Autolus Therapeutics plc (AUTL) Earnings Call Transcript & Summary

Hello, ladies and gentlemen, and welcome to the Autolus Therapeutics EHA Data Update. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Dr. Lucinda Crabtree, Vice President, Head of Investor Relations. Please go ahead.

Thank you, Michelle. Turning to Slide 2. Good morning or good afternoon, everyone, and thank you for taking part in today's call on the EHA Phase I data update. I am Lucinda Crabtree, Vice President of Investor Relations. With me today are Dr. Christian Itin, our Chairman and Chief Executive Officer; Dr. Vijay Reddy, our Chief Medical Officer; Dr. Nushmia Khokhar, our Vice President and Head of Clinical development; Brent Rice, our Chief Commercial Officer in the U.S.; and Andrew Oakley, our Chief Financial Officer. Before we begin, I would like to remind you that during this call, we will be making forward-looking statements. All statements other than statements of historical facts contained in this presentation are forward-looking statements. Our actual results, performance or achievements may be materially different from those expressed or implied by the forward-looking statements. For a discussion of the risks and uncertainties relating to our business and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements please see the section titled Risk Factors in our annual report on Form 20-F filed on March 3, 2020 as well as discussions of potential risks, uncertainties and other important factors in our other periodic filings with the SEC. The forward-looking statements contained in this presentation reflect the company's views as of the date of this presentation regarding future events, and the company does not assume any obligation to update any forward-looking statements. You should, therefore, not rely on these forward-looking statements as representing the company's views as of any date subsequent to the date of this presentation. On Slide 3, the agenda, you'll see the agenda for today, and it is as follows. Christian will provide a brief introduction, and that will be followed by a review of the AUTO1 data by Nushmia. After which, Brent will provide an overview of the commercial opportunity before handing back to Christian, who will summarize the key messages for today to discuss forthcoming milestones and provide concluding comments. And of course, we will welcome your questions following our remarks, which will be taken by the panel outlined. So with that, I'd like to turn the call over to Christian.

Thank you, Lucinda, and good morning to all of you, and thank you for joining us, particularly our colleagues in the U.S. who have a very early start. I'm very pleased to introduce you to the further members of the team, and we can go on to Slide #5. Obviously, you've met in the past, most of you, Vijay Peddareddigari, who's our Chief Medical Officer; Andrew Oakley, our CFO. I'd like to introduce you to Dr. Nushmia Khokhar, who is heading up our clinical development. Nushmia has been active in the industry for quite a significant amount of time working on a number of programs on the multiple myeloma side, but also in broader oncology setting as well, including obviously, in the leukemia and lymphoma side. We also are joined today by Brent Rice, who heads up our U.S. commercial efforts. Brent's been on the commercial side for about 25 years and with significant experience at a number of companies, obviously, in particular, at Amgen, and most recently at Juno Therapeutics. With that, I'd like to actually move over to Slide #6. What you see summarized on Slide #6 are current programs that are in clinical development. Today's presentation will focus on AUTO1, in adult ALL, and we're also going to briefly refer back to the data that we have presented also today, but also at ASCO on AUTO3 in DLBCL. We can move to Slide #7. I'd like to briefly introduce you to the indication. Adult ALL is a very challenging disease setting to work in. It actually impacts a significant number of patients, about 8,400 patients are diagnosed with ALL worldwide. When we look at the addressable population in the relapsed/refractory setting, we're looking at an opportunity of 3,000 patients in the U.S. and top 5 European countries. This is about 3x the population that we see in pediatric ALL. It's a disease setting with a very high unmet medical need. Unfortunately, most of the patients that were initially treated in first-line therapy do relapse and have typically less than a year of overall survival at that point in time. There's no CAR T therapy approved in this setting. The only redirected T cell therapy approved is blinatumomab, which is a standard of care in this setting today. And obviously, this is where we believe AUTO1 will be very well positioned. We also do have orphan drug designation for the program. Slide 8 just summarizes a few of the features in a very simple way, put, what we were trying to do with AUTO1 is create a product that behaves very physiologically. It is active and has a high level of activity against the leukemia, but it also is designed to actually have a good safety profile and avoids overstimulation, over activation, which has been a major challenge in the early CAR T programs in this space. Moving to Slide #9. Slide #9 summarizes some of the key features that we're looking to design to the product to actually create this physiological phenotype. And in essence, what we designed here is a product that actually binds long enough to the leukemia cell to deliver the kill but short enough to avoid high levels of overactivation. And the way we do that is actually by designing a product that has a very fast onrate, similar to the products that have been developed earlier for lymphoma, in particular, or pediatric ALL but then, in addition, has a very fast off rate so that the product doesn't get stuck after delivering the kill, and that gives us overall a very nice set of properties and in particularly, a much reduced release of cytokines associated with the cell kill. With that, what I'd like to do is turn over to Slide #10 and pass the baton over to Nushmia Khokhar, who will actually outline the data that was presented today at EHA. Nushmia?

Thank you, Christian. Good morning, good afternoon, everyone. I'm very pleased to have the opportunity to walk through some of the data updates that we've provided at the series EHA conference and more specifically on the lead ALL program with AUTO1. We go to the next slide, please. Today, I'll discuss the updated follow-up data from the ALLCAR19 study, which is evaluating AUTO1 in adult relapsed/refractory ALL. This was presented at EHA by Dr. Claire Roddie from UCLH, who is the principal investigator for the study. I will be highlighting some of this data in the next few slides. So if we turn to Slide 12, please. As opposed to pediatric ALL, the prognosis in adult patients is poor, where long-term remission rates are fairly limited. The median overall survival is less than 1 year for relapsed/refractory disease, lest there exists an unmet medical need. The only redirected T cell therapy available in this space is blinatumomab. However, with blinatumomab, the duration of response is limited and short, and blina is used as a bridge to transplant. That's not a stand-alone curative option. Furthermore, even with successful subsequent transplants, there can be a significant transplant-related mortality. CAR T cell therapy is our active in relapsed/refractory ALL. However, they have high toxicities with CRS and also fatal neurotoxicities. Thus developing safe and effective therapies has been a challenge. Older patients with leukemia are more fragile, they can have more core morbidities and thus are more susceptible to some of these toxicities. Also, thus far, for CAR T cell therapies, there is no clear sense of the durability of remission without subsequent ALLO transplants. Turning to Slide 13. As we heard from Christian, AUTO1 was designed to address some of these challenges and was subsequently tested in the ALLCAR19 study. This slide highlights the study design. Patients are enrolled and undergo leukapheresis, they can receive bridging therapy if needed, and then they proceed to preconditioning therapy with fludarabine and cyclophosphamide. All patients get a split dose regimen based on the blast count just prior to preconditioning. If the blast count is less than 20%, they'll get 100 million cells given on day 0, followed by 310 million cells given at day 9 for a total dose of 410 million cells. Similarly, if patients have greater than 20% blast in the bone marrow, they will get a smaller dose of 10 million cells on day 0, followed by 400 million cells on day 9. Of note, if patients have Grade 3 or higher CRS or neurotoxicity, they would not receive the second dose. For all patients, the first disease assessment was done at day 28. Turning to Slide 14, please. This slide highlights the key eligibility criteria that's listed here. Just to highlight that this study enrolls adult patients up to the age of 65 years of age, who had relapsed/refractory disease. Some notable exclusions are patients with overt CNS disease and those with isolated extramedullary disease. Also to note that patients could have received prior blinatumomab or inotuzumab, there was no specific exclusion criteria for this. Turning to Slide 15. Overall, 25 patients were registered onto the study, 24 patients underwent leukophoresis. One failed leukapheresis, thus 23 products were manufactured. So I would highlight that 100% of patients undergoing leukapheresis had a product manufactured. Of these 23 patients, 19 patients were dosed, 3 passed away prior to dosing, and 1 patient is pending infusion. The study started by using an open manual process for manufacturing, but transitioned to using a semi-automated closed process, and most products made are utilizing that closed process. So this process allows for standardized manufacturer and also for enrichment for central memory T cells and naive T cells, as can be seen here. The transduction efficiency was consistently high between 50% and 83% with a median of 65%. This closed process is also the Phase II commercial process going forward. Turning to Slide 16. Looking at some of the patient characteristics, the median age of these patients was 43 years of age, and about 30% of the patients had Philadelphia-positive ALL. These patients were heavily pretreated with a median of 3 prior lines of treatment. But as you can see here, the range goes up to 6 power lines of treatment. Almost half the patients that had prior inotuzumab and 26% had been treated with prior blinatumomab. Most patients, at 63%, had failed an ALLO transplant. Also most patients had either primary refractory disease or had 2 or more relapses prior to coming on to the study. Of note, a considerable number of patients, 42%, had very high disease burden with more than 50% blast in the bone marrow at the time of starting preconditioning. Turning to Slide 17. This slide highlights the expansion kinetics and longer-term persistence. As you can see, all patients had robust expansion and most have long-term ongoing persistence. As a comparison to a data set from another CD19 CAR T cell therapy, Kymriah in pediatric and young adult patients. As you can see, the area under the curve, which takes into account the peak of expansion, but also the long-term duration of the expansion is much higher for AUTO1. We believe these kinetics of expansion and persistence are important for sustained responses. Turning to Slide 18. Now this slide highlights the safety profile for AUTO1. Of all patients treated, no patients had Grade 3 or higher CRS. 7 of the 19 patients had a Grade 2 CRS, all of these patients had high disease burden and the CRS was manageable. Overall, 6 patients received tocilizumab for treatment of CRS. Neurotoxicity was seen in 4 patients, of which 3 patients had Grade 3 neurotoxicity. All of these patients had a very high disease burden with more than 50% blasts. Notably, the neurotoxicity resolved quickly with steroids, and it resolved to Grade 1 in all cases within 72 hours or in most cases, within 24 hours. Given the nature of the disease and the prior treatments, Grade 3 neutropenia predates study treatment in a lot of patients. As you can see, 7 of the 19 patients had Grade 3 neutropenia prior to preconditioning therapy. And 8 of 17 patients continued to have Grade 3 or higher neutropenia. However, with most resolving by month 2 or month 3. Overall 6 patients have died on study. And as to be expected, most of these causes are due to disease progression or infectious complications. Specifically, 2 patients died of progressive ALL, 1 died post progression due to complications of transplant and 3 patients died of infection. 2 of them early on in the treatment course and 1 at month 6, while in complete remission. Turning on to Slide 19 now. This slide highlights the efficacy and the durable responses. The overall response rate and MRD-negative CR rate was 84% for all patients. And as you can see in the swimmer lane plot, the responses are durable and notably ongoing past 18 months. Also notable, if I can draw your attention specifically to the 3 patients, that are beyond 18 months in the close process, I would like to highlight that these patients have not been consolidated with a transplant. Overall, for all patients treated, only 2 patients have been consolidated with a transplant. There are 3 patients that progress with CD19 negative disease. Thus, overall, for all patients treated, 11 of the 19 continue to be disease-free with a median follow-up of 12.2 months but the range is ongoing up to 24.4 months. Now we turn to Slide 20, please. This slide shows the durability and the preliminary survival data for all patients, and those patients treated with product made with the closed process. So again, if we look at all patients treated, the overall response rate and MRD-negative CR rate is high at 84%. The median duration of response has not been reached. Also, the event-free survival, or EFS, at 6 months is 62% for all patients and 76% for those treated with the closed process. The 6-month overall survival is 72% for all patients and 92% for patients treated with the closed process. Turning to Slide 21, please. Now I just wanted to take a few minutes and put this data in context with some of the other standard-of-care therapies that are available. So AUTO1 potentially has a superior efficacy profile when compared to standard of care and the safety profile is very manageable. The overall response rate is double that of blinatumomab and also looking at the EFS or median PFS for standard-of-care therapies like blinatumomab or inotuzumab, where approximately half of the patients are consolidated with a transplant. The AUTO1 EFS at 6 months is high at 62% and specifically for patients treated with the closed process, 76%, and most of these patients have not been consolidated with the transplant. Thus, the treatment effect is that of AUTO1 as a stand-alone therapy. Turning to Slide 22, please. Based on available information from some other CAR T trials in adult ALL, if we look at the data, the CR rate is high and comparable of AUTO1 to other CAR T cell therapies. The safety profile in terms of CRS and neurotox is much better for AUTO1. You can see the rates of severe CRS and severe neurotoxicity can be considerably high for some of these other therapies. The other CAR T cell therapies are also being consolidated with a transplant. As an example, if you look at the UCAR19 trial, which is a study of an off-the-shelf ALLO car, most of these patients were consolidated with a transplant. Thus looking at some of this data and evolving clinical profile for AUTO1, AUTO1 has the potential to be a stand-alone therapy. Turning to Slide 23. This is the last conclusion slide for the AUTO1 study. So in conclusion, AUTO1 continues to show a unique and highly differentiated profile. All patients who underwent successful leukapheresis had a product made. Despite being tested in a heavily pretreated population and with patients with high disease burden, the safety profile is manageable with no severe CRS and low rates of neurotoxicity that resolves rapidly. Patients have had a robust expansion and persistence. The efficacy shows high MRD-negative CR rates at 84%. These remissions are durable with 11 of the 19 patients being disease-free and 6-month event-free survival of 62%, which goes higher to 72% when we consider the patients manufactured with the closed process. This preliminary data with AUTO1 supports the potential for best-in-class therapy and development as a potential stand-alone treatment for adult ALL. Turning to Slide 24, please. Now briefly, I will just switch over to diffuse large B-cell lymphoma. We have presented the ALEXANDER trial with AUTO3, which is a bicistronic CD19, CD22 CAR in DLBCL at ASCO and more recently, Dr. Wendy Osborne has presented that data at EHA. I will summarize the highlights of that data on the next slide, which is Slide 25. So AUTO3 data suggests a differentiated clinical profile. Responses have been seen at all those dose levels. But focusing specifically on doses of 100 million cells or higher with day minus one pembro, the overall response rate is 75%, and the CR rate is 63%. All responses in these patients are ongoing. The safety profile is favorable with no severe CRS and neurotoxicity of any grade. Does -- this dose regimen of 150 million to 450 million cells with day minus one pembro is the recommended Phase II dose and is also being evaluated in an outpatient cohort, which is currently enrolling patients. We feel AUTO3 has the potential for use in all settings of care. So with this is the conclusion of the clinical data summary. And now I would like to hand it over to my colleague, Brent, who is going to go over some of the commercial considerations. Thank you.

Thanks, Nushmia, and good morning, everyone, I'm happy to be with you today. I'll be walking you through the commercial opportunity for AUTO1 based on its innovative design. Moving to Slide 27, please. As Nushmia highlighted, adult ALL prognosis is poor and patients spend years receiving treatment, exposing them to significant acute and chronic clinical consequences, as illustrated here. AUTO1 responses have been durable without need for transplant. Turning to Slide 28. Estimated treatment costs for standard of care exceeds $1 million, not including additional cost when patients move on to transplant. Standard of care by line of therapy includes Hyper-CVAD, inotuzumab and blinatumomab therapy. AUTO1 potential is a curative treatment, could reduce health care resource consumption and patient burden. Moving to Slide 29. Adult ALL patients spend over 50% of their treatment hospitalized and relapsed patients have repeated prolonged and costly hospitalizations. In fact, mean hospitalizations range from 90,000 to over 130,000, with average length of stay ranging from over 13 days to approximately 20 days. Patients are hospitalized approximately 3x on average, following relapse. Turn to Page 30, please. As I've illustrated, adult ALL patients have significant unmet need associated with clinical and economic consequences. New innovations like AUTO1 are essential with the potential to address the significant unmet need. Improved patient outcomes is a stand-alone therapy and reduce the economic burden of treatments and disease-related costs. Turning to Slide 31. If we take a look at the payer mix for adult ALL, it represents a balanced mix of public and private payers, representing a more favorable reimbursement landscape, with minimal exposure to Medicare Part A. Turning to Slide 32. AUTO1 has been designed for potential best-in-class use as a stand-alone therapy, and not a bridge to transplant with high rates of durable complete response. The potential for more manageable safety profile in patients with low disease burden, will inform the select feasibility of outpatient administration in both academic and nonacademic centers in our pivotal Phase II trial. Turning to Slide 33. As I conclude the commercial overview, AUTO1 has the potential to reach the full addressable adult ALL population as a result of its potential best-in-class efficacy and safety profile, more favorable reimbursement status and patient mix, and potential stand-alone curative therapy. Unlike in pediatric ALL, where most patients are cured, only 30% to 40% of adult patients will achieve long-term remission with existing therapies. Early evidence suggests AUTO1 could be best-in-class with approximately 3,000 eligible patients in the U.S. and EU. I would now like to hand the presentation back to Christian. Thank you.

Thanks, Brent, and we're moving on to Slide# 35. And here, we have an outline of the pivotal study. We are at the stage where we have started enrollment in the Phase Ib portion of this phase Ib/II clinical -- pivotal study. We're planning to enroll 100 patients that are relapsed or refractory. The primary endpoint is overall complete response rate. Secondary endpoints include MRD-negative CR, event-free survival, duration of response and we're on track for full data by the end of next year. Moving to the next slide. We believe we're in a very good position at this point with our 2 leading programs. We're obviously active now with AUTO1 in the pivotal stage. We're excited about the profiles, Nushmia has walked us through, in terms of the ability of AUTO1 to induce long-term remissions in these patients, and we're very encouraged to see first patients crossing 18 months in molecular complete remission without a need for any additional therapy or any form of consolidation after AUTO1. That is very unusual in terms of data, and I think bodes well in terms of the long-term potential for this program. Secondly, we obviously have very nice data that we have reported first at ASCO now at EHA on AUTO3. Pointing to the very high level of clinical activity, combined with a very unusual safety profile with no high-grade cytokine release syndrome and no neurotoxicity. And that provides an enormous opportunity, as Brent discussed at our last call in terms of reaching actually the patients where they are and are not being confined to the centers of excellence, which is currently where the CAR T therapies are being delivered. We also believe that we have, obviously, additional opportunity for updates in these programs, particularly as we're looking forward to ASH at the end of the year. Overall, from a balance sheet perspective, the company is well capitalized, with $240 million in cash at the end of the first quarter. Moving to the next slide. We have here summarized some of the key data points coming up. I was already alluding to ASH as the next key data update on our leukemia and lymphoma programs. But also want to highlight that we're going to have, just in about 10 days' time, additional data from our preclinical programs, AUTO5 and T-cell lymphoma, AUTO6 NG with an outlook to small cell lung cancer and AUTO7 in prostate cancer. This presentation is scheduled at the AACR II meeting in a few days' time, and we're also -- we'll have an analyst call to review the data after the conference. So with that, I would like to open up for Q&A, and looking forward to your questions.

[Operator Instructions] Our first question comes from Biren Amin of Jefferies.

And congrats on the data. So Christian, just on the profile -- for the safety profile, the neurotoxicity that was reported, I think you had one additional patient with Grade 2 or greater neurotox compared to the last update. And I think you've disclosed now that all 4 patients had greater than 50% blast. Is there anything that you could do from a dosing standpoint that could moderate this event rate? Or are you looking at any approaches? Because clearly, you're using a split dose regimen based on their bone marrow blast count at baseline. So I just wanted to get your impression if you're going to make any modifications based on the safety profile.

Biren, thanks a lot for joining and an excellent question. Obviously, as Nushmia pointed out, the feature that we're seeing with regards to the higher grade neurotoxicity is linked to very high tumor burden. 50% or more tumor burden is an enormous tumor load in these patients. And obviously drives a massive expansion of CAR T cells and a lot of, obviously, T cell activity. What we're planning to do here is actually not to consider a dose adjustment but that we actually will manage the patients after they sort of gone through the initial activity and the initial CRS that's building up. We can manage them at that point in time as neurotoxicity starts to build with steroids. And with that, you can actually manage the steroids very well as it was originally shown for blinatumomab and then later on used in some of the other programs. So we don't have to actually do anything prophylactically. But we can intervene at the time when the adverse event starts to build. And we believe by doing that, we will be able to, even, further manage these patients with regards to neurotoxicity.

Okay. And then if I could have one more question. On cell kinetics, given you've now moved to the semi-automated close process, and you've got greater central memory T cells and naive T cells due to this process. Does the cell kinetics -- have they shifted at all based on this? If you could just provide some more color on that end.

No, we don't see a difference in terms of the cell kinetics that we observe with these patients. As you can see, the -- we have a very robust expansion. I mean that's important in the data that Nushmia presented. What we're comparing our adult patients versus pediatric patients and with the Kymriah data set. Obviously, pediatric patients have an enormous proliferative potential, also the T cells do have that. To see actually that with adult patients to exceed those numbers is quite remarkable. And that gives us a lot of confidence around the data. But also to see that with the exception of 1 patient, we have all patients actually showing long-term persistence, obviously, bodes very well in terms of the long-term ability to put pressure on the leukemia and with that transition, that response into long-term remissions.

Our next question comes from Debjit Chattopadhyay of H.C. Wainwright.

This is Aaron on for Debjit. Congrats on the data. And first, can you talk about the appropriate comparator for AUTO1, especially in terms of the AE parameters. So are we concerned about the neurotox or Grade 5 AEs as being the most important and what frequency or occurrence do you think is necessary to meet for these AEs for commercial viability?

Aaron, thanks for the question. Let me put the data in perspective. And I think the important reference point here is actually blinatumomab. So blinatumomab is also a redirected T cell therapy, but obviously, the way that the cells are being programmed is by using a soluble bite that actually makes a connection between the T cell and the target cell. So it is very similar in terms of overall mechanism of action, but obviously, the engineering behind it is very different. What we do see in terms of the adverse event profile, as you can see from the data that Nushmia presented, is actually very comparable to what we're seeing with AUTO1. And that bodes extremely well because that is obviously the type of profile that, in fact, for blina allows you to manage most of the patients or for the most part, actually outside of the hospital. So it gives us a very good profile. And what you're referring to is Grade 5. So these are patients that actually had developed sepsis. In other words, they actually developed infections. And that is a typical course, in fact, for relapsed/refractory patients. And one of the key risks that he has because of the immunosuppressive nature of the disease itself. So sepsis is, unfortunately, a common cause of death for adult ALL or also pediatric ALL patients that are at that late-stage in their disease. So the critical parameters to look at are the CRS, high-grade CRS and high-grade neurotox. And what you can see, we're obviously below that on the high-grade CRS level below blina. And with regards to the neurotox, we're in a comparable level to blina. And as Nushmia presented, these events actually did stabilize back to Grade 1 very quickly in 3 of the patients literally within a day and 1 of the patients it took 3 days. This is a very fast recovery and it tells us also that it is very well manageable. So we believe we have a remarkable safety profile for this patient population. And -- but combine that with a level of clinical activity that exceeds blina by a factor of 2.

Yes. Okay. Great. And then I had one quick question. So I noticed the 2 cohorts for the Phase II portion are divided at the blast frequency of 5%, not 20%. So does this represent a change in the dosing scheme that you guys were using from the Phase I study?

No. There's no difference there. We were having -- we're using exactly the same dosing for the pivotal study as we're using for the -- have used in the ALLCAR study. The 5% actually links to the level of tumor burden for the patient to be able to be included in the trial. In other words, the 5% level of blast in the marrow defines relapse. And so what it basically is it's the definition of a relapsed patient, and that is an inclusion criteria. It is not related to dosing. The dosing decision is based on whether the patient exceeds 20% of tumor burden, then you go into the dosing regimen that starts at 10 million cells, whereas if you're below 20% tumor burden, you're starting dose is 100 million cells.

Our next question comes from Mara Goldstein of Mizuho Securities.

Just another question on the neurotox. Are you able to sort of characterize the symptoms within that Grade 3 neurotox, for instance, did patients experience seizures? Or were the symptoms more on the disorientation, stupor, those kinds of characterizations?

Mara, thanks for joining. The -- what we did observe with these patients are the milder forms. So as you point out, if you go to particularly the high levels of neurotoxicity, the patients can get into seizures. These are milder forms of neurotox that did actually resolve quickly as indicated before.

Okay. And just on the pivotal study, if you don't mind me asking, the -- can you just give us a sense of the geography of where you will be enrolling patients from?

Yes. So the study is conducted. For the most part in the U.S., where we have the majority of the centers, and it's going to be a smaller number of centers in the U.K., and we will eventually will add a few additional centers in Europe as well. So -- but overall, the majority of the patients, we expect to be treated in the U.S.

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

Just a quick question about the decisions surrounding the 2 patients that did undergo a transplant. Could you talk a little bit about what the gating factor is for moving forward on transplant?

So first of all, and I'll start the answer, and then I'll hand over to Vijay. First of all, I think it's important to understand that today, standard of care is the only opportunity you have to actually get to a long-term remission in these patients is with transplant. So physicians have an option. It's in their discretion to actually transplant patients. The remarkable thing is in this study is it did actually not happen at any frequent level. We have very few patients that did receive a transplant. And the decisions around transplant were actually triggered around the status of the patient with regards to molecular response as one key parameter and as a second parameter of monitoring persistence of the CAR T cells. In other words, if your patient is in molecular response and the CAR T cells persist, there is no reason to transplant. If your cells would start to actually disappear, your CAR T cells would start to disappear. That could be an indicator that the patient might eventually be at risk of relapse, and that could drive a decision for transplant. So those are typically kind of the ways that I think these decisions are being made. Maybe, Vijay, you want to add from your side.

Yes. Thanks, Christian. There were 2 patients that got transplanted in CR. The first one was done very early on in this clinical program. That patient, as you have seen from the study design, every patient gets about 400 million cells in one or the other regimen. That patient, we were only able to make 50 million and he only got 50 million, but did get into molecular CR. And because the durability experience was limited, investigators decided to transplant that patient because he had not received a prior transplant. And the second patient to undergo transplant around 6 months was the patient that you probably have noticed in our expansion kinetics. There was one patient that lost CAR T persistence because of developing immune responses to the CAR. And the patient was still in molecular CR and investigators again took the opportunity to transplant that patient. Most importantly, 70% of the patients had prior transplant. And because of the durability of responses, nobody was keen on re-transplanting because second transplant has a mortality rate of between 20% to 30%. So only 2 out of the treated patients got a second transplant.

That's very helpful. And actually kind of leads into my next question. Can you provide a bit more color around the patient that had relapsed disease with CD19 positive cells at 12 months in remission?

Vijay, do you want to take that?

I mean, at this point, all we know is the patient has CD19 positive relapse. And at that point, they didn't have CAR T cells. And other than that, we don't have additional information on that patient.

Okay. So it appears that this is a type of patient that would probably be amenable for transplant kind of looking forward.

It could be. And those will be the decisions based on a patient by patient. And usually, if the patient had never had a transplant before they may consider a transplant. If a patient already had had transplant earlier, the risk of toxicities are quite high, and physicians are generally more cautious about doing a second transplant.

Our next question comes from Graig Suvannavejh of Goldman Sachs.

I've got 2. First, can you confirm just based on this patient population that care is likely to be limited to the academic centers versus an outpatient setting? And if that is the case, I guess the second question is, and I appreciate, Brent, you providing the picture of the commercial opportunity and some really interesting data around the cost of care for these patients. It would then suggest that relative to existing CAR T prices that there is room from a value proposition to price higher than existing current CAR T therapies, but given kind of the limitations on -- or the pressures on reimbursement in the academic centers, how should we be thinking about potential pricing, assuming the profile in the pivotal holds up relative to what we've seen thus far?

Thanks, Graig. And let me start with just the general picture. Adult ALL patients, particularly in the relapsed/refractory setting, tend to be treated at specialized transplant centers. These patients, as Brent was pointing out, require a substantial amount of care. They're very prone to infection. They tend to have to go into the hospital, as you've seen at least in an average 3x based on data print presented to sort of just be managed for the disease itself. So they tend to be very concentrated in a relatively small number of centers across the country. And that, in fact, centers that are highly specialized to treat and care for these patients because it is such a challenging indication to, sort of, work through and support the patients. So this is a type of setting that is not in the periphery. It is highly concentrated, a small number of centers basically are sort of being carrying most of the patients at this late-stage of the disease. And I think that is important in terms of understanding the sort of the key market that we're actually operating in. Just in general, in terms of price, that's always a function of outcome. And I think that value has to be determined based on the ultimate outcome we're going to get with the trial. We think that we have a very good profile that could be transformational for these patients. And that should actually be attractive for patients, the physicians as well as the payers. But with that, I'd like to hand over to Brent.

Yes. Thanks, Christian. Thanks, Graig, for the question. So I'll just add to Christian's comment relative to price and it being a function of outcome. And it's a function of the innovative nature and design of AUTO1. And based on that innovative design and the data that continues to hold, but I think it gives us some flexibility based on those outcomes. As Christian stated, too, the primary location of these patients will be treated at the academic centers, but there is an opportunity, particularly for patients with lower blast counts to be treated in some nonacademic centers with transplant capabilities. And that provides additional flexibility from a reimbursement standpoint as well. I hope that answered your question.

That's great color. Again, congratulations.

All right. Thanks a lot. Appreciate it.

Your final questions comes from Jim Birchenough of Wells Fargo.

Congrats on the update. I did join a little bit late. So just apologies if this was asked. But just in terms of the patient characteristics here at baseline and what you're seeing enrolling to the pivotal. Any comment on just how comparable those populations are in terms of things like baseline blast counts, cytogenetics, that sort of thing?

Happy to do that. And first of all, apologies to you, Jim. This is an incredibly early start of the day. So we appreciate the actual advantage to join. So maybe, Nushmia can just walk us through kind of the kind of inclusion criteria and the comparability in terms of what we're looking to do between the pivotal study and what we've done here in the ALLCAR19 study.

Yes. Thank you, Christian. So to answer your question, the study is enrolling patients now and we will see in terms of the characteristics, what they will pan out. The eligibility criteria is very similar to the ALLCAR19 study. Patients can come on to study if they have primary refractory disease or if they have high-risk disease with early relapse or if they have had 2 or more prior lines of therapy. So very similar in terms of the patient population that has been tested in ALLCAR19. In terms of the PE exclusion criteria, we also have a similar exclusion criteria of patients cannot be coming on to the study if they have overt CNS disease. There is no exclusion criteria for prepared blinatumomab or inotuzumab. So in terms of the population and the eligibility criteria, it is very similar. The only difference I would highlight, I think Christian also mentioned in the response to an earlier question. Our pivotal cohort will only include patients that have more physiological disease, which is greater than 5% blasts. That is the only difference. Those patients were not necessarily excluded from the ALLCAR19 study. We will look at those patients, but in an exploratory cohort and not the pivotal cohort.

And then maybe just -- and you might have mentioned this earlier, but just in terms of data targeted for year-end '21, what length of follow-up does that assume? And again, apologies if you answered that already.

So in terms of data update with regards to the ALLCAR population, obviously, will give us another 6 months of follow-up, which we believe obviously will get us to a fairly mature data set. And with regards to AUTO3, obviously, the focus will be on additional patients in the recommended Phase II dose, which we're just completing enrollment actually at this point. And the 20-patient -- outpatient cohort, which is enrolling as Nushmia presented.

There are no further questions. I'd like to turn the call back over to Christian. Please start with your comments.

Well, thank you very much all for joining today, and thanks for those of you who are dialing-in from the West Coast. It was a very early start of the day. Really appreciate it, and we're looking forward to keeping you updated. Next update, as indicated, will be on the AACR programs that we're expecting, obviously, to be public within about 10 days' time when the conference is held. All right. Thank you very much, and talk to you soon. Buh-bye.

Ladies and gentlemen, this concludes today's conference. Thank you for participating. You may now disconnect. Everyone, have a great day.