Hello, ladies and gentlemen, and welcome to the Autolus 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 Manser, Director of Investor Relations. Please go ahead.
Thanks, Breanna. 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 Autolus. I'm Olivia Manser, Director of Investor Relations, and with me on today's call as usual are Dr. Christian Itin, our Chief Executive Officer, and Dr. Lucinda Crabtree, our Chief Financial Officer. 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. Turning to slide three, you'll see the agenda for today, which is as follows. 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. Finally, we will of course, welcome your questions. Over to you, Christian.
Thank you, Olivia. 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 II data at a medical conference in the first half of 2023, most likely at ASCO.
We're also looking forward to presenting longer follow-up data from our ALL patients in the ALLCAR19 phase I trials at ASH, and are planning a more in-depth look at the patients that we've treated with non-Hodgkin lymphoma. We're presenting further data at the three phase I trials at ASH in December. First, as indicated on the ALLCAR19 phase I extension study for obe-cel in B-NHL, CARPALL study, which is also a phase I trial with AUTO1/22 pediatric ALL, and from our LibraT1 phase I trial of AUTO4 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 I McCARTY trial exploring AUTO8 in multiple myeloma patients is progressing, and the phase I McCARTY-2 trial exploring AUTO6-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 Autolus. We signed an agreement with Bristol Myers Squibb, granting them access to our proprietary RQR8 rituximab-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 immuno-oncology target for the delivery of their messenger RNA therapeutics. In return for a $1-$9 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 I of the build of our Stevenage facility is on track for transfer to Autolus 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 planned 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 from HMRC of $19.1 million received in October. Slide six. With that, let's talk about our primary focus, our lead product, obe-cel, on Slide seven now. Just to remind you, obe-cel 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 obe-cel, 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. Those of you not familiar, I refer you to a paper by Sara Ghorashian 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 slide setting.
Approximately 3,000 of these cases reside in the U.S. and EU, while a combination chemotherapy enables about 90% of the adult ALL patients to achieve complete remissions, only about 30%-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 BLINCYTO and TECARTUS. Both therapies are highly active but frequently followed by subsequent treatments, for example, allogeneic stem cell transplants. BLINCYTO 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. TECARTUS is more challenging to manage and induces elevated levels of CRS, high levels of ICANS, 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 allograft to achieve durability. Moving to slide nine. Many of you have seen this slide before, but it's useful, it's a useful reminder of why we think obe-cel is a potentially transformational therapy for adult ALL. Building on its unique mechanism of action, obe-cel 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. Obe-cel is in great, what we believe is potentially transformational data from the ALLCAR study. We're conducting the pivotal FELIX trial with approximately 90 patients with morphological disease, treating at 34 sites in the U.S., the U.K., and Spain.
We're on track with our previous guidance and expect to provide a qualitative update in Q4 of 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 obe-cel 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. Obe-cel's 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 I clinical trial. As we said before, we have positive clinical readouts at the recent EHA Congress from the phase I 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 AUTO1/22 phase I data in pediatric ALL patients. 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 ALLCAR19 study has been extended as a basket study where we are testing obe-cel 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. 14 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 initial evaluation as of the last data cutoff, two went into molecular CR in their 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 ALLCAR extension study at ASH in December. Turning to slide 14. We're also exploring obe-cel in primary CNS lymphoma in our academic CAR T-cell study. This is a type of aggressive B-cell lymphoma, but because of its anatomical location, it has a particularly poor prognosis. Initial treatment is often intensive and outcomes for these patients tends to be poor. In the data we presented at EHA, we didn't see high-grade CRS. Two patients experienced neurotoxicity, grade three and four. 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 obe-cel in peripheral blood, and we expect to provide more data from this study in 2023. Moving to slide 15. Our initial experience with obe-cel in children achieved a high level of sustained CRs while without experiencing high-grade CRS. Those children who relapsed after treating with obe-cel, most of them had lost CD19 expression on their leukemic cells at the time of relapse.
Here we're taking the next step in obe-cel's life cycle with AUTO1/22, a dual targeting product building on obe-cel 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 AUTO1/22 in an extension of the CARPALL study in children who were ineligible for KYMRIAH. The children either relapsed after receiving KYMRIAH 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 KYMRIAH 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. AUTO1/22 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. 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 Autolus, 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 obe-cel. A pipeline program we're particularly excited about is AUTO4, which is in phase I study in T-cell lymphoma. I'll give you a refresh of the data we presented at EHA in just a minute. AUTO8 moved into the clinic earlier this year in a phase I clinical study in patients with multiple myeloma, and we're now dosing patients. I also want to mention that our first solid tumor program, AUTO6NG, 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. Horwitz from Department of Medicine Lymphoma Service, Memorial Sloan 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 one or two 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 one and two.
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. In the future, we plan to open a study targeting TRBC2-positive patients with AUTO5 as well. AUTO4 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 LibraT1 study evaluating AUTO4 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.
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 U.K. 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 start-up 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 sq ft facility will provide Autolus 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 I of the build project is scheduled to complete in the fourth quarter, and the equipment installations and qualifications that Autolus 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. With that, I would like to turn to slide 25 and pass the call to Lucinda for our third quarter 2022 financial update. Lucy?
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. The majority of the remainder in USD. Net total operating expenses for the quarter were $43.5 million, which included license 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 obe-cel. An increase of $2 million in salaries and other employment-related costs, mainly driven by an increase in the number of employees engaged in research and development activities. We also had marginally increased legal and IT fees as we transitioned through the quarter, offset by a decrease in facilities costs and depreciation of PPE. General and administrative expenses remained stable year-on-year. Other expense [inaudible], net 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 U.S. 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 totaled $-0.47 compared to $-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. Now back to Christian to give you a brief outlook on expected milestones. Christian.
Thank you, Lucy. Slide 27. Finally, on next steps, we believe we have an exciting period ahead at Autolus, with the summary shown on this slide. The main focus, of course, is obe-cel in relapsed refractory adult ALL patients, with our initial update on this pivotal FELIX study coming before the end of the year. Obviously the planned presentations at a medical conference in middle of 2023. Longer term follow-up will be then shown, planned or is planned to be shown by the end of 2023 as well. Beyond that, the studies of obe-cel in relapsed refractory B-NHL and CLL and primary CNS lymphoma are ongoing, as well as our AUTO1/22 program and our AUTO4 program.
We expect to have more data over the course of this year and next while 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.
Thank you. 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 one one on your telephone and wait for your name to be announced. Our first question is gonna come from Mara Goldstein. Your line is now open.
On FELIX and the data disclosure in the fourth quarter, can you sort of speak to what we will see, whether or not, you know, 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 the data MRD negative cohort that you started enrolling. The other question I had is related 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.
Okay. Thanks, Mara. Thanks for the question. 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 endpoint of the study. That would be premature. The MRD cohort is obviously enrolling and will continue to enroll into next year. Of course, that cohort is not the key data set that will go into or critical data set that would for the BLA. 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. Of course, you do remember that there are very strict disclosure rules if you want to present at ASCO, so which also basically reduces the amount of information that we can share within the press release that we're planning for the end of the year. The second question I think was related to the manufacturing setup. 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 a BLA filing. That obviously is going to be in time for a BLA filing targeted for the end of next year.
All right. Thank you.
Thank you. Operator, do we have another question?
I'm just jumping in. I think Breanna may have dropped that the next question was Asthika at Truist, and I think your line should be open.
Hi there. Hi, guys. Can you hear me okay?
Yes, we can.
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 ALLCAR19 update, you know, beyond what we see in ASH, I'm just curious to know, you know, how many more patients in follow-up would you need to give you the confidence to initiate some pivotal studies based on in these specific indications? And are these pivotal trial initiations something we can expect in 2023?
Lastly, something for Lucy here. Lucy, can you give us some direction on how R&D costs are gonna move next year, given that, FELIX is winding down, and majority of the other studies are kind of early stage? Thanks.
All right. Well, thanks a lot, Asthika. I'm glad we managed to connect. The first question you asked was related to the type of disclosure that we can make. 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 hematologic recovery, so CRs and CRIs.
The statement with regards to the endpoint obviously is statistical 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 basically was coming out. I think that's sort of, if you need the reference point, that gives you reference points in terms of the lower event rates of the outcome that you're looking for, that you have to be sure to be, you know, substantially undercut.
Whether we're gonna be able to give a specific number, I don't think we're gonna be able to give a specific number without actually kinda crossing the line in terms of disclosures for the conference. It'll be the statement around the primary endpoint based on the ORR. That will be the key point there. With regards to the ALLCAR study, we're exploring obviously the non-Hodgkin indications in that study, and we have been adding additional patients in the various cohorts. Obviously for those patients that we already have treated, by 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 ALL program and getting the programs to the BLA 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 gonna start to see across these indications 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 coming to a point wherein I would assume towards the middle of next year we should have a good feel for which dataset we should actually be picking out of the various indications. It's gonna be a decision depending on the market conditions, et cetera, on the exact timing for the start of the pivotal study. From a basic data perspective, we think we have a lot of confidence in the overall profile of the product, and we need to sort of pick the right timing for our next step here beyond ALL.
I think on the R&D cost, Lucy, I think you probably take that one.
Yeah. Hi. Thanks for the question. Look, I'm not gonna 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. You know, I will say there are 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. Yeah, I think you can safely assume the development costs won't be at the same level as 2022.
Great. Thanks a lot, guys.
Good. Thanks a lot. Appreciate it.
Thank you. Our next question comes from Matthew Phipps, and you are now on the line.
Oh, great. Thanks for taking my questions and hosting the call. You know, on the LibraT1 study with AUTO4, do you think at ASH we'll have any patients that were treated with the new manufacturing protocol?
Hey, Matt. Thanks for joining. We started treating patients with the new protocol. I'm not sure we're gonna have data from that, from those patients quite yet. I think we'll be 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, and then when you go through the normal regulatory cycle for amendment, it didn't leave an awful lot of time before data comes here for the ASH conference.
Got it. It's interesting talking to you while the abstracts are coming out real-time here. When will AUTO5 get into clinics, and what's the gating factors at this point?
I think what we're planning to do with AUTO5 is get that program ready towards the end of the year. The gating factor here is to transition, finalize basically the CMC side of the process, and we're gonna be obviously adapting some of the changes that we're making for the AUTO4 process. We wanna actually also include into the AUTO5 process before we get going on the program. So that's one of the key elements that sort of will spill and flow in. The few early patients, you know, 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 gonna transition the modifications into the AUTO5 program as well.
Okay. Lastly, I guess just can you give us any updates on switching or moving to IHC assay for the diagnosis of the patients or the, you know, selection?
Right. 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-generation sequencing. That's obviously very well-established methodology for assessing a diagnostic tool. But it does take a bit of time in terms of turnaround time. As alternatives, we looked at IHC, and we also did look at detection by flow. Both of those are obviously antibody-based, one against denatured antigen, typically in the IHC where you have fixed tissue versus basically live cells in the case of the FACS. Methodologies do work well, and we're currently going through kind of the selection, which one we're gonna take forward.
That decision actually hasn't yet been made. Technology in this space works well. We've shown some of the data right there. The final decision, which one we're gonna take, for full development actually has not yet been taken.
All right. Great. Thanks for answering the questions.
Thanks a lot, Matt. Appreciate it.
Thank you. Our next call or next question will come from James Shin. Your line should now be open.
Oh my God . Can you hear me? Hello?
Hey, James. We can hear you.
Great. Thanks for clarifying on FELIX's 4/2/2022 press release. When the full data is released next year, though, could you share what your view would be for a positive EFS data? Is MRD gonna be available at the conference, or is that gonna be the update you talked about towards the end of the year?
On MRD, I would expect that that's more focused for the end of the year because obviously we wanna understand also some of the follow-up in that cohort. As I explained before, we're continuing to enroll patients into the MRD cohort. The expectation is, I think, MRD data first, data at the ASH next year. There's a target. With regards to the type of secondary endpoint data, obviously we're gonna be looking at various types of data related to the secondary endpoint.
We're probably gonna look at, as we're looking at the data, subsets of the patients earlier in the study that may have longer follow-up that give us some of the information by middle of next year that you're referring to. Including in that is obviously the CR over time, as well as obviously the increased survival. We'll start to build that, but obviously, clearly, as we go through the course of the year and including at ASH, I think, we're obviously gonna 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 CAR T study, you may remember that EFS curve basically showed still drops until about 12 months of follow-up, but we saw a stabilization from 12 months of follow-up onwards. I think what we're gonna look at EFS data, I think to get sort of a sufficient longer term view on the data, we're probably gonna have to go to ASH to really understand what the longer term outlook for that curve actually looks like. 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 ASH.
Understood. Have you disclosed what MRD sensitivity you're looking at for the clonoSEQ? Is it 10 to the - 6 by chance?
Well, that is obviously one of the measures. We're gonna look at, you know, all of those levels. You know, you can obviously measure down to about 10 to the - 6 with the assay. We're certainly gonna 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, specifically the way that was done also in the past using either flow or PCR. That's one of the ways in how you can look at it, but then also you wanna look at the absolute reduction and see whether there's any differences in potentially an outcome that you might see depending on the cut-offs that you're actually looking at.
Understood. If I may, for just one more on McCARTY. I know McCARTY excludes CAR T-cell therapy, but are patients allowed to have failed bispecific, such as the recently approved Teclistamab?
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. The bispecifics, obviously, they're becoming available, and I would assume they're allowed. As you point out correctly is where we haven't allowed CAR T, BCMA targeting CAR T. We're conducting the study in the U.K. and in fact, there is no availability really for these patients in a significant way of you know, CAR T therapies for targeting BCMA at this point. It's more a theoretical exclusion at this point, but it could become a practical exclusion then as the study progresses.
Appreciate it. That's all from my end. Thank you.
Thank you.
Thank you. Our next call or next question, sorry, comes from Gil Blum. Your line is now open. Gil, your line is open.
Good morning and good afternoon. Just a couple of quick ones for Mas. Kind of as a follow-up here, what are you hoping are gonna be the differentiating features for AUTO8 and BCMA given how crowded the space is?
Hi, Gil. Great to have you on. Differentiating features, I think that what we're looking for in a 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 CARVYKTI, is if we do get, you know, high response rates, and also obviously have very meaningful durability and effect. What we see is still challenging is to obviously get a very high percentage of disease down to the level of, you know, 10 to the minus six or below in terms of detection.
There is sort of an element there in terms of the molecular responses are being achieved, where you can actually see differentiation and 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 product. The sense is that in a disease that's relatively slowly progressing and with, you know, challenging microenvironments that you find across the marrow, that you can have pockets that actually where multiple myeloma cells can basically survive and ultimately rebound. There's clearly a sense that we buy a significant amount of time with the 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. I think you wanna see very deep responses. The other aspect is you wanna see indication for good levels of sustained persistence product, persisting 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 differentiated features in the product. Obviously, 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 BCMA, which is one of the fundamental challenges with the target.
All right. Thank you for those details. Maybe one last one. In the AUTO4 study, are you enrolling additional patients at the high dose right now?
We're enrolling patients or we had enrolled, continued to fill the cohort at the 450 level. With the amendment through for the modified manufacturing process, we took a step down in terms of 225, and so the first patients will initially be dosed at 225. Once we have initial data, can then be escalated back up to 450. We haven't gone beyond 450 in terms of cell dose.
Excellent. Thank you for taking our questions.
Thanks a lot, Gil. Appreciate it.
Thank you. Our next question comes from Nick Hallet. Your line is now open.
Hi, Nick. Can you hear us?
I think I maybe missed my name there. Was that for Nick Hallet?
Yes, it is. You're online.
Perfect. Sorry, you just cut out there. It's Nick on for Kaye 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? If possible, would you be able to give us an overview of some of the key design elements of the AUTO6NG trial? Thank you.
Yes. Thanks a lot for joining, Nick. With regards to the update at ASH, the key focus is really on longer term follow-up on the multiple patients with obe-cel. Actually the ALL patients with obe-cel as well. Obviously, remember there's an additional six months or actually more than six months of follow-up since the last update we've given on that cohort, so we will have kind of long-term follow-up on these patients. That's kind of the key focus with regards to obe-cel. There are a few more patients on the non-Hodgkin's cohort, but the primary really, I think the primary readout is really the long-term follow-up, longer-term follow-up. With regards to AUTO1/22, obviously had very early data on the pediatric patients.
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. The data we had at EHA was, I think, indicative. 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. 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 AUTO4 as well, longer follow-up is kind of the key piece there.
Obviously some views with regards to the modified process and what it might do for the product going forward. The critical piece obviously here is that we have limited follow-up on the patients that have achieved metabolic CRs. We're obviously with the additional data cut, you know, we should get closer to one year, between half a year, 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 enrolled in terms of the patients that we enrolled into the study. Those I think are some of the key expectations, I think with regards to the trial.
That's great. Thank you very much, Christian. Did you have any detail you could provide on the AUTO6 trial as well?
Oh, yeah, sure. Thank you.
Thanks.
On the AUTO6 trial, obviously we're planning to have, you know, we're introducing a number of new modules, dSHP2 module, TGFβ module and a constitutively active IL-7 type module. So that's a significant addition. We're still working through kind of the exact initial approach, also with the regulators here in the U.K.
The plan is to obviously have an approach that allows us a lower dose level to go in 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 antitumor activity as well. 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.
Appreciate it. Thank you very much.
Thank you.
Thank you. We now have Kelly Shi now on the line.
Hi. Can you hear me okay?
Yeah. Hi, Kelly. We can hear you fine.
Hi, this is Clara, for Dingding.
Okay, sorry.
For FELIX pivotal trial, can you comment on patient baseline characteristics for the enrolled patients? Is it consistent with phase I-B? according to ClinicalTrials.gov, one of the inclusion criteria for FELIX trial is to screen patients with more than 5% blasts in bone marrow, but 75% CR rate reported phase I-B actually included 25% of the patients with less than 5% blasts in bone marrow. Should we expect lower response rate for FELIX top line data? Lastly, does prior BLINCYTO treatment have impact on the treatment efficacy of obe-cel? Thank you.
With regards to inclusion/exclusion criteria, those are actually consistent between phase I-B and the phase II portion. They're obviously also largely consistent also with the prior development in this space, including the pivotal study in the refractory setting for BLINCYTO or for TECARTUS for that matter. The inclusion, exclusion criteria are you know, very similar across the board in these trials and they're consistent between phase I-B and the phase II. In terms of patients enrolled, obviously the patients that are part of the analysis set that will go into the BLA are patients that have more than 5% tumor burden at the time of enrollment. That is obviously 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 minimal residual disease. They're clearly different. They're just in two different cohorts, and they're analyzed obviously separately. Obviously also in terms of the endpoint, obviously the endpoints are different. The response endpoint that you look at, primary endpoint you look at in the morphological cohort, is complete remission relating to complete remission. Patients with CR and patients with CRi. Both of those measures obviously are looking at going from a level of less than about 5% to a level over 5%, which is the condition to meet that you have to meet to sort of formally get into a CR.
In the cohort of those with the minimal residual disease that are starting below 5%, those patients are technically obviously in complete remission. What we're measuring with those patients, and this 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 then is a massive additional reduction. Typically those cutoffs that you look at there are 10 to the minus four and below. Those are kind of the differences between the two populations. There's no difference that we expect to have in terms of the actual patient characteristics compared to the phase I-B.
When it comes to, you know, general composition of the patients with regards to prior lines of prior therapies, including prior exposure to blinatumomab, we don't expect to see any significant differences.
Got it. Can you also share some details regarding your preparation of obe-cel launch on manufacturing firm? You know, do you expect the same patient baseline, you know, in real world as you have seen in clinical trials for adult ALL, and how would the difference impact the obe-cel's manufacturing success rate and efficacy?
As soon as you actually have a group of patients that are above 5% tumor burden, obviously the range can be quite, can vary quite a bit. You can have patients where they're just slightly above 5% to patients who are, you know, 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. There's a big variability happening 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 trial. With that, we expect the trial to actually be nicely predictive for this, you know, truly advanced stage of disease.
That will be very interesting is then to see what the outcome is for patients that have lower disease burden, that have obviously less than 5% disease burden and are in minimal residual disease. That's obviously the reason why we're running the second cohort. That is obviously not the primary group of patients that obviously will drive the label for the trial.
Okay. Thank you.
Thank you. Appreciate it.
Thank you. Our next question comes from Noah Eisenberg.
Hey, guys. This is Noah on for Eric. Thanks for taking our question. Just a couple of quick ones for us. Could you remind us, does the FELIX trial use the same exact conditioning regimen as the previous phase I trial for obe-cel? And then also, how is enrollment progressing for the CARLYSLE trial, and what can we expect in the data next year? Thanks.
Could you repeat which trial where the enrollment question came?
The CARLYSLE trial.
The CARLYSLE trial. Sorry, I couldn't accurately understand that. The first question is to the preconditioning regimen. In fact, the preconditioning regimen that we're using is consistent, which was used in phase I-B and consistent, which is now typically used across the industry in the various CAR T trials in terms of use with fludarabine and cyclophosphamide. That is very consistent and slightly different from what we had in the old 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.
On the CARLYSLE trial.
With regards to the CARLYSLE trial, well, obviously we expect to have about, you know, somewhere between 10 and 12 patients enrolled in total. We expect to be able to provide an update during the course of next year, probably more towards the middle of the year.
Great. Thank you.
Okay. Thank you.
That was our final question. I'd like to now turn it back to Christian for closing remarks.
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 you joining. Obviously looking forward to keeping you updated as we go through, I think, a very important set of weeks and months ahead of us for at Autolus 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.
Thank you for participating in today's conference. This does conclude the program. You may now disconnect.