Earnings Call Transcript - AUTL Q3 2020

Operator, Operator

Hello, ladies and gentlemen, and welcome to the Autolus Therapeutics Third Quarter 2020 Financial Results Conference Call. 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 of Investor Relations. Please go ahead.

Lucinda Crabtree, Vice President of Investor Relations

Thank you, Brandy. Good morning or good afternoon, everyone, and thank you for taking part in today's call on the financial results and operational highlights for the third quarter 2020. I am Lucinda Crabtree, Vice President of Investor Relations. With me today are Dr. Christian Itin, our Chairman and Chief Executive Officer; and Andrew Oakley, our Chief Financial Officer. Before we begin, I would like to remind you that during today's call, our discussion will contain forward-looking statements. All statements, other than statements of historical facts on this call, are forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the section titled Risk Factors in our annual report filed with the Securities and Exchange Commission on March 3, 2020. These forward-looking statements should not be relied upon as representing the company's views as of any date subsequent to today. Please be advised that today's call is being recorded and webcast. On Slide 3, you will see the agenda for today, and it is as follows: Christian will provide a brief introduction, and that will be followed by our operational highlights for the third quarter of 2020. Andrew will next discuss the company's financial results, and then Christian will conclude with upcoming milestones and other concluding comments. And of course, we will welcome your questions following our remarks. So with that, I'd like to turn the call over to Christian.

Christian Itin, Chairman and Chief Executive Officer

Thank you, Lucinda, and good morning to all of you, and thank you for joining us. I'm pleased to review our progress for the third quarter 2020. Before summarizing our program update on Slide 5, I would like to briefly address the evolving COVID-19 situation and its potential impact on our operations. At our last financial update call in August, we had entered into a more stable period post the first COVID-19 peak in April, May, and our programs have remained on track throughout the third quarter. However, building in September and accelerating through October and into November, we have seen a substantial increase in infection rates in Europe and in the U.S. And with a few weeks lag, increases in hospitalization and ICU occupation rates followed. In reaction, restrictions on public life have increased across all of Europe at the end of October. From a company perspective, what helped us enroll patients through the first peak of the pandemic was the concentration of cases in few geographic areas in the U.S. During that period, most of our U.S. clinical trial sites were not impacted. Going into winter now, with an already broad spread of infections across the entire country, the risk for trial disruptions in the U.S. has increased. We will follow the situation closely, and if need be, may have to adjust patient enrollment into our trials. That said, we're working hard with our supply chain and logistics teams as well as our centers to ensure uninterrupted supply of essential goods and services for our operations. This includes timely continental and transatlantic deliveries of leukapheresis and final products to ensure timelines remain on track. As always, our key focus is on patient safety and ensuring data integrity in our trials. While to date, our lead programs, AUTO1 and AUTO3, have not been significantly impacted, we did experience a delay in patient enrollment for our ongoing Phase I clinical trial with AUTO4 earlier this year. However, for now, the situation has stabilized, and we continue to expect initial data from this Phase I study to be available in 2021. With respect to our preclinical programs, these have so far been minimally impacted, and we continue to expect AUTO5 and our solid tumor programs, AUTO6NG and AUTO7, to enter clinical development in 2021. Our first clinical study with AUTO1/22 in pediatric ALL remains on track to begin in the fourth quarter, and AUTO8 in multiple myeloma is due to start in the first half of next year. So moving to our corporate highlights and starting with our clinical programs on Slide 6. We've had a busy quarter across our portfolio, with a positive data update at ESMO for AUTO3. With respect to AUTO1, as you know, we commenced enrollment of patients with relapsed/refractory adult acute lymphoblastic leukemia into our potential pivotal Phase Ib/II AUTO1 program and are targeting to have data by the end of next year. As indicated before, timelines will be contingent on the evolving COVID-19 situation. Finally, updates on the ALEXANDER study for AUTO3 and the ALLCAR19 study for AUTO1 have been accepted for oral presentations at ASH. We're planning to host an analyst call following the release of the presentations at ASH. We will update you on the details in the coming weeks. Moving to Slide 7. I would like to briefly recap our lead program, AUTO1, in adult ALL. AUTO1 is designed to combine three key features required for a stand-alone therapy in adult ALL: first, a very high level of antileukemic activity to cope with the rapid growth of the leukemic cells in the bone marrow; second, very long persistence to put long-term pressure on the leukemia and achieve a transformational outcome; and third, a tolerable safety profile, which is particularly important for elderly patients. In terms of the market opportunity within the U.S. and the top five European countries, approximately 3,000 patients every year reach the end of their treatment options having failed chemotherapy and stem cell transplant and often also blinatumomab or inotuzumab, therefore, requiring other options. From our Phase I experience, we see that AUTO1 is about two times as active as blinatumomab, the standard of care for these patients, while maintaining a comparable safety profile. At EHA, we could show first patients who reached 18 months in molecular complete remission without receiving a transplant. Data at ASH will provide longer follow-up. Currently, there are no CAR-T therapies approved for adult ALL, and we think we have a very significant opportunity with limited competitive pressure in this high medical need setting. So based on this data, turning to Slide 9, we have started enrollment into the pivotal program, AUTO1-AL1, in adult ALL. As a reminder, the study has a Phase Ib running, and the pivotal program comprises a single-arm study of approximately 100 relapsed/refractory patients. The primary endpoint is complete remission rate, and secondary endpoints include molecular complete remission rates, event-free survival, and duration of response. We're targeting data by the end of '21, assuming no COVID disruptions to clinical trial conduct. Finally, on Slide 10, I wanted to highlight the broader potential of the AUTO1 franchise. In collaboration with our academic partners at UCL, we're exploring AUTO1 across other B-cell malignancies. Exploratory studies include primary CNS lymphoma with a planned study start in Q4 this year as well as obviously AUTO1/22 in pediatric ALL. Let's now turn to Slide 11, where I would like to switch gears and talk about AUTO3, a program that is designed for the treatment of patients with diffuse large B-cell lymphoma. DLBCL is the largest NHL indication with approximately 10,000 patients in the last-line setting with a very high medical need. Two CAR-T products are approved: Yescarta and Kymriah, plus liso-cel, or otherwise known as JCAR-17, is pending approval. AUTO3 is a dual targeting CAR-T product designed to minimize the risks of relapse due to antigen loss. In addition to the unique molecular design of AUTO3, we're also using a short cover of pembrolizumab to counteract PD-L1 mediated checkpoint inhibition as a second potential cause of relapse. On Slides 12 and 13, as reported at ESMO, AUTO3 showed a high level of complete remissions, combined with a very favorable safety profile. Across all those cohorts, the overall response rate was 68%, and the CR rate was 54%. Both cytokine release syndrome and neurotoxicity rates are low across the study. In patients achieving a complete remission and despite robust CAR-T expansion, no patient had experienced any neurotoxicity or high-grade cytokine release syndrome. Turning to Slide 14. Combining a high level of clinical activity with a good safety profile is particularly important in diffuse large B-cell lymphoma as the vast majority of patients are treated outside of centers of excellence and mostly in outpatient settings. In contrast, over 70% of all patients receiving CAR-T products in 2019 were treated in only 17% of the accredited centers of excellence certified to administer these therapies. This concentration on such a small number of centers illustrates how underpenetrated the DLBCL market is with CAR-T therapies. Also, Medicare patients make up a large portion of the DLBCL patients. However, less than 13% of patients treated are on Medicare due to the reimbursement challenges on the part A side. All in all, you can see this creates a significant opportunity for AUTO3 to provide a solution here. So let's turn to Slide 15. As a reminder, the ALEXANDER expansion cohort is designed to further assess the feasibility of AUTO3 use in the outpatient setting. As I have mentioned, we expect to provide efficacy and safety data from patients treated in our outpatient cohort at ASH as well as an update across the completed other cohorts. Turning to Slide 16. As we have discussed, AUTO3 is the first-in-class CD19, CD22 dual targeting CAR designed to combine a high level of clinical activity with a good safety profile for potential use across all settings of care. Finally, on Slide 17, I would like to remind you of the broader pipeline of the next-generation programs we're proud to be developing at the company. Most of the programs are set to move into first clinical trials in 2021. The first is our AUTO1/22 dual targeting program, building on the strong pediatric data for AUTO1 and addressing CD19 antigen loss-driven relapse in pediatric ALL. With that, I will turn over the call to Andrew for the third quarter 2020 financial update. Andrew?

Andrew Oakley, Chief Financial Officer

Thanks, Christian, and good morning or good afternoon. So we're on Slide 19, and it's my pleasure to review our financial results for the third quarter to September 30, 2020. So starting with our cash position, unrestricted cash at the end of the quarter totaled $177.7 million, and that compares with $212 million at the end of June of this year. Net total operating expenses for the three months ending 30 September 2020 were $42.7 million, and that is net of grant income of $400,000 and also license revenues of $200,000. That compares to net operating expenses of $35.6 million, net of grant income of $300,000 for the same period in 2019. Research and development expenses increased to $33.5 million for the three months ended 30 September from $27.3 million for the same period last year. Cash costs, which exclude depreciation and amortization as well as share-based compensation, increased to $30 million from $21.6 million. The increase in research and development cash costs of $8.4 million consisted primarily of an increase in compensation and employment-related costs, net of actually lower travel costs as a result of the ongoing pandemic of $1.5 million, and that's due to an increase in employee headcount to support the advancement of our product candidates in clinical development. Secondly, an increase of $3.6 million in project expenses as a consequence of the advancement of our clinical portfolio, which includes research and process development, manufacturing activities necessary to prepare, activate, and monitor clinical trial programs. Thirdly, an increase of $2.1 million in facility costs related to the commencement of a lease for a manufacturing facility and the continued scaling of our manufacturing operations. Fourthly, an increase of $1.4 million in IT infrastructure and support for information systems related to the conduct of clinical trials. Fifth, an increase of $0.8 million related to cell logistics; and finally, an increase of $0.4 million in license fees, which is offset by decreases in material purchases of $1.3 million. Noncash costs decreased to $3.5 million for the three months ending 30 September from $5.7 million for the three months ending 30 September 2019. This decrease is primarily related to share-based compensation expense that's included in research and development expenses, which decreased by $2.5 million as a result of the lower fair value of stock options recognized in the period, and this was offset by a $300,000 increase in depreciation. General and administrative expenses increased to $9.8 million for the three months ended 30 September from $8.6 million for the same period last year. Cash costs, which again exclude depreciation expense as well as share-based compensation expense, increased to $7.7 million from $5.6 million for the corresponding period last year. There was an increase, firstly, of $1 million in commercial activities; an increase of $700,000 in patent and legal fees and audit fees and other costs that resulted from being a public company; and thirdly, an increase of $300,000 in compensation and employment-related costs due to an increase of headcount. Noncash costs decreased to $2.1 million for the three months ended 30 September 2020, and that's from $3 million for the corresponding period last year. That decrease is also attributed to a share-based compensation expense as a result of the lower fair value of stock options recognized during the period. Interest income decreased by $0.5 million for the three months ended 30 September 2020 due to lower interest rates on cash held on deposit. Other expense income decreased by $5.8 million for the three months ending 30 September from other income of $3.3 million for the three months September 30, 2019, to another expense of $2.5 million. This was primarily due to a decrease of $7.1 million with regard to the weakening of the U.S. dollar exchange rate relative to the pound during the three-month period, and this is offset by lease termination gains of $1.3 million. Income tax benefit increased to $7.9 million for the three months ending 30 September 2020 from $4.6 million for the same period last June, and this is due to increased research and development credits. As research and development credits grew at a faster rate than our net loss before income tax, this led to a higher effective tax rate attributable to these losses. Research and development credits are obtained at a maximum rate of 33.35% of our qualifying research and development expenses, and the increase in the net credit was primarily attributable to an increase in eligible research and development expenses. Finally, the net loss attributable to ordinary shareholders was $37.3 million for the three months ended 30 September 2020, and that compares to a loss of $27.2 million for the same period last year. The basic and diluted net loss per ordinary share for the three-month period this year is $0.72 compared to a basic and diluted net loss per ordinary share of $0.61 for the three-month period ending 30 September 2019. And consistent with previous guidance, the company still anticipates that cash on hand provides a runway into 2022.

Christian Itin, Chairman and Chief Executive Officer

Thanks, Andrew. Let me conclude this part of the management discussion with a review of the upcoming milestones and news flow through the remainder of 2020 and in 2021. Let's move to Slide 21. As we look at the rest of 2020 and into 2021, there are multiple clinical milestones and opportunities for value creation. Our chief and most imminent operational focus will be on continuing enrollment and dosing of patients in the potential pivotal Phase Ib/II trial for AUTO1 in adult ALL. We expect to report clinical data on the AUTO3 ALEXANDER trial at the forthcoming ASH Meeting and further updates from the AUTO1 ALLCAR19 study. AUTO4 data updated in PTCL is planned for 2021. In Q4 2020, we'll also look to progress AUTO1/22, our next-generation program for ALL, into Phase I clinical study in the pediatric setting, together with our academic partner, UCL. In the first half of next year, we expect our next-generation multiple myeloma program, AUTO8, to enter the clinic, and we also expect to progress concurrently from our first allogeneic program into a first exploratory trial with our academic partners. In '21, we will look to progress several other preclinical candidates to a point of Phase I readiness, including AUTO5 and our solid tumor programs, AUTO6NG and AUTO7, all of which we had recently updated you on at AACR. In conclusion, on Slide 22, I'd like to recap the major messages from today's call. AUTO1, our first pivotal program, started in Q2 as planned. Given the positive safety and efficacy profile to date, we believe that AUTO1 has the potential to be a best-in-class CD19 CAR-T in adult ALL, a disease setting with a very high unmet need. We'll have an update from the old CAR clinical study at ASH in early December. Second, AUTO3 and DLBCL will have another clinical data update from our ALEXANDER study at ASH as well. The company is in good position, and combined with a cash on hand of $178 million, we feel we're well positioned for success. We're now happy to take questions.

Operator, Operator

Your first question comes from the line of Jim Birchenough from Wells Fargo.

James Birchenough, Analyst

Yes. Congrats on all the progress. I guess a couple from me. Just first, starting with AUTO3. Christian, could you maybe remind us of your view on what profile would support outpatient use? Is there a certain time course to fever, a certain level of CRS, an ability to discern CRS from other causes of fever? Just as we go at ASH, just interested in your perspective on what would support an outpatient offering.

Christian Itin, Chairman and Chief Executive Officer

Jim, thanks a lot for joining, and thanks for the question. I think the most important aspect of the outpatient core is that we're replicating the safety profile that we have seen in our inpatient population because, obviously, that would give us a lot of confidence around the management of the patients and the consistency of the data, both in the outpatient setting compared to our current experience with the program. And that is ultimately the most important element. For those patients that will experience an admission, we are obviously interested in understanding the time of admission, but then also the duration of the admission to understand actually what's driving that and what the impact is in the setting. So those are the key parameters that we're looking for. And really, the core is to really make sure and be clear that we can replicate the data that we have seen before in the outpatient setting, which is really the foundation for the program to be positioned in the outpatient setting.

James Birchenough, Analyst

That's helpful. For both you and Andrew, could you provide some comments on the supply chain challenges during COVID? It seems that any disruptions would mainly concern the transportation of cells, but are there other risks to the supply chain that you anticipate? Additionally, could you update us on the progress of expanding manufacturing capacity, including the ability to meet market demands and diversifying operations across different countries?

Christian Itin, Chairman and Chief Executive Officer

Yes, that's a great question. Infections can impact several areas significantly. This past spring, we had centers in regions heavily affected by the epidemic, such as New York City and London, that reached a point where they could no longer accept new patients. In New York, this situation was relatively brief, lasting only a few weeks, while in London, it extended for a substantially longer period. There is a real risk that centers overwhelmed by infections may not be able to care for patients in need of transplants or CAR-T therapy. This was one of the most extreme outcomes we encountered in the spring. However, we were able to manage the situation by continuing enrollments at other centers in the U.S. that were not affected. Now, the situation is more complex because we are dealing with a broader distribution of infections rather than isolated hotspots, which raises questions about how centers will manage. On a positive note, many centers have gained valuable experience in patient management, placing us in a better position to handle ongoing infections and patient influx. From a logistics standpoint, we observed a significant reduction in available flights, particularly during the first peak of the pandemic. The volume of flights across the Atlantic dramatically decreased, leading to logistical challenges that need careful management to secure seats on the limited available flights. Airlines are currently in a much weaker position than they were a few months ago due to a depletion of resources and cash. Regarding our manufacturing operations, I believe we've navigated the pandemic exceptionally well, thanks to the strong efforts of our manufacturing team to maintain robust operations throughout this period. The principles and processes we deployed to adapt are still in place and will continue through the upcoming months, likely into the second quarter of next year. However, there are risks related to a significant surge in infections in manufacturing areas, which could impact our workforce. While it’s hard to predict, we managed well during the last wave, and we're dedicated to applying our learnings to maintain operations effectively. We are also focusing on diversifying our manufacturing base in the long term and planning to establish operations for commercial supply in the U.S. In the short term, we won't be able to set up a second site to handle any potential disruptions in our current manufacturing setup.

Operator, Operator

Your next question comes from the line of Chad Messer of Needham & Company.

Gil Blum, Analyst

This is Gil on behalf of Chad. Congratulations on your progress. I have a quick question regarding the data that will be presented at ASH from the outpatient cohort. Can you provide any guidance on the duration of time post-treatment for these patients that will be reported?

Christian Itin, Chairman and Chief Executive Officer

We haven't specifically guided on that, but what we obviously did is we communicated that. That cohort started after ASCO. So it is actually a limited follow-up that we have on those patients. We will not have the full dataset for ASH as we're still managing patients and are finishing the dosing of the cohort.

Gil Blum, Analyst

All right. And on your other programs in solid tumor and AUTO8, should we expect any additional preclinical presentations to be coming in the next few months?

Christian Itin, Chairman and Chief Executive Officer

Well, I think there's an opportunity for the conferences next year to present additional information as well as opportunities for the publication of nonclinical data in peer-reviewed journals as well. I think both opportunities are there for the upcoming months and throughout 2021.

Gil Blum, Analyst

And kind of lastly here, do you guys have any thoughts about the difficulties that we're seeing with some of the allogeneic programs that are currently ongoing? And how would that contrast with the programs you have planned?

Christian Itin, Chairman and Chief Executive Officer

I think it's very difficult to answer that, Gil. I mean we've obviously also seen what everybody else has seen. It's information on a small number of patients. I think it's really hard to interpret. We just have to see what the data releases actually are at the conference. At that point, I think everyone will have a better understanding of the challenges that the companies are dealing with. It's difficult to read at this point.

Operator, Operator

Your next question comes from the line of Gabriel Fung of Mizuho Securities.

Gabriel Fung, Analyst

The first question here is that, is there any chance that we could receive any more updates from CARPALL assessing AUTO1 in pediatric ALL? And are there any learnings here that you have transferred to the next-gen trial that you just started?

Christian Itin, Chairman and Chief Executive Officer

We're not going to provide an update on CARPALL at ASH. However, a significant portion of the data has already been published in the Nature Medicine paper. The main learnings from the CARPALL study are diverse. First, the product demonstrates a notable level of clinical activity, showcasing a very high molecular complete remission rate along with solid safety. We did not observe high-grade cytokine release syndrome in the children, which distinguishes this from other programs. Additionally, we noted exceptional persistence; last year at ASH, we demonstrated the ability to detect circulating CAR-T cells three years post-dosing, allowing us to analyze their composition over that time. This presents a very unique profile. However, we did observe that among patients who relapsed, 80% experienced relapses with CD19 negative disease. With the AUTO1/22 program, our goal is to leverage the remarkable properties of AUTO1, specifically its unusual level of persistence, while also incorporating an optimized CD22 chimeric antigen receptor to reduce the risk of relapses driven by antigen loss in these children. These insights summarize the key takeaways from the study and have shaped the design of the next-generation product for pediatric patients.

Gabriel Fung, Analyst

Great. And another question here on AUTO5. When, in particular, are you looking for in the AUTO4 interim that would prompt the green light for the AUTO5 clinical trial?

Christian Itin, Chairman and Chief Executive Officer

Well, we're obviously working through the nonclinical work for AUTO5. We didn't start at the same time with the two programs. We had AUTO4 first, and then we're engineering the AUTO5 and shared some of the information, particularly around the way we generated the particular binder for AUTO5 at the AACR meeting in the middle of the year. So that program is actually running at this point, not dependent on the progress of the AUTO4 program. But we're looking to catch up as much as we can with the AUTO5 program.

Gabriel Fung, Analyst

I'm just wondering if you could share what the source of the cells would be for the allogeneic program.

Christian Itin, Chairman and Chief Executive Officer

We will do that when the study is up and running and we're introducing the study at that point in time.

Operator, Operator

Your next question comes from the line of Matt Phipps of William Blair.

Unidentified Analyst, Analyst

It's Hunter on for Matt. I was just wondering if you could give us an idea of how many patients we'll see data for here coming at ASH, and then any color on what the next steps will be for AUTO3 coming out the other side of ASH.

Christian Itin, Chairman and Chief Executive Officer

Yes. Well, thanks a lot for joining. And with regards to the update, obviously, what we're going to give at ASH is over and above what we have presented at ESMO, where we presented the recommended Phase II dose cohort with a bit longer follow-up as well. What we're doing now is obviously enrolling patients into the outpatient cohort, and we're going to have somewhere in the range of about 10 to 15 patients worth of data over and above what we have been able to present at ESMO. And then with regards to kind of the path into next year, obviously, one of the key decisions is going to be based on that data to inform the design of the next study. We will inform on that at the appropriate time.

Operator, Operator

Your next question comes from the line of Graig Suvannavejh of Goldman Sachs.

Graig Suvannavejh, Analyst

I've just got a couple. One, I noticed the latest update on AUTO8. That study was moved to the first half of next year. Just wondering if that's just COVID-related, logistics-related, anything else beyond that. My second question has to do with the competitive landscape in DLBCL. We saw J&J and Genmab take a bispecific CD3, CD20 into a Phase III for refractory DLBCL. I would love to get your thoughts on, if not that particular program, but CD3, CD20 bispecifics in DLBCL. And my third question actually is for Andrew. Andrew, you've got a lot of programs moving into the clinic in 2021, and some study starts in the fourth quarter this year. So as we're thinking about R&D, while I don't anticipate you giving formal guidance for 2021, can you just give us a sense of R&D spend from this point going forward versus what we've seen previously?

Christian Itin, Chairman and Chief Executive Officer

Thanks, Graig. Appreciate it. So the first question was related to AUTO8. That program, we initially expected to be able to get going before the end of the year. That will happen now beginning of next year. It is in part related to kind of the impact that COVID had in the middle of the year at our academic partner. A few weeks were lost in the process. I think we're in a good place now in terms of catching up time, so not a significant change from where we look at the program. The second question related to the bispecifics and T-cell engagers, particularly CD20, CD3 T-cell engagers. There are a whole series of programs with Genmab, Regeneron, Benitec, and others as well. What we've seen across all of these programs is the sort of single-agent activity in the range of about 20% CR rate that then actually were combined with other modalities to sort of increase the activity. I think what we see is clearly activity. The durability, I think, is still something that needs to be assessed, and more information is required. But it's an active therapeutic modality with no question about it. However, it also seems to be not quite at the level in terms of activity as what we can see with the autologous CAR-T programs. So it's a relevant modality, and it will be competing with the CD19 ADCs as well that are also moving into the space. All having very similar types of outcomes. At this stage, there's a difference and a significant level of difference in terms of outcome when comparing those with the autologous CAR-T programs. The final question related to the R&D expenses. One of the important things is, as you'll see with our earlier pipeline, we are collaborating quite extensively with academic institutions to run the early part of those trials. That allows us to manage the R&D expenses significantly so that the key investments we're making by a vast margin are going into the late-stage trials. Maybe, Andrew, do you want to continue on that?

Andrew Oakley, Chief Financial Officer

Yes, I can. You've identified the key point regarding the use of academic programs to control expenses during the initial stages of these studies. R&D expenses will naturally rise, but there are establishment costs we experienced in 2019 and 2020, especially on the manufacturing side. As these establishment costs decrease, trial expenditures will increase. We anticipate an uptick in expenses by the middle of next year. In Q2 and Q3, we expect expenses to stabilize, with a slight decline in Q4. We remain confident that our projections regarding cash runway will remain intact, allowing us to have sufficient cash through 2022.

Operator, Operator

And our final question comes from the line of Kelly Shi of Jefferies.

Dingding Shi, Analyst

I will continue the question regarding the outpatient setting cohort. What type of data would support a pivotal trial? For example, do you set a threshold on certain proportions of patients for readmission or getting into ICU? And also a related question regarding the tox profile of AUTO3. Do you see the pattern of CRS on your tox occurrence differentiated from other CD19 CAR-Ts? For example, have you observed the layout side of CRS and the Neurotox, and also what's the middle duration of each toxic now?

Christian Itin, Chairman and Chief Executive Officer

Thanks, Kelly. Thanks for the questions. As I indicated to Jim's question, the key is really demonstrating that we can replicate the safety profile that we've seen in our inpatient cohort, as that would give us confidence around patient management and the consistency of the data. One important aspect with regards to the toxicity profile is that when patients respond to CAR-T therapy, those that achieve complete remission tend to have a lot of CAR-T expansion, and that is actually where most programs see a significant level of adverse events directly related to CAR-T expansion and the activity of the CARs in those patients. Surprisingly, we haven't seen that. Looking at the patients achieving a CR, we don't observe neurotoxicity, and there is limited cytokine release. We haven't observed any high-grade cytokine release so far, which is important because it gives us a profile that is remarkably good concerning CAR-T mediated adverse events. Obviously, patients do experience adverse events that are disease-related, but those are shared across any therapeutic modality you'd be applying. So from an outpatient perspective, we want to see that replicated. If there are admissions, we want to understand the reasons for those and the duration but also whether those admissions require any intense management. That's the key challenge when thinking about these patients; if admissions are required, should they need ICU access? If not, that adds significant burden on the respective institution.

Dingding Shi, Analyst

It's very helpful. May I have a follow-up question regarding the CAR-T space? The competition is heating up, especially in the B-cell setting. Do you have a plan to move AUTO1 and AUTO3 into earlier lines of therapy?

Christian Itin, Chairman and Chief Executive Officer

With every oncology indication, you start at the back end of the disease and work your way up towards the earlier lines of therapy. That is certainly what we would intend to do, both in the ALL setting and in the DLBCL setting. But the first thing to establish is to establish yourself in the last-line setting before moving on. As you go up into earlier lines of therapy, you also have to demonstrate activity and profile against the established standard of care, so the nature of the trials starts to look different, and the time it takes to conduct those trials also tends to increase compared to the third-line setting. That's one of the key reasons to start in the third line, to establish yourself and then move from there.

Operator, Operator

There are no further questions at this time. I would now like to turn the call back over to Christian Itin, CEO, for any additional or closing comments.

Christian Itin, Chairman and Chief Executive Officer

Thank you very much. Thanks all for joining. We appreciate the incredibly busy season, particularly with the overlay of the ASH abstract coming out and a lot of them released quite a bit early. I appreciate your time for the presentation today, and we'll give you an update when we get to ASH. Thank you very much. Bye-bye.

Operator, Operator

Thank you. That does conclude today's conference call. You may now disconnect.