe a clarification on the MRD population. So are current approved CAR-Ts used in patients that are MRD positive?
spk10: Good morning, Gil. Thanks for joining. What we do see is that certainly in the pediatric patients that the physicians have been moving to treating the kids very early on, typically when they have mineral residual disease. So that's an observation that we certainly see in across, I think, many of the centers within this disease setting and where you would start using, in particular, Kimraya very early on. I think, in general, there's a view that you would like to actually treat early, and I think the best visibility at this point we have from the pediatric population, because it's also where, obviously, the CAR-T therapy is probably most established.
spk12: Okay, thank you.
spk10: And maybe a question on... Sorry, Bill, the second item... Sorry, the second part of the answer is that the experience that physicians have gained with BlinCyto, also with adult patients, also moves quite significantly towards patients with mineral residual disease rather than waiting for the patients to develop full-blown morphological disease. The difference in response rate is quite significant. You have about 43% to 44% CR rate in a morphological disease of Glyncytel, but you do have about 78% CRs, molecular CRs, if you go into the MRD population for Glyncytel.
spk12: All right. So it makes sense to have earlier treatment. Maybe a question out of 122. You said Kymriah ineligible. Can you remind us of any of these patients that are being enrolled have experienced CAR T's in the past?
spk10: Right. So Auto 122, obviously, which is a dual-targeting CAR, we treat it in the phase one experience now, kids that are ineligible for Kymriah. And you can be ineligible for Kymriah for a set of reasons. One is that you already have Kymriah and you cannot get a second dose. And that is obviously part of the population that we have involved. Secondly, it can be that the disease is localized in an area where you actually have to exclude patients from the treatment of Kymriah. And in particular, a localization obviously would be CNS localized disease. So it's typically related to either prior therapy with Kymriah and not being eligible anymore for a second go, or having disease that is basically extramedullary disease, disease outside of the marrow, that actually would disqualify you from being offered Kimraya as a therapeutic option.
spk12: All right, so maybe a follow-up there. Will the presented data be stratified based on patients who are, you know, experienced previous CAR-T therapy, or more of a, like, mixed bag.
spk10: We'll have both categories of patients. It's also the phase one experience, so it's a limited number of patients. But you have both patients who either have relapsed post-Kinraya or patients that have disease outside of the normal localization.
spk12: All right. And maybe a last one. I know you guys are showing a bunch of really interesting new technologies modular technologies coming up at ASGCT. Considering the current laser focus on ObaCell, are you guys considering out-licensing some of these technologies to other firms?
spk10: I think there is with, you know, I mentioned the fact that we have a very broad portfolio with about 100 patent families covering the various inventions. There clearly is opportunity for that and opportunity for out-licensing. You know, part of that is what you saw as to last year with the collaboration we put in place with Moderna, and there's additional opportunity. There's some smaller licenses we've granted as well over the years to aspects of technology. So there's clearly opportunity for that outside of the portfolio that we're pushing ourselves.
spk12: All right. Thank you for taking all of our questions. Thanks a lot, Bill.
spk10: Appreciate it.
spk02: Your next question comes from the line of Asika Gunwaruddin from TruViz. Your line is open.
spk08: Hi, thanks for taking that question. This is Bill on for Asika. We were wondering if the MRD cohort, would that data be ready for the first half 23 update? And then also subsequently, we're just wondering in your hands and your experience, on average, how many multiple myeloma cells are double positive for CV19 and BCMA? Thanks.
spk10: Thanks for joining, Gil. First question related to data becoming available from the MRD cohort, whether that's going to be coinciding with the main data release from the morphological cohort. That's something we need to look at. Obviously, we won't have a range of follow-up on these patients. And one of the determination we need to make is how much of a minimal follow-up we want to have in that patient group. But it's the maybe possibility to include some of that data, at least on the initial experience in that group from a safety and the basic activity perspective. So we'll see how that progresses. I think there's an opportunity, but in general, what you would like to have at the MRD cohort is a longer follow-up and actually see how these patients do over time. not only in terms of the initial response you could induce and the safety profile associated with that treatment.
spk08: Thanks. And the CD19 and BCMA double positive in the multiple myeloma population?
spk10: Double positive. Right. So the two aspects to that. So BCMA is the main target that you would find on multiple myeloma cells. The interest from CD19 is sort of twofold. Number one, there is what is believed to be a driving population of multiple myeloma that is CD19 positive. That's one aspect. So it's a smaller number of cells, but having a key role in driving the disease. And secondly, the fact that if you have your therapy and you have an ongoing activation of your compartment using with the de novo generation of CD90 positive cells, not myeloma cells, but generally positive cells, that that probably is going to be helpful to actually sustain activity of the CAR T cells over time as well. So there are likely two elements there that play into the rationale for choosing the targets.
spk08: Thank you so much. Thank you.
spk02: Your next question comes from the line of Kelly Shi from Jefferies. Your line is open.
spk07: Hi, good morning. This is Dave on for Kelly Shee. Just a couple of questions for me. One is on futility analysis. Can you provide more color whether it's safety or efficacy analysis or how many patients were in that analysis? And second is dual CAR. What kind of bar do you think will be suitable to move that program into next step? Thank you.
spk10: All right, thanks a lot, Dave. Appreciate it. So the futility analysis, that was a predefined analysis point, obviously, for the study. And as you typically do in futility analysis, you look at the primary aspects of the program. One is the likelihood of the program to succeed. And that's basically a certain statistical power. You want to see that the program is going to succeed. And secondly, you also obviously look at the overall adverse event profile. and you want to make sure that the profile of that product is as expected and you do not pick up any undue adverse events in the program. So that was pre-specified, and ultimately it's driven by statistical analyses on your likelihood of success in the program as well. With regards to Auto-Om-22, obviously the start of the Phase I, as indicated in Kimbry-ineligible patients, is obviously the initial data set that we're getting. Ultimately, this type of product, you would like to position at the same level of Cabria. So you do not actually want to have sequential CAR-T therapy. That would not be a smart thing to do. But actually, it has a product that has an ability to overall improve the ultimately event-free as well as overall survival in that patient group by minimizing relapses due to antigen loss. And that's ultimately what you'd be looking at. When you look at the space, you see that about the event-free survival one year for pediatric patients is around 50%. So that's the number that you would like to actually look to improve and see improved in a product with a dual targeting approach in pediatric patients.
spk07: Got it. Thanks. And just to follow up on the BCMA CD19 CAR, so what would be the bar for that product because of this changing treatment paradigm of multiple myeloma?
spk10: You have to really postulate a very high bar for the program to proceed into the next steps of development. We do see, obviously, very good results a very good profile for the J&J program, and we see good sustained activity on the BMS program. I think what you would want to see is you want to see very deep molecular CRs that you can induce, and you also would like to see an improved pattern with regards to persistence as well in the product. I think those are two parameters that I think can be picked up relatively early in the evaluation of the program, I think those are certainly two of the parameters we'd be tracking very carefully.
spk07: Got it. Thank you. Thank you.
spk02: Your next question comes from the line of Simon Baker from Redburn. Your line is open.
spk05: Thank you very much for taking my questions. Three, if I may, generally of some more general nature. I just wonder if you could give us your latest observations on the normalisation of enrolment rates as we start, certainly in parts of the world, to emerge from the pandemic. Are we close to normal or is there still some distance to go? Secondly, on the Stevenage facility, you talked about the capacity of 2,000 batches per year. Is that from second half 2023 or is there a ramp-up? And could you give us some idea of the scope to expand? You talked about the option. I wonder if you could give us an idea of how much it could be expanded by. And then finally, a couple of weeks after your full year results, the FDA published their draft industry guidance document on CAR T development. I just wonder if you could give us your perspectives on that document and the direction the FDA is moving in now that you've had a good chance to review it. Thanks so much.
spk10: Well, thanks for joining, Simon. So the first question was related to the enrollment and frankly, the ability of clinical trial centers to support clinical trials. And as I think many of us have seen, there's obviously during the peak of the pandemic, many of the institutions were impacted heavily. not only by a lot of workload, but also as a consequence of losing a substantial amount of staff or a number of staff that are particularly in those individuals who are active in the ICU entities, et cetera. So that's been certainly a significant issue. We've seen a lot of that normalized. There's still some geographic differences. but the vast majority of centers are back in a normal mode of operation, certainly for patients that have the level of medical need, as we're seeing here with OB-cell in patients with acute leukemia that actually do have to get treated. You cannot wait to treat those patients. And we're seeing a normalization, certainly for those patients. I think for some of the less life-threatening diseases, that may still actually take a bit more time. But I think that's where we are. A big chunk is actually, a big, big aspect is going to be the training of nurses and, frankly, the hiring and training of nurses, which will take time. And it certainly will be a significant effort we see all across both the US as well as Europe and the UK. Second question was related to the capacity at Stevenage. The capacity at scale at the new facility will be 2,000 batches. We're obviously going to ramp up that capacity operationally as we're rolling out the product and as we're sort of growing the product. Does it make sense to actually have a full standing operation for that level of capacity and then not fully using that? So that needs to be an adapted approach as you go up. The design of the facility, setup of the facility, supports, about 2,000 products a year. The scope to expand actually would allow us to actually expand physically the facility and with that increase the capacity overall. And then the last question was related to the CAR T guidance documents, a document that was coming out from the agency. I think an important aspect is that obviously we're in a relatively new field still. There's a lot of learning going on. I think having that type of learning and best practices sort of being started to be consolidated and sort of agreed upon I think is very helpful. And so we're, you know, I think, you know, glad to see that we're seeing some of that guidance to be more formalized as it is outlined now in that directive.
spk05: Great. Thanks so much.
spk10: Thank you.
spk02: Your next question comes from the line of Eric Joseph from JPMorgan. Your line is open.
spk09: Oh, hi. Thanks. This is Sean. On for Eric Joseph. So, sorry, my line was dropped for a little bit. I apologize if that's a repeat of the question. So, we are basically wondering of a follow-up question on the utility analysis. So whether you can talk about, you know, some more details on the statistic assumption, you know, patient numbers compressing that analysis. And having passed it, is there, you know, a minimum CR rate or duration or response that can be inferred from that? Thanks.
spk10: Thanks for joining, Sean. And, yes, indeed, the question has been asked before. So the futility analysis, again, is the statistical hypothesis. We obviously haven't communicated it. What you typically want to know is whether the study actually is in a position to reach the design primary endpoint that you have set and the statistical outcome that you set for the overall study. And that is what you want to make sure that, indeed, the program can reach that outcome. And that's typically what you do in your fertility analysis. And that's, you know, from, as indicated, it's primarily based on the clinical activity side. And, you know, in our case, the primary endpoint being the complete remission rate, but then also obviously looking at the overall safety, which is also going to be taken into account as well. So those are kind of the key parameters. We haven't actually given more detail or more resolution on that. Obviously, we nicely passed that point, and we're progressing well with the program.
spk09: All right. Thank you.
spk10: Thank you.
spk02: There are no further questions at this time. I would now like to turn the conference back to Mr. Christian Aydin.
spk10: All right. Well, thank you very much all for joining today. Obviously, an exciting first quarter. We're really looking forward to the second quarter with seven abstracts to be presented in the upcoming weeks. And we also will take the opportunity, particularly around the EHA data, to give you a more in-depth update around the conference as well. And obviously, put the data in context as well outside of just a pure clinical data perspective. All right. With that, I'd like to thank you all for joining and wish you a great day. Thank you.
spk02: Ladies and gentlemen, this concludes today's conference. Thank you for your participation and have a wonderful day. You may all disconnect.
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