Autolus Therapeutics PLC

NASDAQ:AUTL

Earnings Call Analysis

Company Prepares for Regulatory Steps and Growth

The company is approaching significant developments with AUTO8 shaping up positively, expecting to initiate the AUTO6NG Phase I pediatric trial, and the European filing for MAA. Safety databases meet the regulatory size requirements, and the dosing strategy aligns with experience, indicating a good safety profile. Nearly six additional months of patient follow-up data will provide more stability to previously reported outcomes. Manufacturing capacity is robust with a modular 700 unit per annum scale-up per clean room, positioning for successful future scaling.

Advancing Towards Regulatory Milestones with Obe-cel

Autolus Therapeutics has been concentrating on the preparation for the Biologics License Application (BLA) filing for obe-cel, their leading product candidate for adult relapsed/refractory acute lymphoblastic leukemia. The application is on track for submission by the end of 2023. This preparation is based on previously presented data from the pivotal FELIX study and aims for presentation of more in-depth analyses, including longer follow-up and subgroup analysis, at the December ASH conference.

Obe-cel: Preparing for U.S. Market Entry

As obe-cel advances through the regulatory process, Autolus is gearing up for a potential U.S. launch. Efforts include activities in medical affairs, the completion of value dossiers, and the engagement with CAR T centers. Further details on obe-cel's manufacturing performance will also be presented at the ASH meeting, which is critical as the company assures readiness for commercial supply.

Pipeline Growth and Expansion

Autolus continues to broaden the horizon for obe-cel, targeting expansion into the autoimmune disease market. Initiation of a Phase I dose confirmation study in SLE patients is expected in early 2024. Furthermore, ongoing studies in B-cell non-Hodgkin's lymphoma have continued to demonstrate obe-cel's potential best-in-class profile, with completion of the ALLCAR extension study expected by year-end and updates delivered at ASH conference.

Solid Clinical Performance and Extended Applications

The company reported robust clinical results for patients ineligible for commercial CAR T therapy, where a significant majority achieved molecular complete remission. Additionally, studies on AUTO1/22 in pediatric ALL patients have shown promising clinical activity and tolerability. New studies, such as AUTO8 in multiple myeloma and AUTO6NG in neuroblastoma, are making progress, with AUTO6NG expected to commence dosing in a Phase I study by the end of the year.

Robust Clinical Results Amidst Pandemic Challenges

Despite the COVID-19 pandemic posing significant hurdles to patient flow and trial execution, the FELIX study yielded strong results, with a high complete response rate and deep molecular responses. Obe-cel demonstrated exceptional safety, evidenced by low rates of high-grade cytokine release syndrome (CRS) and neurological events. These outcomes are promising for the treatment of patients with higher disease burdens and risk, further supported by the robustness of the manufacturing process which is a critical component for the therapy's delivery.

Earnings Call Transcript 2023-Q3

[Operator]

Hello, ladies and gentlemen, and welcome to the Autolus Therapeutics Third Quarter 2023 Financial Results Conference call and business update. [Operator Instructions]. Please be advised that today's conference is being recorded.

I would now like to turn the conference over to your host, Julia Wilson. Please go ahead.

[Anas Younes]

Thank you, and good morning or good afternoon, everyone, and thank you for joining us to take part in today's call for Autolus's Third quarter 2023 Financial Results and Business Update. I'm Julia Wilson, Communications consultant for Autolus. With me today are Dr. Christian Itin, our Chief Executive Officer; and Rob Dolski, our Chief Financial Officer.

Before we begin, I would like to remind you that during today's call, we will make statements related to our business that are forward-looking under federal securities laws and the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These may include, but are not limited to, statements regarding the status of clinical trials and development and/or regulatory time lines for our product candidates and our expectations regarding our cash runway.

These statements are subject to a variety of risks and uncertainties that could cause actual results to differ materially from expectations and reflect our views only as of today. We assume no obligation to update any such forward-looking statements. For a discussion of the material risks and uncertainties that could affect our actual results, please refer to the risks identified in today's press release and our SEC filings, both available on the Investors section of our website.

On Slide 3, you will see the agenda for today's call, which is as follows: Christian will provide an overview of our operational highlights for the third quarter of 2023. Rob will then discuss the company's third quarter 2023 financial results, before Christian will conclude with upcoming milestones and closing remarks. Finally, we will, of course, welcome your questions. Over to you, Christian.

[Christian Itin, executive]

Thank you, Julia, and good morning to you all. Thank you for joining us. It's my pleasure to review our progress for the third quarter in 2023. Moving to Slide #4. We'll give you here a quick summary of the progress we've made with obe-cel during the third quarter. Key focus has been on preparing the BLA filing, which is on track for a filing by the end of the year. Building on the data we presented at ASCO EHA early in the year for our pivotal FELIX study in adult patients with relapsed/refractory acute lymphoblastic leukemia, we look forward to presenting longer follow-up and subgroup analysis at ASH in December. .

The ASH abstract embargo has just lifted and we have an oral presentation giving longer follow-up data from the FELIX study on Saturday, December 9. In addition, we will, in a poster presentation, provide long-term follow-up data from our prior ALLCAR19 study in the FELIX Ib study on both ALLCAR19 and FELIX Ib, we're approaching up to 5 years and up to 3 years of follow-up, respectively. I'd also like to highlight that before the end of the year, we'll be initiating a pediatric Phase I study of obe-cel to support our filing with the European Medicines Agency.

Which is expected to start in the first half of -- sorry, will be filed in the first half of 2024. Clinical for the successful outcome of the FELIX study was our robust product delivery platform with high manufacturing success rate. Short range to delivery time and high percentage of patients dosed with obe-cel.

During the third quarter, we successfully completed the process performance qualification at the Nucleus manufacturing facility set up for commercial supply and are on track to support a biologics license application with the FDA by the end of 2023. And a market authorization application with EMA in the first half of 2024. Importantly, we will be presenting more detail about the obe-cel manufacturing performance also at the ASH meeting in December. And a poster presentation. As the program is progressing through the regulatory review, we are actively preparing obe-cel for a potential U.S. launch with critical activities underway in medical affairs, completion of value dossiers and onboarding of CAR T centers.

Moving to Slide 5. Here is a quick overview of the pipeline progress during the third quarter. First, we continue to expand the obe-cel opportunity and we are progressing the development of obe-cel in autoimmune diseases, starting with a Phase I dose confirmation study in SLE patients, which we expect to start early in 2024. We held an analyst and investor event last week, where we discussed this in more detail and a replay of this presentation can be found on the Events section of the Autolus website.

In summary, we believe that the excellent clinical profile we have seen for obe-cel cell will translate well into B cell-mediated autoimmune diseases. The differentiated mechanism of action, regulatory package, clinical validation in ALL, substantial safety database and commercial manufacturing and delivery base will provide a differentiated opportunity for obe-cel in autoimmune disease. Data presented at ASH last year demonstrated the potential best-in-class profile of obe-cel supported by the data served from the ALLCAR extension study in B-cell non-Hodgkin's lymphoma. With continued high levels of clinical activity paired with an encouraging tolerability profile across diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia. We expect to complete enrollment in the ALLCAR extension study by the end of the year and to publish the data in a peer-reviewed journal as well as update data at the upcoming ASH conference year as well.

Together with Dr. Sara Grecian from Great Ormond Street Hospital, we published the Phase I experience with AUTO1/22 in pediatric ALL patients in blood. The study showed that patients who were not eligible for commercial CAR T therapy showed a high level of clinical activity and good tolerability with over 80% of patients achieving a molecular complete remission with no antigen negative relapses seen with a median follow-up of up to 8.7 months.

Included also were patients who had relapsed after Kymriah therapy with CD19 negative disease. Our final pipeline updates continue during the quarter include AUTO8 and AUTO6NG, both in collaboration with UCL. AUTO8 is progressing well in the Phase I study in multiple myeloma patients called the [indiscernible] study, and I'll give you more information shortly on the anticipated study data at ASH. With AUTO6NG, we expect the first patient to be dosed in the neuroblastoma Phase I study by the end of the year.

Moving to Slide #6. As well as from there going straight to Slide #7, focusing on obe-cel. As you remember, obe-cel has a unique mechanism of action. What's fundamentally different about our product candidate is that it has an ability to engage physiologically with the target cell. What this allows us is to actually have a product that can rapidly bind the target cell which delivers specificity paired with a fast off right for rapid disengagement from the target cell once the kill has been delivered. This unique engagement drives maximum activity while minimizing toxicity and is at the heart of the differentiated clinical profile we are observing for obe-cel and ALL and we believe provides a great platform for future indication expansions in oncology and autoimmune diseases.

Moving to Slide #8. On this slide, you can see a summary of the FELIX data we presented at ASCO and EHA earlier this year. What we've characterized today that what we continue to hear from KOLs as we share the FELIX data, is that we enrolled this study and studied a patient population, our FELIX trial that is highly representative of a real-world clinical setting. Remember, we did this study during the pandemic, obviously, where patient flow was very challenging, particularly given the challenges with access [ to 30 centers ] and a lot of patients only being moved to centers when there was an absolute need for them to actually move to the next therapy. FELIX patients were refractory to multiple lines of therapy, including stem cell transplants presented with high disease burden with medium bone marrow blast of 50% screening. And extramedullary disease was present in 19% of the patients. Despite this challenging population with high disease burden, lots of risk features overall older than was studied in prior programs. obe-cel delivered complete responses in 76% of patients. And of those responders, 97% actually had deep MRD negative responses. The tolerability is remarkable. obe-cel had 3% high-grade CRS as well as patients with [indiscernible] in the range of 7%. So both of these numbers are very low compared to any other trial conducted in this type of indication and also obviously, it allows for a very good level of control of these patients.

Most of these events, particularly the higher-grade ICANS occurred in patients that have more than 75% tumor burden line for depletion. And as you know, we were providing longer-term follow-up from this study as well as further subgroup analysis at the ASH meeting. Regarding the manufacturing process, irrespective of disease burden and adverse prognostic factors, the manufacturing was robust and reliable. The majority of patients for whom leukophoresis was received achieved and released product with a median rent delivery time of 21 days, 84% of the enrolled patients were also dosed. CAR T cell engraftment and precision look consistent with our prior observations in the [indiscernible], where we showed that all patients with long-term outcome had also long-term persistent CAR T cells.

Moving to Slide #9. As I've mentioned, the ASH abstracts were released this morning and are available online by the ASH conference platform, and we just would like to briefly highlight the presentations at the conference. We have had 4 abstracts accepted 2 oral presentations and 2 poster presentations. In an oral presentation on Saturday afternoon, December 9, Professor Claire Rodi will present the pooled safety and efficacy as well as longer follow-up data from the FELIX study, including subgroup analysis in addition. Data from all patients treated in the FELIX study continue to demonstrate high rates of overall responses, CRS and CRIs and a very favorable safety profile.

Additionally, data suggests better outcomes in the subgroup of patients with low leukemia burden at screening and liquid depletion. Data presentation will be based on a median follow-up of approximately 15 months versus 9 months at ASCO earlier this year. And we look forward to sharing more details, obviously, at the actual presentation. Second, in a person presentation, we'll look in addition at data from a pooled analysis of relapsed/refractory ALL patients that were treated in the ALLCAR19 study. As well as the FELIX Phase Ib study. So this was the precursor of the running part of the study before we conducted the pivotal study. After a median follow-up of more than 3 years between those 2 studies, we have approximately 30% of patients that remain in remission without subsequent transplant or other anti-leukemia therapy, indicating that we have a proportion of patients that are likely to experience a long-term benefit. When we then look into the CLL and NHL cohorts of the ALLCAR19 extension study, we have there more than 2 years of follow-up at this point in time.

And the study also shows durable responses and the low incidence of serious infections as well as a very good overall safety profile, which gives us, I think, a very strong, I think, rationale for moving over time into these additional disease settings. Continuing on with the obe-cel abstracts, we'll also be presenting data on our manufacturing capabilities in a poster presentation. Data gathered in the FELIX study successfully demonstrated the robust operability of obe-cel manufacturing. All of resi starting materials were successfully processed despite the multitude of constraints posed by the COVID-19 pandemic and many patients have had very high levels of leukocytes and cancer cells, frankly, in collected in the leukapheresis.

Further optimization improvements were made during the start-up of the study and increased reliability, consistency and precision of the manufacturing process as well as improved analytics helped to minimize turnaround time and support the development of obviously, the nucleus as well as our new obe-cel manufacturing facility.

Shifting gears to our dual CD19/BCMA tasgeting CAR T program, AUTO8 from multi myeloma. In an oral presentation, we'll be sharing preliminary data from the ongoing Phase I [indiscernible] study at ASH. All patients treated achieved a response as doses were well tolerated with no ICANs or CRS larger than Grade 3 with a median follow-up of 4.5 months at the time of the abstract.

With that, we're transitioning to Slide #11, and we're looking at the preparation for commercial launch of obe-cel. As you can see on Slide #11, we are well on track with the activities that we have laid out. Key, obviously, is getting the manufacturing supply all set up, and that obviously has progressed really well. I'll spend a little bit on the next slide on that as well. Remember, what we're designing this -- what we designed the facility for is for capacity that will allow us to actually address and support 2/3 of the total market in the U.S. and Europe for relapsed/refractory ALL patients. So we have an initial capacity set for 2,000 batches a year, the full capacity of the facility actually exceeds that level.

Secondly, obviously, we're working towards the filing of the BLA. The target is to get the filing in before year-end, and we're on track of delivering that important milestone for the program and the company. We then also will, as we go through the early part of next year, obviously, we'll go through a set of inspections. Of the facility. We will certainly have one from the MHRA, which we expect in the early part of next year. as well as in the context of a BLA review, obviously, additional inspections that are expected during that process. The filing for an EU registration is expected in the first half of next year and is also conducted under a prime designation similar to the RMAT designation that we have with the FDA. From a commercial perspective, there's been a significant amount of activities this year, particularly in the medical affairs side, where we also are very active sharing the data, running medical education et cetera.

The second key area that we're working on is really working through the value proposition for the program and the value doses. So that's a key set of activity. that we're well on track with and exactly where we expect it to be at this point in time. And third, obviously, we have started the onboarding of clinical centers for obe-cel, which is a process as we had indicated in the past, it typically takes somewhere between about between probably 9 and probably 15 months depending on the center to actually get fully onboarded and registered.

When we look into next year, obviously, we'll start to build up towards U.S. launch preparation and that obviously will be one of the key activities that we really -- we're going to get seriously focused on in terms of buildup as we're -- after we have filed the BLA, and we're in the review process of the application. So with that, we're going to Slide #12, and this is a brief overview of the Nucleus facility. As you remember, this is a very compact facility, quite unusual in its design. A total square footage of 70,000 square feet. It's a 4-story building, industrial height. And in order to actually get this building off the ground and operationally ready in a very, very short period of time. We have taken on an approach that built on -- or it was based on a high degree of off-site building of the facility. In fact, we had about 70% of the facility built off-site move to the actual construction site and they're actually assembled by doing taking this approach and then also taking an unusual start-up approach in order to get the facility up and running and qualified. We're actually able to from November 8 to 2021 with the groundbreaking in less than 2 years or actually to the full qualification of the facility, which is complete at this point in time.

And obviously, if we look at the timing for the BLA filing, we've been just around a little bit above probably 2 years of time to go from groundbreaking to a full package and a submittable in its complete form. So that's an exceptionally fast process that we're able to run through, had a lot to do with the innovation that we're applying to both the design as well as the buildup. The design has was not just chosen for the reason of actually being fast and be able to actually set up this facility in probably less than half the time than anyone actually had done it in the space so far. But also because it is -- it gives us an ability to replicate the facility with increased demand elsewhere and also be able to do that with relatively short time lines from decision-making to operational activity. That is going to be important because there's been impact on your -- the risk profile of investments and the timing of investments. What you then see on the right-hand side is the actual inside of the initial operating suite. This is a suite that's designed to deliver about 700 products a year. And what you see here is the -- this suite actually in full at full activity level during the capacity challenge. The manufacturing process, as you remember, is highly automated, and that gives us an ability to really run a relatively large number of products in parallel within the same environment. And in fact, what you see here is, in fact, a picture that comes from the actual capacity challenge. Where we pushed the output of that particular clean room to its limits. And obviously, with the key objective to be able to demonstrate sustained control throughout that level of pressure and be able to deliver high-quality products during this period. So a key aspect actually also of data that goes into a BLA filing as well. When we look beyond the ALL opportunity and moving to Slide 14, what you see summarized on Slide 14, is basically the evolution of the obe-cel program as we see it currently. First of all, as you've seen, obviously, with its anchor indication in ALL gives us very unique product with an exceptional level of activity, combined with a remarkable level of safety. And that gives -- creates a unique opportunity, not only for the development of the product in patients with acute lymphoblastic leukemia, but also, obviously, for indication sets in non-Hodgkin's lymphoma as well as in disease. So that's the core opportunity we see with obe-cel and obviously, we're active on all those fronts with the program. When we think about sort of the next steps of the program and building on the unique features of the CD19 CAR that's utilized in obe-cel, we developed obviously 2 next-stage products. One is AUTO1/22 that I mentioned before, where we published the data in blood from our Phase I initial clinical trial which is a dual targeting approach with the aim to minimize the risk of patients relapsing with CD19-negative disease, which is one of the major for relapse in acute lymphoblastic leukemia, both in children as well as in all patients.

This product obviously gives us sort of a next leg up. It builds on the unique properties on the CD19 targeting utilizing the same CD19 CAR as obe-cel does, but actually adds a highly potent a CD22 car that was designed to recognize cells that express very low levels of CD22 on their surface, which is one of the known escape mechanisms for CD22. So this is the next-generation program for cell which is really designed for oncology indications as to the primary area of opportunity.

The second program, AUTO8, I mentioned before, we're going to be presenting an overall on the Phase initial Phase I data and generated together with our colleagues at UCL. This program, again, builds on the CD19 CAR from obe-cel ,and it adds a highly potent BCMA CAR in this case as well, optimized for recognizing very low levels of BCMA on the surface of target cells. This is a known challenge with BCMA targeting is that we do have -- that the target is selective but the target is often expressed at copy numbers that are maybe as low as 10 or 20 molecules on the cell surface for molten myeloma cells. And as you can imagine, that creates somewhat of a challenge to actually efficiently recognizing these cells and making sure you can really get at all the cells and not just the higher-level expressing multi myeloma or plasma cells.

So this program, obviously, is, again, as with [ AUTO22 ] dual targeting program. And so it starts opening up opportunities that could go both on the oncology as well as the autoimmune side. And depending on the development of the data, we'll make decisions in which direction we think we're going to be taking this program.

Moving to Slide 15. This is just a slide that we have shown last week and explained and sort of walk through in more detail. Fundamentally, we believe we're in a very good position with our program. given that we do obviously have a substantial amount of clinical validation. We have a large data set and an incredibly difficult to treat patient population, where we show sort of a best-in-class benefit-risk ratio for sure across this indication, but also highly attractive profile. In the non-Hodgkin's lymphoma settings as well. This gives us a lot of confidence around the product. What you need to do is you need to obviously in these autoimmune diseases, make a very deep cup into the B-cell compartment. This is what we've demonstrated, obviously, in all of these patients, driving or -- where we can demonstrate and show that, indeed, these patients do experience B-cell aplasia. But I think much more stringently, we can demonstrate that we also get the patients that have leukemia into an MRD-negative state, which gives us a much higher level of resolution and a much more stringent measure of removal of all CD19 positive cells. In these patients. So it gives us a strong amount of information about the quality of the clinical activity that we can see in these patients and obviously, combined with an exceptional safety profile. Safety matters a lot in autoimmune disease. It's more important actually than in oncology. And one of the advantages that we have with obe-cel is that we always have a substantial safety database now that we have generated in the development leading up to the evident filing in -- for patients with ALL.

Now the -- this safety data becomes important, particularly when you think about the opportunity that we have seen from the work that was done by a [indiscernible] and Andreas Mackison, in inducing deep responses in SLE patients. And in fact, by now actually have shown then indeed, those responses are sustainable at least for a 3 years to 2 years, which is the observation time that's currently available for those initial patients treated.

With their own CD19 CAR T therapy, which they manufactured on the academic side. Now this level of activity creates also an interesting opportunity with regards to the development path you can take in which is a much more aggressive, much more compact development path as you would normally have seen with the standard add-on trial designs that have been used for the various monoclonal antibodies that have developed for the space. Which tend to do sort of a limited or can show a limited improvement over the standard of care and obviously require very large patient numbers to demonstrate the effect as a consequence of it. Here, we believe that if those -- that level of activity can actually be confirmed that was originally seen in the airline study that he would be able to actually run the relatively compact studies that you would then actually have to supplement with safety information from other studies to actually discharge the safety risks for the product. We believe this puts us in a very strong position because obviously, we do have a substantial amount of data from our current development. We also obviously will do have a very significant level of derisking from a manufacturing perspective, from a regulatory perspective as well as from a commercial perspective. And I think one point I wanted to just highlight is that we believe it's going to be important in this indication to also have an ability to deliver product with a good cost of goods.

As we think that the range of prices that ultimately will be realized will be similar but may not exceed what we're seeing on the oncology side. And clearly, that requires you to actually have attractive cost of goods to actually maintain profitability across these indications. And that's going to be very difficult to actually generate if you had to, for an example, utilize CDMO on the way there. So this is a few considerations here for why we think we're exceptionally well positioned. Obviously, we're in -- we're going to be starting with the dose confirmation study early next year. And with data from that study, we'll then discuss the pivotal study designs and take it from there. But we believe that this is obviously with all the work that we've done and enabling work and infrastructure pieces we have in place. put obe-cel in a very, very strong position.

Moving to Slide #16. This is just a quick overview in terms of the the competitive environment where we have either companies that have a significant presence in the CAR T field, but have changed the manufacturing process to a point where the product as far as we can tell, will not be comparable to what they have used in the past in the oncology setting. At that point, you do lose the ability to actually utilize the safety information that you generated on the oncology side, and you need to actually generate more clinical data to discharge the safety risk. There's also obviously investment required to sort of adjust manufacturing, et cetera, to the new manufacturing process, which we do not have to do. And then obviously, we have additional new programs coming in, which lack clinical data as well as infrastructure. which obviously will require very substantial investments to be in a competitive place going forward.

And it will be interesting to see over time what the potential allogeneic approaches might do. At this point, obviously, there's still a lack of data and obviously needs to be built, frankly, across the board in terms of capability. So with that, I'll move on to just a quick update on the pipeline. We touched on most of the programs. What I briefly want to just highlight is that we're in the process of writing up the clinical experience with AUTO4, which we expect to publish in a peer-reviewed journal.

As well as with regards to AUTO6NG, our neuroblastoma program, where we expect to dose our first patient during the quarter, the fourth quarter now as well. That program we're excited about as we're sort of in included in that program, quite a range of cell programming technology we've developed for the last few years and they're now basically bringing together in this indication, solid tumor indication.

So with that, I'd like to actually hand over to Rob and we're moving to Slide #19.

[Robert Dolski, executive]

Thanks, Christian, and good morning or afternoon to everyone. It's my pleasure to review our financial results for the third quarter ended September 30, 2023. Our [ cash in cash ] equivalent at September 30 totaled $256.4 million as compared to $382.4 million in December 31, 2022. .

Total operating expenses net for the 3 months ended September 30 were $47.8 million as compared to $43.5 million for the same period in 2022. Our research and development expenses decreased by $0.4 million to $37.2 million for the 3 months ended September 30 compared to the same period in 2022. This was primarily due to decreases in clinical trial and supply costs related to our obe-cel clinical program. And these were partially offset by increases in operating costs related to our new manufacturing facility as well as salaries and employee-related costs driven by increased headcount. On the G&A side, general and administrative expenses increased by $2.4 million to $10.6 million for the 3 months ended September 30 compared to the same period in 2022. This increase was primarily due to salaries and other employee-related costs, driven by an increase in general and administrative head count supporting the overall business growth primarily related to pre-commercialization activities. Our net loss attributable to ordinary shareholders was $45.8 million for the 3 months ended September 30, 2023 compared to $42.8 million for the same period in 2022. Autolus estimates that our current cash and cash equivalents on hand and anticipated future milestone payment from Blackstone will extend the company's cash runway into 2025. And just as a reminder, in our projections, we do anticipate an R&D tax refund from the U.K. HMRC in Q4 of this year. And would anticipate being eligible for a tax refund in a similar fashion next year as well.

I'll now hand back to Christian to wrap up with a brief outlook on expected milestones. Christian?

[Christian Itin, executive]

Thank you, Rob. And so we're moving to Slide 21. The -- this is a quick summary of kind of the plant news flow. And as you can see, -- there's a lot of activity coming up towards the end of the year and into the early part of next year. As mentioned before, a big item of focus. And clearly, where most of the organization is working towards to get the BLA filing in before the end of the year. We obviously talked about the obe-cel nFELIX data update as well as the update around ALLCAR19 and the FELIX Ib study, which gives us longer-term information. and I think a very nice proxy in terms of what to expect in terms of longer-term outcome from the larger pivotal FELIX study. We then obviously we'll have the update on AUTO8, which is a program that is shaping up very nicely, and I think will give us sort of a first interesting look at the profile of that program. then as mentioned just before, the start of the AUTO6NG Phase I trial in children with neuroblastoma, which we expect to actually get the first child in before the year-end. Importantly, as we go into early next year, we expect to get the Phase I up and running the first patient in, in the early part of next year. .

Treating patients with autoimmune disease, particularly focus, obviously, here is SLE in this initial study. And the study is designed to confirm the dose and with that, able to have a basis for the regulatory discussions around the pivotal study design. And then as indicated also in the earlier part of next year, we're expecting to get the filing in Europe and the MAA application with the European agency as well. So a lot of activity in the upcoming months. I think a lot of very significant value steps for the company. I think we're very well set up, and we have a fantastic team also on the now building up on the commercial side and I think will put us in a very strong position to get to the next steps once we're through the actual interactions on the regulatory side. So a lot of good stuff ahead of us.

Really looking forward to seeing many of you probably at ASH, and happy to take questions now.

[Operator]

[Operator Instructions] Our first question comes from the line of Matthew Phipps of William Blair.

[Matthew Phipps, analyst]

All the updates. I guess, first on ASH will be the obe-cel FELIX update, do you think of sufficient follow-up to really show EFS curves at ASH? And then for AUTO8, another 6 value patients, were those just from the BCMA alone CAR in cohort 1? Or were there some of those with cohort that the CD19 as well? And I guess, maybe how many patients do you expect from Cohort 2 at ASH? .

[Christian Itin, executive]

Yes. Very good questions. Thanks for joining, Matt. So first question is, are we expecting to update or present event survival data? And the answer is yes. on the FELIX study. And then with regards to the AUTO8 program, what Matt was referring to is that we are starting the Phase I clinical study dosing patients with the BCMA CAR alone to establish the base profile for the BCMA CAR. And then actually after that was initially established, added the -- also the CD19 CAR component to the product. And we're actually going to have data from both patients with BCMA only as well as with both cars present. And we're at a point where we're probably going to be in the range of about 10 patients, maybe slightly above that.

[Matthew Phipps, analyst]

And if I can ask just 1 other 1 on the autoimmune side again. Can you remind me, I can't remember if this was discussed last week. But is there a safety kind of DLT period like in between patients for the initial like you have to wait a month before you can to a subsequent patient or anything like that? .

[Christian Itin, executive]

We would expect that there is a gap between probably the initial patients. And then as soon as you actually have initial data you can then actually enroll at that level. Obviously, we do have quite a number -- quite a good level of data at this level of dose across particularly the air mill population. So there's a lot of safety data already in place. So we should be able to enroll the differ quickly.

[Operator]

[Operator Instructions] Our next question comes from the line of Dev Prasad of Jefferies.

[Dev Prasad, analyst]

This is Dev on for Kelly at Jefferies. So I have a quick question on SLE. How do you think about the cell persistence that can have an impact on efficacy and safety in contrast to the oncology indications that we have seen so far?

[Christian Itin, executive]

Dave, very good question. And so as mentioned before when you look to sort of achieve is a very deep cost into the compartment to remove both to the other reactive precursor cells and memory cells as well as the autoreactive plasma cells. So deep cut is what you need, given that this is a cell-based therapy that will take some time to be effective and complete. So you will need a certain level of persistence to be able to do that. What we've seen and what I think is very encouraging is that the program in Airline and showed very nicely that they did get very deep response. They got obviously, a good transition in terms of translation from a clinical efficacy perspective, and when you look at the persistence of the CAR T cells, you see that the CAR T cells are pretty much arrived for about 6 months. .

And after that, you do start to see the B cell compartment REGENERATE. You see the maturation of B cells from the various cell types antibody subtypes perspective. But what you do not see is actually a recurrence of ordering activity. So there is a certain amount of precisions that clearly will be important. What we do see is that our product and in fact, the product that was used in airline in pediatric ALL patients has quite very similar behavior in terms of persistence. Also in their hands to we do see that they have children with long-term systems. We're talking 2 years that at least the current experience. And that's quite -- that is similar to what we have seen with obe-cel. And so we think actually that the profile should match very nicely.

[Operator]

[Operator Instructions] Our next question comes from the line of Gil Blum of Needham & Company.

[Gil Blum, analyst]

So a couple of items from First of all, for AUTO8, it looks like the data is really interesting, but to super crowded market, and there's a lot of assets going into it, what do you think is going to be a key differentiator, maybe on the angle of safety?

[Christian Itin, executive]

So first of all, thanks, Gil, for joining. A very interesting question. And I think one that we sort of see actually quite a bit of an evolution in the field as well. In order for what we designed the product for is to be able to get, on the one hand, deep responses. So we want to actually see that indeed, we can get to very low levels of disease [indiscernible] Patients. And obviously, you can measure in multi myeloma, similar to AML, you can measure invasive disease levels, and that gives you a bold parameter. I think that we're clearly very interested in looking at and pursuing. The second aspect was one -- was a bit of a conundrum, I think, from -- in the field in the sense that what we're seeing with regards to cell dynamics, CAR T cell dynamics in multimyeloma patients is that the CAR-T cells tend to actually not persist well. And so one of the things we wanted to achieve is see that indeed we can actually get a longer-term persistence through the CD19 CAR component. .

With the various regression at , you do have, obviously, new CD19-positive cells being formed that can actually help drive a certain level of baseline activation and maintain that for the CAR T cells. The other aspect, the third aspect, I think, goes actually links quite nicely with the conversation we just had on the autoimmune side. Which is that there is an early stage of the partner cell compartment with CD19-positive and certainly has been sort of [indiscernible] more than 25 years. then that the driver sales from multi myeloma might, in fact, for CD19 -- CD19 expression. So what it also will allow us to do the combination is to obviously get into that part of the compartment.

And may actually also help us get at some of the driver cells. And so the on the 3 hypotheses. In terms of the data that we're looking for is want to see a high level of responses in these patients. We want to see whether these responses get deep over time, usually depending on what to score for can take a bit of time to develop up fully. And secondly, we want to see the cellular dynamics of the products in the patients as a consequence of adding CD19 component to the product.

So those are probably the key things. And I think once we have that data -- and with a reasonable number of patients taking it, and I think that's been the time for us to sort of think about the approach that would be suitable for the development for the program going forward. But in terms of the hurdle for development, clearly, you need to have an exceptional profile of the product to develop that email myeloma. So that's sort of where we are in our current pacings.

[Gil Blum, analyst]

Makes sense. I do want to go back to a point that you made during the SLE event. So why does the company believe that other commercial states CAR T we need to maybe redo their production and do more clinical studies in order to move into SLE despite the fact that they already have commercial stage assets?

[Christian Itin, executive]

That's a really good question. And I think what we're seeing with 2 programs that are being moved forward. is that the company has decided to massively change their manufacturing. So in 1 case, it's moving from a manual very lengthy manufacturing process to highly automate it over a 2-day process. That's a massive change in terms of the actual manufacturing process. It will lead to, frankly, different products. And particularly if you go to this very early stage of a short manufacturing process around the additional issue that -- at that point in time, the CAR, the covering antigen receptors are not yet expressed properly on the surface. And with that, the sales are not yet functional, biologically functional from a potency perspective or an ability to from a sales perspective.

So it creates clearly a very, very different type of product, a different set of product properties. And with that, you have a new product. And that means that you have to obviously we do or to generate new clinical safety data, et cetera, and build and as. And from a commercial manufacturing base, it's a fundamentally different setup from the manual setup, which is required, as an example, a high-grade clean room environment. Versus [indiscernible] or the automated platform as we use it where you basically go to a low rate room environment. It's a very different environment to be optimal. The way you have the flows in the facility and be optimal for that from a cost perspective looks different. And we would expect it will require a pretty significant investment structure change.

Or build new manufacturing facilities to sort of accommodate this very different manufacturing process. The second company in the space also has made very significant changes, calls the product differently as well in terms of its coding. And we do not believe that the product will be comparable and these goals are going to be certainly some level of adjustment that will have to be made to the commercial manufacturing infrastructure. To adjust to the new process and plan to be effective with a decision. So those are probably some of the key considerations. What they obviously do have is the base set of systems for commercialization to sell orchestration and so on. That's obviously straight usable and can be straight applied. So there is clearly an advantage there of being able to align on that as we will rely on the systems we're setting up natural ALM.

[Operator]

[Operator Instructions] Our next question comes from the line of Yanan Zhu of Wells Fargo.

[Yanan Zhu, analyst]

I have a couple for the SLE and a couple for FELIX. Perhaps let's start with the SLE. I was wondering, Christian, you were talking about the benefit of us having one of the benefits of having the same product as your other soon-to-be commercial product is that may be discharged of some of the safety database size requirements in your new indication. I was just wondering is that something that you have had some preliminary agreements with the agencies on? Or is that your general expectation? Also, I was wondering if you have any thoughts on Novartis's [ YTB ] 323 abstracts at ACR. Any comment on their dose level early efficacy and also early safety? And how does that have any implication for your confidence for obe-cel in SLE. And I'll ask the critics question afterwards.

[Christian Itin, executive]

Okay. Well, thanks, Yanan, for joining. Really good questions. So first off, on the safety. Also, this is based on sort of the regulatory guidance you have in terms of the general size of safety databases to get after discharge, the respective level of risk. And that's actually consistent when you look at the various indications and the way you can actually use information, gain in one indication, applied to another for as long as you're working with the same product. .

So this is not specific guidance. This is the general guidance that you have in terms of safety requirements and discharging safety business. The second aspect -- a second part of the question was related to the abstract from the [indiscernible] program, which I think things look good. I think it's very encouraging because overall, it looks like they were able to replicate the data from the airline and team. I think that's great news. I think for the active for the approaches. That we're working on, and particularly also for the approach we're working on. In terms of the dose, the dose is relatively low, and that is actually, I think, quite consistent with our own experience where we have been able to obviously show in adult patients, we can go at dose 10 million cells, and we get high degrees of activity and responses. So -- we know that the cells are active at that level, and they're operating at a somewhat lower level that was used in on. But again, it's a different product that they're using.

So -- there's going to be some differences. And it may also be guided and to some extent from needing sub-safety data at the respective dose levels. So I think overall, I think, very encouraging and I think good news because we start to get, I think, a clear view that the data Candu implicated that the Eviti Airline have generated I think that's frankly good news for weaning for you.

[Yanan Zhu, analyst]

Great. Okay. So on FELIX and the ASH update, I was wondering -- is the data cutoff for the abstract which we are seeing now, would that be the same as the actual presentation -- and also, I think we noted the median DOR is now stated as not reached. I think back at ASCO, there was a median DOR. So it feels like the curve has probably fluctuated around the median and was bumped up somewhat with newer patients and longer additional patients or longer follow-up. I was just wondering if that the right understanding? And also if you can comment on how much it was bumped up, that will be super helpful. Chris?

[Christian Itin, executive]

Yes. So in terms of the data costs, obviously, the data comp that we're going to have at the -- for the ASH meeting will give us about the 6 months additional view on the patients. I did any case that the median follow-up at ASH was 9 months, we expect the median follow-up at ASCO was 9 months. we expect the median follow-up for ASH to be at around 15 months. So it's essentially the data cut. And it's also different from the abstract, the data cut that went into the abstract I think one of the things that we're pointing out in the context of the ASCO data. As the ASCO presentation was the fact that the time-dependent measures clearly were not mature by any stretch of the imagination.

We have most of the patients still in the very early part of the curves when we presented at ASCO, which means that there's still a significant amount of variability that we had in the curve, and we're seeing obviously some of that play out. And usually, it's one patient up or down that can move the curve, particularly if you're focused on the median and that's almost arbitrary.

So you need to -- clearly, we're going to have more follow-ups, 6 additional months of follow-up that obviously will give us more stability into the curve. But clearly, the compared to where we were at ASCO. Was predominantly driven by the fact that most of the data were still very early.

[Operator]

[Operator Instructions] Our next question comes from the line of Asthika Goonewardene of Truist

[Unknown Analyst]

This is Kareena for Asthika Goonewardene on the progress. I had a question on -- a few questions on quota. So what kind of data can we expect at ASH will this have like baseline characteristics and percentage of patients with [ EMD ] and other high-risk agnostic factors? And I think you said it's going to be 8 patients worth of data at ASH. Can you just confirm that?

[Christian Itin, executive]

The data, obviously, this is a Phase I study. So yes, we'll obviously we'll have a review of the patients that were included, the state there condition to range and we'll also give a full characterization of those patients on the treatment. Overall, we think we're probably going to be in the range of 10-plus patients as as mentioned before, so this is still as indicated, a Phase I study.

[Unknown Analyst]

Okay. And will there be enough follow-up for 6 months, 9 month [indiscernible] .

[Christian Itin, executive]

No, that's -- well, there is some follow-up, but I think we need more patients and more follow-up to sort of reaffirm around those types of information.

[Operator]

Our next question comes from the line of Simon Baker of Redburn Atlantic.

[Simon Baker, analyst]

Two, if I may, please. Firstly, on SLE. As you say, you have an advantage over most, if not all, competitors in the space in terms of the size of the safety database and the suitability of the manufacturing process. So I just wondering if you could give us some idea of how much in terms of time that that advantage eats or alternatively, I suspect it probably won't, but some more idea on when we should think about pivotal trial starting and potential commercialization, should it be successful? And then secondly, on the manufacturing capacity and the nucleus, could you give us an idea of the validated capacity here and now of new [indiscernible]. I know it's a modular facility that can be expanded, but some idea of where -- what the capacities at the moment will be very handy?

[Christian Itin, executive]

All right. Well, thanks, Simon. Thanks for joining. The -- on the SLE side, the question was when do we expect a pivotal trial to be -- run. Obviously, that's slightly premature, but the basic notion is that we're planning to the dose confirmation during the course of next year. With that data, we'll then approach the regulators, which would sort of point to the following year as the start point than the starting point for a pivotal study. I think it is too early to point to kind of what the duration of a trial, a pivotal trial will be in the absence of having an agreement on the trial design with the agency. So that's probably too early. With regards to the capacity question at the nuclear. So the facility is -- basically, it's a modular setup, as indicated, it has for the initial setup for ALL 3 clean rooms. Each one of those scaled for 700 products a year. And we're obviously going to be launching out of the first clean room. So that gives us an immediate 700 capacity. .

And that was will bring online the second and the third clean room because it doesn't make sense to operate clean rooms that are not being utilized from a capacity perspective yet. But the facility is fully built and obviously validated. But in terms of the actual ramp and how you run that is that you make sure that you have the right level of capacity at the right point in time. But the important thing is here is we have no limitation to actually ramp ahead of demand here. And I think that sets us apart from all the other launches that we've seen over the last few years. Thank you, Simon.

[Operator]

This concludes our question-and-answer session. I would now like to turn it back to Christian Itin for closing remarks.

[Christian Itin, executive]

Well, first of all, thanks all for joining. The -- looking forward, obviously, to seeing you at ASH with the additional data updates. And for those of you who happen to be in on middle of November, we're looking to -- or having a visit at the actual manufacturing facility. So if either on the analyst or investor side, there is interest, to visit the facility, please contact [indiscernible]. To join us for that reason. But you might find it interesting and helpful to sort of understand what the reality looks like on the CAR T therapy side and what you need to have in place to be able to launch.

So with that, I'd like to thank you all for joining. I appreciate your time and speak to you soon. Thank you.

[Operator]

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.