Good day everyone, and welcome to the Autolus Investor Event Spotlight on Acute Lymphoblastic Leukemia, ALL Program. At this time, all participants are in a listen-only mode. After the presentation, there will be a question and answer session, but you can submit your questions via webcast. Now it's my pleasure to turn the call over to Amanda Cray. Please proceed.
Thank you, Carmen. Good afternoon or good evening, everyone, and thank you for joining us for today's presentation. With me, our Chief Executive Officer, Dr. Christian Itin, and Chief Development Officer, Dr. Matthias Will. Before we get started, I'd like to remind you that during today's call, we will make statements related to our business that are forward-looking under federal securities laws. These may include, but are not limited to, statements regarding the status of development plans, clinical trials, and market opportunities for obe-cel. These statements are subject to a variety of risks and uncertainties that could cause actual results to differ materially from expectations and reflect our views only as of today. We assume no obligation to update any such forward-looking statements.
Please note that in today's presentation, we will discuss obe-cel, which is indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia, or B-ALL. The safety information of obe-cel includes a boxed warning for cytokine release syndrome, neurologic toxicities, and secondary hematological malignancies. Please refer to the full prescribing information for additional important safety information. With that, I'm pleased to turn it over to Matthias.
Thank you, Amanda. Welcome to our ALL business update day. Today, I have the pleasure to introduce our esteemed panel of speakers. None of them really needs an introduction because they are internationally renowned researchers and clinicians in the field of ALL. Here we go. The first speaker will be Dr. Jae Park, who is the director of the Adult ALL Program and chief of cellular therapeutics at Memorial Sloan Kettering Cancer Center. Dr. Park was also an investigator on the FELIX trial , and he will speak today about ALL treatment landscape and the unmet medical need. He will be followed by Lori Muffly. She is a professor of medicine, blood and bone marrow transplantation, and cellular therapeutics at Stanford University. While she is leading multiple national clinical trials and investigations, she will speak today about the real-world experience of obe-cel in adult ALL. Dr.
Muffly will be followed by Dr. Eli Jabbour, who is a professor at the Department of Leukemia at MD Anderson Cancer Center in Houston, Texas, and he also serves as the section chief of acute lymphoblastic leukemia. Dr. Jabbour was also an investigator on the FELIX trial and will speak today about the investigator-sponsored trial efforts to evaluate obe-cel in frontline adult ALL. Last but not least, we are joined by Dr. Michael Pulsipher, who is the leading pediatric hematologist-oncologist at the Huntsman Cancer Institute at the University of Utah. He serves as the division chief of pediatric hematology-oncology and also directs major research initiatives, including those with the Children's Oncology Group. He will be speaking today about the pediatric medical unmet need in ALL, as well as the ongoing Autolus study, Catalyst, in relapsed/refractory pediatric ALL. With that, I turn it over to Dr. Park.
Okay. Well, thank you for having me here. I think we're seeing slide five, and then I'll be going rather briefly and just highlighting and setting the stage for unmet needs in relapsed/refractory in adult patients with B-cell ALL. Go to the next slide six. Adult relapsed/refractory B-cell ALL, we have about roughly 1,800 new relapsed/refractory cases annually diagnosed in the U.S. Five-year overall survival for those who have relapsed disease with a frontline chemotherapy-based approach is less than 40%. Of the relapsed patients, roughly about 50% of the patients might be ineligible or decline an allogeneic transplant for different reasons. In the current state, those are the patients we're targeting for CAR T-cell therapy, including those patients who relapsed after transplant.
On average, prior lines of therapy before CAR T-cells or at the time of CAR T-cell infusion, is about two lines of therapy. The clinical reality, where we stand with an adult B-cell ALL is, first, they are different than pediatric B-ALL in terms of biology, and then outcomes tend to be poor, unfortunately, in adult patients compared to children. Median overall survival after first relapse is about 6-9 months with prior immunotherapy, such as blinatumomab and inotuzumab, including with bone marrow transplant afterwards. There is a continued unmet need to develop to target those patients to improve the outcome of relapsed ALL patients, and hopefully even without the need to proceed to post a CAR T bone marrow transplant. Next slide, please.
For the relapsed/refractory ALL treatment pathway, as we kind of briefly walk through, there's a cascade of attrition, those patients who do get to CAR T. These are some of the clinical unmet need that we will need to address. Among the relapsed/refractory ALL patients, about a little over half of the patients will achieve a complete remission to blinatumomab or inotuzumab or any salvage therapy. Subset of those patients will then proceed to allogeneic transplant. Not all those patients, again, remain relapsed, and there are patients who don't get to bone marrow transplant, and these are the patients where there's a CAR T-cells are applicable and appropriate for those patients. That still leaves a large proportion of the patients who can benefit from new therapies such as CAR T-cells. On the right side, there are some unmet need concentrate.
We talked about transplant-ineligible, and we can probably include transplant-declining patients, as there are more and more patients who are opting for less life-altering kind of treatment options with fewer kind of chronic long-term side effects. The patients who relapsed after blinatumomab and other immunotherapy are still an unmet need for those patients, especially now that blinatumomab is incorporated into the frontline treatment. For those patients who have Philadelphia chromosome-positive ALL, which is a subset of ALL patients who typically do receive concomitant tyrosine kinase inhibitors, TKI. For those who do fail those agents are an unmet need. Lastly, for those patients who have a central nervous system disease, including extramedullary disease, are an unmet need because those patients also tend to do poorly with the conventional and the monoclonal-based antibody immunotherapy that we do have and chemotherapy. Next slide, please.
In the FELIX study, which is a study that study the obe-cel for adult patients with relapsed/refractory B-cell ALL, it reported 77% overall response rate across all patients. There are subset of the patients who got durable remissions, which means greater than three year of a sustained remission, without bone marrow transplant after receiving CAR T-cell therapy. The patients who had a lower disease burden at the time of CAR T-cell infusion did especially better compared to those patients who had a higher disease burden or leukemic cells in their bone marrow. Majority of the responses were MRD negative, meaning undetectable disease by NGS or flow cytometry post the CAR T-cell infusion.
As we know, the obe-cel does have a different CAR T-cell binder or the binder to CD19, that is again distinguishing itself from the other, the CD19 CAR T-cell that's out there for ALL and lymphoma patients. On the right side is just kind of briefly highlighting that disease burden at infusion is important, which we have seen in other prior CAR T-cell studies, including our own previously. It also turns out to be true in the context of FELIX study with an obe-cel relapsed/refractory patients. The other encouraging finding and trend is that with the two and three year follow-up that has recently been presented, that roughly 40% of the patients are remaining in remission without bone marrow transplant after CAR T, suggesting for some of these patients, CAR T might be a definitive treatment without requiring subsequent bone marrow transplant.
There are some emerging data that has been presented. The product phenotype, the cell phenotype might matter as much as cell dose of achieving a good, optimal outcome after a CAR T-cell infusion. Next slide is where is the current limitations and some of the unmet need currently. The one is a toxicity profile of a CAR T-cell therapy. Previously, adult ALL patients suffered the most severe toxicity in terms of cytokine release syndrome neurotoxicity that had limited applying this type of a treatment to older patients, frail patients, or patients with different medical comorbidities. Now with obe-cel, with a better safety profile, with a less severe CRS and ICANS or neurotoxicity rate, it allows application of such therapy to those patient population.
CAR T product fitness and manufacturing reliability has been pretty successful in the real-world setting and post-launch, which has been encouraging that the majority of the patients are able to get the manufacturing and get delivered in timely manner for them to receive the treatment. We're also seeing the long-term persisting CAR T-cells, which might correlate with a better durable response, at least in the context of FELIX study, the obe-cel patients. That is encouraging trend as we're further monitoring the CAR T-cell persistence that might be available commercially in the real-world setting. Lastly is the vein-to-vein time. Operational barriers are not just unique to obe-cel, but is kind of unique to this field in general.
That, as we continue to work to increase potentially appropriate patients to receive CAR T and distance and the logistics not being the major reason for these patients not to receive CAR T, is a continued area that we should focus on. The next slide. What is some of my assessment as to kind of where the field is heading, which will be touched upon in the subsequent presentations, is that we have seen the CAR T-cell therapy does work very well, getting high initial response rates in the relapsed/refractory setting, but we also do know that these CAR T-cells do work better when patients receive them in the lower disease burden and earlier line of a therapy.
That suggests that CAR T-cell therapy might be more efficacious and might be most beneficial in terms of as a definitive therapy without needing a bone marrow transplant in the earlier line of frontline setting as a consolidation in MRD positive or MRD negative remission in first remission setting. The product biology might be important and suggest that in the having a low side effect profile, toxicity profile, CRS and ICANS is certainly encouraging, which might be driven by the different biology, different product phenotype of the cells, as we are learning from not only in ALL setting, in the myeloma settings as well. Third is that manufacturing speed and reliability are key clinical outcomes for sure for cell therapy, because reliability in manufacturing is everything for these patients once the cells are taken away and they're receiving back.
Timely manner of receiving and high turnaround time and manufacturing success is key. There has been encouraging sign for this and other products as well too. The lastly is that, the single agent CAR T-cell therapy might be beneficial for most patients. However, there are some subsets that we do experience relapse after CAR T. We're not getting as durable outcomes. For those patients, I think the future studies will address combination or enhancing further CAR T-cell efficacy and product modification. Next, lastly, kind of just ending this, how I define the success and what we need for patients are pretty simple, but not always easy to deliver. That we need a powerful enough product to achieve very deep remission for ALL patients, for this leukemic patients, but also needs to be safe enough to deliver to most patients.
It also needs to be fast that we can deliver and administer the cell products in a timely fashion when we want to deliver and then not limited by the kind of the turnaround time. Then lastly, we all want the durable CAR T-cells that we don't need a subsequent treatment or maintenance, certainly no bone marrow transplant, and for this to be a kind of definitive standalone treatment. With that, I will turn it over to Dr. Muffly to talk about the next topic.
Thank you, Dr. Park. It's my pleasure to be here today talking about the real world experience of obe-cel. I will start with the next slide, introducing the audience to our real world consortium in the United States studying CAR T-cell therapy in adult acute lymphoblastic leukemia. Our consortium has the name of ROKA. This group, which is denoted in part on the map, comprises now approximately 50 U.S. CAR T-cell therapy and leukemia centers. We make up approximately 60% of U.S. commercial products, and that is actually growing as more sites are coming on. This consortium allows us to study real world questions regarding new commercially approved cellular therapy products. I think there's really a great strength in this approach.
The first data presented regarding the use of obe-cel in the United States, in the commercial setting, was presented both at ASH and the TANDEM meeting this past year. We included patients for this initial analysis if they were apheresis for obe-cel between November 18th, 2024, and the data cutoff, which was January 8th, 2026. Next slide, please. In this initial analysis, 96 patients were apheresis for obe-cel within just approximately one year and included in the consortium. 91 of the 96 patients received their first infusion of obe-cel. The five patients that did not receive their infusion were mostly dropped out due to progressive disease, and one had lost CD19 expression. Importantly, between first and second dose of obe-cel, there was no drop off, so all patients who received first dose went on to receive second dose.
The median follow-up at the time of this presentation, which was in February at the TANDEM meeting, was 137 days between the first CAR T-cell infusion and follow-up. 84 patients were evaluable for day 28 response at this point. Again, these data represented 60% of U.S. commercial patients treated in total. Next, please. This table shows the cohort of patients who were included in this initial consortium presentation, n equals 96, versus the 127 patients treated on the FELIX trial , which led to the approval of obe-cel. I think it's important to recognize that FELIX required certain characteristics and had strict inclusion, exclusion, just like any clinical trial. Whereas patients treated in the real world in the U.S. really represent an array of different features, and you can see this when comparing the two.
The first notable thing is that the patients treated in the real world are just a bit older and a larger proportion of them are frailer with ECOG performance status of two or higher. We also see that patients treated in the real world had increased or more lines of prior therapy, were more likely to have adverse genetics with the PH-like signature. As you can see here, 68% of patients treated in the ROKA consortium had three or more prior lines of therapy prior to obe-cel versus 35% in FELIX. Patients in the real world were highly likely to have received prior blinatumomab, inotuzumab.
Then the final thing is that the blast percentage was higher for patients treated in the FELIX trial , but that is because one of the inclusion criteria for most of the cohorts of the trial required 5% blasts or greater in the bone marrow. Whereas in the real world, many of these patients are being treated in a low disease burden setting, as you just heard from Dr. Park. Next slide. The next slide shows the snapshot of the results from this initial real world cohort of approximately just under 100 patients. I think it's quite encouraging. I'm going to point out what I find to be most important as a treater. The first is that this is really the only CAR T-cell therapy I'm aware of, where the rates of CRS are approximately 50% in the real world.
This is very important because it allows us to treat these patients safely outpatient. There are no instances of higher grade CRS. The other thing is that if you look at the ICANS, the ICANS rate in the real world with this product, any grade ICANS, is under 20%. The vast majority is grade one or two, and really grade one. Only 17% of patients experience ICANS, which again, really sort of brings this outside of the typical CAR T realm and into a more comparable to a very safe treatment that we would give to leukemia patients, irrespective of CAR T. Finally, the efficacy. We only have day 28 response rates because this is a relatively short follow-up time for this first data cut. What you can see is that the response rates overall are nearly 95%.
Over 70% of patients achieve an MRD negative CR, which is actually superior to what was seen in the trial. In summary, we see that in the real-world setting, we are treating patients with lower disease burden, but they do tend to be older and more frail. The safety and efficacy look comparable or superior to what was seen in the trial. The safety is really, like I just said, quite phenomenal, 3% high-grade ICANS and 17% overall ICANS. We believe that based on the FELIX trial , that the response rates will only deepen with time. Remember, this is a split-dose product, so day 28 is a bit of an early look.
My summary from just looking at this initial data, which you can see on the next slide, is that again, really this product's minimal side effect profile, along with its efficacy profile, allow us to treat patients who wouldn't otherwise be receiving CAR T-cell therapy, and also at some centers, to treat patients exclusively in the outpatient setting. You can see that we're using obe-cel to treat a variety of disease burdens, from MRD-negative all the way to high-burden disease. We're also treating patients with both medullary and extramedullary leukemia, which I'll show you on the next slides. Really, our strategy, I think, at many of the high volume centers, is to offer obe-cel, or at least consider obe-cel for all patients with relapsed/refractory B-ALL. We do typically use bridging for patients with high-burden disease or high-level MRD.
Increasingly, we are not routinely offering transplantation following obe-cel, as we think that a fairly sizable proportion of these patients will be cured with this cellular therapy. On the next two slides, I like to profile two patients who I think probably would not have received this therapy in the adult setting if it weren't such a safe and effective CAR T-cell. These happen to be both my patients in clinic, so these are real stories. The first is a 33 year-old woman with Down syndrome. She is a minimally verbal patient, but very active with Ph-negative B-ALL that was refractory to three prior lines of therapy. At the time I met her, she went from being a happy, bubbly woman to really being unable to move or do any of the things that gave her pleasure due to her leukemia.
We decided to take her to obe-cel. She had both extramedullary disease and bone marrow and circulating disease at the time of leukapheresis. She did receive two doses of inotuzumab as bridging and post-bridging. She had persistent extramedullary disease, as well as 5% bone marrow involvement. She got standard obe-cel. Both doses were given inpatient due to her developmental needs and functional needs. She had grade 2 CRS, got one dose of tocilizumab, one dose of dexamethasone, no ICANS. I'm very, very happy to say that her day 28 response assessment showed an MRD-negative complete remission. She's now just crossed one year. She spends most of her time at Disneyland with her family, which is her favorite place, and she is fully functional. This was absolutely a life-saving treatment for her, and she has persistence of CAR T-cells with no return of normal B-cells.
The second patient is another really interesting case of a 26 year-old woman with multiple relapse/refractory Ph-positive ALL, who had involvement of the spinal cord and was paraplegic at the time that we decided to move forward with obe-cel. I will say that we would not have given any other CAR T-cell product to this patient, but we did go out on a limb with obe-cel, given its side effect profile. This patient, as I said, was paraplegic and catheter-dependent in terms of her bladder function. At the time of obe-cel, she was also treated inpatient. She had grade 1 CRS, which was treated with supportive care only, and grade 1 ICANS, for which she received a single dose of dexamethasone. She also achieved an MRD negative CR, and on PET and MRI, her spinal lesions have entirely resolved. She just crossed her six month point.
She is walking, she is urinating independently, and really, this has been probably one of the biggest success stories I've ever seen in my career. Finally, I'd just like to wrap up by, again, going back to the consortium. This is a really vibrant and growing community of researchers and clinicians that treat patients with adult ALL with CAR T-cell therapies. There's a whole bunch of domains that we are currently and will be studying. You can see here some of the areas of interest, including healthcare utilization with different CAR T-cell products, including obe-cel, correlative analyses using samples to try to understand T-cell phenotypes and persistence, and a whole array of, I think, really interesting and important questions that we can answer through this collaboration. With that, I'd like to turn this over to Dr. Jabbour.
Thank you very much, Dr. Muffly. Good afternoon, everybody. I'm so fortunate to be here today to be part of this journey where we will cure cancer, we cure ALL, and not only we cure ALL, with sensitive.
Ladies and gentlemen, please stand by. We're having some audio difficulties. Please stand by. Gentlemen, please continue to stand by. We're having some audio technical difficulties. Please stand by. Hi, Dr. Jabbour. Please continue.
I'm very sorry for these technical issues. I was saying I'm very fortunate to be part of a journey where we cure ALL. Curing ALL is not only by giving therapy for the lifetime of four or three years. We have a unique opportunity today to cure ALL with immune therapy and obe-cel as a frontline consolidation. The reason. Next slide. The reason why I'm so confident and what is the rationale behind it. What we know and what you've heard so far from my colleagues, that obe-cel and CAR T in general, work better in somebody with tumor burden. Means if you have a minimal disease or even less, you're going to have a better outcome. That has been shown in the FELIX. What we know today with our frontline therapy, we're inducing a high MRD negativity remission by NGS approaching 70%.
Furthermore, when you get somebody in frontline, the T-cells are well fit. When you give CAR T in a multiple-relapse setting, you're going to have a T-cell, at best, they don't have great fitness. Here we have fit cells, where we collect them at the beginning, and finally, CD19 expressed on all these patients. There's no shortage of CD19 expression. We have a full target expressed, we have a low tumor burden, we have a very fit T-cells, and therefore, I think it's a major opportunity today to consider collection of the cell at the beginning and give obe-cel as a consolidation. We published back in 2025 in multiple reviews highlighting our hypothesis and where we're going. In Houston, we pioneered the work of blinatumomab in a frontline.
We were the first to have a trial with blinatumomab in a Ph-negative, in a Ph ALL, and we've shown that integration of human therapy upfront can deepen the response and improve survival. The next question is, we give therapy for lifetime, we give allo transplant. By adding CAR T-cell upfront, can we further deepen the response and spare it for transplant? Second, can we shorten the treatment duration from three years to 6- 7 months or one year? Now in USA, a lot of patients cannot complete the therapy because allo therapy require a lot of time and investment. If we can offer something quite effective in using a deep sustained remission, then we can change the outcome of all our patients in USA today and hopefully worldwide. Next slide, please. How the frontline landscape is changing, how it's being redefined today.
What we know for 30 years, we've used chemotherapy, and we had a hyper-CVAD in Houston, and we had a five year survival at 40% altogether. Of course, older patient did worse. The revolution came when we had the TKI for Ph-positive ALL, and then the immune therapy. We designed in 2016 the blinatumomab strategy in a Ph-positive ALL. That was transformative to alleviate the need for chemotherapy. We add chemotherapy and blinatumomab in hyper-CVAD. We added, we moved to purely immune therapy upfront in a Ph-positive ALL, where we have blinatumomab and TKI having a survival of 90%. In a Ph-negative ALL, we pioneered the work with the blinatumomab and inotuzumab combination. We improved the survival to 80%-90%. There's still work to do, and that is where in 2025...
In 2024, to go back with the collaboration with Autolus, where we designed the first obe-cel configuration of frontline. The idea is we take high-risk patients where transplant is offered, and we will replace allo transplant with a CAR T-cell in the vast majority of our patients who are defined by high risk, MRD positive, and those who cannot afford transplant. Now, what we know is and why obe-cel? We picked obe-cel because it works so well in minimal disease. It will be a great continue to our frontline strategy. In a frontline, you cannot afford to have any safety concerns. obe-cel had the lowest rate of adverse events grade 3 and 4 ICANS and CRS, make it ideal for the frontline combination. We know furthermore that obe-cel can lead when you infuse the cells are persistent via the 4-1BB cognitive domain, and therefore that's what acts as surveillance.
Today, if we design our study based on MRD has become an integral part of our management of ALL, and it's recommended by every societies where we must tailor our therapy on MRD, and therefore CAR T will be great for it, and post-CAR T, we can measure MRD and persistence and make a decision whether to pursue treatment or not. Next slide, please. I mentioned why obe-cel. Because of the mechanism of action being a fast-off , leading to less toxicities and less grade 3 and 4 ICANS and CRS. We've seen obe-cel quite effective in an unaffected setting, with a 77% response rate. We've seen, and I reported it at ASH, that those high MRD negativity and those who respond, they can become MRD negative if they have a low risk of relapse and the outcome is highly predictable.
We've seen as well from the obe-cel experience that when you give the obe-cel, you have memory preservation, and these cells act as surveillance towards any leukemic cells present, and therefore, having somebody NGS MRD negativity and having persistence, you can predict the greatest outcome in the long run, where you have a plateau for survival, and the manufacturing has been very reliable. Furthermore, in a frontline setting where we collect only one time cells, I schedule my infusion, therefore it's elective, and therefore vein-to-vein time is very manageable, very short, and that is not an issue. For these reasons, we select obe-cel as our partner to be used as a consolidation in a frontline setting. Next slide, please. Now, who are these patients who may benefit from this approach? Ideally, I'd like to give everybody obe-cel in frontline. Every patient get obe-cel frontline and improve their outcome.
Now, we started by selecting patients at high risk, Ph-like, CLS2 positive, K to RHD, P50 mutation, complex hypodiploidy. We know these patients have a very poor outcome and require transplant, and even with a transplant, they do not do so well. We know that blinatumomab may not work so well on a hypodiploidy, and we believe CAR T can via their independence of action, can offer a remedy for these patients at high risk. We will take patients who are MRD positive. We know these patients who had a blinatumomab upfront MRD positive, they have persistent disease, and we know obe-cel will offer the optimal approach for these patients with minimal disease to improve their outcome. We will take patients who are not fit for transplant. Because of the nature of the disease, all the people are not transplant candidate.
Finally, I get so often patients coming to Houston. They will tell me, "Doctor, I've seen Dr. So-and-So and they offered me transplant. I'm coming to see you because you have trial where you can spare me the transplant." I said, "Okay, great." I have several patients treated who came to me just because they don't want to get transplant elsewhere, and they want to get something else, and we offer them obe-cel consolidation, and we measure MRD post obe-cel persistence, and if it's MRD negative and persistent, then the deal is done. Here the scheme of our trial, where we get everybody getting immunotherapy-based regimen upfront, being hyper-CVAD or mini-CVAD, depends on the age of the patient with inotuzumab and blinatumomab. We assess them after cycle one and cycle two, and here we have two risk factors, dynamic based on MRD and static based on biology.
We will collect patient after cycle one. We engineer the cells, and we continue our bridging therapy or our chemotherapy plan. The cells already, we infuse the cells. We measure post-CAR T-cell persistence and MRD negativity. If patient is persistent and MRD negative, then the game is over. It's done. We cross our fingers for cure. If not, then we consider strategy to escalate, among them stem cell transplantation. We believe this will be transformative and will shorten therapy in ALL from three years to 6-7 months. If we're successful here, which we hope we will be, and so far, we opened the study in December of this year, and we've enrolled 15 patients so far. Of course, too early to tell, but I can tell you the excitement and the results are so far promising, but still too early.
I believe this will be transformative and will change the way we treat ALL forever. Next, please. We went from a deadly disease in ALL Ph-positive and same for Ph-negative ALL, to a curative disease. We went from cure rate of 10% in a Ph-positive to 90% today. In a Ph-negative, went from 40%- 80%, 90%. Yes, we rely on immunotherapy and transplant, and today we have the opportunity to write the next chapter by offering obe-cel frontline to our patient and cure ALL with six and seven months of therapy and make this treatment the best for all ALL diagnosed in USA, in the world. The biology favors CAR T upfront. obe-cel is the safest product and the best because of the upfront, because of safety, because of the persistence and mechanism of action.
Finally, this will be an unmet need that will fill the need of patients worldwide with ALL. With that's all what I have to share with you today. I'll next pass the baton to Dr. Michael Pulsipher to go with his presentation. Thank you for your support today.
Thank you. It's a great opportunity to be able to share the pediatrics perspective of this data with you. Hopefully, you all hear me well. If you could advance to the next slide. What I'd like to do today is share with you a few things. One thing that's important to understand is that CAR T- cells targeted at CD19 are really a mainstay. The approval for children occurred in 2017 with a different product, and it has come to be something that we are using very significantly. We're very excited to get obe-cel on board. We have a number of research gaps and challenges that I'm going to briefly review with you.
What I'd like to do is to share some of the early results of the Catalyst phase Ib, which is the first experience of this specific product in children, and then finally finish by talking about our plans moving forward in order to get regulatory approval. Next slide, please. Currently, CAR T- cells really are used extensively in children, but mainly used in children who have refractory or relapsed disease. As I mentioned earlier, the original approval of tisagenlecleucel occurred in 2017, and this was the first approval, actually, and it was done in children before adults. This particular approval has, over the years, been refined. What we've learned with using a 4-1BB based CAR T- cell targeted at CD19 for pediatric ALL is that we can have better outcomes when we use low burden and use it earlier in the disease course.
The use has increased every single year over the last several years. The year that I have data from is 2022. One thing that's occurred over that time period is an interesting shift more toward earlier phase patients. It used to be patients who had relapsed multiple times, and almost 70% of the initial patients who were treated had relapsed after transplant. Now it's being used much more for primary refractory or secondary refractory patients. The other thing that has come up as an issue is trying to understand exactly when CAR T- cells should be followed by transplant in children in order to maximize outcome. We've developed a few assays that may give us some insight to really understand who can be rescued just with CAR T- cells and who may need additional therapy.
One key thing to understand about all of this is that these very high-risk patients who initially had a survival of less than 10% now have an overall survival greater than five years that is greater than 60%. Next slide, please. There are a number of research questions that we need to understand better in children, adolescents, and young adults. Some of those are going to be addressed with the obe-cel trial. The first is that we know that early first relapse of ALL in children has dismal outcomes. In children, the landscape's a little bit different. We can cure a lot of patients with chemotherapy. Although we're all working hard to try to move CAR T- cells into the very upfront therapy, we have such good outcomes that we're not able to approach it yet.
What we're trying to do, though, is get CAR T- cells to be used at first relapse. We know that almost all patients who relapse end up having very poor outcomes. Our hope and goal is to move it into first relapse. We also know that MRD level after consolidation when patients are initially treated means that they generally need to move to transplantation. Our hope is to use CAR T- cells instead in that population in order to avoid transplantation and improve outcomes. We also have a wide variety. Dr. Muffly showed a really nice example of a woman with Down syndrome. We have many special populations that really need CAR T- cell early in therapy, including Down syndrome, frail patients who have multiple complications of chemotherapy, organ damage, and infection, specific genetic subtypes that Dr.
Jabbour mentioned that are highly susceptible to have complications and problems associated with intense therapy, and infants who have very high-risk B-ALL and a very poor prognosis. Next slide, please. These things are being partially addressed by some of the early studies with obe-cel, and I want to go over that with you briefly. Move to the next slide, please. This was presented at ASH this past year with a follow-up presentation at Tandem. What this is essentially is a brief overview of the trial. This was a single-arm, open-label trial. All patients had to be true pediatric, less than 18 years old. They had to be relapsed refractory. They were collected, given bridging therapy, and treated as per standard CAR T procedures. Next, please.
23 patients received obe-cel at the target dose, and all of their products were within specifications with no manufacturing failures. Of the 23 patients who were treated, what you can see is they got various things to bridge them, most with chemotherapy, some with immunotherapy as well. Next, please. Our safety, as with the adults, was really much, much better than we're used to with other CAR T products, with exceptionally low rates of Grade three or above CRS. In fact, we only had two patients who experienced Grade three or above, and one was a highly refractory, very challenging patient. We also had very little infection, in addition, much lower infection rates than we're used to seeing in these patients as well. Next slide. What you can see here is neutrophil recovery, and this is quite remarkable.
Generally, having studied this extensively using other CAR products, a vast number of patients have significant neutropenia at day 28, which is then prolonged, with 30% having it at three months and up to 20% having prolonged neutropenia later. As you can see here, we're getting much more rapid recovery of counts than what I would expect. Next, please. The efficacy is really outstanding with 21 of 22 patients having a response, CR achieved in 20 of those patients. All responders were MRD negative, and these responses have continued. Again, a really excellent outcome. These are early results, but the outcome is outstanding, which has really set us up, next please, to move into the next phase.
Now, this final slide that I want to show you about this just shows the pharmacokinetics and pharmacodynamics, and what we see here is with excellent expansion and persistence of this CAR for extended periods of time. Next. The conclusions I'll mention just briefly, and that is essentially a great safety profile, extremely high response rate, and while longer follow-up is needed, this really gave us encouragement to move forward with regulatory approval studies. Next, please. That leads into what's currently going on in order to get this product approved in children. Working carefully with the Children's Oncology Group, the initial group that did this study is bringing in several more centers. We decided to do a joint study along with the Children's Oncology Group to have more rapid accrual.
What you can see here is a little bit of background that focuses on that first relapse group that I mentioned to you. In a study, 1331, that we performed in the Children's Oncology Group a short while ago, patients were treated with induction followed by blinatumomab, followed by transplantation. What was noted was extremely high rates of toxicity and very poor outcomes in that 40% of patients didn't even go into remission to go on to get Blina randomization and chemo study. The overall intent to treat relapse from the beginning of the study was only 25%. There are no current indications for CAR T-cell therapy use in first relapse in children, and this is a really critical need. Next, please.
Our planned expansion is, of course, working with the Children's Oncology Group and the centers that were already participating in the phase I-B and adding an additional 30 ALL patients for a total of 54, with at least 15 slots for high-risk first relapse. The reason for that, of course, is we want it listed on the FDA indication that high-risk first relapse can be treated in this way. What you can see there is a number of secondary endpoints that we think are very important. Our study design is almost identical to the initial study with screening enrollment, bridging therapy is needed, followed by lymphodepleting chemotherapy and infusion. The expansion again includes that first relapse, and this is bolded in the next slide, where you can see our inclusion criteria.
Primary refractory, as defined, is what you can see, first relapse, and then the higher risk patients in second or greater relapse or relapse after transplantation. Next, please. These are some exclusions which I won't dwell on, but essentially we are treating almost all patients that we can with this group. The study was activated in the Children's Oncology Group. It's been activated and open, and three patients have accrued so far on the phase II portion of it. The study's currently open at CHOP, Primary Children's in Utah, and Methodist in San Antonio, and you can see eight additional COG sites that are in the process of opening it. Our hope, of course, is to move rapidly forward with this study.
The next slide shows acknowledgments of a number of individuals who've helped develop this, and I want to just move to the next slide to open this up for any questions that the group would like to ask of our group.
Thank you, Dr. Pulsipher, and thank you to all of our speakers. We are happy to take questions via the webcast platform. I have a few queued up here so we can jump right in. First is: Any comments on other forms of toxicity in the RoCo study? This may be important given older patients being treated.
Thanks a lot, Amanda. I think, Lori, that would be clearly one for you. Obviously, you're focused on particularly the immunological toxicities with CRS and ICANS, but clearly these patients do experience other adverse events. I think it'd be great to get a perspective.
Yeah. Thank you. In our initial look at the data that were presented this past winter, we did not dive into other side effects very deeply, such as infections. We did an analysis looking at hematologic recovery and found overall, the rates of hematologic recovery really mirrored other CAR T-cell therapies in this space. I think as time goes on and our numbers grow, as obe-cel becomes the sort of the CAR T of choice in this country, I think, we'll have an opportunity to delve a little bit deeper. I will tell you anecdotally, I think because the immunologic side effect profile is so favorable, we are seeing fewer and fewer infections and fewer related issues in the clinic.
Thank you, Lori. Next question. Is there any potential downside for long-term obe-cel surveillance in patients getting frontline consolidation?
That's also a very interesting question. I think, Eli, when you think about kind of the frontline treatment, obviously these patients are very heavily treated today, and they're monitored for long periods of time. How would you see kind of the inclusion of obe-cel into that upfront treatment, how that would impact in terms of the needs for long-term follow-up and surveillance?
FELIX, that earlier use of obe-cel has been associated with a better outcome when it comes to MRD negativity, sustained fitness, less relapses. That will translate into the frontline as well, where you get somebody in a frontline with very fit T-cells. You give them the obe-cel early on with minimal disease or no disease, therefore fitness is preserved. The cells are persistent and expanding, and we monitor by NGS for MRD thereafter. The way I foresee the future is that instead of giving therapy for three or four years, in ALL, we have an opportunity here to give therapy for six months, for example, give obe-cel and monitor these cells that are very fit for persistence in MRD negativity and cure the disease. I don't see any downside of this. I think nothing but great outcome.
Now, of course, we need to have a long-term follow-up, and what you've seen so far from obe-cel with three and four years of follow-up, there are no adverse events, nothing major significant. The most adverse events were encountered the first month or two, and in fact, we know for FELIX at three years of follow-up, there was no adverse event. We have to watch for infections, B-cell aplasia, and that is routine practice to give immunoglobulin replacement if needed, and antibiotic, much as before, but nothing out of this world.
Thank you.
Thanks, Dr. Jabbour. Next question. For frontline consolidation, what would be considered positive in terms of MRD negative rate and durability of CR or MRD?
Thank you very much. What we have so far when we give blinatumomab upfront, our MRD negativity rate by NGSP at 10 to minus 6 is around 70%, 75%. Here there's one caveat, that time to MRD matters, too. We know that high risk do not get into MRD negativity at the beginning, and that is detrimental. Of course, they require transplantation. We can improve on that because we know today from obe-cel given in a frontline or our own real-world evidence data or from the FELIX, that most of the patients can get into an MRD negativity early on at month one post-CAR T. I think improvement MRD is feasible. It's granted. I think the second part of the question is how durable this will be.
The primary tool of the study is relapse-free survival to see if we can really induce sustained MRD negativity rate that can translate into a cure. Today for the FDA, for example, such an MRD negativity rate sustained can be surrogate for approval of new drugs. So far what you've seen when, separate from the FELIX, the patient who had less disease treatment, low tumor burden, MRD was highly predictable for a long-term outcome and therefore patient were durable. We extrapolate from the FELIX, salvage one, to the frontline. If you get into 90% MRD negativity, which higher at one month post obe-cel infusion, this based on historical evidence, should be sustained in a vast majority of the patients, and of course, we monitor them.
Now, in case of patients who do not achieve the level of response or any time with a molecular conversion into positivity, we can go for transplantation. Again, extrapolating from FELIX, that is very reassuring, and that's what the hypothesis to go into the frontline.
Thank you very much.
Thank you.
Amanda, any additional questions?
Yes, just a couple more, Christian.
Yes. Very good.
Can you remind us about the path to getting frontline consolidation onto the label and potential timing and next data presentation?
Okay, great question. This study is ISD and Dr. Park with me and Dr. Muffly will have another study with Dr. Aldoss as well, is ongoing. We have a 30-patient study, and with their study, we can have good evidence to go into NCCN and make this product available to all U.S. patients. Of course, that will not be worldwide available. The next step will be to discuss with the agency, based on this evidence, if we can run into a single-arm trial solid enough to get approval or a randomized trial, but that will be discussed down the road once we get the studies conducted and completed. From my side in Houston, I think we can complete the study this year, in 2026, and have a long-term follow-up for a year or two, and then it should be part of NCCN in 2027.
Thank you. RoCo data looks pretty good, and we can see where there is evidence beyond FELIX. How has this changed the uptake of obe-cel in your practice, or how do you envision it changing your usage in the 2026 or 2027 timeframe?
Lori, can you-
Christian, would you like me to take that?
Yeah, please.
Sure. Yeah. I think that's a great question. I think that the RoCo data as well as the lived experience of these now 50 centers that participate, suggest that the transformation to using obe-cel as the best-in-class CAR T for adult ALL has already happened. We see the numbers increasing in our consortium, and our next data output will be at this coming ASH. I think the data, of course, help, but they're not surprising to those of us that use this product because it's very, very easy to use. I agree with what Dr. Jabbour said, and I think that there is an enormous opportunity to move this into the front line and to move this into children.
Really using obe-cel, and this is what I tell my team, which we are a large CAR T-cell center, is that this is a CAR T, but you don't need to think about it like a CAR T. These patients can remain at home. They really do not require nearly the same amount of side effect management. It's just a really nice, smooth, easy therapy, and I think that the increase in use in this coming year will reflect the toxicity profile that we're seeing in the real world.
Thank you, Dr. Muffly . Final question here. Can you put into context the risks from transplant-related mortality compared to CAR T tox?
That may be a question for Jae.
Sure. The transplant-related mortality, typically in a national average, has been about 20%-25%, although that depends on comorbidities and type of a transplant and disease status they do get, but that's the national statistics. Some are a little bit lower in experienced centers. The CAR T, the treatment-related mortality or, those are extremely low, especially with an obe-cel, because of the CRS and ICANS rate or the infectious complications, which are the predominant reasons that some of these patients die within a few weeks of receiving CAR T-cell therapy. I think the data from the FELIX study has been very encouraging with a very, very low rate.
It's certainly much, much better than a transplant, which is exactly the reason why that we are excited about moving to frontline setting that we would not have done it, obviously, if the risk of a transplant-related or treatment-related mortality was very high.
Thanks, Dr. Park. Christian, that concludes the questions, so happy to turn it back to you.
Very good. Thank you very much. I'm just going to wrap up briefly on slide 47. Obviously, what we wanted to do with you today is look at what we've achieved so far with the product and the initial launch of the product. I think the data coming from the RoCo consortium was a real reality check for how the product actually performs and is frankly giving us an opportunity to broaden the patient population that can actually be considered for CAR T therapy. Ongoing, in terms of immediate next steps, obviously, the work that Michael Pulsipher was going through, looking at the pediatric work that we've been doing. We have, obviously, good initial evidence for the activity based on the data that we presented at ASH at the end of last year on the CATALYST-py1 study. We're now obviously enrolling the phase II portion.
We had very good momentum also over the last month in the study, and we think we're going to be able to drive this study with a good momentum. The idea here is really to get obe-cel to a place where it becomes a treatment for any relapsed refractory patient across the entire age range. That is obviously what the medium term and the ongoing activity is. As we look forward, as you heard from Eli, but also Jae Park and Lori Muffly engaged with their study, to look at the ability to consolidate patients in the frontline setting with the drive towards a definitive consolidation and ultimately an abbreviated treatment in that important patient group. Moving to slide 48.
This is just a brief summary on how obe-cel and obe-cel actually have an ability to get activity across refractory first-relapse, second-line, plus relapse across the age groups based on the clinical work that we're doing currently in the peds, and expanding with that, the utility that we already have achieved on the adult side. Moving to slide 49, this sort of tacks on to what Eli was describing on the frontline approach. What we see in these data sets is that really it's the older patients, the MRD positive patients, the patients with complex genetics, tend to actually still, after all the intensification of the frontline therapy that we've seen over the last probably 15, 20 years, still actually have limited outcomes, and there is a real opportunity to improve outcomes for those patients.
The first step as we go to the last slide 50, is really to obviously drive and generate initial data and collect experience through the ISTs. With that, I think we start to get a good understanding of the profile of the product in the frontline setting and then take it from there and with certainly the aspirational goal to ultimately move the product fully into the frontline setting as well. With that, I'd like to wrap up here. I would like to thank our fantastic speakers, Dr. Jae Park, Dr. Lori Muffly, Dr. Eli Jabbour, and Dr. Michael Pulsipher, for fantastic presentations. Thank you for sharing your insights with us. We're looking forward to obviously continue the interaction with all of you and looking forward to making a real contribution here to moving the ALL field forward. Thank you very much.
Thank you so much.
Thank you. This concludes our conference. Thank you for participating, and you may now disconnect.