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spk09: Hello, ladies and gentlemen. Welcome to the Autolist Therapeutics Second Quarter 2022 Financial Results Conference Call. As a reminder, this conference call is being recorded. Towards the end of the call, we will have a Q&A portion. If you would like to be put in the queue, first come, first serve, press star 1-1, and at that time, you will be called upon to ask your question. Without further ado, I would like now to turn the conference over to your host, Olivia Mansour. Director, Investor Relations. Olivia, thanks.
spk01: Thanks, Corey. 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 Mansour, Director of Investor Relations, and with me on the call are Dr. Christian Eysen, our Chief Executive Officer, and Dr. Lucinda Crabtree, our Chief Financial Officer. So on slide two, 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 three, 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.
spk08: we'll then turn over for q a i'll now hand over to christian to begin the presentation 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 number four for those who are new to auto lists and as a refresher for those of you who know as well we're 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 give us a 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 OB cell for the treatment of relapsed refractory and 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 OB cell in all key territories, the US, Europe, and the UK, 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 announce 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 dataset 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 leukemia triggers treatment of the patients rather than waiting for full-blown morphological relapse to occur. This additional cohort does not impact our plan filing timelines 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 OB cells for the treatment of adult patients with acute lymphoblastic leukemia. and remain confident in OV-cell'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, OV-cell continues to show what we believe to be best-in-class activity with a high level of sustained complete remissions in BNHL patients, without inducing severe cytokine release syndrome or any neurotoxicity. In addition, we have now seen first activity in primary CNS lymphoma patients. Beyond Dovizel, we've seen first and promising results from the dual-targeting OTO1-22 program in children with acute lymphoblastic leukemia who are ineligible for chemoriotherapy. 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 ORO4 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 populations. With two new programs reaching clinical proof of concept, our pipeline beyond OV cell 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 one study, auto eight, for the treatment of patients with relapsed refractory multiple myeloma, and are also on track for auto six NG, our first solid tumor program, to start a phase one 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 five. With that, let's focus on our lead product, Obicel, and move to slide six. Just to remind you, Obicel 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 fast disengagement is based on the fast off rate of the cat binder and drives three key properties of OB cell. Reduction of the amount of cytokine release per target cell encounter, 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 Sarah Garroshian at Nature Medicine in 2019. Moving to slide seven, 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. While its 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 are Blincyto and Ticardis. Ticardis is currently approved in the U.S. and has received a favorable CHMP opinion in Europe, and it's expected to be approved in Europe later in the year. Both therapies are highly active, but frequently followed by subsequent treatments, typically including allostem cell transplants. Blinzaito has a favorable safety profile with few patients experiencing severe cytokine release syndrome and ICANS, but with limitations on convenience due to the need for continuous IV infusion during its four-week treatment cycles. Descartes is more challenging to manage and induces elevated levels of severe CRS, high level of ICANS or neurotoxicity, and requires 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 a subsequent allograft to achieve durability. Moving to slide eight. Building on its unique mechanism of action, Obicel has shown a high overall response rate with a favorable safety profile and sustained event-free survival that tracks long-term persistence in those patients. As mentioned before, Obicel has been granted orphan drug designation by the FDA and EMA for ALL and obtained prime designation by EMA for the EU, ILAC designation by the MHRA for the UK, and most recently, RMAT designation by the FDA for the US. Moving to slide nine. Based on what we believe is potentially a transformational data from the Olkar study, we are a 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 initial cohort of up to 50 patients in the second related complete remission, and 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 timelines, 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. OBSEL's unique profile means it could be applicable to a broad range of indications. We're consequently evaluating the product outside of acute lymphoblastic lipidia in B-cell non-Hodgkin's lymphomas in a set of ongoing phase one clinical studies. As I mentioned, we have positive clinical readouts at the recent IHA Congress from phase one studies in B-cell non-Hodgkin's lymphoma and primary CNS lymphoma presented by way of a poster each as well as an oral presentation of the first auto 122 phase one data in pediatric ALL patients at that event. And I'll cover these data in the upcoming slides. Slide 12. As a reminder, the academic OLCAR19 study has been extended as a basket study where we're testing OV-cell in a variety of B-cell malignancies. To date, we've treated 17 patients with follicular, DLB 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 BLBCR patients, and three of three mantle cell lymphoma patients. We lost one patient to COVID and one mantle cell lymphoma patient relapsed. Fourteen 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 Olkar extension study again in the second half of this year. Turning to slide 13. We're also exploring OB cell in primary CNS lymphoma in our academic carousel study. This is a type of aggressive B cell lymphoma, but because of its anatomical location, it has a particularly poor prognosis. Initial treatment is often intensive, and outcomes for these patients tends to be poor. In the data we presented at EHA, we didn't see high-grade cytokine release syndrome. Two patients experienced neurotoxicity, grade three and grade four, respectively. One patient improved for 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 OB cell in peripheral blood, and we expect to provide more data from this study in 2023. Moving to slide 14. Our initial experience with OB cell in 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 of their leukemic cells at the time of relapse. Here, we're taking the next step in OB cells' life cycle with OTO-122, a dual-targeting product building an OB cell 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 ODO-122 in an extension of the CAR-PAL study in children who were ineligible for chemriya. The children either relapsed after receiving chemriya and could not be retreated, or they had extramedullary disease, i.e., single 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 chemoriotherapy, and three of them had lost CD19 expression. Seven of the children had extramedullary disease. Moving to slide 15. Data were presented at EHA in an oral presentation and showed that nine of the 11 patients achieved a molecular CR on day 28. Auto-122 was well manageable with no patients experienced high-grade cytokine release syndrome. No patient relapsed 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 will 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 products and cell programming technologies. Recent illustrations of three technology applications were shown at ASGCT annual meeting in May. Each 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 18. This slide shows more of our next generation programs beyond ObieCell. A program we're excited about is Auto4, which is in phase one study in T cell lymphoma. I'll give you an update of the data we presented at EHA in just a minute. During the first quarter, as I mentioned, Auto-8 moved into the clinic in a phase one clinical study, multiple myeloma patients, and we're now dosing patients. I also want to reiterate our first solid tumor program, Auto-6-NG in 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 where 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 1 or 2, 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 NKT 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 auto 5 as well. Auto 4 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 auto 4 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 mild cytopenias. In terms of cytokine release syndrome, we just saw one 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 UK. 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 expeditious and efficient way, both minimizing startup risks and costs for the commercial supply. As evidenced by our successful manufacturing of CAR-T's 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 seven-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?
spk03: 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 30th, 2022. We continued in the second quarter of 2022 to focus our research and development efforts on our lead product candidate, Ovisel, as well as certain of our pipeline assets addressing cancers with limited treatment options. Cash at June 30th, 2022 totaled 216.4 million dollars. 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 of $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 30th, 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 over-sale clinical product candidate, the tune of $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 engaged in R&D activities. An increase of $1.4 million in legal and professional consulting fees in relation to the company's R&D activities. 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 half a million dollars in facility costs related to the termination and closure of the company's US manufacturing facility in 2021 and shift in its manufacturing strategy. And also a decrease of 0.2 million dollars 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 30th, 2022, compared with $7.2 million for the three months ended June 30th, 2021, primarily due to the following, an increase of $1.3 million in salaries and other employment-related costs, including share-based compensation expenses, 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 again these increases were offset by a decrease of 0.2 million dollars in facilities costs related determination by the company of certain lease agreements in the prior year and a decrease of 0.1 million million dollars in depreciation and amortization related to property plant and equipment and intangible assets other expense net decreased by half a million dollars to 1.3 million dollars for the three months ended june 30th 2022 from $1.8 million for the three months ended June 30th, 21, relating primarily due to the strengthening of the US dollar exchange rate relative to the pound sterling. Interest expense increased to $1.8 million for the three months ended June 30th, 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 dollars to 7.5 million dollars for three months ended June 30th 22 from 6.4 million dollars for the three months ended June 30th 21 due to an increase in qualifying R&D expenditures for the quarter. Net loss attributable to ordinary shareholders was 42.1 million dollars the three months ended June 30th 22 as compared to 33.2 million dollars 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 dollars or 46 cents per share compared to a basic and diluted net loss for ordinary share of 47 cents for the three months ended June 30th 21. Autolist estimates that its current cash on hand, including anticipated milestone payments from Blackstone, extends 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.
spk08: 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 Obicel in relapsed refractory adult ALL patients reaching 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, a type B meeting with the FDA in the context of the RMAP process. Now, the studies of OVCL and relapsed refractory, BNHL, CLL, and primary CNS lymphoma are ongoing, as well as our OTA-122 program and our OTA-4 program, and we expect to have more data over the course of this year and next year. As I mentioned, we dosed our first patient in our multiple myeloma study. We look forward to all the 6NG getting started in neuroblastoma. And finally, as a result of our collaboration with Blackstone and 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 where we're happy to take questions. So, operator, please let's start the Q&A.
spk09: Thank you very much. All right, now time for the Q&A portion. In order to have your hand raised and get in line, please press star 1 1 on your telephone and you will be answered in the order received. Our first question is from Mara Goldstein at Mizuho. So, stand by. Yep. All right. Mara will be up any second here. Mara, you're up.
spk02: Great. Thank you. Can you hear me?
spk09: Yes, we can.
spk02: Awesome. Thanks. Hi. 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, You know, from this point on, what's the next interaction with them, and how does manufacturing also fit into that discussion?
spk08: Yeah, 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 VLA towards the end of next year, so we will certainly have data from those patients that we can actually support. And there's obviously an ability as we're going into the DLA 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 review. The second part of the question was related to the engagement of the interactions with the FD&E. What you can do under the RMAC designation is also you get a facilitated and simpler access to the review the program across its entire range so that includes manufacturing non-clinical as well as the clinical side of the program so it's a very broad range of topics that you can cover within the type II meeting and actually start to you know get appropriate guidance etc as you move forward So that's sort of the way it starts out. There's then, obviously, opportunities for interaction, both as you 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 the nice thing about an RMAT is that it gets you into a collaborative setting with the agency and gives you the ability to really have a level of access during the process that is really helpful and supportive as just preparing for VLA and then also getting to the review process. Okay.
spk02: Thank you. Thank you.
spk09: Thank you, Mara. Next up is Rob Andrews with William Blair. Stand by. And Rob, you're in.
spk06: Okay, good morning. This is Rob Andrew on for Matt Fitz here. Thanks for taking our questions as well. Just on also for the slide specifically called out one, 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 EHA update that you're implementing some manufacturing improvements. You know, 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 update at the end of the year?
spk08: Well, thanks for joining, Rob. You're correct. Obviously, as we have the presentations of the analyst call following the EHA meeting, we did point out the fact that we're going to adjust the manufacturing process. improvements into the manufacturing process that were sort of developed also originally in the context of the OB cell program. That is ongoing. So that work is now available and the process can be used for the new patients coming in. So we are actually in the process of actually manufacturing for patients with the new manufacturing process. Whether those patients and how many of those patients might be available by year end, I think, is too early to tell from just an analysis perspective and having a reasonable level of data around them. But we certainly expect during the course of next year to also have the full data from that additional cohort of patients that are treated with the improved manufacturing process.
spk06: Okay, great. And then just on AutoAid, you know, Pierre kind of noted the dual BCMA CD19 design. I think the plan had originally been to start with just the BCMA car to test the efficacy of that car construct alone since it was a novel construct 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?
spk08: So, first of all, your recollection is correct. This is a program that includes two targeting approaches, one against BCMA, the other one against CE90. 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 chromatic 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, and we'll 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 is probably a bit premature. We're starting to treat patients. We have to have initiated, obviously, dosing patients now, and we'll have to see, obviously, how the study progresses and how the data comes along. But I think there should be a good chance for, you know, I think a very instructive and informative data set by the end of next year. But, you know, it is a dose escalation study, and it is a phase one study. So we'll have to see as we go through the course of the year, get a better feel for the nature of the data we'll be able to present at the end of next year.
spk06: Got it. Thanks for taking the questions.
spk07: Thanks, everyone.
spk01: I think our next question is from Bill with Truist, and it looks like your line's open. I think our host may be on mute. So, Bill, go ahead with your question.
spk05: Hi, this is Bill. I'm on for AUSTAGA. We just had a question about the Auto 8 program and some recent updates we saw over the summer. We saw a Graycells 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 CARTITUDE. And I think there's about a 10% differential in response rates between those two. We were wondering what you think is the appropriate bar for AutoAID. And we were hoping you could comment on discrete construct differences between the three constructs.
spk08: Well, first of all, Bill, thanks for joining. I think interesting set of questions. Obviously, we do know from the CAR-D2 trial that we do have a very significant level of activity we're seeing with the program. And obviously, now we're getting longer-term observation, which looks 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 the binding is described to BCMA are two binders, single-domain binders that seem to be acting in conjunction and provide a very tight, very efficient binding to DCMA, which seems to be part of the mechanism that drives the high level of activity. So that's kind of what certainly was known about that. I think we'll have to go 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 multiple 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. So there's quite a bit of optimization that went into it. In that sense, from a molecular perspective, It looks different from, you know, obviously the election J&J program and also as far as we know, 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, you know, I think at that point, I think we'll have more information to share.
spk07: Thank you.
spk09: Thanks a lot. Thanks, Bill. Next up is Gil Blum with Needham & Company. Stand by.
spk10: Thanks for taking our question. Maybe a broader question first. So given kind of emerging data from bi-specific and B-cell lymphoma, do you think there's, you know, still a lot of onus on developing novel T-cell-based therapeutics, particularly non-Hodgkin's lymphoma?
spk08: 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 in ALL where we're active, where we do have Blink-Syto, which is still the most active bispecific T-cell engager that we have seen described. And when we look at the activity between BlinCyto and OviCell, there is a very significant level of difference that we do pick up in that setting. And it's sort of a highly comparable data set, including the ability to provide long-term remissions, which is certainly what the OviCell data would suggest from the Olkosh study. And which is something that was, you know, not feasible or not to not be demonstrated with the model by specific data. And the bi-specifics and non-Hodgkin's 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 see play out with a number of companies I think it is interesting just to note that Roche decided to enter into a deal on cell therapy actually with a product that targets CD20 and CD19 as well. So clearly going into the BNHL space, which before the primary focus of the company was on bispecifics, and they still felt that that's an area they wanted to get into, which to me is certainly 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 the OVCL, the activity of those programs appears to be higher and potentially more sustained compared to what we've seen to date on the buy-specific crop. 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 reconsider and seem to broaden out, including moving into cell therapy. Thank you for that.
spk10: Considering we're expecting quite a few updates across your Heme platform in the second half, should we expect these presentations of ASH or you're not giving guidance right now?
spk08: Yeah, I think for the most part. I mean, if you look in kind of the Heme you know, segments of conferences. You know, you've got two time points typically in the year. You've got at the end of the year, you've got the ASH meeting. At the middle of the year, you've got the European meeting, the EHA meeting. And those are kind of the two primary events for data releases. And certainly, as we're looking through at the end of the year, the primary focus is going to be on ASH.
spk10: And on Auto4, how would you describe the data that's evolving for a TRBC targeting CAR-T when, say, compared to data evolving from CB70 targeting CAR-Ts in the same indication?
spk08: I think what we're seeing with our own data is that we're able to induce complete remissions at a pretty, you know, significant or elevated level, leave more patients to sort of be, you know, I think, I think precise around it, obviously very encouraging that the first three patients dose the highest dose level to achieve the metabolic CR. I think we're still continuing 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 any significant level of toxicity, particularly without inducing having a major impact on the actual overall B cell compartment and thus are in a good position to maintain immunity in these patients. So that looks really encouraging. I think the data on CD70, 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'll be interesting to see how some of these programs evolve is a huge medical need these patients need desperately additional treatment options and 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 is actually as well tolerated. Thank you.
spk10: And a last one for Lucy. Can you provide any information on situational cadence of Blackstone milestones, particularly given that you're going to have a pivotal readout in the fourth quarter and a filing in 2023?
spk03: Yeah, thanks, Gil. I mean, as you know, we haven't specifically broken out those milestone payments, but, you know, what we have said is that these are related to development and regulatory milestones. So, I mean, you know, read into that as you will, Gil. Okay.
spk10: Very helpful. Thank you for taking our questions, and congrats on the progress.
spk08: Thanks, Gil.
spk09: Thank you, Gil. Next up is Kelly Shi from Jefferies.
spk04: The next question is for pediatric ALL. Could you share any color on the enrollment pace? And is the focus only on Kymriah ineligible patients? And any timeline you're targeting for the next phase of the study? And also, I'm curious, which programs beyond auto one will be prioritized for internal pipeline development, given the focus on commercialization in adult ALL probably should be expected for the next two years? Thank you.
spk08: Yeah, thanks, Kelly. Really good question. So with regards to the patient population we've been targeting in pediatric ALL, Obviously, for the initial patients, we were going for kids that had basically no option left to have access to proper therapy. And that is certainly the case.
spk04: Next phase of the study. And also, I'm curious, which programs beyond auto one will be prioritized for internal pipeline development? given the focus on commercialization in adult ALL probably should be expected for the next two years. Thank you.
spk08: Yeah, thanks, Kelly. Really good question. So with regards to the patient population we've been targeting in pediatric ALL, obviously for the initial patients, we were going for kids that have basically no option left to have access to proper therapy. And that is certainly the case with children who sort of passed or beyond patients. And what we could demonstrate is obviously a very high level of activity, good safety. And with that, I think, you know, 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 involve patients that will be Kibari 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 we'll 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 then 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 OBSEL and get OBSEL to market. That's clearly 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 Auto 122 as well as Auto 4, which I think both of them will start reaching interesting data points during the course of next year. will become programs that, you know, can be fully developed at that point in time.
spk04: Thank you very much.
spk08: Thanks, Kelly.
spk09: All right, next up we have Chuan Hong from J.P. Morgan. Stand by.
spk07: Hi, this is Chuan. Hi, this is Chuan. I'm for Eric Joseph. Thanks for taking our question. So just a follow-up. On the auto floor, program so things the updates are you are there any new interpretation of the lack of auto for expansion in the peripheral and do you expect the product made from the modified manufacturing process to have an impact you know the fourth hour phenotype and expansion potential so yeah that's it thanks yes thanks John good question so what we did see obviously with auto for is we did see the clinical responses and we also
spk08: see nicely expanded CAR T cells in the actual tumor lesions. That's 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 the CAR T cells, but we don't see significant elevated levels. Now, this is not too uncommon if you have also, depending on looking at the ELBCL patients as an example, that you can also have patients that actually do show complete remissions 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 or we're 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. In this particular case, we're removing TRDC1 positive cells. So we start actually with a reduction of cells as 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 cell behavior, as we've seen in some of the other programs as well. Whether that ultimately will show a difference in terms of, you know, the T cells we see in vivo formed in these patients or not, I think that remains to be seen. This is frankly an experiment that actually hasn't been done. It's a, you know, there's no really precedence that I think we can build on here. But it'll be interesting to look at that, and then we'll figure out something we're gonna need now.
spk07: That's very helpful. Thanks.
spk05: Thanks, all.
spk09: All right. That's very much. Now I'd like to turn it back to Olivia for closing remarks.
spk08: All right. So this is Christian. I'd like to thank everyone for joining and for taking the time for today's update. We're looking forward to keeping you posted. Meanwhile, and see you probably back in September and onwards. 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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