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..

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..

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 over cell 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 updates 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 a fast proliferating disease, 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 CUSTOMERS, 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 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 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 blina- and inotuzumab, as well as patients experience with regards to previously receiving blinatumomab or inotuzumab.

The primary endpoint of the study is complete response rate and the secondary endpoints include molecular responses as well as event-free survival and duration of response. So let us turn to the market size and the current market size on Slide 15, please.

I touched upon the opportunity in ALL in an earlier slide in terms of patients, but what I'd like to just highlight is the sales performance of the current standard of care, Blincyto, otherwise known as blinatumomab.

Amgen reported yesterday sales growth of 40% in the third quarter -- sorry, 40% growth in the third quarter on a year-by-year basis as compared to third quarter last year.

As you can see, if we look at the first half sales in 2021 and 20 -- sorry, 2020 and 2021, there were sales of $187 million and $215 million, with a growth in the region of around 20%.

If we apply publicly available information on the proportion of use in pediatric and adult patients, and by using a very simple extrapolation that patients typically receive on average about 2 cycles of this product, this provides further evidence and translates to approximately 2,000 patients currently receiving this commercial product globally in 2021.

Amgen has stated that one of the underlying key drivers for sales increase has been the expansion to the Community Hospital segment in the U.S. beyond academic transplant centers. While Blincyto in ALL is moving to nonacademic centers, we also expect the launch of in DLBCL to also establish CAR-T experience in those centers.

Both of these developments bode well for a product with the properties of 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 CR achieved without subsequent stem cell transplant and durability of remissions that are highly encouraging with 50% efs at 12 and 24 months. Obe-cel is well tolerated despite being used in a heavily pretreated patient pool with high disease burden.

We observed no grade 3 or higher CRS. And in the 20% 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 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 CRS.

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 AES. 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 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..

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 expense, 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, with $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 on expected milestones.

Christian?.

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 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. Overall, we believe the company is in a very good position, combined with our cash on hand.

We feel well polished for success across our pipeline. We're now happy to take questions.

Operator?.

Our first question comes from Mara Goldstein with Mizuho..

I wanted to ask on the FELIX program. You'll have the full data set 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 data set, 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?.

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..

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

Can you give us any updates on the 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, initiate the Phase I study 4 to 5 in first half of 2022? Thank you..

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 sort of 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, and 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..

Our next question comes from Nick Abbott with Wells Fargo..

First question, Christian. So we'll get an update on the ALLCAR extension study later on this year. And then very early next year, we'll get the data for -- or sorry, we'll also get the AUTO 1/22 data.

So how do you choose between those 2 assets as you think about next steps beyond the adult ALL indication?.

It's a very good question, Nick, and thanks for joining. And so basically, the underlying question you're asking is what is the profile and the opportunity you see in pediatric ALL versus the opportunity you would see for obe-cel in some of the non-Hodgkin's indications. It's sort of the underlying, I think, element of the question.

And so what we'd like to see, obviously, with the -- when we look at these indications, we actually look at them independently. Because there is a -- I think, the thought process around AUTO1/22 is actually as part of the overall ALL program that we're conducting with obe-cel.

We're looking at AUTO1/22 as the first next-generation program that we'll expect to build up over time. And obviously, pediatric ALL being the key indication to establish the utility of having a CD 22 CAR that is highly effective added to the obe-cel program. So that program stands on its own feet and its own merit.

And one of the key things we want to see with that program is a reduction in the relapse rate in the pediatric patients. And that's the key entry point that we think would actually then trigger the full development in pediatric ALL.

So that's sort of a part of the overall, if you think about it, overall ALL approach that we're taking, and it's a component of it. The opportunities that we look at for obe-cel itself outside the ALL space, I think, is a second question.

And I think what we're going to understand is, obviously, where can we see a profile that is -- stacks up not just well, but potentially an improvement over and above of the other programs in the space, in the additional non-Hodgkin's settings. And this is what we're starting to explore with the extension program that we're doing on the ALLCAR study.

And that data will help guide us actually to then the choices of the path that we are planning to develop within the non-Hodgkin's indications. So it's really going to be data-driven.

But fundamentally, we're looking at those 2 approaches as sort of being separate in the sense, as AUTO1/22 really being part of the overall ALL strategy that we're building up to build a significant presence in that indication set. And secondly, it's then the branching out into the broader non-Hodgkin's opportunities..

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 ped ALL?.

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..

And then last one for me is, it's a 2-parter. So can you provide us with an update on the MRD-positive cohort of FELIX? And also, you're comparing the sort of milestone slides back to previous ones. We're not seeing a mention of either AUTO ALLO or AUTO7 programs in the current slide.

Can you provide some -- let us know what the status of those programs are as well?.

So the other approach is continuing, obviously, with -- in our collaboration with our academic partners. So that's slated to go in first half of next year. And the AUTO7 program, we're planning to run in sequence to AUTO6 NG.

We want to get in some experience around the various modules that we're introducing into that program, which obviously also is part of the AUTO7 program. So there will be a staging that we expect to run between those 2 solid tumor programs.

So I think that was the totality of the questions or did I miss anything?.

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

Oh, the MRD-positive cohort, yes. So 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..

Our next question comes from Asthika Goonewardene with Truist Securities..

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?.

So when we look at what we're planning to do with regards to the Phase Ib portion, obviously, the key question that we're asking with the Phase Ib portion was really to move from a single country, almost single center study, which is what the ALLCAR study is, to a multicenter, multi-country environment.

And with that, obviously, a significant increase in complexity and logistics into everything else. So that was the goal to really make sure we're demonstrating that transition. We're demonstrating that we're replicating the data. Obviously, we also move to commercial supply for vector and so on.

So there's a few changes that we made along the way to sort of transition the program into commercial stage -- towards commercial stage. And that's sort of one of the key topics that we expect to update at ASH.

And then our context also will share key aspects of the Phase Ib trial that we've conducted, which obviously was designed to confirm the activity level that we've seen during the ALLCAR study. So that update will be given. We'll give that experience, which I think is important, as we indicated.

The data that we're seeing is consistent in terms of the key parameters that we're looking at, which is really around safety.

We want to obviously be sure we replicate the safety, but also replicating the overall activity, and that's sort of the high -- kind of high-level statement that we made today, and we're obviously going to show the corresponding data to that.

When we look into the updates around the ALLCAR19 study and actually moving into the non-Hodgkin's side, what we did is we added additional cohorts with 10 patients in each. And we're going to give an update on the progress, on the exploration around these various cohorts. And some of the cohorts will be fully involved.

Others will still be enrolling, so we'll see basically a snapshot as we're transitioning through those data sets as we go through the end of the year. And then on the pediatric study, obviously, we'll give an overview on the overall program, key characteristics, et cetera, but also kind of share some of the initial clinical data on that program.

The key update we're expecting actually for the pediatric program will be towards the middle of next year when we have about 6 months of follow-up for the patient group, which we believes gives us a good feel for how we're tracking with regards to the ability to minimize relapses indicates once they achieve a response.

So that's just a framework, I think, is sort of framing expectations for the end of the year..

And if I may just add, so in this data that you talked about in terms of transitioning AUTO1 into commercial stage here. This present -- what should be showing at ASH.

Will there be actual patient-level data from FELIX study then in this presentation?.

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..

Our next question comes from Matt Phipps with William Blair..

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..

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 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..

Our next question comes from Kelly Shi with Jefferies..

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 randomized controlled trial instead of single-arm trial given the evolvement of a competitive landscape? And second question is, can you set expectation on data in first quarter of next year for primary CNS lymphoma?.

With regards to the FELIX study. First of all, in terms of the way that the study obviously is designed, it's designed to give us the complete remission rate out of a single-arm study. When we look at the history of recent approvals within ALL, we have blinatumomab or Blincyto, which is approved in the single-arm study, approximately 100 patients.

We have now the approval of Tecartus in adult ALL with just 54 patients in a single-arm study. And we expect that there is no change that we'll see here. So we expect that the single-arm study with level of robust data that we have seen in our early experience, I believe is absolutely adequate to submit or apply for registration for the program.

And I think that is entirely consistent with what we've seen before. We've seen the same also on the pediatric ALL side. And obviously, we've also seen it in the various trials that led to approvals in the DLBCL space, which is obviously a much larger space, and the program is not showing much differentiation actually between themselves.

So I don't think there is any change there. I think the fact that indeed, Tecartus got a full approval for relapsed/refractory independent of line, I think is a very good -- is a very positive development. And I think it bodes well for us and for our program. And so I think we're in a very good place there..

Our next question comes from Eric Joseph with JPMorgan..

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 s that we're expecting over the course of next year? Or are they completely distinct patient populations?.

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, that sort of -- 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 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.

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..

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. That the readout -.

I get it. No, these are distinct in terms of actual datasets. So there is a Phase Ib dataset. There is a Phase II dataset. And there is -- actually, there are 2 data sets.

I mean, what you did see, when you looked at the Tecartus review that the FDA did, the FDA actually took into account its Phase I experience for Tecartus, at least in some aspects on safety. That's what we've seen certainly in that dataset.

So there may be some view -- a broader view on safety, but from an efficacy perspective, we expect that that will be focused on the Phase II dataset alone..

So just an update on -- or can you give us a progress update on enrollment in the Phase IIb, and if you're just kind of thinking about the size and duration of follow-up in the midyear readout from FELIX Phase II? I guess, how should we be thinking about that?.

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..

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?.

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..

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

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..

It's a really good question. I mean, one of the interesting things about follicular lymphoma, if you compare it to the ALL setting that we're active in is that in follicular lymphoma, you have basically an indolent disease. So a disease that is relatively slowly progressing, relatively slowly growing.

But it is a disease that we actually have no way at this point to cure. So everything we do in that disease setting is designed to buy time. Now, we do have many options for these patients.

They have obviously a lot of chemotherapy backbones combined with biologicals as to the mainstay of the options that are available to those patients, buying them years of time, but not curing actually the patients along the way.

What they do experience is obviously the level of burden of toxicity, but also quote-unquote, the convenience of a lot of these therapies to obviously be administered in outpatient settings, so they typically don't have to go into a hospital to be treated, but they get managed actually in the periphery for the most part.

So that's sort of the setting. So what you need in order to sort of actually reach these patients, I think there's 2 things.

First of all, you want to actually be able to show that indeed, you have a safety profile where the patients can get treated in much more into the periphery and certainly in an outpatient setting because that is sort of what they're used to and what they're comparing to.

Secondly, I think you would want to see long-term remissions in these patients so that indeed, this onetime intervention gives you a meaningful amount of time hopefully. But that data is still outstanding in the field, converting some of these patients into cures.

And what you really need to look at it, when you look at it from a patient's perspective is that you have, on the one hand, your standard chemo-biological backbone, which means that you're going to get treated every 2, 3, 4 weeks, and you're going to go back in.

You're going to get another series of chemos, you get another load of antibody or some sort, and you just keep doing that. And so you have to do that on an ongoing basis until you're relapse and all of these treatments are designed to be treated or to actually provide treatment until relapse.

I think the opportunity for CAR-T in that field would be to have an opportunity to get a meaningful response and adjustment of the disease through a single intervention. And then actually have, hopefully, a year to several years, maybe longer, where you don't need additional intervention. And I think that is part of the attractivity.

It's also when you think about it from a cost perspective, the fact that the regimens are given until relapse obviously racks up a lot of cost over time. And that's what's driving a lot of the revenue lines that we see in the space. I think also in that context, that's very costly.

And if you can actually have a onetime intervention, there's a lot of treatment associated costs that, obviously, you could take out of the equation. So there's also, I think, an interesting economic argument to be made.

A very strong one from a patient perspective of having sort of a single intervention that then actually keeps you in good shape for an extended period of time as well as, I think, an element of patient management cost that's there.

And so when we look at -- in terms of the profile for a product, I think you want to have a product that has an ability to actually have a very good safety profile, it's very well manageable. But actually then combined with an ability to sustain pressure on the lymphoma because that's in essence what any other therapy does.

It's maintaining pressure on the lymphoma. In order to do that, you also would actually ask of the CAR-T therapy to have an extended persistence so that indeed, you're able to actually put a long-term pressure on the lymphoma and sustain that over time to really convert the patients into long-term remissions.

So I think those are probably the 2 key characteristics. And obviously, it's one of the key features that we're seeing in our program in probably the most challenging disease setting, which is the adult ALL population. And we do see that very nicely, those 2 features.

And that's why we're interested in exploring that obviously in the context of the initial experience in the ALLCAR study..

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?.

Well, I think first of all, I think it's a very interesting question. And what we're seeing, and I think Matt asked the question before in a slightly different way. And is that we're seeing that the data start to actually come forward in terms of some of the allogeneic approaches.

And the fact that many of the companies talk about multiple dosings that are sort of heading towards obviously indicates that while there is activity, in order to sort of get a more sustained activity in DLBCL patients, which is really -- you need to get, frankly, you have to get to a certain level of cures in these patients to make your therapy worthwhile.

But that may take a few more steps. And of course, the more you add in terms of dosings and reconditioning and so on and so forth, you add complexity to the therapy. You add complexity from a management perspective, complexity from a treatment group perspective.

And you take away differentiation from a, frankly, a standard chemotherapy, antibody drug conjugate, antibody type of combination approach that we also are a bispecific approach, that is also active in this space.

And I think that's one of sort of the key questions will be, what's the stand-alone activity? And can you really differentiate yourself away with those approaches from other approaches that are currently being pushed.

What we do see is that still the level of sustained CRS that are seen on the CAR-T side and the autologous CAR-T side, at this point, at least, has not been matched by any other therapeutic modality.

And I think that, I think, certainly creates an opening and to part of the comment I made before about follicular lymphoma, having a good safety profile will be important in order for patients to really gain access to the therapy.

Because those patients, as we pointed out many times during the course of the last 24 months or so, tend not to be treated at the academic hospitals in DLBCL. They're actually much more further out into the periphery. And with that, you need a product that actually has a good level of safety. And those are obviously hallmarks. We're seeing both.

We've seen it with AUTO3, and we're now obviously exploring with AUTO1, obi-cell, and I think we're going to get a very good feel where that's going to go. But certainly, there's more complexity in the DLBCL space than probably, I think, many folks anticipated earlier this year..

All right. Congrats on the continued progress..

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

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..

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