Earnings Call Transcript - AUTL Q3 2021

Operator, Operator

Hello, ladies and gentlemen, and welcome to the Autolus Therapeutics Third Quarter 2021 Financial Results Conference Call. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Dr. Lucinda Crabtree, Vice President, Business Strategy. Please go ahead.

Dr. Lucinda Crabtree, Vice President, Business Strategy

Thank you, Daniel. Good morning or good afternoon, everyone, and thank you for joining us to take part in today's call on the financial results and operational highlights for the third quarter of 2021. I am Lucinda Crabtree, Vice President of Business Planning and Strategy. With me today are Dr. Christian Itin, our Chief Executive Officer; Christopher Vann, our Chief Operating Officer; and Andrew Oakley, our Chief Financial Officer. Before we begin, I would like to remind you that during today's call, our discussion will contain forward-looking statements. All statements other than statements of historical facts on this call are forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the section titled Risk Factors in our annual report on Form 20-F filed with the Securities and Exchange Commission on March 4, 2021, which can be accessed on the EDGAR database at www.sec.gov, and in subsequent filings we make with the SEC from time to time. The forward-looking statements on this call reflect the company's views as of today, November 3, 2021, regarding future events and should not be relied upon as representing the speakers or the company's views as of any subsequent date. While the company may elect to update these forward-looking statements at some future point, the company specifically disclaims any obligations to do so even if the company's views change. These forward-looking statements should not be relied upon as representing the company's views as of any subsequent date to today. Please be advised that today's call is being recorded and webcast. So on Slide 3, you will see the agenda for today, and it is as follows. Christopher will provide an overview of our operational results for the third quarter of 2021. Andrew will then discuss the company's financial results before Christian will conclude with upcoming milestones and any other concluding comments. Finally, we will, of course, welcome your questions following our remarks. Turn to Christopher.

Christopher Vann, Chief Operating Officer

Thank you, Lucinda, and good morning to you all. Thank you for joining us. It's my pleasure to review our operating progress for the third quarter 2021. If we move to Slide 5, I'd like to give a quick update on the key pipeline activities. And first of all, our multicenter FELIX study for our lead program, obe-cel, which is progressing very well. Enrollment in the Phase II portion of the study is on track. And consequently, we are reiterating our guidance that the primary endpoint data will be delivered in the middle of next year with the full pivotal data available by the end of 2022. Furthermore, we are pleased to be in the position to update you that the initial observations from the 16 patients in the Phase Ib running portion of this multicenter Felix study, where we observed the 1-month complete response rate and safety data, are so far consistent with the data reported from the academic ALLCAR study of obe-cel in relapsed/refractory adult acute lymphoblastic leukemia. Clearly, this is very encouraging, and we plan to present this early data from the Phase Ib cohort later this year at ASH. In addition, we also expect to update you at ASH on additional data from the ALLCAR19 extension study of obe-cel in indolent B-cell non-Hodgkin's lymphoma indications as well, as the first early clinical data from the CARPALL extension study, which is evaluating our next-generation product, AUTO 1/22, in pediatric. In addition to the obe-cel news flow, we also plan to provide an update on our Phase I trial of AUTO4 in peripheral T-cell lymphoma in the first half of 2022. If we move to Slide 6, we'd like to walk you through a general corporate update from the third quarter. Firstly, during this period, we were delighted to announce the appointment of John H. Johnson as Nonexecutive Chairman. John brings a wealth of commercial oncology and business experience to Autolus and is a recognized leader in the biopharmaceutical industry, having held a number of executive, operational and commercial leadership roles. This experience will clearly be invaluable as we look towards the commercial launch of obe-cel. We're also very pleased to announce that in September, planning approval was granted to build the company's new manufacturing facility in Stevenage, U.K. This 70,000 square foot facility will be leased to Autolus and is another important step for Autolus on our journey to becoming a fully integrated commercial company. We anticipate that this will meet the global demand for our initial indications for obe-cel, and as it will be built for a capacity of approximately 2,000 GMP batches a year, it will also have a further scope to expand beyond that if needed. In terms of other updates, we promoted Chris Williams to Senior Vice President of Corporate Development; and Alex Swan, to Senior Vice President of Human Resources. This follows a departure from Matthias Alder, our Chief Business Officer, and we're extremely grateful to Matthias for his service to Autolus and wish him all of the best for the future. We are delighted to welcome Chris and Alex to the senior leadership team. As announced as part of the Q2 earnings as post-period events, we were very pleased to also announce the appointment of Dr. Edgar Braendle, who has now joined us as the new Chief Development Officer of the company; as well as Wolfram Brugger, who joined us as the new Head of Clinical Development. Finally, we announced an option and license agreement with Moderna, where we granted Moderna an exclusive license to develop and commercialize mRNA therapeutics incorporating Autolus' proprietary binders for up to 4 immuno-oncology targets. This is further tangible recognition of the technology base that we have developed within the company. With that, let's move on to the next slide, Slide 7. What we'd like to do is to provide a brief overview with regards to obe-cel, which is on track to be the first product commercially launched by Autolus. As you remember, our focus for the company is on delivering the FELIX study in adult patients with relapsed/refractory ALL. With the study enrolling patients who are both post-blinatumomab and inotuzumab, as well as patients that are just progressing in the relapsed setting but have not or may not have yet received inotuzumab and blinatumomab. As we mentioned earlier, we're also exploring the activity of obe-cel beyond all in the context of the ALLCAR19 Extension study, and we expect to provide further updates in Q4 2021 to the data already released at EHA in June of this year. In addition to the updates on follicular lymphoma and mantle cell patients, we will also include data on patients with DLBCL and CLL. In addition, we are also now treating pediatric patients with AUTO1/22, which is a newer product that builds upon the obe-cel backbone by adding a novel CD22 antigen receptor. As mentioned previously, we also expect to share some of the initial clinical data on this product also in Q4 2021. Next slide, please, Slide 8. Focusing specifically on adult acute lymphoblastic leukemia, it's worth remembering what are the key features of a successful CAR cell therapy for this indication. Obe-cel was specifically designed to tackle the underlying biology of adult ALL, and that's why we believe it's uniquely placed to address the current limitations of therapy in this indication. One of the core challenges with this disease is that it's fast proliferating, being cell-like in nature. And another challenge is that patients often present in very poor condition. The fast off-rate binder of obe-cel, whereby the cell interacts with its target and releases more quickly, means that the cells will experience less exhaustion and hence, better engraftment and persistence. Then at the same time, because of the quicker and more efficient interaction with the target, we would also expect to see less inflammation and lower levels of toxicity. Please move to Slide 9. Let me remind you, this still remains a very high unmet medical need for adult ALL with approximately 8,400 new cases diagnosed yearly worldwide in the last-line setting. Approximately 3,000 of these cases reside in the U.S. and EU. Whilst combination chemotherapy enables 90% of adult ALL patients to achieve CRS, only about 30% to 40% will achieve longer-term remission. Once relapsed, patients have a median overall survival of less than a year. The approved products include blinatumomab and elotuzumab for this indication, and in some countries, Tecartus is in the process of being launched. We believe, however, there remains a real opportunity for a product candidate with obe-cel's profile in this setting. And to remind you all, obe-cel has been granted orphan drug designation by the FDA for ALL; Prime designation by EMA; and ILAC designation by MHRA. Moving on to Slide 10. So let's just take a moment to recap on the data presented to date. Key new data were recently presented at EHA for the ALLCAR study, notably an update on durability of response as measured by event-free survival. As we've already communicated, and as you would expect of the CAR-T cell product in this indication, obe-cel has high levels of initial response. However, as the patients go out post-treatment, what we're seeing now is that the event-free survival is maintained in the Kaplan-Meier curve, with it stabilizing over time. This emerging evidence gives us a level of confidence that obe-cel has the potential to get a good proportion of these patients into long-term remission. So turning to Slide 11. To our knowledge, this is the first time that such a plateau of long-term response has been seen in this disease setting. Furthermore, it provides a degree of validation for the basic design premise of obe-cel since its long response is correlated with the exceptional persistence that we're seeing with the product. Not only do we see about a tenfold increase in the maximum number of CAR-T cells that have been reported in other programs, but the level of CAR-T cells is maintained over time. And it's our belief that persistence is actually a prerequisite to be able to translate a molecular response into a long-term remission in this indication, and the emerging data seems to support this. On the right-hand side of the slide, you'll also see the adverse event profile. And as reported previously, we haven't seen high-grade cytokine release syndrome. Furthermore, this was achieved without prospective intervention and with only limited use of supportive care such as tocilizumab and steroids and no vasopressor use in these patients. So again, as would be anticipated based upon the design hypothesis for the product, obe-cel has a very good safety profile, which should render the product more easily manageable in the clinic. In conclusion, the data is very encouraging with obe-cel having a potentially unique efficacy and safety profile in this clinical setting. So moving on to Slide 12. To put this data into context with the data published for the other products used in the space, I'd like to first compare it to the existing standard of care and the datasets that were the foundation for the approvals of blinatumomab and inotuzumab. Overall, as you can see, the available data for obe-cel thus far stacks up very well against both of these programs, particularly in respect of offering potential for high levels of activity with a more sustained response. Turning to Slide 13. Tecartus was recently approved in adult patients with relapsed/refractory ALL. The data supporting this approval shows a 24% high-grade cytokine release syndrome, neurotoxicity of 87% in patients experiencing any grade neurotoxicity in the label. And on the efficacy side, I would like to point you to obe-cel's complete response rate and compare it with the excellent persistence and event-free survival observed in the ALLCAR study. In conclusion, taken in context, we believe ALLCAR19 data is very encouraging with obe-cel having a potentially unique efficacy and safety profile in this clinical setting. And we feel we have a very nicely differentiated product for this high medical need patient population based on both the durability of response and overall safety profile. Slide 14, please. Moving on to the obe-cel registration study, FELIX. This is a 100-patient study in relapsed/refractory adult ALL patients. It has 2 subpopulations, relapsed/refractory post-exposed patients to blinatumomab and inotuzumab, as well as patients experienced regarding previously receiving blinatumomab or inotuzumab. The primary endpoint of the study is the complete response rate and the secondary endpoints include molecular responses as well as event-free survival and duration of response. Let us turn to the market size on Slide 15. I previously discussed the opportunity in ALL in terms of patients, but I want to emphasize the sales performance of the current standard of care, Blincyto, also known as blinatumomab. Amgen reported a 40% sales growth in the third quarter compared to the same period last year. Looking at the sales figures for the first half of 2021 and 2020, they were $187 million and $215 million respectively, reflecting approximately 20% growth. If we consider the proportion of use in pediatric and adult patients and estimate that patients typically receive about 2 cycles of this product, this suggests around 2,000 patients were receiving this commercial product globally in 2021. Amgen noted that a key factor driving sales growth has been the expansion into Community Hospital facilities in the U.S. beyond academic transplant centers. As Blincyto for ALL is being adopted in non-academic centers, we also anticipate the introduction in DLBCL to help establish CAR-T experience in those facilities. Both of these trends are positive for a product like obe-cel. Slide 16, please. Slide 16 summarizes the current situation for obe-cel in ALL. From the ALLCAR19 study, we have observed a subset of patients with a high level of sustained complete response achieved without subsequent stem cell transplant and durability of remissions that are highly encouraging with 50% event-free survival at 12 and 24 months. Obe-cel is well tolerated despite being used in a heavily pretreated patient pool with a high disease burden. We observed no grade 3 or higher cytokine release syndrome. And in the 20% of patients experiencing any grade ICANS, these resolved swiftly. Overall, we're very excited about the opportunity for obe-cel in a sizable market with clear unmet medical need. Now, taking a different tract and moving on to other indications. Please move on to Slide 12. At EHA in June, we shared data from the ALLCAR extension phase. In this study, all of the 9 patients that were dosed achieved a metabolic complete response. And in this small population, the safety profile was consistent with that observed in ALL with no patients experiencing high-grade cytokine release syndrome. Furthermore, none of the patients experienced any form of neurotoxicity. One of the patients, unfortunately, contracted COVID and died as a consequence of COVID-related adverse event. The patient, however, died in complete metabolic remission. There was one further patient who developed a single lesion in the skin, which could be removed surgically, but obviously, that event was also considered a progression. No other patients progressed and all other patients were in remission. Moving on to Slide 18. Given obe-cel's mechanism of action and profile, we're also evaluating its use in other B-cell malignancies. Non-Hodgkin's lymphoma patients as well as CLL patients are being evaluated as part of the extension in the ALLCAR19 study. We're also conducting in collaboration with our academic partners at UCL in the CAROUSEL study, the use of it in primary CNS lymphoma and aggressive lymphoma similar to DLBCL that is exclusively localized in the brain. In addition, as already mentioned, we're conducting an extension of the CARPALL study with AUTO1/22 in pediatric patients. These programs taken together will give us a very good overview of the activity of obe-cel across the spectrum of CD19 positive malignancies. Moving on. On Slide 19, a brief reminder of the broad and exciting technology toolkit that we have developed in Autolus, particularly as it relates to the suite of next-generation programs, some of which you will recall we showcased at AACR last year. We're looking to move these programs forward into the clinic through 2021 and into 2022, including in our first solid tumor programs. It's worth also reiterating the deal we recently signed with Moderna, which highlights the highly skilled in-house binder discovery team we have here in Autolus and the applicability of our work to other potential modalities. Finally, on Slide 20, you can see that we have tabulated these next-generation programs alongside the expected Phase I start dates. You will note, as discussed, we started the pediatric ALL clinical trial of AUTO1/22 in Q4 2020. We also expect the AUTO6 NG study in GD2 positive solid tumors to start enrolling in the first half of 2022. AUTO4 is also likely to move into the clinic in the first half of 2022. And finally, AUTO8, our next-generation multiple myeloma product, will move into the clinic in Q4 2021. With that, I'd just like to turn over to Slide 21 and turn over the call to Andrew. Thank you.

Andrew Oakley, Chief Financial Officer

Thanks, Chris, and good morning or good afternoon to everyone. If we can move to Slide 22. It's my pleasure to review our financial results for the third quarter of 2021. So if we start with our cash position. Our cash at the end of September totaled $173.1 million, and that compares to $216.4 million that we had at the end of June. I will note, however, that this cash figure does not include an R&D tax credit that we received in October of this year to the tune of approximately $25 million. Net total operating expenses for the 3 months ending September 2021 were $40.4 million, and that's net of grant income of $0.2 million, and this compares with net operating expenses of $42.7 million, net of grant income of $0.4 million for the same period in 2020. The research and development expenses decreased to $32.3 million for the 3 months ended 30th of September 2021 from $33.5 million for the 3 months ending 30th of September 2020. Cash costs, which exclude depreciation and amortization as well as share-based compensation, decreased to $29.4 million from $30 million. Noncash costs decreased to $2.9 million for the 3 months ending 30th of September '21 from $3.5 million for the 3 months ending 30th of September 2020, and this decrease is primarily related to share-based compensation expense. General and administrative expenses decreased to $8.3 million for the 3 months ending 30th of September 2021 from $9.8 million for the 3 months ending 30th of September 2020. And cash costs, and I just said it, but I'll say it again, which exclude depreciation expense as well as share-based compensation expense, decreased to $7.2 million from $7.7 million. The noncash costs in G&A decreased to $1.1 million for the 3 months at review from $2.1 million for the 3 months in the prior year. And this decrease is also mainly attributable to share-based compensation expense. Other income expense increased by $3.5 million for the 3 months ending 30th of September 2021 from an other expense of $2.5 million for the 3 months ending 30th of September 2020 to other income of $1 million. This increase was primarily due to the strengthening of the U.S. dollar relative to the pound during the 3-month period. Income tax benefit decreased to $5.4 million for the 3 months ending 30th of September 2021 from $7.9 million for the 3 months of the corresponding period last year, and that was due to a decrease in research and development expenditures, which qualified for the quarter. And as research and development credits fell at a faster rate than our net loss before income tax, this has led to a lower effective tax rate. The net loss attributable to ordinary shareholders was $34 million for the 3-month period, and that compares to $37.3 million for the same period last year. The basic and diluted net loss per ordinary share for the 3 months ending 30th of September 2021 was $0.47 per share, and that compares to a basic and diluted net loss per ordinary share of $0.72 per share for the corresponding period last year. At this point, we estimate that our current cash on hand provides us with a cash runway into the first half of 2023. And with that, I will now hand over the call to Christian to give you a brief look at expected milestones.

Dr. Christian Itin, Chief Executive Officer

Thanks, Andrew. Let me conclude this part of the management discussion with a review of the upcoming milestones and news flow to the end of this year and into 2022. Let's move to Slide 24. As we look at the remainder of this year and into next year, there are a number of clinical milestones and opportunities for value creation. Key and most eminent operational focus, obviously, is on the conduct of the pivotal FELIX study with initial primary endpoint data expected around the middle of next year. As Chris mentioned earlier, we are very encouraged by our observations that the CR rate and safety data on the multicenter Phase Ib part of the study is consistent with the data reported from the academic ALLCAR19 study of obe-cel, which, as you remember, was conducted exclusively within the U.K. We plan to provide a little more detail on this initial clinical experience later this year at ASH. Further, we expect to report an update from the obe-cel ALLCAR19 extension trial, particularly from the remaining cohorts in the relapsed/refractory B non-Hodgkin's lymphoma population, as well as CLL patients, again, planned for the end of the year at ASH. We're also hopeful that we're going to be updating you on the AUTO1/22 Phase I study in pediatric patients as well at that point in time. In Q1 next year, we plan to provide an update on the Phase I study called CAROUSEL, where we are testing obe-cel in patients with primary CNS lymphoma. And then as we go to the remainder of the first half of next year, we also expect an update on the AUTO4 clinical experience from the dose escalation portion of the Phase I program. As we then look forward into the next programs behind our lead programs, we expect to obviously move several programs forward. You heard from Chris. AUTO8 will get into the clinic still at the end of this year. We expect our revised solid tumor program with additional cell programming modules, AUTO6 NG, to get into the clinic during the first half of next year, and we're also moving obviously forward with AUTO5. Overall, we believe the company is in a very good position, combined with our cash on hand. We feel well poised for success across our pipeline. We're now happy to take questions.

Operator, Operator

Our first question comes from Mara Goldstein with Mizuho.

Mara Goldstein, Analyst

I wanted to ask on the FELIX program. You'll have the full dataset in the first half of 2022. And then can you talk about just what the regulatory path is from there for that program? And then on the ALLCAR extension studies, you've said you want to gather the data and see where that information takes you in terms of looking at additional programs. And so I'm curious as to how quickly you are able to execute on that once you have the full dataset, I'm assuming this year? And then lastly, I apologize. But I thought at your last comment, you said something about a revised solid tumor program, and I don't know if I heard that word revised incorrectly. So if you could just help me on that?

Dr. Christian Itin, Chief Executive Officer

Hi, Mara. Great to hear your voice, and thanks for joining. So AUTO6 NG is, as you may remember, a program that we built on AUTO6, which is the original CAR, and we basically went back and reengineered the program and probably I should have used the term reengineered. So there's no change, absolutely consistent with what we have been reporting before. With regards to the ALLCAR extension, obviously, what we're doing within the ALLCAR extension is adding approximately 10 patients in this additional set of indications to get a feel for the activity of the program within those indications. That work is ongoing. And obviously, depending on the indication, we would like to have a certain amount of follow-up to understand the level of differentiation of the data that we can actually see across these various indications. And we'll be guiding accordingly as we go through the course of next year in terms of the next steps. Getting to the FELIX study and the program of obe-cel in adult ALL. As we pointed out, we expect to reach the primary endpoint middle of the year. That is based on complete remissions, the complete remission rate and which is obviously established early on after treatment has started within these patients. We will then, by the end of the year, expect to also then have the 6 months follow-up data on all of these patients. And the expectation is that that will be the basis for the key regulatory filings that we're planning to do. And those filings are currently projected to be happening in 2023.

Operator, Operator

Our next question comes from Nishant Gandhi with Needham & Company.

Nishant Gandhi, Analyst

Can you give us any updates on the studying that you're exploring with AUTO8 for multiple myeloma therapy? I believe you mentioned that you're exploring BCMA. And if you can give us any information about the second target. Apart from that, can you give us any update on AUTO5? Like obviously, you initiate the Phase I study in the first half of 2022? Thank you.

Dr. Christian Itin, Chief Executive Officer

On AUTO5, obviously, one of the key things we're doing is that we're taking information we're getting from AUTO4 to inform the way we're going to actually conduct the study around AUTO5. So that's key information that we're still collecting and it will flow into the approach we're taking with AUTO5. With regards to AUTO8, we have disclosed, obviously, that we have generated a very sensitive BCMA CAR, which is a key component of the program, and that is going to be initially tested to establish the activity of that CAR on its own. And at that point, once that's established, we're expecting to add a second antigen, and we'll disclose that at that point in time.

Operator, Operator

Our next question comes from Nick Abbott with Wells Fargo.

Nick Abbott, Analyst

First question, Christian. We'll receive an update on the ALLCAR extension study later this year. Additionally, very early next year, we will also obtain the data for AUTO 1/22. How do you decide between these two assets as you consider the next steps beyond the adult ALL indication?

Dr. Christian Itin, Chief Executive Officer

That's a great question, Nick, and I appreciate your participation. Essentially, you're inquiring about the potential and profile of pediatric ALL compared to the opportunities for obe-cel in certain non-Hodgkin's indications. We analyze these indications separately. The development of AUTO1/22 is part of our broader ALL program associated with obe-cel. We view AUTO1/22 as an important next-generation initiative that we plan to expand over time, with pediatric ALL being a critical area for demonstrating the effectiveness of a highly effective CD 22 CAR in conjunction with the obe-cel program. This program is significant on its own merits, and a key objective is to reduce the relapse rate in pediatric patients. Achieving this would be instrumental in advancing our full development in pediatric ALL. This fits within our overall ALL strategy. As for obe-cel in non-Hodgkin's areas, we are focused on identifying opportunities that not only compare well but potentially outperform existing programs in those settings. We are beginning to examine this through the extension program of the ALLCAR study, and the resulting data will inform our development choices for non-Hodgkin's indications. Thus, we regard these two approaches as distinct, with AUTO1/22 being integral to our ALL strategy and the subsequent exploration of broader non-Hodgkin's opportunities.

Nick Abbott, Analyst

And maybe just to add to that, you said the initial U.K. manufacturing facility will support 2,000 patients per annum, which obviously will cover the adult ALL indications. What do you need to see? And what would the timeline be for adding additional capacity to support, for example, a lymphoma or pediatric ALL?

Dr. Christian Itin, Chief Executive Officer

So the way we're building the capacity around the facility in the U.K. gives us actually a very nice level of capacity in the ramp-up as we're launching the obe-cel program. And I think it will give us ample time to get a feel for the trajectory and then also a feel for the timing for additional indications to come online, to then actually time the build-out, not only of the facility in the U.K. but also consider establishing additional manufacturing capacity in the U.S. But it puts us in a very good space. It gives us a level of capacity that we believe actually will put us in a very good spot. And I think when you look at the trajectory we've seen in some of the other CAR-T programs, I think the 2,000 mark, we believe, is actually a good mark to work with, and it gives us an ability to react in time.

Nick Abbott, Analyst

Could you provide us with an update on the MRD-positive cohort of FELIX? Additionally, we noticed that the current milestone slides do not mention the AUTO ALLO or AUTO7 programs. Could you share the status of those programs as well?

Dr. Christian Itin, Chief Executive Officer

The other approach involves continuing our collaboration with academic partners, which is set to begin in the first half of next year. The AUTO7 program is planned to follow in sequence with AUTO6 NG. We aim to gain experience with the various modules we are introducing in that program, which is also part of AUTO7. Therefore, we expect a staging process to occur between these two solid tumor programs. That covers all the questions, or is there anything I might have missed?

Nick Abbott, Analyst

Yes, just on the MRD-positive cohort, how that's going?

Dr. Christian Itin, Chief Executive Officer

Oh, the MRD-positive cohort is obviously part of the FELIX study and runs alongside the FELIX study. And I’m sure we’ll be giving updates as we go through the course of next year on that patient pool. But right now, obviously, the enrollment focus is very much on the relapsed/refractory population with morphological relapse.

Operator, Operator

Our next question comes from Asthika Goonewardene with Truist Securities.

Asthika Goonewardene, Analyst

Christian, just want to connect back on that little Easter egg you dropped about giving us a little bit of a view on POX at ASH. Can you maybe talk to us a little bit more about that? In which presentation will that be and number of patients, et cetera, that we could expect? And then on that topic of ASH, could you maybe also give us a little bit more color on the number of patients we should be expecting for AUTO1 in NNHL and CLL as well as AUTO1/22?

Dr. Christian Itin, Chief Executive Officer

When we consider our plans for the Phase Ib portion, a primary focus is transitioning from a study primarily conducted in one country and center, like the ALLCAR study, to a more complex multicenter, multi-country setting. This shift brings considerable logistical challenges. Our goal is to showcase this transition by replicating data and advancing to commercial supply for the vector, among other changes we’ve implemented to guide the program toward commercialization. We'll provide updates on this at ASH and also share key elements from the Phase Ib trial designed to confirm the activity levels observed in the ALLCAR study. We will present our findings, emphasizing the consistency in safety metrics, which we aim to replicate along with overall activity levels. Regarding the ALLCAR19 study and our progress in non-Hodgkin's lymphoma, we have added new cohorts with 10 patients each and will report on their progress, providing a snapshot as we analyze those datasets throughout the end of the year. For the pediatric study, we will give an overview of the program's features and share initial clinical data. However, we expect significant updates for the pediatric program around mid-next year, after about six months of follow-up for the patient group, which we believe will provide insights into how well we can reduce relapses after achieving a response. This sets the stage for what to anticipate as we wrap up the year.

Asthika Goonewardene, Analyst

If I could add to that, regarding the data related to transitioning AUTO1 into the commercial stage, will there be patient-level data from the FELIX study included in the presentation at ASH?

Dr. Christian Itin, Chief Executive Officer

Well, the data that we will be sharing, obviously, is exclusively from the Phase Ib portion. Because as you can imagine, you do not want to share pivotal data ahead of actually getting the study completed and everybody treated. So this will be focused on the Ib experience of the study.

Operator, Operator

Our next question comes from Matt Phipps with William Blair.

Matt Phipps, Analyst

I guess, Christian, we've had a couple of updates in the third quarter with some CD19 allogeneic CAR-T programs. And wondering if you have any high-level thoughts on those. And if this is kind of influencing any of your allogenic approach, which I believe does not fully knock out the TCR, if I'm remembering correctly from the UCL presentation.

Dr. Christian Itin, Chief Executive Officer

Thanks for the question. Obviously, there is a kind of limit to what we know about what’s going on in those programs. Obviously, there’ve been some public statements that I think most of you have commented on. I think most on the call actually are covering probably the companies involved. So I think we’re seeing, obviously, emerging data, which I think is interesting, and sort of gives us a sense of the performance of the product, and I would expect more updates also around ASH. I think that’s a development in its own light. Obviously, the various ways of technology and some of the players were pointing to elements of their technology that might give them an element of potential differentiation, either on efficacy or safety. I don’t think I want to comment on that. The approach we’re taking with regards to the program we’re exploring with our academic partners is really to trap the T-cell receptor within the secretory pathway. So in other words, what we’re doing is basically expressing a protein module that actively traps the actual protein, TCR protein, within the secretory pathway and targets it into the degradation pathways. Now, that’s a fundamentally different approach to any approach that actually aims to knock in or knock out genes in whatever way that technology actually does that. So it’s a different approach. We’re not operating in that sense, at the genome level, but we’re operating with at the protein level. And so there’s sort of quite a different technological approach that we’re taking here. But I don’t want to get to speculate on the current technologies in play with other companies. I think they will update. I think the field at the upcoming conferences, and I think we’ll learn what’s going on there in that context.

Operator, Operator

Our next question comes from Kelly Shi with Jefferies.

Unidentified Analyst, Analyst

This is Dave on for Kelly Shi at Jefferies. So my question is regarding AUTO1 FELIX. Beyond AUTO1 FELIX in adult ALL, do you see the possibility that FDA might ask for a randomized controlled trial instead of a single-arm trial, given the evolution of a competitive landscape? And second question is, can you set expectations on data in the first quarter of next year for primary CNS lymphoma?

Dr. Christian Itin, Chief Executive Officer

Regarding the FELIX study, it is designed to provide the complete remission rate from a single-arm study. If we look at recent approvals in acute lymphoblastic leukemia (ALL), we see that blinatumomab, or Blincyto, was approved based on data from approximately 100 patients in a single-arm study. Similarly, Tecartus received approval in adult ALL with just 54 patients in a single-arm study. Therefore, we believe there will be no changes in expectations here. We anticipate that the single-arm study, supported by robust data from our early experience, is sufficient for submitting or applying for registration for the program, consistent with previous examples. This holds true also for pediatric ALL and the various trials that led to approvals in the diffuse large B-cell lymphoma (DLBCL) area, which, while larger, have not shown significant differentiation among programs. Hence, I see no reason for change. The full approval of Tecartus for relapsed/refractory conditions, irrespective of therapy line, is a positive development that bodes well for us and our program, putting us in a strong position.

Operator, Operator

Our next question comes from Eric Joseph with JPMorgan.

Eric Joseph, Analyst

Maybe just a housekeeping one related to the upcoming Phase Ib FELIX screen-out. I guess how should we be thinking about what might be included in a submitted abstract? And should we be expecting sort of material data there as it runs into? And then secondly, I'm wondering if you could give us a bit of an enrollment progress update with the Phase II. And are patients in the Phase Ib contributing at all to the Phase IIb readout that we're expecting over the course of next year? Or are they completely distinct patient populations?

Dr. Christian Itin, Chief Executive Officer

Thanks for the question. So obviously, the way that we designed the study does not make any distinction or differentiation in terms of inclusion criteria between the Phase Ib and the Phase II. So we're enrolling the exact same patients into the Phase II portion as we have enrolled into the Phase Ib portion. And that's obviously one of the values of the Phase Ib data that it actually gives us a good read on not only the inclusion-exclusion and the characteristics of the patients. But also, it obviously also enrolls the patients at the centers that were enrolling the majority of the centers in the Phase Ib were in the U.S. And we're enrolling patients in the U.S. So it reflects very well what we expect the composition of the patients to be in the Phase II portion. So in that sense, we believe that the data actually is very meaningful and is important in that context. And it also obviously includes, as I indicated before, complexities related to logistics, et cetera, which all obviously have an impact on delivery time and so on and so forth. So it gives you that overall level of consistency across. And so from that perspective, we expect the data to be very helpful and a very good guidance as we go forward. And the other way, actually, I think that is worthwhile thinking about the data is that this is now going to be the third set that will become available around obe-cel in ALL. We obviously have the first dataset in the pediatric ALL population, which is, obviously, was published in early 2021. We then have the experience in the adult population, the ALLCAR setting, and we're now adding the experience in the FELIX Phase Ib portion. And I think that's another way of looking at the data and actually, just looking at the level of consistency of the data across datasets, which I think is another way to sort of actually get a good understanding of the profile of the product, and I think, an understanding of consistency between these various slightly different populations. But of course, and I indicated, the Ib population is the same population that the Phase II population actually is. So I think that's where the real value is and I think where the key opportunity is.

Eric Joseph, Analyst

I think actually misspoke a little bit, Christian. I just wanted to clarify that none of the Phase Ib patients roll over or comprise the cohort that we're looking at in Phase II.

Dr. Christian Itin, Chief Executive Officer

I understand. These datasets are indeed distinct. There is a Phase Ib dataset and a Phase II dataset, and actually, there are two datasets in total. When reviewing the Tecartus application, the FDA did consider its Phase I experience, particularly in some safety aspects. We've definitely observed that in the dataset. While there may be a broader perspective on safety, from an efficacy standpoint, we anticipate that focus will be solely on the Phase II dataset.

Eric Joseph, Analyst

Can you provide a progress update on enrollment in the Phase IIb and share your thoughts on the size and duration of follow-up for the midyear readout from the FELIX Phase II? What should our expectations be regarding that?

Dr. Christian Itin, Chief Executive Officer

Right. So what we're guiding is that we expect the study to be fully enrolled during the course of the first half of next year with the primary endpoints reading out in the middle of next year. So that's the guidance. The primary endpoint is established by 2 measurements. One measurement at 1 month and then a confirmatory measurement at 2 months after dosing. And in both cases, in order for a CR to be counted as a CR, you want the CR to be actually established at both time points. And that actually goes into the assessment of the primary endpoint. And so that's sort of the key data you have at that point. And then obviously, the full follow-up of these patients is then with all patients 6-month follow-up will be expected to read out towards the end of next year.

Eric Joseph, Analyst

And then final question. Are you providing further updates, further follow-up from the adult ALL cohort of ALLCAR 19? Either at ASH or in 2022?

Dr. Christian Itin, Chief Executive Officer

We expect to do that. Obviously, we're updating the non-Hodgkin's experience, and there's an opportunity to sort of update on the durability data.

Operator, Operator

Our next question comes from Gil Blum with Needham & Company.

Gil Blum, Analyst

Just a quick one on the indolent lymphoma. There's been some pretty good results for autologous CAR-Ts and other programs for FL. Maybe you could kind of put in context for us, how important it is to have an autologous option that is relatively safe in this particular patient population.

Dr. Christian Itin, Chief Executive Officer

It's a great question. Follicular lymphoma is an interesting case compared to the ALL setting we are involved in, as it is essentially an indolent disease that progresses and grows slowly. Unfortunately, we currently do not have a cure for this disease. The treatments available are aimed at buying time rather than providing a cure. Patients have various options including chemotherapy combined with biological therapies, which can extend their lives significantly, though without curing them. While these treatments do come with some toxicity, they are often convenient as they can be administered on an outpatient basis, allowing patients to be treated outside of the hospital. To effectively reach these patients, two key things are necessary. First, demonstrating a safety profile that allows for outpatient treatment is crucial, as this aligns with what patients are accustomed to. Secondly, achieving long-term remissions through a single intervention would be valuable, providing meaningful duration of disease control. However, evidence of transforming some patients into cures is still needed. From the patient's viewpoint, traditional chemotherapy and biological treatments involve regular visits every few weeks to receive more chemotherapy or antibodies, continuing until relapse. The potential for CAR-T therapy in this area lies in providing a significant response and adjustment of the disease through a single treatment, ideally leading to a long period, perhaps years, without needing further intervention. Cost is also a consideration, as the ongoing nature of traditional treatments increases overall expenses over time, which contributes significantly to revenue in this field. A one-time intervention could eliminate many of these ongoing costs. Therefore, this presents a compelling economic argument, alongside the clear patient benefit of a single intervention that maintains health for an extended period and reduces management costs. For a CAR-T product profile, key characteristics should include an excellent safety profile for manageability and the capacity to maintain pressure on the lymphoma, similar to existing therapies. An extended persistence is necessary to keep that pressure over time and promote long-term remissions. These elements are seen in our program in the challenging adult ALL population, where both of these features are effectively demonstrated. This is why we are keen to explore this in our initial experience with the ALLCAR study.

Gil Blum, Analyst

And if I may, maybe a related question. So we've been seeing the allogeneic space, particularly in DLBCL, kind of moving towards multiple doses of the cellular therapeutic. We're also involving additional chemo. Do you think that this might provide kind of an opening again for an autologous CAR-T therapy with a better safety profile like what you have with AUTO3?

Dr. Christian Itin, Chief Executive Officer

I believe this is an intriguing question. What we're observing, as Matt previously inquired in a different context, is that data is starting to emerge regarding some allogeneic approaches. Many companies discussing multiple dosing strategies suggest that while there is activity, achieving sustained effectiveness in DLBCL patients requires reaching a certain level of cures to make the therapy worthwhile. This may involve additional steps, and increasing dosages and reconditioning adds complexity to the therapy and from a management and treatment group perspective. It also detracts from differentiation compared to standard chemotherapy or other combined approaches, including bispecific options that are also effective in this area. A significant question is about the standalone efficacy and whether you can distinctively position these approaches against other advancing therapies. Currently, the sustained cytokine release syndrome levels observed in CAR-T, particularly the autologous type, have not been replicated by any other treatment method, creating an opportunity. Regarding follicular lymphoma, having a solid safety profile is essential for patient access to the therapy, especially since these patients are often treated outside academic hospitals in DLBCL, necessitating a product with a good safety record. We’re seeing this with AUTO3, and we are now exploring it with AUTO1 and obe-cel, which should give us a clearer indication of their trajectory. However, it’s evident that the DLBCL landscape is more complex than many anticipated earlier this year.

Gil Blum, Analyst

All right. Congrats on the continued progress.

Operator, Operator

I'm showing no further questions at this time. I would now like to turn the conference back over to Christian Itin.

Dr. Christian Itin, Chief Executive Officer

All right. Well, thanks, everybody, for joining. Much appreciated you took the time today, and we’re looking forward to obviously updating you around the ASH meeting. And looking forward to an exciting 2022. And with that, I’d like to thank you all and looking forward to connecting hopefully in person not too far out. Thanks a lot. Bye-bye.

Operator, Operator

This concludes today's conference call. Thank you for participating. You may now disconnect.