Autolus Therapeutics plc (NASDAQ:AUTL) Q2 2022 Earnings Conference Call August 4, 2022 8:30 AM ET
Company Participants
Olivia Manser – Director, IR
Christian Itin – CEO
Lucinda Crabtree – CFO
Conference Call Participants
Mara Goldstein – Mizuho
Rob Andrews – William Blair
Bill Jahangiri – Truist
Gil Blum – Needham & Company
Kelly Shi – Jefferies
Chuan Hong – JPMorgan
Operator
Hello, ladies and gentlemen, and welcome to the Autolus Therapeutics Second Quarter 2022 Financial Results Conference Call. As a reminder, this conference call is being recorded. [Operator Instructions]
Without further ado, I would like now to turn the conference over to your host, Olivia Manser, Director, Investor Relations. Olivia?
Olivia Manser
Thanks, Gory. 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 second quarter of 2022. I’m Olivia Manser, Director of Investor Relations. And with me on the call are Dr. Christian Itin, our Chief Executive Officer; and Dr. Lucinda Crabtree, our Chief Financial Officer.
So on Slide 2, before we begin, I would just like to remind you that during today’s call, our discussion will contain forward-looking statements. Please make sure you are familiar with this disclosure slide.
On Slide 3, you should see the agenda for today, which is as follows: Christian, will provide an overview of our operational highlights for the second 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 we’ll then turn over for Q&A.
I’ll now hand over to Christian to begin the presentation.
Christian Itin
Thank you, Olivia, and good morning to you all, and thank you for joining us. It’s my pleasure to review our progress for the second quarter in 2022.
Please move to Slide 4. For those who are new to Autolus and as a refresher for those of you who know us well, we are building a fully integrated CAR T company. Building on our broad platform of cell programming technologies, we’re generating CAR T products that are tailored to the specific tumor setting we’re addressing.
We had a successful quarter with multiple readouts from our clinical programs at the European Hematology Association Congress in Vienna in June, which gives us great confidence in the inherent value of our pipeline and the progress achieved. We continue to enroll patients into the pivotal FELIX trial, where we’re investigating obe-cel for the treatment of relapsed/refractory adult acute lymphoblastic leukemia patients.
And in April, we obtained a Regenerative Medicine Advanced Therapy or RMAT designation from the FDA. As a consequence, we now have preferred regulatory access for obe-cel in all key territories, the U.S., Europe and the U.K. and have met with the FDA in the context of a Type B meeting to discuss the regulatory pathway going forward.
We’re on track to enhance the initial results for the FELIX trial in Q4 2022, which will be provided by way of a press release, and we’re planning on presenting the full data set at a medical conference in mid-2023, most likely at ASCO.As previously announced, in addition to the primary morphological cohort in the FELIX trial, we have expanded the MRD cohort to enroll up to 50 patients.
In clinical practice, patients get evaluated on a regular basis for recurrence of disease, typically using flow analysis or PCR of their bone marrow samples. Indication of minimal residual disease levels of leukemic – leukemia triggers treatment of the patients rather than waiting for full-blown morphological relapse to occur. This additional cohort does not impact our planned filing time lines as the primary data will be based on the data from the morphological cohort. However, we do believe the MRD cohort will broaden the data set across the full range of tumor burden and align with current clinical practice.
We remain fully focused on generating the data package needed to file for BLA approval for obe-cel for the treatment of adult patients with acute lymphoblastic leukemia and remain confident in obe-cel’s potential to be a best-in-class treatment in a growing market. As I mentioned, EHA was a very busy meeting for us with data readouts from multiple clinical programs, and I’ll go into more detail about the specific data later in this presentation.
But in summary, obe-cel continues to show what we believe to be best-in-class activity with a high level of sustained complete remissions in B-NHL patients without inducing severe cytokine release syndrome or any neurotoxicity. In addition, we have now seen first activity in primary CNS lymphoma patients.
Beyond obe-cel, we have seen first and promising results from the dual targeting AUTO1/22 program in children with acute lymphoblastic leukemia, who are ineligible for chemotherapy. The data presented at EHA, we believe, are demonstrating clinical proof of concept with a high level of activity and a well-manageable safety profile.
We’re particularly excited about AUTO4 reaching clinical proof of concept in patients with peripheral T cell lymphoma, reaching metabolic CRs while maintaining a well-manageable safety profile. This data validates a novel targeting approach, which is very important, given the high unmet need and difficult to treat patient population. With two new programs reaching clinical proof of concept, our pipeline beyond obe-cel is advancing well, and we’re pleased with how it’s shaping up.
Finally, we’re pleased in the quarter to dose our first patient in the Phase 1 study of AUTO8 for the treatment of patients with relapsed refractory multiple myeloma and are also on track for AUTO6 NG, our first solid tumor program to start a Phase 1 in the second half of the year. The build of our commercial manufacturing facility in Stevenage is progressing on track and within schedule, and I’ll cover that in more detail later in the presentation.
Moving to Slide 5. With that, let’s focus on our lead product, obe-cel and move to Slide 6. Just to remind you, obe-cel has a unique mechanism of action built on a highly specific engagement of CD19 coupled with a fast release from CD19 once the kill of the leukemic cell has been initiated.
This fastest engagement is based on the fast off-rate of the CAT binder and drives three key properties of obe-cel, reduction of the amitocytokine release per target selling counter, which in turn will reduce the amount of immunotoxicity in the patients, reduced exhaustion in the CAR T cell and improved engraftment and overall persistence of the product. And those of you not familiar, I refer you to a paper by Sara Ghorashian at Nature Medicine in 2020.
Moving to Slide 7. There still remains a very high unmet medical need for adult ALL patients with approximately 8,400 new cases diagnosed yearly worldwide in the last-line setting, approximately 3,000 patients of these cases reside in the U.S. and Europe. Whilst combination chemotherapy enables 90% of adult ALL patients to achieve CRS to achieve CRs, complete remissions, only 30% to 40% will achieve long-term remission.
Once relapsed patients have a median overall survival of less than a year. Current approved therapies for adult patients of Blincyto and Tecartus and Tecartus is currently approved in the U.S. and has a favorable CHMP opinion in Europe and is expected to be approved in Europe later in the year.
Both therapies are highly active, but frequently followed by subsequent treatments typically including ALLO stem cell transplant. Blincyto has a favorable safety profile with few patients experiencing severe cytokine release syndrome and ICANs, power limitations on convenience due to the need for continuous IV infusion during its 4-week treatment cycles. Tecartus is more challenging to manage and induces elevated levels of severe CRS, high level of ICANs and neurotoxicity and 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 8. Building on its unique mechanism of action, obe-cel has shown a high overall response rate with favorable – with a favorable safety profile and sustained event-free survival that tracks long-term persistence in those patients. As mentioned before, 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 the MHRA for the U.K., and most recently, RMAT designation by the FDA for the U.S.
Moving to Slide 9. Based on what we believe is potentially a transformational data from the ALLCAR study, we are treating patient – we’re conducting the pivotal FELIX study trial with approximately 90 patients in the so-called morphological cohort. We’re treating currently patients at 34 sites across the U.S., the U.K. and Spain. We’re on track with our previous guidance and expect to announce initial results in the fourth quarter this year, which will be in the shape of a press release.
We’re planning on presenting full data at a medical conference in the first half of 2023, as indicated, currently thinking about ASCO. In order to maximize outcomes from the FELIX trial, in parallel, we’ve initiated an additional cohort of up to 50 patients in the second related complete remission in second or later complete remission, we have minimal residual disease, so-called MRD-positive patients. However, this additional cohort does not impact our planned filing time lines as the primary data will be based on the data from the morphological cohort.
Moving to Slide 10 and switching gears as we move into Slide 11. Obe-cel’s unique profile means it could be applicable to a broad range of indications. We’re consequently evaluating the product outside of acute lymphoblastic leukemia in B-cell non-Hodgkin’s lymphomas in a set of ongoing Phase 1 clinical studies.
As I mentioned, we have positive clinical readouts at the recent EHA Congress from Phase 1 studies in B-cell non-Hodgkin’s lymphoma and primary CNS lymphoma presented by a way of a poster EHA as well as an oral presentation of the first AUTO1/22 Phase 1 data in pediatric ALL patients at that event, and I’ll cover this data in the upcoming slides.
Slide 12. As a reminder, the academic ALLCAR19 study has been extended as a basket study where we’re testing obe-cel in a variety of B-cell malignancies. To date, we’ve treated 17 patients with follicular lymphoma, DLBCL and mantle cell lymphoma and no patient experienced high-grade CRS and none had any grade of neurotoxicity. Of the 17 patients dosed, 16 achieved a metabolic complete remission, seven of seven follicular lymphoma patients, six of seven DLBCL patients and three of three mantle cell lymphoma patients.
We lost one patient to COVID and one mantle cell lymphoma patient relapsed. 14 of the 16 patients remain in metabolic CR with a median follow-up of 9.2 months, the longest being 19.1 months in follow-up at the last data cut. And obviously, the data will continue to mature and will give us more insights as we go forward. We’ve also started treating some CLL patients and from the three patients that have reached initial evaluation two went into molecular CR in the bone marrow, but have some residual lymphadenopathy on CT scan. We expect to have follow-up data from this ALLCAR extension study again in the second half of this year.
Turning to Slide 13. We’re also exploring obe-cel in primary CNS lymphoma in our academic carousel study. This is a type of aggressive B-cell lymphoma, but because of its anatomic location, it has been – it has a particularly poor prognosis. Initial treatment is often intensive and outcomes for these patients tends to be poor.
And the data we presented at EHA, we didn’t see high-grade cytokine release syndrome, two patients experienced neurotoxicity grade three and grade 4, respectively. One patient improved with steroids and anakinra. The second patient had several neurological deficits consistent with progressive disease and did not respond to steroids and anakinra. Overall, you can see on the right-hand side of this slide, that despite these patients having no disease outside of the CNS and having had lots of rituximab treatment, we still see really nice expansion of obe-cel in peripheral blood, and we expect to provide more data from this study in 2023.
Moving to Slide 14. Our initial experience with obe-cel and children achieved a high level of sustained complete remissions while without experiencing high-grade cytokine release syndrome. For those children who relapsed, most had lost CD19 expression on their leukemic cells at the time of relapse.
Here, we’re taking the next step in obe-cel life cycle with AUTO1/22 a dual-targeting product building 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 expression on their surface. We evaluated AUTO1/22 and an extension of the CARPALL study in children who were ineligible for Kymriah.
The children either relapsed after receiving Kymriah and could not be retreated or they had extramedullary disease, i.e., singular lesions in tissue without having disease in the bone marrow, the normal location of acute leukemia. This is a very challenging group of patients to treat out of 11 children, four had prior Kymriah therapy, and three of them had lost CD19 expression, seven of the children have extramedullary disease.
Moving to Slide 15. Data were presented at EHA in an oral presentation and showed that 9 of the 11 patients achieved a molecular CR on day 28. AUTO1/22 was well manageable with no patients experienced high-grade cytokine release syndrome. No patient relapse with antigen loss and two of the CD19 negative patients achieved a molecular complete remission, demonstrating the isolated activity of the CD22 CAR. We will continue to follow the patients and we’ll update you later in the year.
Moving to Slide 17. Here is a brief depiction of our broad cell programming toolkit we developed over the last few years. All in, the technologies cover programming modules for targeting, control, shielding and enhancing CAR T cell activity. More than 100 patent families cover our product and sell programming technologies. Recent illustrations of three technology applications were shown at ASGCT Annual Meeting in May. Each one of our product candidate applies one or several of the technologies to maximize its impact on the specific cancer it is designed to tackle.
Moving to Slide 18. This slide shows more of our next-generation programs beyond obe-cel. A program, we’re excited about is AUTO4, which is in Phase 1 study in T-cell lymphoma, and I’ll give you an update of the data we presented at EHA in just a minute.
During the first quarter, as I mentioned, AUTO8 moved into the clinic in a Phase 1 clinical study in multiple myeloma patients and were now dosing patients. I also want to reiterate our first solid tumor program, AUTO6NG and GD2-positive solid tumors will be moving into the clinic second half of this year. This program has a clinically de-risked chimeric antigen receptor to GD2 and contains multiple programming modules to enhance its activity.
Turning to Slide 19. 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 by Dr. Horwitz from the Department of Medicine Lymphoma Service at Memorial Sloan Kettering Cancer Center, talked about the majority of patients being either refractory or relapsing after initial treatment.
Standard of care is variable and often based on intensive chemotherapy treatment. Median survival for patients with relapsed or refractory disease is less than six months. T-cell lymphomas are clonal diseases that either express TRBC1 or TRBC2. The T cell receptor beta chain constant domain one or two or short TRBC1 or TRBC2 are expressed on more than 95% of all T-cell lymphoma subtypes. Only lymphomas derived from gamma-delta T cells or NK T cells lack TRBC1 or TRBC2. AUTO4 targets TRBC1 and it is the first product candidate to do so using next-generation sequencing, we identify patients with TRBC1-expressing T-cell lymphoma. These TRBC1-positive patients are then 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.
Turning to Slide 20. To date, we’ve treated 10 patients with increasing doses of AUTO4 in the so-called LibrA T1 study. We evaluated four dose levels ranging from 25 million cells to 450 million cells and have seen no dose-limiting toxicities and only mylotytopenias.
In terms of cytokine release syndrome, which just saw 1 grade three cytokine release syndrome at the highest dose level, so the four was generally very well tolerated. We’ve seen metabolic complete remissions in five of the seven evaluable patients with three of three patients at 450 million cell dose achieving a metabolic CR. Two of the complete remissions at 450 million cell level are ongoing at three and six months, and we expect to have longer follow-up on these patients in the second half of this year.
Moving to Slide 22. The manufacturing of cell therapies is complex and requires a great deal of skill and experience. We’re building a new manufacturing facility in Stevenage in the U.K. This location is about a mile from our current clinical manufacturing operations at the so-called CGT facility and will allow us to transition our entire operation, including our experienced staff to the new facility in an expedition and efficient way, both minimizing start-up risks and costs for the commercial supply.
As evidenced by our successful manufacturing of CAR T products for the pivotal study with centers across the U.S. and Europe, the location is well suited for global supply with easy access to several international airports, including London Heathrow. The new 70,000 square foot facility will provide all of us with a capacity of approximately 2,000 cell therapy batches a year with the ability to expand further when needed.
You can see on this slide a rendering of what the facility will look like once completed by the end of the year. We’re on track to commence GMP operations in mid-2023. For our clinical supply operations, we currently operate with four shifts seven days a week, our commercial manufacturing model will continue the 7-day a week pattern for the 365 days a year.
With that, we’re moving to Slide 24, and I’d like to pass over to Lucinda for our second quarter 2022 financial update. Lucinda?
Lucinda Crabtree
Thanks, Christian, and good morning or good afternoon to everyone.
It’s my pleasure to review our financial results for the second quarter to June 30, 2022. We continued in the second quarter of 2022 to focus our research and development efforts on our lead product candidate obe-cel, as well as certain pipeline assets addressing cancers with limited treatment options. Cash at June 30, 2022, totaled $216.4 million as compared to cash of $310.3 million at December 31, 2021.
Total operating expenses for the three months ended June 30, 2022, were $46.5 million as compared to total operating expenses, which was net of grant income and license revenue of $1.6 million, up $37.7 million for the same period in 2021. Research and development expenses increased by $6.1 million to $38.2 million from $32.1 million for the three months ended June 30, 2022, as compared to the same period in ’21.
The net increase in research and development expenses of $6.1 million was primarily due to the following: An increase in clinical costs and manufacturing costs primarily related to the obe-cel clinical product candidate, which is $3.5 million, an increase of $1.4 million in salaries and other employment-related costs, including share-based compensation expense, which is mainly driven by an increase in the number of employees in Asian R&D activities, an increase of $1.4 million in legal and professional consulting fees in relation to the company’s R&D activity, an increase of $0.5 million related to information technology infrastructure and support for information systems related to the conduct of clinical trials and manufacturing operations.
And these increases were offset by a decrease of $0.5 million in facility costs related to the termination and closure of the company’s U.S. manufacturing facility in 2021 and shift in its manufacturing strategy and also a decrease of $0.2 million in depreciation and amortization related to property, plant and equipment and intangible assets.
Moving to general and administrative expenses. These increased by $1.1 million to $8.3 million for the three months ended June 30, 2022, compared with $7.2 million for the three months ended June 30, ’21, primarily due to the following: an increase of $1.3 million in salaries and other employment-related costs, including share-based compensation expenses and an increase of $0.1 million primarily related to higher directors and officers liability insurance premiums as well as certain professional fees and information technology costs.
And again, these increases were offset by a decrease of $0.2 million in facility costs relating to the termination by the company of certain lease agreements in the prior year and a decrease of $0.1 million in depreciation and amortization related to property, plant and equipment and intangible assets.
Other expense net decreased by $0.5 million to $1.3 million for the three months ended June 30, 2022, from $1.8 million for the three months ended June 30, ’21, relating primarily due to the strengthening of the U.S. dollar exchange rate relative to the pound, sterling.
Interest expense increased to $1.8 million for the three months ended June 30, ’22 and relates to the liability related to sales of future royalties and sales milestones, which arose upon the company’s entry into the strategic collaboration and financing agreement with Blackstone in November 2021. There was no interest expense during the comparable period in 2021.Income tax benefit increased by $1.1 million to $7.5 million for the three months ended June 30, ’22 from $6.4 million for the three months ended June 30, ’21 due to an increase in qualifying R&D expenditures for the quarter.
Net loss attributable to ordinary shareholders was $42.1 million for the three months ended June 30, ’22 as compared to $33.2 million for the same period in ’21. The basic and diluted net loss per ordinary share for the period ended 30th of June ’22, totaled $0.46 of interest expense per share compared to a basic and diluted net loss per ordinary share of $0.47 for the three months ended June 30, ’21.Autolus estimates that its current cash on hand, including anticipated milestone payments for Blackstone extends the cash – the company’s cash runway into 2024.
And with that, I conclude my remarks and pass back to Christian to give you a brief outlook on expected milestones. Thanks, Christian.
Christian Itin
Thanks, Lucy.
Moving to Slide 26, and we’re getting to next steps. We do believe we have an exciting period ahead of us with obe-cel in relapsed/refractory in adult ALL patients rating readout of the pivotal FELIX study starting in Q4 2022. And then obviously, as we indicated earlier, planning on presenting the full data at a medical conference in the first half of next year. We’re also excited to sort of engage obviously, in more intense interactions with the FDA, and I did mention before that we had a very positive meeting Type B meeting with the FDA in the context of the RMAT process.
Now the studies of obe-cel in relapsed/refractory, B-NHL, CLL and primary CNS lymphoma are ongoing as well as our AUTO1/22 program and our AUTO4 program, and we expect to have more data over the course of this year and next. As I mentioned, we dosed our first patient in our multi myeloma study. We look forward to AUTO6NG along getting started in neuroblastoma. And finally, as a result of our collaboration with Blackstone and it has the anticipation of the milestones we expect to receive, we do have and maintain a cash runway that sees us into 2024.
We’re now at the point, we’re happy to take questions. So operator, please let’s start the Q&A.
Question-and-Answer Session
Operator
[Operator Instructions] Our first question is from Mara Goldstein at Mizuho. Mara, you’re up.
Mara Goldstein
Just with respect to the timing on the MRD study, how does that line up with BLA filing potentially? And then just to circle back on the RMAT and the meetings that you’ve had with FDA. From this point on, what’s the next interaction with them? And how does manufacturing also fit into that discussion?
Christian Itin
Yes. Very good question, Mara, and thanks for joining. So the MRD cohort will obviously continue enrolling into next year. Our plan is to file for BLA towards the end of next year, and so we will certainly have data from those patients that we can actually support and that is obviously an ability as we’re going into the BLA review process to update also on clinical data and will give us an opportunity to add on some additional data there as well. So we’ll definitely have information on that cohort with a reasonable level of follow-up.
But I think it’s important to understand that the primary data that will actually drive an approval of the product will come from the morphological cohort. So the data from the MRD cohort will be supportive or supplemental in that sense, it will not be the primary data for new.
The second part of the question was related to the engagement of the interactions with the FDA. What it can do under the RMAT designation is obviously, you get facilitated a simpler access to the agency. And the first key meeting that you run through is the so-called Type B meeting. And what that allows you to do is really review the program across its entire range that includes manufacturing, non-clinical as well as the clinical side of the program, there’s a very broad range of topics that you can cover within the Type B meeting and actually start to get appropriate guidance, et cetera, as you move forward.
So that’s sort of the way it starts out. There’s been obviously opportunities for interaction, both as we move forward to continue to actually address questions related to the clinical data set, but also separate sets of track that actually then focuses more on the questions related to the CMC section of the BLA.
So both of those actually will be ongoing, and it’s – the nice thing about an RMAT is that it gets you into a collaborative setting with the agency and gives you an ability to really have a level of access during the process that is really helpful and supportive, just preparing for a BLA and then also get into the review process.
Operator
Next up is Rob Andrews with William Blair. Rob, you’re in.
Rob Andrew
Okay. Good morning. This is Rob Andrew on for Matt Phipps. Thanks for taking our questions as well. Just also for the slide specifically called out along the follow-up in the second half. Should we assume there’s going to be additional patients there? I think you mentioned at the time of the EHA update that you’re implementing some manufacturing improvements. Are those in place for clinical trial product now currently being used in the trial? And would you expect some data from patients treated with that product in that okay, at the end of the year?
Christian Itin
Well, thanks for joining, Rob. You’re correct. Obviously, as we have the presentation of the analyst call following the EHA meeting, we did point out back that we’re going to adjust the manufacturing process and actually get some improvements into the manufacturing process that we’ve sort of developed also originally in the context of the obe-cel program. That is ongoing.
So that work is now available and the process can be used within the new patients coming in. So we are actually in the process of actually manufacturing four patients with the new manufacturing process, whether those patients and how many of those patients might be available by year-end. I think it’s too early to tell from just an analysis perspective and having a reasonable level of data item. But we certainly expect, during the course of next year obviously the full data from that additional cohort of patients that are treated with the improved manufacturing process.
Rob Andrew
Okay. Great. And then just on AUTO8, yes kind of noted that dual BCMA CD19 design. I think the plan had originally been to start with just the BCMA cost, that’s the efficacy of that CAR construct alone since it was a novel contract before adding in CD19. Is that still the case? And I suppose, if so, would you expect the data in the second half of next year to be primarily BCMA CAR alone or some dual CAR as well?
Christian Itin
So first of all, your recollection is correct. This is a program that includes two targeting approaches, one against the BCMA, the other one against CD19. On the BCMA side, there’s really the focus initially to test that novel and highly potent BCMA CAR. What we’ve done with this particular chimeric antigen receptor is really optimize it against multiple myeloma cells that carry very low levels of BCMA on their surface.
So it’s a highly potent approach. I will want to first see the impact of the BCMA CAR alone and then add on, as you pointed out, the CD19 CAR as we move forward. I think making a prediction to kind of the type of data we’re going to be able to see at the end of next year, it’s probably a bit premature.
We’re starting to treat patients or have to have initiated dosing patients now. And we’ll have to see, let’s say, how the study progresses and how the data comes along? But I think there should be a good chance for having. I think a very instructive and formative data set by the end of next year. But it is a dose escalation study, and it is a phase long study. So we’ll have to see as we go through the course of the year and can better be for the nature of the data that we present at the end of next year.
Operator
I think our next question is from Bill with Truist and it looks like your line is open. So Bill, go ahead with your question.
Bill Jahangiri
Hi, this is Bill. I am on for Asthika. We just had a question about the AUTO8 program and some of the recent updates we saw over the summer. We saw Grace’s fast manufacturing update, and we assume that there’s a preferable phenotype in their bag of cells as well along with their results, and we saw long-term follow-up with Catapult and I think there’s about a 10% differential in response rates between those 2. We were wondering what you think is the appropriate bar for AUTO8. And we’re hoping you could comment on discrete contract differences between the three contracts.
Christian Itin
Well, first of all, Bill, thanks for joining. I think interesting set of questions. Obviously, we do know for – from the CARTITUDE trial that we do have a very significant level of activity we’re seeing with the program. And obviously, now we are getting longer-term observation, which look very encouraging, and I think will be a big improvement for this patient group. The design of that product in terms of the way that it the binding is described to the BCMA are two binders, single domain binders that seem to be acting in conjunction and provide a very tight, very efficient binding to BCMA, which seems to be part of the mechanism that drives the high level of activity.
So that’s kind of what certainly what’s noted by that. I think we’ll have to see where some of the other programs are getting to. I think it’s still early days for some of those. I think what we focused on with our program is really to make sure we do get this very high level of activity against BCMA expressing multi myeloma cells, and in our case, obviously optimized very much on the binder itself as well as, in fact, actually the actual construct of the CAR, which looks slightly different than what is more broadly used in the space. There’s quite a bit of optimization that went it I think from a molecular perspective, the product looks different from obviously, the Legend J&J program and also as far as the sales program.
But I think that’s probably what we do know at this point in time. And I think we need to see kind of how these programs shape up over time and to that point, I think we’ll have more information to share.
Operator
Next up is Gil Blum with Needham & Company.
Gil Blum
Thanks for taking our question. Maybe a broader question first. So given kind of the emerging data from bispecifics in B cell lymphoma, do you think there’s still a lot of honors on developing novel T cell-based therapeutics, particularly non-Hodgkin’s lymphoma?
Christian Itin
It’s a really interesting question, Gil. And I think what we do know, I think where we probably have the best data to sort of compare contrast activities and outcomes. Obviously is an ALL where we’re active or we do have Blincyto, which is still the most active bispecific T-cell engager that we have seen to describe.
And when we look at the activity between Blincyto and obe-cel, there is a very significant level of difference that we do pick up in that setting inside sort of a highly comfortable on the data set, including the ability to provide long-term remissions, which is certainly what the obe-cel would suggest from the ALLCAR study, which is something that was not feasible to not be demonstrated with title after the model bispecific and the initial data.
Now the bispecifics and non-Hodgkin’s obviously are interesting because in the sense from that they might be able to combine with some of the other antibody mediated or antibody-based modalities. And that certainly kind of was a big play that you’ve seen play out with a number of companies. I think it is interesting just to note that Roche decided to enter into the home cell therapy actually with the product that targets CD20 and CD19 as well.
So clearly going into the iNHL space, which before the primary focus of the company was the bispecifics and they still felt that that’s an area that we wanted to get into, which to me it certainly is interesting and suggests that as we have seen in the space, it looks like the level of activity described by the initial CAR T programs that came to market in DLBCL, the activity of those programs appears to be higher and potentially more sustained compared to what we’re seeing today on the bispecific role.
So I think it’s interesting, but it also seems to be a motion, and it looks like some of the parties who have some very specific stakes in the game seem to be considered and seem to broaden that, including moving into cell therapy.
Gil Blum
Considering we’re expecting quite a few updates across your heme platform in the second half. Should we expect this presentation at ASH or you’re not giving guidance right now?
Christian Itin
Yes. I think for the most part. I mean, we’re – if you look kind of the heme segment of conferences, you got two time points typically in the year. You got at the end of the year, you got the ASH meeting at the middle of the year, at the European meeting, the EHA meeting. And those are kind of the two primary events for data releases. And certainly, as we’re looking towards the end of the year, the primary focus is going to be ASH.
Gil Blum
And on AUTO4, how would you describe the data that’s evolving for TRBC targeting CAR T when they compare to data evolving from CD70 targeting CAR Ts in the same indication?
Christian Itin
I think what we’re seeing with our own data is that we’re able to induce complete remissions at a pretty significant or elevated level. I think more patients to sort of be – I think precise around it, obviously very encouraging that the first three patients dosed the highest dose level achieved the metabolic CR. I think, we’re still continuing to observing – observation of the patients that have achieved the CR to understand for how long these CRs can be maintained. I think that’s something we do not know yet at this point in time.
And I think the data is very encouraging because we seem to be getting to that level of CR without inducing a significant level of toxicity, particularly without inducing a major – or having a major impact on the actual overall B cell compartment and thus, I would say, are in a good position to maintain immunity in these patients.
So that looks really encouraging. I think the data on CD70, which is – I don’t think we know enough about it at this point in time to really get a good feel for that data. But what we do have with TRBC1 targeting is certainly a very unique way of targeting and a very selective way of targeting T cells and being really focused on that population.
So it will be interesting to see how some of these programs evolve. There’s a huge medical need. These patients need desperately additional treatment options. And we’re very – I think, excited about the fact that clearly, with the TRBC1 and we also expect TRBC2 providing and having two novel ways of actually going after this disease setting in a way that exactly as well as tolerating.
Gil Blum
And a last one for Lucy. Can you provide any information on potential cadence of Blackstone milestones, particularly given that you’re going to have a pivotal readout in the fourth quarter and a filing in 2023?
Lucinda Crabtree
Yes. And I mean, as you know, we haven’t specifically broken out those milestone payments. But what we have said is that these are related to development and regulatory milestones. So I mean, read into that as you will go.
Gil Blum
Okay. Very helpful. Congrats on the progress.
Operator
Next up is Kelly Shi from Jefferies.
Kelly Shi
Question is for pediatric ALL. Could you share any color on the enrollment pace? And is the focus only on Kymriah in eligible patients? And in time line you’re targeting for the next phase of the study. And also, I’m curious which programs beyond AUTO1 will be prioritized for internal pipeline development, given the focus on commercialization, about ALL probably should be expected for the next two years?
Christian Itin
So with regards to the patient population we’ve been targeting in pediatric ALL. Obviously, for the initial patients we were going for kids who have basically no option left to be – to have access to a proper therapy. And that is certainly the case with children who sort of passed or beyond issues. And what we could demonstrate is obviously the very high level of activity, good safety. And with that, I think we have sort of established kind of the basic profile of the product.
As we go forward, I think there’s an opportunity to also enroll patients that are – will be eligible. I think that becomes a possibility as we start to move forward. Some of the key activities that we’re engaged in, in that program is also to do some modifications of the manufacturing process as well and kind of actually will explore that in a group of additional patients. And I think that data set will then actually sort of form the basis for any decision on moving the program forward. So we expect that data to become available of this initial cohort during probably the middle of next year. And that also then actually gives us the basis for moving the program forward.
In terms of prioritization, you’re correct. We have obviously quite a set of interesting opportunities we’re building to. The key focus is going to be on delivering obe-cel and get obe-cel to market. That’s clear where the primary focus of the organization is. But there will be opportunities as we go through the course of next year to actually look at advancing some of the earlier programs, including AUTO1/22 as well as AUTO4, which I think both of them will start reaching interesting data points during the course of next year, and I think will become programs that can be fully developed at that point in time.
Operator
Next up, we have Chuan Hong from JPMorgan.
ChuanHong
Hi, this is Chuan on for Eric Joseph. Thanks for taking our question. So just a follow-up. On the AUTO4 program. So since the update for EHA, are there any new interpretation of the lack of AUTO4 expansion in the porphyria? And do you expect the product made from the modified manufacturing process to have an impact, the full sale of phenotype and expansion potential. So yes, that’s it.
Christian Itin
So what we did see, obviously, with AUTO4 is we did see the clinical responses, and we also see nicely expanding CAR T cells in the actual tumor lesions, that data that we shared at the conference. What we did not see is elevated levels of CAR T cells in the periphery. Obviously, we can detect CAR T cell, but we don’t see significant elevated levels.
Now this is not too uncommon, if you have also depending on looking at the B cell patients as an example, that you can also have patients that actually do show complete information without actually showing any significant increase in level of CAR T cells. Now what we’re expecting to do with the changes in the manufacturing process is really to help us in this patient pool, which obviously has – what we collecting cells from the patient that could also potentially include lymphoma cells, the first step in the manufacturing process is you actually have to get removed cells that potentially could also include lymphoma cells and is to take our case we’re removing TRBC1 from the B cells.
So we start actually with a reduction of cells at the first step and then we go into the manufacturing process. So the process is somewhat different than what you normally would use. And what we’re going to do is adjust the process such that we can actually run the process in a shorter period of time, and that may actually have an impact on some of the cells behavior, as we’ve seen in some of the other programs as well.
Whether that ultimately will show a difference in terms of the T cells we see in vivo formed and these patients are not. I think that remains to be seen. This is frankly an experiment that actually hasn’t been done. There’s no really precedent that I think we can build on here. But it will be interesting to look at that and they all see [indiscernible].
Operator
All right. That’s very much. Now I’d like to turn it back to Olivia for closing remarks.
Christian Itin
All right. So this is Christian. I’d like to thank everyone for joining for – and take the time for today’s update. And we’re looking forward to keeping you posted. Meanwhile, and see you probably back in September and onwards. And meanwhile, for those of you who can get away, I wish you a great summer break and get some rest, and we’re looking forward to seeing you and keeping you updated on what’s going to be an exciting second half of the year for us. Thank you.
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