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spk14: Hello, ladies and gentlemen, and welcome to the Autolist Therapeutics Third Quarter 2022 Financial Results Conference Call. As a reminder, this conference call is being recorded, and I'd like to now turn the conference over to your host, Olivia Manson, Director of Investor Relations. Please go ahead.
spk08: Thanks, Brianna. Good morning or good afternoon, everyone, and thanks for joining us to take part in today's call on the Financial Results and Operational Highlights for the Third Quarter for Autolist. I'm Olivia Manser, Director of Investor Relations and with me on today's call as usual are Dr Christian Eichten our Chief Executive Officer and Dr Lucinda Crabtree our Chief Financial Officer. So before we begin I'd just like to remind you as usual that during today's call our discussion will contain forward-looking statements. Please make sure you're familiar with our disclaimer slide which is on slide two. And then turning to slide three, you'll see the agenda for today, which is as follows. So Christian will provide an update of our operational highlights for the third quarter of 2022. Lucinda will then discuss the company's financial results before Christian will conclude with the upcoming milestones and any other concluding comments. And finally, we will of course welcome your questions. Over to you, Christian.
spk02: Thank you, Olivia, and good morning to you all, and thank you for joining us. It's my pleasure to review our progress for the third quarter of 2022. Moving to slide four. We're really pleased with our strategic and operational progress during the third quarter of 2022, which is highlighted over the next two slides. Firstly, we remain on track to provide an update on our Pivotal Felix trial in Q4 2022, and we plan to present Felix Phase 2 data at a medical conference in the first half of 2023, most likely at ASCO. We're also likely, we're also looking forward to presenting longer follow-up data from our ALL patients in the old CAR-19 phase one trial at ASH and are planning a more in-depth look at the patients. Sorry. Looking forward at the patients that we've treated with non-Hodgkin's lymphoma. We're presenting further data at the three phase one trials at ASH in December 1st as indicated in the old CAR-19 phase one extension study for OB-CELL in BANHL, a CAR-PAL study, which is also a phase one trial with auto-122 in pediatric ALL, and from our LIBRA T1 phase one trial of auto-4 in peripheral T-cell lymphoma. The abstracts of these data updates will be online later this morning, so we won't be discussing them during this morning's call. In addition, the phase one McCarthy trial exploring auto-8 in multiple myeloma patients is progressing, And the phase one MCAR-TD2 trial exploring Oto6-NG is expected to start in the first half of 2023. Turning to slide five, we've made some great operational progress during the quarter and post-period end. We're very pleased to report on two technology deals in October 2022, which underscore the scientific capabilities and expertise at Otilus. We signed an agreement with Bristol-Myers Squibb, granting them access to our proprietary RQRA gritoximab-induced safety switch for incorporation into a set of selected cell therapy programs in return for a low to mid-single-digit million upfront payment with potential for near-term option exercise fees and development milestones plus royalties. Moderna exercised an option on one of the proprietary binders being developed against an undisclosed immune oncology target for the delivery of their messenger RNA therapeutics. in return for a low single-digit million upfront payment, as well as development and commercial milestone payments for each product successfully commercialized, plus royalties on net sales of all products commercialized under the agreement. The license option stems from the deal we signed with Moderna in August 2021. We also continue to make progress in our manufacturing and CMC operations. Phase one of the build of our Stevenage facility is on track for transfer to Odalus before the end of the year, to start the qualification and validation work of the facility and remains on track for good manufacturing practice operations commencing in the second half of 2023. We're also on track with the CMC workflow and report generation for the CMC package plan to support a BLA submission to the FDA. Cash and cash equivalents at the end of September were $163.1 million, not including the R&D tax credits for HMRC of $19.1 million received in October. Slide six. With that, let's talk about our primary focus, our lead product, Obicel, on slide seven now. Just to remind you, Obicel has a unique mechanism of action built on highly specific engagement of CD19, coupled with a fast release from CD19 once the kill of the leukemic cell has been initiated. This fast disengagement is based on the fast off rate of the cat binder and drives three key properties of Obicel. reduction of the amount of cytokine release per target cell encounter, which in turn will reduce the amount of immunotoxicity in the patients, reduced exhaustion of the CAR T cell, and improved engraftment and overall persistence. And those of you not familiar, I refer you to a paper by Sarah Garroshian at Nature Medicine published in 2019. Moving to slide eight. We show this slide as a reminder that there remains a very high unmet medical need for treatment of adult ALL patients with approximately 8,400 new cases diagnosed yearly on a worldwide basis in the last line setting. Approximately 3,000 of these cases reside in the US and the EU. And whilst a combination chemotherapy enables about 90% of the adult ALL patients to achieve complete remissions, only about 30% to 40% will achieve longer-term remission. Once relapsed, patients have a median overall survival of less than a year. Current approved therapies for adult patients are Blinsaito and Tecardis. Both therapies are highly active, but frequently followed by subsequent treatments, for example, allogeneic stem cell transplants. Blinsaito has a favorable safety profile with few patients experiencing severe CRS and ICANS, but with limitations on durability of effect and convenience due to the need for continuous IV infusion during its four-week treatment cycles. Tecardis is more challenging to manage and induces elevated levels of CRS, high levels of ICANNs, and requires steroids and vasopressors for many patients to manage adverse events. Both therapies have been shown to be highly active. However, most patients progress rapidly and require subsequent allografts to achieve durability. Moving to slide nine. Many of you have seen this slide before, but it's a useful reminder of why we think OBSL is a potentially transformational therapy for adult ALL. Building on its unique mechanism of action, Obicel has shown a high overall response rate with a favorable tolerability profile and sustained event-free survival that tracks long-term persistence in those patients. Obicel has been granted orphan drug designation by the FDA and EMA for ALL and obtained prime designation by EMA for the EU, ILAP designation by MHRA for the UK, and most recently, RMAT designation by the FDA. Moving to slide 10. Based on what we believe is potentially transformational data from the old CAR study, we're conducting the pivotal Felix trial with approximately 90 patients with morphological disease, treating at 34 sites in the US, the UK, and Spain. We're on track with our previous guidance and expect to provide a qualitative update in Q4 2022, which we would expect to reference whether the primary endpoint has been met. We're planning on presenting data from the FELIX study at a medical conference in mid-2023. In order to maximize outcomes from the FELIX trial in parallel, we're also assessing OB-cell in additional cohort of up to 50 patients in second or later complete remission who have developed minimal residual disease. However, this additional cohort does not impact our planned filing timeline as the primary data will be based on the data from the morphological cohort. Moving to slide 12, OB cells unique profile means it could be applicable to a broad range of indications. We're consequently evaluating the product candidate outside of ALL in B-cell non-Hodgkin's lymphoma indications in an ongoing phase one clinical trial. As we said before, we have positive clinical readouts at the recent EHA Congress from the Phase 1 studies in B-cell non-Hodgkin's lymphoma and primary CNS lymphoma presented by way of the poster, as well as an oral presentation of the first Auto-1-22 Phase 1 data in pediatric ALL patients. And I'll cover these data in the upcoming slides. As I said, we'll be presenting additional data at ASH in December this year with abstracts due to go online later today. On slide 13, As a reminder, the academic All-Coron-19 study has been extended as a basket study where we are testing OB-cell in a number of B-cell malignancies. To date, we've treated 17 patients with follicular DLBCL and mantle cell lymphoma, and no patient experienced high-grade CRS, and none had any grade of neurotoxicity. Of the 17 patients dosed, 16 achieved a metabolic complete remission, seven of seven follicular lymphoma patients, six of seven diffuse large B-cell lymphoma patients, and three of three mantle cell lymphoma patients. We lost one patient to COVID and one MCL patient relapsed. Fourteen of the 16 patients that have responded remain in metabolic CR with a median follow-up of 9.2 months, the longest being 19.1 months as of the last reported data cut, and the data continues to mature. We've also started treating some CLL patients, and from the three patients that have reached the initial evaluation, as of the last data cutoff, two went into molecular CR in the bone marrow, but have some residual lymphadenopathy on CT scans. We're looking forward to presenting additional patients and longer follow-up data from this all-care extension study at ASH in December. Turning to slide 14, we're also exploring OV-cell and primary CNS lymphoma in our academic carousel study. This is a type of aggressive B-cell lymphoma, but because of its anatomical location, it has a particular poor prognosis. Initial treatment is often intensive, and outcomes for these patients tend to be poor. In the data we presented at DHA, we didn't see high-grade CRS. Two patients experienced neurotoxicity, grade 3 and 4. One patient improved with steroids and anakinra. The second patient had several neurological deficits consistent with progressive disease and didn't respond to steroids and anakinra. Overall, you can see on the right-hand side of this slide that despite these patients having no disease outside of the CNS and having had lots of rituximab treatment, we still see really nice expansion of OB cell in peripheral blood, and we expect to provide more data from this study in 2023. Moving to slide 15. Our initial experience with OB cell in children achieved a high level of sustained CRs without experiencing high-grade CRS. Those children who relapsed after treating with OB cell had, most of them had lost CD19 expression on their leukemic cells at the time of relapse. Here we're taking the next step in OB cell's life cycle with Auto-122, a dual targeting product building an OB cell and adding a highly potent CD22 targeting chimeric antigen receptor. The CD22 CAR was designed to be active against leukemic cells with low levels of CD22 expressed on their surface. We evaluated all the 122 in an extension of the Carpal study in children who were ineligible for Kimraya. The children either relapsed after receiving Kimraya and could not be treated, or they had extramedullary disease, i.e., singular lesions in tissue without having disease in the bone marrow, the normal location of the leukemia. This is a very challenging group of patients to treat. Out of 14 children, four had prior Kimraya therapy, and three of them had lost CD19 expression. seven kids had extramedullary disease. Moving to slide 16, data were presented at EHA and showed that nine of the 11 patients achieved a molecular CR on day 28. On the one, 22 was well manageable with no patients experiencing high-grade CRS. No patient relapsed with antigen loss, and two of the CD19 negative patients achieved a molecular CR demonstrated the isolated activity of the CD22 CAR. We're continuing to follow the patients and we'll be presenting this data at ASH in the upcoming weeks. Slide 17 and moving straight to slide 18 on the pipeline. Here is a brief depiction of our broad-cell programming toolkit we have developed over the last few years and drove the deals with BMS and Moderna. All in, the technologies cover programming modules for targeting, control, shielding, and enhancing CAR T-cell activity. At Odalis, we have more than 100 patent families covering these products and cell programming technologies. Recent illustrations of three technology applications were shown at ASGCT, the annual meeting in May this year. Each of one of our product candidates applies one or several of the technologies to maximize its impact on the specific cancer it is designed to tackle. Moving to slide 19. This slide shows more of our next generation programs beyond OV-cell. A pipeline program we're particularly excited about is OTO4, which is a Phase 1 study in T-cell lymphoma. I'll give you a refresh of the data we presented at EHA in just a minute. OTO8 moved into the clinic earlier this year in a Phase 1 clinical study in patients with multiple myeloma, and we're now dosing patients. I also want to mention that our first solid tumor program, OTO6-NG in GD2-positive solid tumors, will be moving into the clinic in the first half of next year. Turning to slide 20, we're actively exploring T-cell lymphoma, which is an aggressive disease with a very poor prognosis for patients. You might recall our EHA analyst call where Dr. Horvitz from the Department of Medicine Lymphoma Service Memorial Kettering Cancer Center talked about the majority of patients being either refractory or relapsing after initial treatment. Standard of care is variable and often based on intensive chemotherapy treatment. Median survival for patients with relapsed or refractory disease is less than six months. T-cell lymphomas are a clonal disease that either express TRBC1 or TRBC2. The T-cell receptor beta chain constant domain 1 or 2 are expressed on more than 95% of all T-cell lymphoma patients. Only gamma delta T-cell or NKT-cell derived lymphomas lack T-cell receptor beta chain constant domains 1 and 2. Auto4 targets TRBC1 and is the first product candidate to do so. Using next-generation sequencing, we identify patients with TRBC1 expressing T cell lymphoma, and then these TRBC1 positive patients are treated on the currently open Auto4 study. And in the future, we plan to open a study targeting TRBC2 positive patients with Auto5 as well. AutoIV is designed to selectively kill lymphoma cells in a manner that we believe will preserve a portion of the patient's normal healthy T cells to maintain immunity in that patient. Turning to slide 21, we presented data at EHA on the LIBRA T1 study evaluating AutoIV in patients with T cell lymphoma. We've seen encouraging activity and a favorable tolerability profile, indicating clinical proof of concept for the new approach for targeting T cell lymphoma. We're looking forward to presenting longer follow-up at ASH. So with that, we'd like to turn to slide 23. The manufacturing of cell therapies is complex, and we've developed a great deal of skill and experience manufacturing products throughout the pandemic and for a range of product candidates. We're building a new manufacturing facility in Stevenage in the UK. This location is about a mile away from our current clinical manufacturing operations at the Cell and Gene Therapy Facility and will allow us to transition our entire operation, including our experienced staff, to the new facility in an expeditious and efficient way, both minimizing startup risks and costs for commercial supply. As evidenced by our successful manufacture of CAR-T products for the pivotal study with centers across the U.S. and Europe, the location is well-suited for global supply with easy access to several international airports, including London Heathrow. The new 70,000 square foot facility will provide otoliths with a capacity of approximately 2,000 cell therapy batches a year and with the ability to expand capacity further when needed. You can see on this slide a rendering of what the facility looks like once completed by the end of the year. In the middle, you can see the actual facility a few weeks ago when the large preassembled HVAC units were lifted onto the roof. I mentioned our progress earlier, Phase one of the BUILD project is scheduled to complete in the fourth quarter, and the equipment installations and qualifications for all of this is on track for GMP operations for the second half of next year. For our clinical supply operations, we currently operate with four shifts, seven days a week. Our commercial manufacturing model will continue with that pattern of a seven day a week throughout the year. So with that, I would like to turn to slide 25 and pass the call to Lucinda for our third quarter 2022 financial update. Lucy?
spk13: Thanks, Christian, and good morning or good afternoon to everyone. It's my pleasure to review our financial results for the third quarter to September 30th, 2022. We'll start with our cash position, which at September 30th, 2022, totaled $163.1 million. This doesn't include a $19.1 million R&D tax credit we received from HMRC post-period end in October. With regards to our cash, I will note, given the majority of our spend is in GBP, we actually hold a large portion of our cash as reported, in fact, approximately 80% in pounds, and the majority of the remainder in USD. Net total operating expenses for the quarter were $43.5 million, which included licensed revenue income, totaling $2.4 million, which primarily resulted as a result of the Moderna option exercise announced in October. Research and development expenses increased by $5.3 million to $37.6 million during Q3. This was primarily due to the following, an increase of $3.6 million in clinical and manufacturing costs, primarily related to OBSEL, An increase of $2 million in salaries and other employment-related costs may be driven by an increase in the number of employees engaged in research and development activities. We also have marginally increased legal and IT fees as we transition through the quarter, offset by a decrease in facilities costs and depreciation of PPE. General and administrative expenses remain stable year on year. Other expense stroke income or net expense income decreased to an expense of $3.7 million from an income of $1 million in the three months ended September 30th, 2021. The decrease of $4.7 million is primarily due to the weakening of the pound sterling relative to the US dollar exchange rate during the three month period. Interest expense increased to $1.9 million in the quarter, which relates primarily to the liability related to sales of future royalties and sales milestones through our agreement with Blackstone in November 2021. Finally, net loss attributable to ordinary shareholders was $42.8 million for the quarter. The basic and diluted net loss per ordinary share for the quarter totals negative 47 cents, compared to negative $0.47 for Q3 2021. We estimate that our current cash on hand, including anticipated milestones in the relevant period from Blackstone, extends the company's runway into 2024. And now back to Christian to give you a brief outlook on expected milestones. Christian.
spk02: Thank you to see slide twenty seven finally on next steps. We believe we have an exciting period ahead of our adults with the summary shown on this slide. The main focus, of course, is cell and relax refractory adult patients with our initial update on this pivotal Felix study coming before the end of the year. And obviously, the plan presentations at a medical conference in middle of twenty, twenty three. Longer-term follow-up will be then shown, or is planned to be shown, by the end of 2023 as well. Beyond that, the studies of OBCL and relapsed refractory BNHL and CLL and primary CNS lymphoma are ongoing, as well as our Auto-122 program and our Auto-4 program. And we expect to have more data over the course of this year and next, whilst we progress the other Phase I programs in our pipeline. Finally, as a result of our collaboration with Blackstone and in anticipation of the milestones we expect to receive during the relevant period, we project our cash runway unchanged into 2024. We're now happy to take questions.
spk10: Thank you.
spk14: And at this time, we'll conduct the question and answer session. As a reminder, you can ask a question. You'll need to press star 1-1 on your telephone and wait for your name to be announced. So our first question is gonna come from Mara Goldstein. Your line is now open.
spk01: On Felix and the data disclosure in the fourth quarter, can you sort of speak to what we will see, whether or not, I'm assuming there will be some read on the primary endpoint of response rates, but I'm curious about the secondary endpoints and again, that MRD negative cohort that you started enrolling. And then the other question I had relates to the manufacturing and where that process will be with respect to the filing of the BLA and how you'll be able to layer those two things for filing of the BLA.
spk02: Okay, thanks, Mara. Thanks for the question. So first off, what we're planning to do at the end of the year is obviously provide an update on the FELIX study. It will be a high-level update. We'll be able to make a statement towards the primary endpoint of the study. I do not believe that we'll be able to actually make comments with regards to secondary endpoints of the study. That would be premature. And the MRD cohort is obviously enrolling and will continue to enroll into next year, but of course that cohort is not the key data set that will go into or critical data set that for the BLA. So the focus is on the Felix data. The data itself will then be targeted to be shown middle of next year as we said we target ASCO. And of course you do remember that there are very strict disclosure rules if you want to present at ASCO, which also basically reduces the amount of information that we can share within the price release that we're planning for the end of the year. The second question, I think, was related to the manufacturing setup. And as we had indicated, the commercial manufacturing site is on track to obviously go through all the qualification validation work that needs to go into the VLA filing. And that obviously is going to be in time for VLA filing targeted for the end of next year.
spk01: All right. Thank you.
spk02: Thank you.
spk11: Operator, do we have another question?
spk08: I'm just jumping in. I think Brianne may have dropped, but the next question was asked at Truist, and I think your line should be open.
spk10: Hi there. Hi, guys. Can you hear me okay? Yes, we can.
spk12: Oh, hey. Good afternoon, guys. Thanks for taking the question. Maybe just want to build on Mara's question first. Can you specifically disclose in the press release a number, maybe like the percentage of patients in remission at the first scan and the primary endpoint? Can you actually provide a number in the press release? Or is this something that you think you want to hold back, given how strict ASCO is? And then looking forward to the All-Car-19 update. Beyond what we've seen, Ash, I'm just curious to know, how many more patients in follow-up would you need to give either confidence initiates and pivotal studies based in these specific indications. And are these pivotal trial initiations something we can expect in 2023? And then lastly, something for Lucy here. Lucy, can you give us some direction on how R&D costs are going to move next year? Given that Felix is winding down and majority of the other studies are in the early stage. Thanks.
spk02: All right. Well, thanks a lot, Astika. I'm glad we managed to connect. So the first question you asked was related to the type of disclosure that we can make. So the statements, obviously, as I indicated, will be about the primary endpoint. The primary endpoint of the study is the overall remission rate, which is based on complete remissions and complete remissions with incomplete hematological recovery. So CRs and CRIs. The statement with regards to the endpoint, obviously, is physical tests that we have to pass. to actually be sure that, indeed, the signal is truly above the threshold that was set for the study, which is obviously, basically, in very simple terms, basically getting us substantially above the level where the current standard of care was coming out. So I think that sort of, if you need a reference point, that gives you reference points in terms of an lower bind rates of the outcome that you're looking for that you have to be sure to be, you know, substantially at a cost. So when are we going to be able to give a specific number? I don't think we're going to be able to give a specific number without actually kind of crossing the line in terms of exposures for the conference. So it'll be the statement around the primary endpoint based on objective on the ORR. That will be the key point there. With regards to the old CAR study, we're exploring obviously the non-Hodgkin's indications in that study, and we have been adding additional patients in the various cohorts. And obviously for those patients that we already have treated, by the middle of the year, we start to have meaningful long-term follow-up. And I think we start to get a good feel for the program. I think this gives us opportunity to move the program forward into those indications as we sort of progress with the program overall. The primary focus for 2023 will clearly be on the execution of the adult DLL program and getting the program to DLL filing. and also the additional activities around the ALL indication, which is really the primary focus. We're evaluating our options with regards to initiating a pivotal trial. I think the data that we're going to starting to see across these indications, I think is starting to shape up to a point where that decision in terms of picking the pivotal program that has the potential to go pivotal is certainly becoming too actually be picking out of the various implications, and then it's going to be a decision depending on the market conditions, et cetera, on the exact timing for the start of the field study. But from a basic data perspective, we think we have a lot of confidence in the overall profile of the product, and that we need to sort of pick the right timing and afford our next step here beyond AOL. And then I think on the RD cost, Lucy, I think you probably take.
spk13: Yeah, hi, thanks for the question. I'm not going to go into specifics at this stage. I mean, you know, I think you can assume that development costs headed into 2023 won't be at the same level as 2022. However, you know, as you can imagine, we're in the process of re-reviewing these things as part of the company's normal budgetary process. But, you know, I will say there is still a number of, a reasonable number of activities in 2023 related, you know, that fall under that development bracket, you know, on the regulatory side, as we anticipate patient follow-up, et cetera. But, yeah, I think you can safely assume the development cost won't be at the same level as 2022.
spk02: Great. Thanks so much, guys. Good. Thanks a lot. Appreciate it.
spk14: Thank you. And our next question comes from Matthew Phipps, and you are now on the line.
spk03: Okay. Thanks for taking my questions and asking the call. You know, on the LibriT1 study with Auto4, do you think that ASH will have any patients that were treated with the new manufacturing protocol?
spk02: Hey, Matt. Thanks for joining. We started treating patients with the new protocol. I'm not sure we're going to have data from those patients quite yet. I think we've been able to make some statements around the process change itself and the properties that we generate, but it's probably still premature to actually expect data from patients treated with the new protocol. Transition, as you may remember, was made after the EHA presentation. through the normal regulatory cycle for amendments. I didn't leave an awful lot of time before data come here for the ASH conference.
spk03: Got it. It's interesting talking to you while the abstracts are coming out real time here. But when will auto five get into clinics and what's the gating factors at this point?
spk02: I think what we're planning to do with all the five is get that program ready towards the end of the year. We do, the gating factor here is to transition, finalize basically the the CMC side of the process, and we're going to be also adapting some of the changes that we're making for the Auto IV process. We want to actually also include into the Auto V process before we get going on the program. So that's one of the key elements that sort of was still flowing. And, you know, a few early patients, I think, on the new process, the modified process, I think, will be indicative and will tell us an awful lot about how we're going to transition the modifications into the Auto V program as well.
spk03: Okay. And then lastly, I guess, just can you give us any updates on switching or moving to an IHC assay for the diagnosis of the patient or the selection?
spk02: Right. So what we had indicated for the program is that we have basically three ways to detect tumor cells. What we're using in the clinical trial is based on next-gen sequencing. That's also a very well-established methodology for Diagnostic and diagnostic tool, but it does take a bit of time in terms of turnaround time And so as alternatives you looked at IHC and we also did look at the detection by flow both of those are obviously antibody based the one against the Nature damage and typically in the IHC where you have fixed tissue horses Basically life and settled in the case of the fact Methodologies do work well, and we're currently going through kind of the selection which one we're going to take forward. And that decision actually hasn't yet been made. So technology works well with some of the data right there. But the final decision, which one we're going to take for full development, actually has not yet been taken.
spk03: All right. Great. Thanks for answering the questions. Thanks a lot, Matt. Appreciate it.
spk14: Thank you. And our next Our next question will come from James Shin. Your line should now be open.
spk04: Hey, guys, can you hear me? Hello?
spk02: Hey, James, we can hear you.
spk04: Great, great. Thanks for clarifying on Felix's 4Q22 press release. When the full data is released next year, though, could you share what your view would be for a positive EFS data? And is MRD going to be available at the conference, or is that going to be the update you talked about towards the end of the year?
spk02: So on MRD, I would expect that that's more focused for the end of the year, because obviously what I understand, also some of the follow-up in that cohort, as I explained before, we're continuing to involve patients into the MRD cohort. So the expectation is, I think, MRD data first, data at ASH next year, so there's a target. With regards to the type of secondary endpoint data, obviously we're going to be looking at various types of data related to the secondary endpoint. And we're probably going to look at, as we're looking at the data, probably look at subsets of the patients earlier in the study that may have longer follow-up, that give us some of the longer follow-up information by middle of next year. that you're referring to, and including in that is obviously the CR8 over time, as well as obviously in free survival. So we'll start to build that, but obviously clearly as we go through the course of the year, including in ASH, I think we're also going to gain additional information in terms of longer-term follow-up. What you may remember is when we looked at the EFS curve from the old COVID-19 study, you may remember that that EFS curve basically showed still drops until about 12 months of follow-up, but then we saw a stabilization from 12 months of follow-up onwards. And so I think what we're going to look at EFS data, I think to get sort of a sufficient longer-term view on the data, we're probably going to have to go to ASH to really understand what the longer-term outlook for that curve actually looks like. So, there will be early data, but I think in terms of actually getting a better understanding and more stability in the data, we'll probably have to go to that.
spk04: Understood. Have you disclosed what MRD sensitivity you're looking at for the Clonaseq? Is it 10 to the negative 6 by chance?
spk02: Well, that is obviously one of the measures. We're going to look at all of those levels. You can always measure down to about 10 to the minus 6 with the assay. And we're certainly going to look at the drop all in that you can get to. Typically, what you want to see is at least a lockstep reduction to actually call it a response, an MRD response. That's typically the way that was done also in the past using either flow or PCR. So that's one of the ways in how you can look at it, but then also you want to look at the absolute reduction and see whether there's any differences in potential in outcome that you might see depending on the cutoff that you're actually looking at.
spk04: I understand. And if I may, for just one more on McCarty. I know McCarty excludes prior cell therapies. But are patients allowed to have failed biospecifics, such as the recently approved teclistamab?
spk02: I don't think we have excluded in that study the targeting of BCMA. Obviously, what's already available with regards to BCMA targeting are ADCs to BCMA, which are actually available in the market. Some of the biospecifics are becoming available, and I would assume they're allowed. As you point out correctly, it's what we have in the lab. It's CAR T, BCMA-targeted CAR T. We're conducting the study in the UK, and in fact, there is no availability really for these patients in a significant way of CAR T therapies for targeting BCMA at this point. So it's more a theoretical exclusion at this point, but it could become a practical exclusion as the study progresses.
spk04: Appreciate it. That's all from my end. Thank you. Thank you.
spk14: Thank you. And our next call, or next question, sorry, comes from Gil Blum, and your line is now open.
spk10: Gil, your line is open.
spk05: Good morning and good afternoon. Just a couple quick ones for Moss. Kind of as a follow-up here, What are you hoping are going to be the differentiating features for AutoAID and BCMA, given how crowded the space is?
spk02: Hi, Gil. Great to have you on. So differentiating features, I think that what we're looking for in sort of a second-generation approach in multiple myeloma, I think that what we do know from the current products, and particularly if we're looking at CARB-V, is that we do get high response rate. And and also they have very meaningful durability and effect what we don't what we see is still challenging is to get a very high percentage of Disease down to the level of you know 10 to the minus 6 or below In terms of the detection so so there is sort of an element there in terms of the molecular responses are being achieved where you can actually C differentiation can pick that up, not on the standard response rate, but when you look at molecular CRs. The second aspect is what we're seeing with all the products is that there clearly is much more of a challenge in multiple myeloma to actually generate products that have longer persisting products. And the sense is that in a disease that's relatively slowly progressing and with challenging microenvironments that you find across the marrow, that you can have pockets that actually where well-developed cells can basically survive and ultimately rebound. And there's clearly a sense that we buy a significant amount of time with current therapies, but it's difficult, it appears difficult to actually switch it to a state where there is a high degree of confidence that you have true long-term remissions. So I think you want to see very deep responses, and the other aspect is you want to see indication for good levels of sustained persistent product. I think those are two features that I think we'd be looking for and I think would give us a very clear indication that we're starting to have features in the product. Also the fundamental piece in terms of design that we put in on the BCMA side is obviously a very potent BCMA approach that allows us to target cells with very low expression levels of PCMA, which is one of the fundamental challenges with the target.
spk05: All right. Thank you for those details. And maybe one last one. In the AutoIV study, are you still, are you enrolling additional patients at the high dose right now?
spk02: Yes, so we're enrolling patients at the, or we have enrolled a continued leftover of the cord at the 450 level. And with the advancement through for the modified manufacturing process, we took a will initially be dosed at 225. And once we have initial data, can then be back up escalated to 450. But we haven't gone beyond 450 in terms of cell dose. Excellent. Thank you for taking our questions. Thanks a lot, Gil. Appreciate it.
spk14: Thank you. And our next question comes from Nick Hallett. Your line is now open.
spk11: Nick, can you hear us?
spk09: Sorry, I think I may have missed my name there. Is that for Nick Hallett?
spk14: Yes, it is. You're online.
spk09: Perfect. Sorry, you just got out of there. Yeah, it's Nick on for care here, and thank you for taking my questions. Just a couple, if I may. First of all, for the ASH updates later this year, could you just help us frame expectations for what we might expect in terms of patient numbers and what the key data points we should be looking out for are? And then, if possible, would you be able to give us an overview of some of the key design elements of the Auto6 NG trial? Thank you.
spk02: Yes, thanks a lot for joining, Nick. With regards to the updates at ASCO, the key focus is really on longer-term follow-up on the non-Hodgkin patients with OB-cell. Actually, the ALL patients with OB-cell as well, obviously, remember there is an additional six months or actually more than six months of follow-up. Since the last update we've given on that cohort, we will have kind of long-term follow-up on these patients. So that's kind of the key focus with regards to OBCL. There are a few more patients on the non-Hodgkin's cohort, but the primary, really I think the primary readout is really a longer-term follow-up. With regards to auto-122, we always have very early data on the pediatric patients. So we have longer-term follow-up, which will be important, particularly as we're obviously looking to minimize or eliminate the risk of CD19 negative relapses in these kids. And the data we had at EHA was, I think, indicative, but of course we didn't quite have that much follow-up on some of the patients, so at least theoretically there might have been a risk that we might still be picking up target negative relapses. And so the additional follow-up, I think, is meaningful and will give us sort of a good additional confirmation of the design premises of the program. With regards to AutoPOR as well, longer follow-up is kind of the key piece there, and then obviously some views with regards to the modified process and what it might do for the product going forward. But the critical piece, obviously, here is that we have limited follow-up on the patients that have achieved metabolic CRs. When obviously with the additional data comp, you know, we should get closer to one year between, you know, between half a year and one year on some of these patients. I think that starts to be meaningful. Remember, these patients typically pass away within about six months at the stage of the disease that they're in and that we involve in terms of the patients that we involved into the study. So those, I think, are some of the key expectations, I think, with regards to the trial.
spk09: That's great. Thank you very much, Christian. And did you have any detail you could provide on the Auto6 trial?
spk02: Oh, yeah, sure. Thank you. On the Auto6 trial, obviously, we're planning to have, you know, we're introducing a number of new modules, two modules, each a beta module and a constitutively active L7 type module. So that's a significant addition, and we're still working through kind of the exact initial approach, also with the regulators here in the UK. The plan is to obviously have an approach that allows us to lower dose levels going with the modules and be able to sort of actually start generating safety data first, obviously, in that trial, and then obviously push the doses up once demonstrated safe to start actually looking at the impact on the activity, the anti-tumor activities. But the details are still in part being negotiated with the regulators, so I don't think I can give you a final answer at this point.
spk09: Appreciate it. Thank you very much. Thank you.
spk14: Thank you. And we now have Kelly Shih now on the line.
spk07: Hi, can you hear me? Okay.
spk02: Yeah. Hi, Kelly. We can hear you fine.
spk07: Hi, this is Clara. I'm for Kelly. So, for so pivotal trial, can you comment on patient baseline characteristic for the enrolled patients? Is it consistent with space? 1 day and 1 B stage? And also, according to clinicaltrial.gov, one of the inclusion criteria for FELIX trial is to screen patients with, you know, more than 5% blasting bone marrow, but 75% CR rate departed from Phase 1b actually included 25% of the patient with less than 5% blasting bone marrow. So, should we expect lower response rate for FELIX topline data? And lastly, does prior Blaine Cyto treatment have impact on the treatment efficacy of OV-cell? Thank you.
spk02: So with regards to inclusion-exclusion criteria, those are actually consistent between the Phase 1b and the Phase 2 portion. And they're also largely consistent also with the prior development in the space, including or for tachycardias for that matter. So the inclusion, exclusion criteria are very similar across the board in these trials, and they're consistent between the phase 1B and the phase 2. In terms of patients involved, obviously the patients that are part of the analysis set that will go into VLA are patients that have more than 5% tumor burden at the time of enrollment. And that is also the key inclusion criteria. Patients that have less than 5% tumor burden can actually be enrolled into the second cohort that we're running, which are patients in mineral residual disease. But they're clearly differently. They're in two different cohorts, and they're analyzed obviously separately. And also in terms of the endpoints, those endpoints are different. The response endpoint that you look at, A primary endpoint to look at in the morphological cohort is complete remission, relating to complete remission. Patients with CR and patients with CRs with incomplete recovery and even logical recovery. Both of those measures, obviously, are looking at going from a level of blast above 5% to a level below 5%, which is the condition to meet that you have to meet. to sort of formally get into a CR. In the cohort, obviously, with the minimal residual disease that are starting below 5%, those patients are technically, obviously, in complete remission. And what we're measuring with those patients, and this just goes back to, I think, the question that Gil asked before, is that you then actually can look at the conversion of these patients into a molecular complete remission which actually is a massive additional reduction, but typically those cutoffs that you look at there are 10 to the minus 4 and below. So those are kind of the differences between the two calculations. patient characteristics compared to the phase 1b, and also when it comes to general composition of the patients with regards to prior alignments with prior therapies, including prior exposure to the site that we don't expect to see any significant differences.
spk07: Got it. Can you also share some details regarding your preparation? preparation of OB cell launch on manufacturing film? Do you expect the same patient baseline in real world as you have seen in clinical trials for adult ALL? And how would the difference impact the OB cell's manufacturing success rate and efficacy?
spk02: So as soon as you actually have a group of patients that are above 5% tumor burden, obviously the range can vary quite a bit So you can have patients where there's just slightly above 5% of patients who are in the 95% range of tumor burden in the marrow. The patients can also vary in terms of the amount of leukemic cells that are not just in the marrow, but they're also in circulation. So there's a big variability you have in there. We believe that we have a very good representation across the entire board of those levels of tumor burden, as well as levels of circulating leukemic cells in the nicely predicted for this, you know, truly advanced stage of disease. What would be very interesting is then to see what the outcome is for patients that have lower disease burden, that have less than 5% disease burden and are in minimal residual disease. And that's obviously the reason why we're running the second cohort. But that is obviously not the primary group of patients that obviously will drive the label for the trial.
spk07: Okay. Thank you.
spk02: Thank you. Appreciate it.
spk14: Thank you. And our next question comes from Noah Eisenberg.
spk06: Hey, guys. This is Noah on for Eric. Thanks for taking our question. Just a couple of quick ones for us. So could you remind us, does the FELIX trial use the same exact conditioning regimen as the previous phase one trial for Obacill? And then also, How is enrollment progressing for the carousel trial, and what can we expect in the data next year? Thanks.
spk02: Could you repeat which trial where the enrollment question came?
spk06: Oh, the carousel trial.
spk02: The carousel trial. Okay, sorry. I couldn't understand that. Okay. All right. So the first question is to the preconditioning regimen. In fact, the preconditioning regimen that we're using is consistent which was used in the phase 1b and consistent which is now typically used across the industry in the various CAR-T trials in terms of use with fluaridine and cyclophosphamide. So that is very consistent and slightly different from what we had in the oil car study, which was obviously a study that started a few years before and was still closer to some of the original work that was done at Penn.
spk04: And then on the carousel trial.
spk02: And then with regards to the carousel trial, well, we expect to have about somewhere between 10 and 12 patients enrolled in total. And we expect to be able to provide an update during the course of next year, probably more towards the middle of the year.
spk06: Great. Thank you.
spk11: Okay. Thank you.
spk14: And that was our final question. I'd like to now turn it back to Christian for closing remarks.
spk02: All right. Well, thank you very much. Well, thanks, everybody, for joining today. It's obviously a very busy season also with the ASH abstracts coming out. Appreciate your joining. And I was looking forward to keeping updated as we go through, I think, a very important set of weeks and months ahead of us at Autoless as we're sort of progressing the pivotal study and that we're gearing up towards the actual data presentations in the middle of next year. All right, thanks, everybody, and speak to you soon. Thank you.
spk14: Thank you for participating in today's conference. This does conclude the program. You may now disconnect.
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