Autolus Therapeutics plc (AUTL) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by, and welcome to the Autolus Therapeutics ASCO AUTO3 Data Update Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. [Operator Instructions] I would now like to hand the conference over to your speaker today to Dr. Lucinda Crabtree, Vice President Investor Relations. Thank you. Please go ahead.

Thank you. Good morning or good afternoon, everyone, and thank you for taking part in today's call on the ASCO AUTO3 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. Robert Chen, our AUTO3 and Lymphoma Program lead; Dr. Vijay Reddy, our Chief Medical Officer; Dr. Nushmia Khokhar, our Vice President of Clinical Development; Brent Rice, our Chief Commercial Officer in the U.S.; and Andrew Oakley, our Chief Financial Officer. Before we begin, turning to Slide 2, 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 related 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 period 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, you will 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 AUTO3 data by Dr. Robert Chen. After which, Brent Rice will provide an overview of the commercial opportunity before handing back to Dr. Christian Itin, who will summarize the key messages for today, 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 thanks for joining us. I know this has been a very busy weekend for all of us. But obviously, it's been a very different format. But great for you to join. And what I'd like to start out with is actually introducing you to the group that we have on the panel today. In particular, I'd like to introduce you to our clinical team, led obviously by Dr. Vijay Peddareddigari, who is our Chief Medical Officer, and many of you have met over the years. We have, in addition, Dr. Nushmia Khokhar, who has joined us from Janssen quite a while back and is heading up our clinical development. She's an expert in multi myeloma as well as other oncology indications. Robert Chen, you'll hear more from Robert during the course of this presentation. He has joined us from the City of Hope, where he's been an Associate Professor at the Medical Center City of Hope and was also an Associate Director of the Toni Stephenson Lymphoma Center. He has authored more than 100 papers and abstracts in the field and obviously has been very experienced on actually conducting clinical trials as a principal investigator as well. In addition, we're going to be joined today by Brent Rice, who is our commercial lead in the U.S., our Chief Commercial Officer in the U.S. Brent has a very broad range of experience on, obviously, the commercial side, but also in particularly about global access, and he also heads out our global access team. Brent prior to joining us was at Juno and before that, spent 18 years with Amgen in commercial roles. But with that, I'd like to move to Slide #6 and just briefly introduce you to the product that we're discussing today, which is AUTO3, first dual targeting approach for the treatment of diffuse cell B cell lymphoma. Now one of the, I think, hallmarks, when we look at the CAR T field, as it has been building over the last 2 years, has certainly been the activity of CAR T therapies in DLBCL and particularly at the back end of the disease in a relapsed/refractory disease. What we have seen with these programs, in particularly, programs like Yescarta and Kymriah, is that, in fact, the programs were able to induce persistent persisting complete remissions. It is obviously the hallmark and the key clinical outcome that I think we're all driving for, which is lasting complete remissions in these patients. The rate of those complete remissions that were sustained over time were somewhere in the range of 29% to 37%. And it was really a first in this field that we've seen at last-line setting, third-line setting, patients actually in a substantial amount of patients being in continued remission. Now what we also did learn as these programs evolved and more experience was gained in -- with the programs is that we're seeing patients that are relapsing out of complete remission, and it's quite a substantive amount of those patients still do relapse, although they initially might have achieved a complete remission. The reasons for relapse are basically falling in 2 categories. The first is actually loss of antigen. And in fact, loss of CD19 is one of the key features that is found not only as part of the clinical trials, but also now reported on the actual experience post-approval by a number of centers. Loss of antigen, obviously, is a difficult thing to work with because, in essence, your therapy becomes pliant and can no longer work. The second particular mechanism that is quite prevalent is actually the prevalence of checkpoint inhibition, in particularly of PD-L1 on the surface of lymphoma cells. Now there is already a proportion of lymphoma cells at the start of therapy that are already expressing PD-L1. There is then an additional proportion that upregulate PD-L1 in response to the therapy itself. In fact, as a consequence of the sensing of Interferon gamma in the environment, which obviously is a cytokine that is being secreted by activated T cells. And what we also do see is that, obviously, the CAR T cells themselves, while they may have no PD-1 on the surface to start out with, which is the binding partner to PD-L1, over time do actually upregulate PD-1. And in fact, PD-1 is -- can be considered an element of an exhaustion marker that actually the cells do upregulate. And of course, when it becomes available on the surface, it starts to actually allow the lymphoma cells to inhibit the CAR T cells through that mechanism. So we've designed 2 particular features into this program to counteract these 2 mechanisms that holds back the activity of redirected T cells against lymphoma and diffuse B cell lymphoma cells. The first one is around antigen loss and the way to actually reduce the impact of antigen loss. In order to do that, we engineered 2 chimeric antigen receptors into each cell in our product. One, in particular, chimeric antigen receptor recognize CD19. And the second one recognizes CD22. And the basic principle is that, of course, what the cell in order to become invisible to the therapy would have to lose both antigens simultaneously. And that is obviously a much more difficult event to occur. And as a consequence, what you basically see and what you expect is a significant reduction of cells that are capable of actually escaping recognition through antigen loss. And I also point just briefly to some of the design features that you see on the CARs. What you see actually on the right-hand side is that, in fact, those chimeric antigen receptors have features that are different from the first generation product. On the CD19 side, we're actually using different types of binders to recognize the CD19 antigen than what is used previously. But we also, on the inside, of the cell actually activate the cells in a slightly different way. In fact, what we use is so-called OX40 domain as a costimulatory signal, which is different from any other program in the space. Secondly, obviously, when you look at the CD22 CAR, you see this is a very different structure that you see normally with the chimeric antigen receptor. And indeed, obviously, was optimized for the engagement of CD22. So it is a very different product at the level of molecular design. Now the final part I'd like to sort of highlight is the fact that as we learned with the programs getting on to the market, the first generation programs is that while they could be managed from a safety perspective within Academic Centers of Excellence, they had a difficulty actually reaching broader into periphery. And as you'll hear from Brent later on, that is actually where the majority, in fact, the vast majority of patients are and that also becomes an important feature. So one of the things that we're hoping to address with the program, and you'll hear from Robert about the data, is that we were hoping that we could actually get a safety profile that would make the program manageable and also manageable in an outpatient setting. So those are the features that we're designing into the product. I think important to remember is that, in fact, the molecular design of this product is very different from any other product that has been tested in the space. So with that, I'd like to sort of switch gears and briefly talk about DLBCL on Slide #7. And obviously, DLBCL is quite a sizable indication. We have in the U.S., approximately 25 -- sorry, 24,000 patients diagnosed with DLBCL every year. It is an aggressive disease. It rapidly progresses. And the typical therapeutic approach encompasses chemotherapy combined with rituximab in various formats. If that fails or you fail post that, you then actually can either look at a transplant or you'd be moving fairly quickly into sort of a refractory or third-line setting. So we mentioned the fact there are 2 approved products in the space today. There is also liso-cel, which is in the process of moving towards an approval and when we look at AUTO3, what we'd like to see with AUTO3 is a positioning DLBCL that will allow us to sort of capture the broader opportunity in this disease setting, which requires us to be able to reach patients outside of the Centers of Excellence. And ultimately, obviously drive for a higher sustained complete remission rate, which is really the indicator of the clinical benefit that he can induce with the program. So with that, I'd like to actually pass on to Robert, who will talk you through the presentation that was given during this weekend at ASCO. Robert?

Thank you, Christian, and good morning, everyone. I'm very pleased to walk you through the data update that we provided at this year's ASCO conference on our lead program in lymphoma, AUTO3. So turning to Slide 9. Let me begin by reminding you of the key eligibility criteria for our Alexander trial Phase I/II study with AUTO3 in relapsing refractory DLBCL. Essentially, these are very similar to the pivotal Phase II trials of Yescarta and Kymriah. Moving to Slide 10, where we outlined the Alexander study design. We're exploring dose levels of 50 million, 150 million and 450 million of AUTO3 cells in dose escalation. The precondition regimen included fludarabine, 30 milligram per meter square for 4 days; and cyclophosphamide, 500 milligrams per meter square for 2 days. The first 3 patients at a 50 million dose did not receive any pembrolizumab. And after that, we explored 2 dose regimen of pembrolizumab. Regimen A of pembrolizumab was added starting on day 14 for 3 doses and the 50 million, 150 million and 450 million dose. As emerging data shows the lack of severe CRS or neurotoxicity and the profile with, say, regimen B of pembrolizumab, which is single dose on day minus 1, was then initiated at the 450 million cell dose. We're pleased to announce on Friday that the study has established RP2D of the 150 million to 450 million out of 3 with day minus 1 pembrolizumab. And currently, the expansion cohort in outpatient is enrolling to explore outpatient administration of AUTO3. Turning to Slide 11. And I want to spend a brief moment outlining the patient characteristics in the study. Again, the trial includes relapsed refractory DLBCL patients. The breakdown were 74% with DLBCL NOS and 26% with transformed DLBCL. We did not have any follicular lymphoma patient without transformation in this study. This is a very high-risk population. Majority patient has stage 4 disease, high IPI, refractory disease and heavily pretreated. The median SPD, as outlined here, shows the median tumor burden and is similar to the AUTO CARs CD19 CAR trials. Important to also note that only 4 patients were able to undergo autologous stem cell transplant. This means that these patients did not achieve enough response to establish regimen to make them eligible for autologous stem cell transplantation. Moving to Slide 12, regarding Cytokine Release Syndrome. The most important observation is that no severe CRS was seen at all. Majority of the CRS were Grade 1 and no prophylactic tocilizumab was used. Only 4 patients required the use of toci to treat CRS. And as per Dr. Ramakrishnan, who gave our ASCO video presentation based on his clinical experience, this profile appears better than approved CD19 CAR Ts. Now we move to Slide 13 regarding neurotoxicity. Again, consistent with prior observations reported we do not see any neurotoxicity of any grade was seen a doses of 150 million or higher. There was only 1 case in neurotoxicity, which was Grade 3 at a 50 million dose cohort. However, that had a very atypical presentation. And again, as per Dr. Ramakrishnan's presentation, based on his clinical experience, this profile appears better than the approved CD19 CAR therapies out there. Now to Slide 14, where we have some interesting observations from our translational work. We believe that our low rates of severe CRS or neurotoxicity can be explained by the low production cytokines. In-vivo, when we compare AUTO3 to Yescarta, AUTO3 had a lower production IL-6. And when we compare CD19 to 28z CARs, which is similar Yescarta to AUTO3 in-vitro, all 3 had lower production of IL-6 TNF alpha, GM-CSF and IL-10, all contributing cytokine. Now we can turn to Slide 15. I would like to walk through you the activity we observed at the most recent data cut. Notably, we've seen complete responses at every dose level. At 150 million cell dose were higher, the overall response rate was 69% and a complete response rate was 56%. And at 150 million cell dose higher and day minus 1 pembro, which is our declared RP2D, the overall response was higher at 75% and CR rate at 63%. It's also worth noting that we had 2 patients that were considered inevaluable but we did count them as non-responders in the current data, just to be more conservative. Now turning to Slide 16, where we see encouraging signs of durable complete response. Eleven out of 23 patients achieved CR in our study, and 10 of the 11 are ongoing. In fact, at doses at 150 million and higher and also with pembrolizumab, all of our CRs are still ongoing. And again, this appears different from the other CD19 CARs where there's a relapse rate of around 25% from CRs. On Slide 17, I want to spend a brief moment illustrating 2 patient cases where CRs are obtained. So this case shows that AUTO3 can eliminate lymphoma even in bulky patients and highly refractory patients even to polatuzumab. And the AUTO3 can do as safely without any severe CRS or neurotoxicity, even in the elderly population, where our oldest patient here was 83 years old. Finally, on Slide 18. The updated Alexander study suggests a very unique clinical profile for AUTO3 that we're very excited by. AUTO3 product was successfully manufactured for all patients. We have a tolerable safety profile with 0% of patients having severe CRS and only 1 case of neurotox with atypical presentation. And no neurotox of any grade in patients treated 150 million or higher cell dose. At the RP2D dose range of 150 million to 450 million, day minus 1, our CR rate is 63%, and we achieved the CR with minimal management of patients. And what's most important is that also the CRs are durable with 10 or 11 ongoing. Given the evolving profile of AUTO3 and excellent safety profile, we decided to take certain outpatient expansion cohort that has already commenced enrollment. With that, let me pass you to Brent Rice, our Head of Market Access.

Thanks, Rob, and good morning, everyone. Happy to be with you today. I'll be walking you through the commercial opportunities for AUTO3 based on its innovative design. Turn to Slide 20, please. So AUTO3 was designed to reach the full addressable population of patients and overcome the limitations of the first-generation CAR Ts. In fact, the full outpatient opportunity is like -- unlikely to be realized with the current therapies due to their clinical profile and high rate of severity of toxicities. Below on this slide are some excerpts from recent publications highlighting some of these limitations that would prevent broad adoption in the outpatient setting. For example, nearly 50% of patients requiring a lengthy ICU and/or inpatient stay, prehospitalization and implications of prolonged steroid use on mortality. Turning to Slide 21. We've designed AUTO3 for potential best-in-class efficacy and safety to reach the full addressable market opportunity. As you know, AUTO3 is a bicistronic dual targeted CAR, with novel signaling domains in OX40 and 41BB. AUTO3 has been designed with enhanced durability and safety with the need for less intense patient management. This innovative design and highly differentiated profile allows for true outpatient administration across all settings of care being setting of care agnostic. As Rob touched on earlier, we have already initiated our outpatient cohort with the potential to start our pivotal study in early 2021. However, I'd like to reiterate the importance of this outpatient cohort AUTO3 has been designed to go where the patients reside versus relying on where referral networks -- rely on referral networks to Academic Centers of Excellence. Turn to Slide 22. As I mentioned, AUTO3 has been engineered to reach the full addressable relapsed/refractory DLBCL population with the potential to be a true outpatient therapy representing over $4 billion. In fact, if you look at the chart on the left, the current therapies have been primarily relegated to Academic Centers of Excellence only and in the inpatient setting due to the high rate and severity of toxicities and intense patient management that's required. This limits the size of the market and available patients to approximately 20% of the total opportunity. Based on AUTO3's clinical profile, it should allow treatment across all settings of care thus growing the size of the market and reaching the full addressable population while enhancing the available reimbursement options. In fact, if we take a deeper look, over 80% of third line plus and second line patients are treated outside of Academic Centers of Excellence. Turn to Slide 23. As I mentioned, widespread adoption of current CAR T products has been limited due to the high rates and severity of toxicities requiring intense patient management. When we look at AUTO3, our best CRR is 63% with no high-grade CRS and no neurotox of any grade. This reinforces the innovation that has gone into the design of AUTO3, which minimizes loss of CRs with a safety profile suitable for all settings of care, including outpatient. Turn to Slide 24. Let's take a deeper look into where the DLBCL patients reside and where the greatest market opportunity exists. Currently, Yescarta and Kymriah utilization is capped within the Academic Centers of Excellence and highly concentrated within 7 PPS exempt comprehensive cancer centers, as you see at the top of the pyramid. AUTO3 has the potential to democratize use across all settings of care, including nonacademic hospitals and sophisticated network community oncology clinics, realizing the full potential opportunity. Turn to Slide 25. In summary, AUTO3 is uniquely positioned to leapfrog the competition and includes the incorporation of academic, nonacademic and community oncology clinics in the Alexander trial. This allows AUTO3 to mitigate referral networks by going where patients reside. AUTO3 is positioned to reach the full addressable second and third line plus patient opportunity with the potential to more than double the initial $4 billion market opportunity that I referenced earlier. It should be noted that the majority of second-line patients are treated outside of Academic Centers of Excellence and in community clinics, which generally do not refer to Centers of Excellence and they keep the patients in their practice. In conclusion, AUTO3's product attributes and flexible reimbursement options make it poised to be best-in-class. I would now like to hand the presentation back over to Christian.

Thanks, Brent. So let me conclude this part of the presentation and the AUTO3 discussion by briefly reviewing the upcoming milestones and news flow through the remainder of 2020. On Slide 27, just obviously, very much a focus on -- within the organization on the delivery of AUTO1 and AUTO3 and AUTO1, we initiated the pivotal study. And we obviously also received, obviously, orphan drug designation for the ALL program. We're also moving on the pediatric side with a new program as well that is getting into the clinic second half of the year. On AUTO3, you just heard, obviously, the expansion cohort is ongoing. We're very keen to obviously completing the cohort on the recommended Phase II dose and actually see the durability of effect of the CRs that we have been able to induce, obviously getting the data on 3 months and 6 months, which will be, I believe, will be important and give us a very good view on the program. The data will, taken together, then form the basis for the design of the pivotal study. And we obviously expect that with all holding up that we'd be moving into a pivotal study in early 2021. And now we also have, obviously, additional programs that we're running through, and there's a bit more of an update on the next slide. When we look in terms of the balance sheet of the company, we have $243 million in the bank at this point in time, so well-capitalized and well-poised to deliver on these value inflections. Finally, on Slide 28, is a quick summary on the remaining data points that we expect for the second half of this year and into next year. Obviously, a key opportunity, obviously, coming up at EHA, which is just about 2 weeks away with an update on the ALLCAR19 data for AUTO1, followed at the 2nd AACR meeting with updates on AUTO5, AUTO6 and NG and AUTO7. So there's going to be a good set of additional information around key programs within our portfolio. And then obviously, we're gearing up for the ASH presentations at the end of the year with substantive updates, in particular on the AUTO3 side where we expect to have a significant number of additional patients and experience to report on. With that, I'd be, I think, happy to move over to the Q&A session. I would like to ask the operator to open up the line for questions.

[Operator Instructions] I show our first question comes from Debjit Chattopadhyay from H.C. Wainwright.

This is Aaron on for Debjit. So the outpatient cohort has started, that's great. Can you talk about how many patients have been enrolled or any dose? Any clinical sites open? And what do you think about, in the era of COVID with fewer patients traveling, do you think you're going to end up with more advanced patients in the community settings than would normally be anticipated?

Aaron, well, first of all, thanks for joining, and thanks for the questions. As Robert indicated, the cohort has been initiated. So this is obviously activity that happened this quarter. And we're enrolling patients. With regards to the -- what we're looking to accomplish with this cohort, obviously, we're looking to enroll approximately 20 patients into this cohort. And that should give us a good understanding of the profile of the product in an outpatient setting. Now with regards to the COVID situation and the impact on patients, in fact, we do believe that the outpatient setting is almost a bit easier to manage than the inpatient situation because, obviously, patients do not have to travel across the country to get to clinical centers and can obviously be managed without having to stay an extended period of time at the clinical centers, which we believe actually might be an advantage in the current situation. So we don't think this is an added risk. We rather think it might be the other way around. It might actually be more resilient with regards to the conduct of the study. And we also do not expect that the patients are worse off in this current situation. We've seen centers across the U.S. continue to treat patients in many areas, not all areas, but even the hardest-hit areas have resumed enrollment of patients. If we look at New York, where we have opened an open center as well as some of the other areas that actually are in fact on track and enrolling patients. So we don't expect an immediate impact or a significant impact from the COVID situation.

I show our next question comes from the line of Biren Amin from Jefferies.

Christian, I just want to ask on the cytokine profile data that you showed us with IL-6 and how it compares to Yescarta on the cytokine storm. Can you maybe just talk about what you think is driving that difference versus other CD19 CARs? Do you think its lower cell expansion? Or are there other factors that you would attribute this to?

Thanks for joining, Biren. I think with regard to the cytokine profile, it has to do with, obviously, the translation of the signal on the intracellular side. So we believe the choice of costimulatory domains do have an impact here. And also possibly, actually, the choice of the binders to the target antigens as well. Not too dissimilar from what we have observed with AUTO1, where the binding property of the -- to the target antigen actually had a big impact on the cytokine and activation profile of the product. So we think both of those components are likely contributing here. I don't think there's sort of a single factor that we can point out. But I think the design elements that we put in have been favorable with regards to the cytokine release profile.

Okay. And then maybe if I could have just 1 follow-up. Can you just talk about the transduction efficiency of the CAR as it relates to the -- what are the go-forward doses of the 150 million to 450 million cells?

So the transduction efficiency with these products is in the range of anywhere from 20% to 30% at this point in time. And -- but -- and that is actually not dose-dependent, but that is a question of the transduction process.

I show our next question comes from the line of Jim Birchenough from Wells Fargo.

Congrats on the update. I guess just on the outpatient management, just wondering how fever will be managed. When we talk to experts in the field, one of the areas of uncertainty on outpatient management is just how to distinguish the patients with fever that are going to get in trouble quickly and those that could be managed on the outpatient basis. So could you speak to that a bit more?

Jim, thanks for joining. Excellent question. And I would like to actually pass that question on to Vijay.

Yes. Thanks, Christian. So you're correct, if we were in an outpatient setting in CAR T -- post CAR T infusion, it is difficult to distinguish between CRS or neutropenic fever. So the general protocols are that most hospitals would follow the neutropenic sepsis protocol. So if a patient has gotten chemotherapy or CAR T and they develop fever, they would be brought into the hospital to get IV antibiotics and observe for up to 2 days and then decide whether it was sepsis or CRS. And if it has resolved, then they would be discharged. That said, our median time to CRS is 7 days. So we anticipate that should patients come in with fever, it would still be a week after the CAR T infusion and that would not impact the current reimbursement issues.

That's actually a very helpful answer. And then maybe just in terms of starting the pivotal, I guess what's left to do? Is it just longer follow up? Or is it just confirming the profile with existing with more patients? Just trying to understand what's rate-limiting to starting that pivotal in early 2021?

Very good question, Jim. So what we'd like to see with, as indicated, the key driver in understanding the profile in DLBCL is really around sustained CR rate. And so what we'd like to understand is kind of the sustained CR rate at the recommended Phase II dose and want to confirm that. And we'll see that data obviously mature as we go through the third quarter, frankly. And then secondly, we'd like to confirm the safety profile and the general experience that we have in the outpatient cohort as well because if we can actually include an outpatient in the pivotal study, we believe that, that actually would be a significant part of the value proposition for the product. And it would be highly desirable to actually be able to do that in -- during the pivotal study rather than in a separate follow-on study. So that's what we're looking to do is actually get those 2 data sets and then actually have them inform the design of the study with the goal if any possible, to actually include outpatients in our pivotal design.

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

This is Rob on from Matt Phipps here. Just a question, maybe is there anything emerging from in the data biomarkers or anything like that among the nonresponding patients that can kind of guide the potential for getting up response rate a little? And then maybe looking at the PRs, what's the general outcome in terms of durability therein? Maybe any thoughts on potential for retreatment following the Yescarta retreatment presentation at ASCO?

Well, thanks a lot for joining. Thanks for the questions. When we look at the responders here, particularly the partial responders, there is actually not -- as you've seen, we have very few partial responders. And in fact, there is not enough data to help us guide what might be different between those patients and patients that achieved a complete remission. We haven't actually delineated individual biomarkers that could sort of give us indication, either in the transition from partial to complete, but also the 4 potential nonresponders. So the data is still too small, the data set to have sort of a conclusive answer to what potential markers might actually play a role. But very clearly an area we're looking into and hoping that with a larger data set that we can actually delineate individual markers, but none at this point in time.

Okay. Great. And just a follow-up, if I may. Any info on the CR that did relapse antigen whilst PD-L1 upregulation or anything like that?

Very good question. So the -- so the CR was actually -- or the patient was relapsing out of CR after 1 year. So it's kind of a very late protracted process. We did look at that particular patient. There was -- antigen was present. There was no obvious checkpoint marker that we have identified that could have explained kind of what we're seeing. So at this point in time, we do not know the reasons for that particular relapse.

Our next question comes from Mara Goldstein from Mizuho.

Just a follow-up on the prior question. In any of the non CR, either partial responders or nonresponders, were you able to look at the same issues around upregulation of PD-L1 any loss of expression in any types of clinical biopsy samples that might have occurred there?

This is -- obviously, Mara, thanks for the question. It's an area we're actively looking into. We haven't identified at this point, I think markers that would sort of explain the particular behavior that we've seen with those patients. We'll continue to look. We'll continue to expand the panels we're looking at. But at this point in time, we do not have a lead.

Okay. And if I could just also ask on the outpatient trial, are there any -- can you just, I guess, clarify where the protocol for that may deviate from the existing Alexander protocol?

Vijay, would you like to take that?

Yes. Sure. So we're keeping the protocol very similar to patient eligibility is very similar to the current Phase I. So all we are doing is transitioning the mandatory hospital or ambulatory kind of monitoring of patients to an outpatient monitoring of the patient. So other than that, we're not changing anything. So the eligibility characteristics remain the same.

Okay. And I apologize, if I could just ask 1 more question. On the 4 patients who did receive tocilizumab for CRS, can you give some color on those 4 and how the decision to utilize that treatment was initiated there?

Sure. Rob, would you like to take that?

Sure. Basically, you see that we have 4 patients that received tocilizumab, 3 patients had grade 2 CRS. So by the guidelines, those 3 patients received tocilizumab and all events resolved very quickly. The first patient that developed grade 1 CRS also got tocilizumab, as this was the first patient [ the site PI ] just decided to give toci. And again, resolved very fast.

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

Very excited to be talking about a potential pivotal trial for AUTO3. Just in that regard, other than including an outpatient sort of cohort in the pivotal study, which would clearly be a huge differentiator. Are there any other sort of design aspects or sort of label desirables that you were sort of considering as you move towards a pivotal study?

I think at this point in time, what we're really aiming for, Chad, is to obviously get a very good view on the manageability of the program and really maintaining a sustained high rate of complete remissions. And that is really what we're aiming for. We're doing a lot of healthcare resource utilization information that we're also collecting. So there's a lot of those types of information that we're collecting that actually helps us and supports. Then, the market access work that Brent's engaged in. So there's a lot of data and information we're collecting for those activities, of course. But from a basic clinical perspective is aim high for the CR rates, sustained CR rates and confirm a well-manageable safety profile so that you have actually indeed, the type of product that can be used. In fact, where, as Brent pointed out, is where the patients are. The challenge in the space has really been that we have an exceptional set of category of therapeutic here with an enormous amount of clinical benefit that can be induced. And in terms of sustained CR rate is over and above what we've seen with any other therapeutic modality. But most of the patients just never get to the place where they can actually receive that type of therapy. And I think for us to confirm the aspect about the program being well manageable and can be operated with a limited amount of support to the patient, I think is critical for not only getting an overall sustained good clinical outcome, but also to be able to actually get the product where the patients are and actually make sure it can be taken up in the indication as we would hope that this type of therapy actually should be accessible, too.

All right. Great. Certainly, look forward to seeing the data develop.

Excellent. Thanks, Jeff. Appreciate it.

I show our next question comes from Graig Suvannavejh from Goldman Sachs.

Congrats on the progress with the ASCO presentation. It's really great news. I've got 2, if I could, at least to start with. One, I know that you've got an official go, no-go decision expected in the third quarter. What -- I mean the data looks pretty good here. So what left do you think you need to see or are you hoping to see before you actually make that decision? That would be my first question. And then my second question just has to go back to the commercial opportunity that may exist in the more community setting. Could you just -- if you have it, paint a picture of what the reimbursement looks like and any potential challenges there that differ in the Centers of Excellence?

Excellent. Thanks for joining, Graig. With regards to the reimbursement landscape, I would actually ask Brent to answer that question. And maybe we start there, Brent, if you could get -- start on that question first.

Yes, sure, Graig. Thanks for the question. So there's quite a bit difference in the reimbursement schema when you're looking at Centers of Excellence and the inpatient setting versus outpatients and then when you migrate out of Centers of Excellence into nonacademic centers and community clinics. So the challenges that you've seen and the headwinds right now are relative to the Medicare Part A reimbursement. There's a lot of movement happening in that space right now. The existing paradigm has been kind of a surrogate transplant MS-DRG with an NTAP and then an outlier payment. It's been complicated for hospitals to secure adequate reimbursement, and many have been underwater. As a result of that, a lot of centers have opted to instead of putting patients on commercial products when there are Medicare patients, they've put them into clinical trial. And so you've seen that opportunity really be muted in this setting. When you move to the outpatient setting, it's a completely different reimbursement schema, it is based on average selling price, plus 6%. It's a proven pathway, and it's a pathway that is embraced by all providers, and particularly when you move out of the inpatient setting and into the outpatients with the community clinics and nonacademic centers.

Okay. And then back to the first question, which was around what are we looking for with the program? As indicated, one of the key parameters that we're really looking for is to sustain CR rates. We want to have a good sense, particularly of the 3-month CR rate of the patients at the recommended Phase II dose as well as, obviously, longer observation of the patients that we had induced CRs beforehand. I think that is going to be to give us a very strong basis for the go, no-go decision. And in particular, we've obviously added additional patients into the recommended Phase II dose that obviously will add the data set. So we'll have a more robust data set with a 3-month value that we're going to be looking out for.

Great. If I could ask an additional follow-up. So in terms of the outpatient setting and the trial that you're running right now, the cohort. So it seems as if you've given some kind of sense of 3-month CR rates are what you're looking for is the key there. But in terms of maybe on the safety side, is there a bar that you're considering for CRS or neurotox or fever? Or is it just as long as it's consistent with what you're seeing, and that's good enough?

I think if we're consistent with what we're seeing at this point, I think that gives us what we're really looking for. This is all about the manageability of the therapeutic approach. And obviously, we've seen and as Robert pointed out, a very good manageability of the program. And we're now corroborating that in that extended cohort and also collecting a lot of the information around resource use as well within that cohort. And that also will be a very strong indicator for us to be able to move much more aggressively into the outpatient setting during a pivotal study as well.

Congrats on the progress with that program, too.

Thanks, Graig. Appreciate it.

I show no further questions in the queue. At this time, I'd like to turn the call back over to Dr. Christian Itin, Chairman and CEO, for closing remarks. Please go ahead.

All right. Well, thank you very much for joining today. Obviously, we're very excited about where we are with the program. And we're obviously looking forward to keeping you updated over the second half of the year, and how we're progressing and give you an additional update on the durability of effect. What ultimately, CR rate will end up at the recommended Phase II dose for a large inpatient group and obviously confirm the manageability and adverse event profile that we've seen for the product in the outpatient setting. So with that, I'd like to thank you all and wish you a great day, and I'm looking forward to the next update in about 2 weeks' time on the AUTO1 -- additional AUTO1 data that we will have from the ALLCAR19 program as well. All right. Thanks a lot. Have a great day. Bye-bye.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.