Autolus Therapeutics plc (NASDAQ:AUTL) Q3 2022 Earnings Conference Call November 3, 2022 8:30 AM ET
Company Participants
Olivia Manser – Director, Investor Relations
Christian Itin – Chief Executive Officer
Lucinda Crabtree – Chief Financial Officer
Conference Call Participants
Mara Goldstein – Mizuho
Matthew Phipps – William Blair
James Shin – Wells Fargo Securities
Gil Blum – Needham & Company
Operator
Hello ladies and gentlemen and welcome to the Autolus Therapeutics Third Quarter 2022 Financial Results Conference Call. As a reminder, this conference call is being recorded.
And I’d like to now turn the conference over to your host Olivia Manser Director of Investor Relations. Please go ahead.
Olivia Manser
Thanks Breanna. Good morning or good afternoon everyone and thanks for joining us to take part in today’s call on the financial results and operational highlights for the third quarter for Autolus. I’m Olivia Manser, Director of Investor Relations. And with me on today’s call as usual are Dr. Christian Itin, our Chief Executive Officer; and Dr. Lucinda Crabtree, our Chief Financial Officer.
So, before we begin, I’d just like to remind you as usual that during today’s call our discussion will contain forward-looking statements. Please make sure you are familiar with our disclaimer slide which is on slide two.
And then turning to slide three, you’ll see the agenda for today which is as follows. Christian will provide an update of our operational highlights for the third quarter of 2022. Lucinda will then discuss the company’s financial results, before Christian will conclude with the upcoming milestones and any other concluding comments. And finally we will of course welcome your questions.
Over to you Christian.
Christian Itin
Thank you, Olivia. Good morning to you all and thank you for joining us. It’s my pleasure to review our progress for the third quarter 2022.
Moving to slide four, we’re really pleased with our strategic and operational progress during the third quarter of 2022, which is highlighted over the next two slides. Firstly, we remain on track to provide an update on our pivotal FELIX trial in Q4 2022 and we plan to present FELIX Phase 2 data at a medical conference in the first half of 2023 most likely at ASCO.
We’re also looking forward to presenting longer follow-up data from our ALL patients in the OLCAR19 Phase 1 trial at ASH and are looking forward at the patients that we’ve treated with non-Hodgkin’s lymphoma.
We’re presenting further data at the three Phase 1 trials at ASH in December 1st as indicated in the LCAR19 Phase 1 extension study for OBCelinDANHL CARPALL study which is also a Phase 1 trial with AUTO 1/22 pediatric ALL and from our LIBRA T1 Phase 1 trial of autologous peripheral T-cell lymphoma.
The abstracts of these data updates will be online later this morning so we won’t be discussing them during this morning’s call. In addition, the Phase 1 CAR T trial exploring AUTO8 in multi myeloma patients is progressing. And the Phase 1 CAR TD2 trial exploring AUTO6NG is expected to start in the first half of 2023.
Turning to slide five, we’ve made some great operational progress during the quarter and post period end. We’re very pleased to report on two technology deals in October 2022, which underscore the scientific capabilities and expertise at Autolus.
We signed an agreement with Bristol-Myers Squibb granting them access to our proprietary RQR8 rituximab induced safety switch for incorporation into a set of selected cell therapy programs in return for a low to mid-single-digit million upfront payment with potential for near-term option exercise fees and development milestones plus royalties.
Moderna exercised an option on one of the proprietary binders being developed against an undisclosed immuno-oncology target for the delivery of their messenger RNA therapeutics in return for a low single-digit million upfront payment as well as development and commercial milestone payments for each product successfully commercialized, plus royalties on net sales of all products commercialized under the agreement. The license option stems from the deal we signed with Moderna in August 2021.
We also continue to make progress in our manufacturing and CMC operations. Phase 1 of the build of our Stevenage facility is on track for transfer to Autolus before the end of the year to start the qualification and validation work of the facility and remains on track for good manufacturing practice operations commencing in the second half of 2023. We’re also on track with the CMC workflow and report generation for the CMC package plan to support a BLA submission to the FDA.
Cash and cash equivalents at the end of September were €163.1 million not including the R&D tax credits from HMRC of €19.1 million received in October. Slide six — with that let’s talk about our primary focus our lead product Obe-cel on Slide seven now. Just to remind you Obe-cel has a unique mechanism of action built on highly specific engagement of CD19 coupled with a fast release from CD19 once the kill of the leukemic cell has been initiated.
This fast engagement is based on the fast off-rate of the CAT binder and drives three key properties of Obe-cel: reduction of the amount of cytokine release per target cell incanter which in turn will reduce the amount of immunotoxicity in the patients; reduced exhaustion of the CAR T cell; and improved engraftment and overall persistence. And those of you not familiar I refer you to a paper by Sara Ghorashian at Nature of Medicine published in 2019.
Moving to slide eight, we show this slide as a reminder that there remains a very high unmet medical need for treatment of adult ALL patients with approximately 8,400 new cases diagnosed yearly on a worldwide basis in the last line setting. Approximately 3,000 of these cases reside in the US and EU.
And whilst a combination of chemo three enables about 90% of the adult ALL patients to achieve complete remissions only about 30% to 40% will achieve longer-term remission. Once relapsed patients have a median overall survival of less than a year.
Current approved therapies for all patients are Blincyto and Tecartus. Both therapies are highly active but frequently followed by subsequent treatments. For example, allogeneic stem cell transplants.
Blincyto has a favorable safety profile with few patients experienced severe CRS and iCAMs but with limitations on durability of effect and convenience due to the need for continuous heavy infusion during its four-week treatment cycle.
Tecartus is more challenging to manage and induces elevated levels of CRS. High levels of eye cancer require steroids and vasopressors for many patients to manage adverse events. Both therapies have been shown to be highly active. However, most patients progress rapidly and require subsequent allograft to achieve durability.
Moving to slide nine. Many of you have seen this slide before, but it’s a useful reminder of why we think Obe-cel is a potentially transformational therapy for adult ALL.
Building on its unique mechanism of action Obe-cel has shown a high overall response rate with a favorable tolerability profile and sustained event-free survival that tracks long-term persistence in those patients.
Obe-cel has been granted orphan drug designation by the FDA and EMA for ALL, and obtained PRIME designation by EMA for the EU, ILAP designation by MHRA for the UK, most recently, RMAT designation by the FDA.
Moving to slide 10, based on what we believe is potentially transformational data from the OLCAR study, we’re conducting the pivotal FELIX trial with an approximately 90 patients with morphological disease treating at 34 sites in the US, the UK, and Spain.
We’re on track with our previous guidance and expect to provide a qualitative update in Q4 2022, which we would expect to reference whether the primary endpoint has been met. We’re planning on presenting data from the FELIX study at a medical conference in mid-2023.
In order to maximize outcomes from the FELIX trial in parallel, we’re also assessing obe-cel in an additional cohort of up to 50 patients in second or later complete remission who have developed minimal residual disease. However, this additional cohort does not impact our planned filing timeline as the primary data will be based on the data from the morphological cohort.
Moving to Slide 12. Obe-cel’s unique profile means it could be applicable to a broad range of indications. We’re consequently evaluating the product candidate outside of ALL in B-cell, non-Hodgkin’s lymphoma indications in an ongoing Phase 1 clinical trial. As we said before, we have positive clinical readouts at the recent EHA Congress from the Phase 1 studies in B-cell non-Hodgkin’s lymphoma and primary CNS lymphoma, presented by way of the poster as well as an oral presentation of the first AUTO1/22 Phase 1 data in pediatric ALL patients. And I’ll cover this data in the upcoming slides. As I said we’ll be presenting additional data at ASH in December this year with abstracts due to go online later today.
On Slide 13, as a reminder, the academic ALLCAR19 study has been extended as a basket study where we are testing obe-cel in a number of B-cell malignancies. To-date, we’ve treated 17 patients with follicular DLBCL and mantle cell lymphoma and no patients experienced high-grade CRS and none had any grade of neurotoxicity. Of the 17 patients dosed, 16 achieved a metabolic complete remission. Seven of seven follicular lymphoma patients, six of seven diffuse large B-cell lymphoma patients and three of three mantle cell lymphoma patients.
We lost one patient to COVID and one MCL patient relapsed. 14 of the 16 patients that have responded remain in metabolic CR with a median follow-up of 9.2 months, the longest being 19.1 months as of the last reported data cut and the data continues to mature. We’ve also started treating some CLL patients and from the three patients that have reached the initial evaluation as of the last data cutoff two went into molecular CR in the bone marrow but have some residual lymphadenopathy on CT scans. We’re looking forward to presenting additional patients and longer follow-up data from this ALLCAR extension study at ASH in December.
Turning to slide 14. We’re also exploring obe-cel in primary CNS lymphoma and our academic carousel study. This is a type of aggressive B-cell lymphoma, but because of its anatomical location, it has a particular poor prognosis. Initial treatment is often intensive and outcomes for these patients tend to be poor.
In the data we presented at EHA, we didn’t see high-grade CRS. Two patients experienced neurotoxicity grade three and four. One patient improved with steroids and anakinra; the second patient had several neurological deficits consistent with progressive disease and didn’t respond to steroids and anakinra.
Overall, you can see on the right-hand side of this slide that despite these patients having no disease outside of the CNS and having had lots of the rituximab treatment, we still see really nice expansion of obe-cel in the peripheral blood and we expect to provide more data from this study in 2023.
Moving to slide 15. Our initial experience with obe-cel in children achieved a high level of sustained CRs while without experiencing high-grade CRS. Those children who relapsed after treating with obe-cel, most of them have lost CD19 expression on their leukemic cells at the time of relapse.
Here we’re taking the next step in Obe-cel’s life cycle with AUTO1/22, a dual targeting product building on obe-cel and adding a highly potent CD22 targeting chimeric antigen receptor. The CD22 CAR was designed to be active against leukemic cells with low levels of CD22 expressed on their surface.
We evaluated AUTO1/22 in an extension of the CARPALL study in children who were ineligible for Kymriah. The children, either relapsed after receiving Kymriah and could not be treated or they had extramedullary disease i.e. singular lesions in tissue without having a disease in the bone marrow, the normal location of the leukemia. This is a very challenging group of patients to treat. Out of 14 children four had prior Kymriah therapy and three of them had lost CD19 expression and seven kids had extramedullary disease.
Moving to slide 16. Data we presented at EHA showed that nine of the 11 patients achieved a molecular CR on day 28. AUTO1/22 is well manageable with no patients experiencing high-grade CRS. No patient relapsed with antigen loss and two of the CD19-negative patients achieved the molecular CR, demonstrated the isolated activity of the CD22 CAR. We’re continuing to follow the patients and will be presenting this data at ASH in the upcoming weeks.
Slide 17 and moving straight to slide 18 on the pipeline. Here is a brief depiction of our broad cell programming toolkit we have developed over the last few years and drove the deals with BMS and Moderna. All in, the technologies cover programming modules for targeting, control, shielding and enhancing CAR T-cell activity.
At Autolus, we have more than 100 patent families covering these products and cell programming technologies. Recent illustrations of three technology applications were shown at ASGCT the annual meeting in May this year. Each of one of our product candidates applies one or several of the technologies to maximize its impact on the specific cancer it is designed to tackle.
Moving to slide 19. This slide shows more of our next-generation programs beyond obe-cel. A pipeline program, we are particularly excited about is AUTO4, which is in a Phase 1 study in T-cell lymphoma. I’ll give you a refresh of the data we presented at EHA in just a minute. AUTO8 moved into the clinic earlier this year in a Phase 1 clinical study in patients with multiple myeloma and we’re now dosing patients. I also want to mention that our first solid tumor program AUTO6NG in GD2-positive solid tumors will be moving into the clinic in the first half of next year.
Turning to slide 20. We’re actively exploring T-cell lymphoma which is an aggressive disease with a very poor prognosis for patients. You might recall our EHA analyst call where Dr. Horwitz from the Department of Medicine Lymphoma Service Memorial at Kettering Cancer Center, talked about the majority of patients being either refractory or relapsing after initial treatment.
Standard of care is variable and often based on intensive chemotherapy treatment. Median survival for patients with relapsed or refractory disease is less than six months. T-cell lymphomas are a clonal disease that either express TRBC1 or TRBC2. The T-cell receptor beta chain constant domain one or two are expressed on more than 95% of all T-cell lymphoma patients.
Only GammaDelta T-cell or NKT-cell derived lymphomas LAC T-cell receptor beta chain constant domains one or two. AUTO4 targets TRBC1 and is the first product candidate to do so. Using next-generation sequencing, we identified patients with TRBC1-expressing T-cell lymphoma and then these TRBC1-positive patients are treated on the currently open AUTO4 study.
And in the future, we plan to open a study targeting TRBC2-positive patients with AUTO5 as well. AUTO4 is designed to selectively kill lymphoma cells in a manner that we believe will preserve a portion of the patient’s normal healthy T-cells to maintain immunity in that patient.
Turning to Slide 21. We presented data at EHA on the LIBRA T1 study evaluating auto patients with T-cell lymphoma. We’ve seen encouraging activity and a favorable tolerability profile indicating clinical proof-of-concept for the new approach for targeting T-cell lymphoma. We’re looking forward to presenting a longer follow-up at ASH.
So with that we’d like to turn to slide 23. The manufacturing of cell therapies is complex and we’ve developed a great deal of skill and experience manufacturing products throughout the pandemic and for a range of product candidates. We’re building a new manufacturing facility in Stevenage in the UK. This location is about a mile away from our current clinical manufacturing operation at the cell and gene therapy facility and will allow us to transition our entire operation, including our experienced staff to the new facility in an expeditious and efficient way both minimizing start-up risks and costs for commercial supply.
As evidenced by our successful manufacturer of CAR T products for the pivotal study with centers across the US and Europe location is well-suited for global supply with easy access to several international airports including London, Heathrow. The new 70,000 square foot facility will provide Autolus with a capacity of approximately 2,000 cell therapy batches a year and with the ability to expand capacity further when needed.
You can see on this slide a rendering of what the facility looks like once completed by the end of the year. In the middle, you can see the actual facility a few weeks ago when the large preassembled HVAC units were lifted on to the roof. I mentioned our progress earlier. Phase 1 of the build project is scheduled to complete in the fourth quarter and the equipment installations and qualifications that Autolus is on track for GMP operations for the second half of next year. For our clinical supply operations, we currently operate with four shifts seven days a week. Our commercial manufacturing model will continue with that pattern of seven days a week throughout the year.
So with that, I would like to turn to slide 25 and pass the call to Lucinda for our third quarter 2022 financial update. Lucy?
Lucinda Crabtree
Thanks Christian, and good morning or good afternoon to everyone. It’s my pleasure to review our financial results for the third quarter to September 30, 2022. We’ll start with our cash position, which at September 30, 2022 totaled $163.1 million. This doesn’t include a $19.1 million R&D tax credit we received from HMRC post-period end in October.
With regards to our cash, I will note given the majority of our spend is in GBP, we actually hold a large portion of our cash as reported at approximately 80% in pounds and the majority of the remainder in USD. Net total operating expenses for the quarter were $43.5 million, which included license revenue income totaling $2.4 million, which primarily resulted as a result of the Moderna option exercise announced in October.
Research and development expenses increased by $5.3 million to $37.6 million during Q3. This was primarily due to the following; an increase of $3.6 million in clinical and manufacturing costs, primarily related to Obe-cel, an increase of $2 million in salaries and other employment related costs mainly driven by an increase in the number of employees engaged in research and development activities. We also have marginally increased legal and IT fees as we transition through the quarter offset by a decrease in facilities costs and depreciation of PPE. General and administrative expenses remained stable year-on-year.
Other expense, income or net expense income decreased to an expense of $3.7 million from an income of $1 million in the three months ending September 30, 2021. The decrease of $4.7 million is primarily due to the weakening of the pound sterling relative to the US dollar exchange rate during the three month period. Interest expense increased to $1.9 million in the quarter, which relates primarily to the liability related to sales of future royalties and sales milestones through our agreement with Blackstone in November 2021.
Finally net loss attributable to ordinary shareholders was $42.8 million for the quarter. The basic and diluted net loss per ordinary share for the quarter totaled $0.47 compared to a negative $0.47 for Q3 2021. We estimate that our current cash on hand including anticipated milestones in the relevant period from Blackstone extends the company’s runway into 2024.
And now back to Christian to give you a brief outlook on expected milestones. Christian?
Christian Itin
Thank you Lucy. Slide 27. Finally on next steps, we believe we have an exciting period ahead at Autolus with a summary shown on this slide. The main focus of course is Obe-cel in relapsed/refractory all-ALL patients with our initial update on this pivotal Felix study coming before the end of the year, and obviously the planned presentations at a medical conference in the middle of 2023. Longer term follow-up will be then shown or are planned to be shown by the end of 2023 as well.
Beyond that, the studies of Obe-cel in relapsed/refractory B-NHL and CLL and primary CNS lymphoma are ongoing as well as our AUTO-1/22 program and our AUTO4 program, we expect to have more data over the course of this year and next whilst we progress the other Phase 1 programs in our pipeline.
Finally as a result of our collaboration with Blackstone and in anticipation of the milestones we expect to receive during the relevant period, we project our cash runway unchanged into 2024. We’re now happy to take questions.
Question-and-Answer Session
Operator
Thank you. And at this time we’ll conduct the question-and-answer session. [Operator Instructions] So our first question is going to come from Mara Goldstein. Your line is now open.
Mara Goldstein
On FELIX and the data disclosure in the fourth quarter. Can you speak to what we will see whether or not — I’m assuming there will be some read on the primary endpoint of response rates, but I’m curious about the secondary endpoints and again a MRD-negative cohort that you started enrolling?
And then the other question I had relates to the manufacturing and where that process will be with respect to the filing of the BLA, and how you’ll be able to layer those two things for filing of the BLA?
Christian Itin
Okay. Thanks Mara. Thanks for the question. So first off what we’re planning to do at the end of the year is, obviously, to provide an update on the FELIX study. It will be a high-level update. We’ll be able to make a statement towards the primary endpoint of the study. I do not believe that we’ll be able to actually make comments with regards to the secondary endpoints of the study. That will be premature. And the MRD cohort is, obviously, rolling and will continue to enroll into next year. But, of course, that cohort is not the key data set that will go into or a critical data set for the BLA.
So the focus is on the FELIX data. The data itself will then be targeted to be shown in middle of next year. As we said we target ASCO. And, of course, you do remember that there are very strict disclosure rules if you want to present at ASCO, which also basically reduces the amount of information that we can share within the press release that we’re planning for the end of the year.
The second question, I think was related to the manufacturing setup. And as we had indicated the commercial manufacturing side is on track to obviously, go through all the qualification validation work that needs to go into the BLA filing. And that is going to be in time for a BLA target for the end of next year.
Mara Goldstein
All right. Thank you.
Christian Itin
Thank you. Operator, do we have another question?
Operator
I’ll just jump in. I think Breanne, may have dropped. So the next question was asked through us and I think your line should be open.
Unidentified Analyst
Hi guys. Can you hear me okay?
Christian Itin
Yes we can.
Unidentified Analyst
Okay. Good afternoon. Thanks for questions. Maybe I just want to build on Mara’s question first. Can you specifically, disclose in the press release a number of maybe like the percentage of patients in remission at first scan and the primary endpoint? Can you actually provide a number in the press release, or is this something that, goes to want to hold back given how strict ASCO is?
And then looking forward to the OLCAR-19 update, beyond what we see in ASH, I’m just curious to know how many more patients in follow up would you need to give confidence and initiate some pivotal studies, based on in these specific indications? And are these pivotal trial initiations something, we can expect in 2023? And then lastly, something from Lucy, here can you give us some direction on how R&D costs are going to move next year, given that Felix is winding down and majority of the other studies are kind of early stage? Thanks.
Christian Itin
All right. Well thanks a lot. Glad we managed to connect. So the first question, you asked was related to the type of disclosure that we can make. So the statements obviously, as I indicated will be about the primary end point. The primary end point of the study is the, overall remission rate, which is based on complete remissions and complete remissions with incomplete hematological recovery. So CRs and CRIs.
The statement with regards to the endpoint obviously, is a statistical test that we have to pass to actually be sure that indeed the signal is truly above the threshold that was set for the study, which is obviously, in very simple terms basically getting us substantially above the level where the current standard of care is basically, and what’s coming out. So I think that if you need to reference point that gives, you a reference point in terms of, lower binaries of the outcome that you’re looking for that you have to be sure to be substantially on the cost.
So when we’re going to be able to give a specific number, I don’t think we’re going to be able to give a specific number without actually kind of crossing the line in terms of, disclosures for the conference. So it will be the statement around the primary endpoint based on the data. That will be the key point there.
With regards to the OLCAR study, where exporing obviously the non-Hodgkins indications in that study and we have been adding additional patients in the various cohorts. And obviously, for those patients that we already have treated by middle of the year, as we start to have meaningful long-term follow-up. And I think, we start to get a good feel for the program. I think this gives us opportunity to move the program forward into those indications, as we progress with the program of role.
The primary focus for 2023, will clearly be on the execution of the adult ALL program and getting the program to BLD filing. And obviously, the additional activities around the ALL indication, which is really the primary focus. We’re evaluating our options with regards to initiating a pivotal trial. I think the data that we’re starting to see across these indications, I think it’s starting to shape up to a point where that decision in terms of picking pivotal, the program that has the potential to go pivotal, is certainly coming to a point wherein I would assume there’s the middle of next year actually, we should have a good feel for which data set we should actually be thinking out of the various indications.
And then it’s going to be a decision depending on the market conditions, et cetera, on the exact timing for the start of the pivotal study. But from a basic data perspective, we think we have a lot of confidence in the overall profile of the product and that we need to sort of pick the right timing and afford our next step here beyond ALL. And then, I think on the R&D costs Lucy, I think take that.
Lucinda Crabtree
Yes. Hi. Thanks for the question. Look, I’m not going to go into specifics at this stage. I mean I think you can assume that development costs headed into 2023, won’t be at the same level as 2022. However, as you can imagine we’re in the process of rereviewing these things as part of the company’s normal budgetary process. But I will say, there are still a reasonable number of activities in 2023 that fall under that development bracket on the regulatory side, as we anticipate patient follow-up, et cetera. But yes, I think you can safely assume the development costs won’t be at the same level of 2022.
Unidentified Analyst
Thanks so much guys.
Christian Itin
Thanks, Rob [ph] Appreciate it,
Operator
Thank you. And our next question comes from Matthew Phipps [ph] and you are now on the line.
Q –Matthew Phipps
Thanks for taking my question. On the LibrA T1 study with AUTO4, do you think at ASH will have any patients that were treated with the new manufacturing protocol?
Christian Itin
Hi, Matt thanks for joining. We started treating patients with the new protocol and I’m not sure we’re going to have data from those patients quite, yet. I think we were able to make some statements around the process change itself and the properties that we generate, but it’s probably still premature to actually expect data from patients treated with the new protocol. Transition as you may remember, was made after the EHA presentation and then when you go through the normal regulatory cycle for amendment. I didn’t leave an awful lot of time before data comp here for the ASH conference.
Q –Matthew Phipps
Got it. It’s interesting talking to you while the abstracts are coming out real time here. But when will AUTO5, get into clinics and what’s beginning factors at this point?
Christian Itin
I think what we’re planning to do with AUTO5 is get that program ready towards the end of the year. The dating factor here is to transition. Finalize basically, the CMC side of the process and we’re going to be also adapting some of the changes that we’re making for the AUTO4 process. We want to actually also include into the AUTO5 process, before we get going on the program. So that’s one of the key elements that are still flowing.
And the few early patients I think on the process of — modified process, I think, will be indicative — will tell us an awful lot about how we’re transition the modifications into the AUTO5 program as well.
Matthew Phipps
Okay. And then, lastly, I guess, just can you give us any updates on switching or moving to IHC assay for the diagnosis of the patient rollout or the selection?
Christian Itin
Right. So what we had indicated for the program is that, we have basically three ways on to detect tumor cells. What we’re using in the clinical trial is based on next-gen sequencing, that’s mostly a very well-established methodology for — as a diagnostic and diagnostic tool. But it does take a bit of time in terms of turnaround time.
And so, as alternatives we looked at IHT and we also did look the detection by flow. Both of those are obviously antibody-based. One against — the nature of antigen typically in the IHC where they have fixed tissue, versus basically live cells in the case of the facts.
Methodologies do work well and we’re currently going through kind of the selection which one we’re going to take forward. And that decision actually hasn’t yet been made. So technology works well with certainly some of the data around them. But for the final decision which one we’re going to take for full development actually has not yet been taken.
Matthew Phipps
All right. Great. Thank you for answering my questions.
Christian Itin
Thanks, Matt. Appreciate it.
Operator
Thank you. And our next cal or next question will come from James Shin. Your line should now be open.
James Shin
Hey, guys. Can you hear me? Hello?
Christian Itin
Hi, James. We can hear you.
James Shin
Great, great. Thanks for clarifying on Felix’s 4Q 2022 press release. When the full data is released next year though, could you share what your view would be for a positive EFS data? And is MRD going to be available at the conference, or is that going to be the update you talked about towards the end of the year?
Christian Itin
So, on MRD, I would expect that that’s more a focus for the end of the year, because obviously we want to understand also some of the follow-up in that cohort. As I explained before, we continue to enroll patients into the MRD cohort. So the expectation is that the MRD data first data at ASH next year. So there’s a target.
With regards to the type of secondary endpoint data: obviously, we’re going to be looking at various types of data related to the secondary endpoint. And as we’re look at — as we look the data, we’re probably looking at a subset of the patients earlier in the study that may have had longer follow up that gave us some of the longer follow-up information by the middle of next year, that you’re referring to. And including in that is obviously the CRA over time, as well as obviously event-free survival.
So we’ll start to build that. But, obviously, clearly, as we go through the course of the year and including at ASH, I think, we’re also going to gain additional information in terms of longer-term follow-up.
What you may remember is, when we looked at the EFS curve from the ALLCAR19 study. You may remember that that EFS curve basically showed, still drops until about 12 months of follow-up, but then we saw a stabilization from 12 months before onwards.
And so, I think, when we will look at EFS data I think to get a sufficient longer-term view on the data we’re probably going to have to go to ASH to really understand what the longer-term outlook for that curve actually looks like. So there will be early data, but I think in terms of actually getting a better understanding and more stability in the data we probably going to have to go to ASH.
James Shin
Understood. Have you disclosed what MRD sensitivity you’re looking at for the quota seek? Is it 10 to negative 6 by chance?
Christian Itin
Well, that is, obviously, one of the measures we’re going to look at all of those levels. You can obviously measure down to about 10 to the minus 6 with the assay. And we’re certainly going to look at the drop all-in that you can get to. Typically what you want to see is at least a lockstep reduction to actually call it a response, an MRD response.
That’s typically the way it was done also in the past and using either flow or PCR. So that’s one of the ways in how you can look at it, but then also you want to look at the absolute reduction and see whether there’s any differences in potentially in the outcome that you might see depending on the cutoff that you’re actually looking at.
James Shin
Understood. And if I may, for just one more on McCarty. I know, McCarty excludes prior cell therapies, but are patients allowed to have scaled bispecifics such as the recently approved tocilizumab?
Christian Itin
I don’t think we have excluded in that study the targeting of BCMA. Obviously, what’s already available with regards to BCMA targeting, our ADCs to BCMA which are actually available in the market. So devices they discover that are coming available and now assume they’re allowed.
As you point out correctly is, where we haven’t or have CAR T — BCMA-targeting CAR T. We’re conducting the study in the UK. And in fact, there is no availability really for these patients in a significant way to have CAR T therapies for targeted BCMA at this point. So it’s more a theoretical exclusion at this point, but it could become a practical exclusion than rest of the study progresses.
James Shin
Appreciate it. That’s all from my end. Thank you.
Christian Itin
Thank you.
Operator
Thank you. And our next call — our next question, sorry, comes from Gil Blum and your line is now open. Gil, your line is open.
Gil Blum
Good morning and good afternoon. Just a couple of quick ones from us. Kind of as a follow-up here. What are you hoping are going to be the differentiating features for AUTO8 and BCMA given how crowded space is?
Christian Itin
Hi, Gil. Great to have you on. So differentiating features. I think that what we’re looking for in a sort of a second-generation approach in multiple myeloma. I think that what we do know from the current products and particularly, if we’re looking at CAR T piece, if we do get higher response rates. And also, obviously, have very meaningful durability effect.
What we don’t — what we see is it is still challenging here, is to get a very high percentage of disease position down to the level of 10 to minus 6 or below in terms of detection. So there is sort of an element there in terms of the molecular responses are being achieved where you can actually see differentiation and can pick that up. Not on the standard response rate, but when you look at molecular CRs.
The second aspect is, what we’re seeing with all the products is that, there clearly is much more of a challenge in multiple myeloma to actually generate products that have longer persisting product. And the sense is that, in a disease that’s relatively slowly progressing and with challenging microenvironments that you find across the marrow that you can have pockets where multiple myeloma cell can basically stabilize and ultimately rebound.
There was clearly a sense that we buy a significant amount of time with the current therapies, but it’s difficult to actually switch it to a state where there is a high degree of competency they have true long-term remissions.
So I think you want to see very deep responses. And the other aspect is you want to see indication for good levels of sustained persistence decisioning products. And I think those are two features that I think we would be looking for. And I think will give us a very clear indication that we’re starting to differentiate features in the product.
Obviously, the fundamental piece in terms of design that we put in on the BCMA side is obviously a very potent BCMA approach that allows us to target cells with very low-expressed — expression levels of BCMA which is one of the fundamental challenges with the target.
Gil Blum
All right. Thank you for those details. And maybe one last one, on the AUTO4 study, are you enrolling additional patients at the high-dose right now?
Christian Itin
Yes. We had enrolled and continued left over the core at the 450 level. And with the amendment through for the modified manufacturing process we took a step down in terms of 225. The first patients will initially be dosed at 225. And once we have initial data can then be back up and escalated to 450. But we haven’t gone beyond 450, in terms of sole dose.
Gil Blum
That’s fine. Thank you for taking our questions.
Christian Itin
Thanks a lot Gil appreciate it.
Operator
Thank you. And our next question comes from Nick Hallett. Your line is now open.
Christian Itin
Hi Nick. Can you hear us?
Unidentified Analyst
So I think I missed my name there. Is that for Nick Hallett?
Operator
Yeah, it is. You’re online.
Unidentified Analyst
Perfect. Sorry you just cut out there. It’s Nick on for Keyur here. Thank you for taking my questions. Just a couple if I may. First of all, for the ASH update later this year could you just help us frame expectations for what we might expect in terms of patient numbers and what the key data points we should be looking out for are? And then if possible would you be able to give an overview of some of the key design elements of the AUTO6NG trial? Thank you.
Christian Itin
Yes. Thanks a lot for joining, Nick. With regards to the update at ASCO the key focus is really on longer-term follow-up on the expectations with obe-cel, actually the ALL patients with obe-cel as well. Obviously remember there’s an additional six months or actually more than six months of follow up.
I think the last update was given all that cohort so we will have kind of long-term follow-up on these patients. So that’s kind of the key focus with regards to obe-cel. There are a few more patients on the non-Hodgkin’s cohort but really I think the primary readout is the long-term follow-up.
With regards to AUTO1/22 we obviously had very early data on the pediatric patients. So we have longer-term follow up which will be important particularly as we’re obviously looking to minimize or eliminate the risk of CD19 negative relapses in these kids. And the data we had at EHA was I think indicative.
But of course we didn’t quite have that much follow-up on some of the patients. So at least theoretically there might have been a risk that we might still be picking up target negative relapses. And so the additional follow-up I think is meaningful and will give us sort of a good additional confirmation of the design premises in the program.
With regards to AUTO4 as well a longer follow-up is kind of the key piece there and then obviously some views with regards to the modified process and what it might do for the product going forward. But the critical piece obviously here is that we have a limited follow-up on the patients that have achieved metabolic CRs. Obviously with the additional data cut we should get closer to one year.
Between half a year and one year on some of these patients, I think that starts to be meaningful. Remember, these patients typically pass away within about six months at this stage of the disease entering and that we evolved in terms of the patients that we enrolled into the study. So those I think are some of the key expectations with regards to the trial.
Unidentified Analyst
That’s great. Thank you very much Christian. And did you have any detail you can provide on the AUTO6 trial design?
Christian Itin
Yeah. Sure. Thank you.
Unidentified Analyst
Excellent.
Christian Itin
On the AUTO6 trial we’re introducing a number of new modules. A shift two module, future beta module and continuously active L7 type module. So that’s a significant addition. And we’re still working through the exact initial approach also with the regulators here in the U.K.
The plan is to obviously have an approach that allows us to have lower dose levels going with the modules and be able to sort of actually start generating safety data first obviously in that trial.
And then also push the doses up once it is demonstrated it’s safe to start actually looking at the impact on the activity the anti-tumour activity as well. But the details are still in part being negotiated with the regulators. So I don’t think I can give you a final answer as well.
Unidentified Analyst
Appreciate it. Thank you very much.
Christian Itin
Thank you.
Operator
Thank you. And we now have Kelly Shi now on the line.
Unidentified Analyst
Hi. Can you hear me okay?
Christian Itin
Yeah, Hi Kelly, we can hear you fine.
Unidentified Analyst
Hi. This is Clara for Kelly.
Christian Itin
Okay. Sorry.
Unidentified Analyst
So for the FELIX trial can you comment on patient baseline characteristics for the enrolled patients? Is it consistent with Phase 1a and Phase 1b stages? And also according to clinicaltrial.gov one of the inclusion criteria for FELIX trial is to screen patients with more than 5% plas in bone marrow, but 75% CR rate reported from Phase 1b actually included in 25% of the patient with less than 5% plas in bone marrow.
So should we expect lower response rates for FELIX top line data? Lastly does prior Blincyto treatment has the impact on the treatment efficacy of obe-cel? Thank you.
Christian Itin
So with regards to the inclusion and exclusion criteria those are actually consistent between the Phase 1b and the Phase 2 portion. And they’re obviously also largely conditioned with the prior development in the space including the pivotal study in the factory setting for Blincyto or Tecartus. So the inclusion-exclusion criteria are very similar across the board in these trials and are consistent between the Phase 1b and the Phase 2.
The terms of patients enrolled. Obviously, the patients that are part of the analysis set that will go into BLA or patients that have more than 5% tumour burden at the time of enrollment. And that is the key inclusion criteria. Patients that have less than 5% tumour burden can actually be enrolled into the second cohort that we’re running which are patients in mineral residual disease. But they translate in two different cohorts and their analyzed separately.
And also in terms of the endpoint the endpoints are different. If you look at a primary endpoint, you look at the morphological cohort it is complete remission of patients with CR and patients with CRs with incomplete recovery even morphological recovery. Both of those measures obviously are looking at going from a level of plas of about 5% to the level above the 5%, which is the condition to meet that you have to just sort of formally get into in the CR.
In the cohort with the mineral residual disease that are starting below 5%. Those patients are technically in complete remission. And what we’re measuring with those patients and this goes back to I think the question that Gil asked before is that they actually can look at the conversion of these patients into a molecular complete remission which actually is a vast additional reduction. But typically those cutoffs that you look at there are into the minus four and below.
So those are kind of the differences between the two populations. There’s no difference that we expect to have in terms of the actual patient characteristics compared to the Phase Ib. And also when it comes to general composition of the patients with regards to prior lung private therapies including prior exposure to BLINCYTO, we don’t expect to see any significant differences.
Unidentified Analyst
Got it. Can you also share some details regarding your preparation of Obe-cel long-term manufacturing firm? Do you expect the same patient baseline in real world whereas you have seen in clinical trials for adult ALL? And how would the difference impact the OBC’s manufacturing success rate and efficacy?
Christian Itin
So I assume you actually have a group of patients that are above 5% tumor burden. Obviously the range can vary quite a bit. You can have patients who are just slightly above 5%. You can have patients who are in the 95% range of tumour burden in the marrow. The patients can also vary in terms of the amount of leukemic cells that are not just in the marrow but they’re also in circulation. So there’s a big variability you’re having here.
We believe that we have a very good representation across the entire board of those levels of tumour burden as well as levels of circulating leukemic cells in the trial. And with that we don’t expect the trial to actually be nice to predict for this truly advanced stage of the disease. What will be interesting is to see what the outcome is for patients that have lower disease burden that have less than 5% disease burden and minimal residual disease. And that’s obviously the reason why we’re running the second cohort. But that is not the primary group of patients that obviously will drive the label for the product.
Unidentified Analyst
Okay. Thank you.
Christian Itin
Thank you. Appreciate it.
Operator
Thank you. And our next question comes from Noah Eisenberg.
Q – Unidentified Analyst
Hey, guys. This is Noah on for Eric. Thank for taking our questions. Just a couple of quick ones for us. So could you remind us does the Felix trial use the same exact conditioning regimen as the previous Phase I trial for Obe-cel? And then also how is enrollment progressing for the Carousel trial? And what can we expect in the data next year? Thanks.
Christian Itin
Could you repeat which trial from where the enrollment question came?
Q – Unidentified Analyst
The Carousel trial.
Christian Itin
The Carousel trial. Okay. Sorry I could not visit understand that. Okay. All right. So the first question is to the preconditioning regimen. In fact the preconditioning regimen that we’re using is consistent with what was used in the Phase Ib and consistent with what is now typically used across the industry in the various CAR T trials in terms of use with fludarabine and cyclophosphamide. So that is very consistent and slightly different from what we had in the OLCAR study which was obviously a study that started a few years before and was still closer to some of the original work that was done at Penn.
Q – Unidentified Analyst
And then on the Carousel trial?
Christian Itin
And then with regards to the Carousel trial we obviously we expect to have about somewhere between 10 and 12 patients enrolled in total and we expect to be able to provide an update during the course of next year. Probably more towards the middle of the year.
Q – Unidentified Analyst
Great, thank you.
Christian Itin
Thank you.
Operator
And that was our final question. I’d like to now turn it back to Christian for closing remarks.
Christian Itin
All right. Well thank you very much. Well thanks everybody for joining today. It’s obviously a very busy season also with the ASH abstracts coming out. I appreciate you joining. And I look forward to keeping updated as we go through I think a very important set of weeks and months ahead of us at Autolus. Assets that are progressing the pivotal study and we’re gearing up towards the actual data presentation in the middle of next year. All right. Thanks everybody and speak to you soon. Thank you.
Operator
Thank you for participating in today’s conference. This does conclude the program. You may now disconnect.
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