Autolus Therapeutics PLC (AUTL) 2024 Q2 法說會逐字稿

Hello, ladies and gentlemen, and welcome to the Autolus Therapeutics Call to discuss its second quarter 2024 financial results and business updates. As a reminder, this conference call is being recorded. And I would now like to turn this conference over to your host, Olivia Manser. Please go ahead.

Thanks, Sean. Good morning or good afternoon, everyone, and thanks for joining us on today's call. With me today are Dr. Christian Itin, our Chief Executive Officer; and Rob Dolski, our Chief Financial Officer. So on slide 2, before we begin, I just want to remind you again that during today's call, we will make statements related to our business that are forward-looking under federal securities laws and the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995.

These may include but are not limited to statements regarding the status of clinical trials and development and regulatory timelines for our product candidates and our expectations regarding our cash runway. These statements are subject to a variety of risks and uncertainties that could cause actual results to differ materially from expectations and reflect our views only as of today.

We see no obligation to update any such forward-looking statements. For a discussion of the material risks and uncertainties that could affect our actual results, please refer to the risks identified in today's press release and our SEC filings, both available on the investor section of our website

On slide 3, you'll see the agenda for today's call. Christian is going to provide an overview of our operational highlights. Rob will then discuss the financial results before handing back to Christian to conclude and take Q&A. So over to you, Christian.

Thanks, Olivia, and welcome everybody to our second quarter earnings call. A real pleasure to have you all along, and I'd like to start on slide number 4 with just a brief summary of the key highlights for the quarter. As you can imagine, we're in the process of going through the various review processes for Obe-cel, both in the US as well as in Europe and most recently now also in the UK. So that's been the primary focus from an operational perspective.

I think we're making good progress and are on track with all the various interactions that we have with the regulatory authorities. The FDA PDUFA, as you may remember, is November 16 this year, and we're tracking well towards that time line. We've also obviously initiated or have currently ongoing 2 Phase one clinical trials.

One is in pediatric B-ALL which is a trial that is moving very nicely. And obviously, we're excited about applying and having OB cell evaluated in pediatric patients. And that's ongoing, and we'll report obviously in the upcoming periods on that trial.

And in addition, the Phase 1 trial with patients that have an advanced stage relapsed type flash refractory stage of systemic lupus. This is the correlative study. We opened this study in the beginning of the year, and we dosed our first patient in the second quarter, and we continue enrollment in that study as we have projected.

And importantly, as we went through the course of the quarter, we did focus obviously very much on uptake of the clinical data from our pivotal field study, the Phase 2 study that's underpinning the regulatory filings that we've made with the various authorities.

Importantly, we looked at a number of aspects that we haven't actually explore to the same extent in our prior publications and presentations about the program. One, of course, is to look for the longer-term outcome and what we do see is that we do start to see a stabilization of both event-free survival as well as overall survival in the patients in the study and we're starting to see a plateau forming, which is obviously something we've been very keen to evaluate, and we start seeing that actually stabilize with more follow-up in the study.

What was quite interesting and I'll show you the data a little later as well, is that quite typically what we have in this particular patient setting is that you actually look to consolidate the effect that you could reduce that particular therapy to induce longer-term outcome. And typically, what you do is you actually have the patients undergo a stem cell transplant when they are in complete remission and that deal a margin negative, which was the case for all their patients.

What was quite surprising to see and you'll see the data on this in a short while as well is that it didn't appear that the consolidation with the stem cell transplant improve the outcomes for the patients, which is very different from the other therapeutic options that are currently available in the space.

We also, I think, had a closer look at the role of persistence into longer-term outcome as well as the impact of bridging therapies and particularly also the use of inotuzumab in patients that have very high tumor burden at time of inclusion and where we did see a very effective approach here in terms of bridging with inotuzumab.

Now in terms of the operational side of the business and the governance side, we did strengthen our Board. We had Mike Bonney joined as the new Chair of the company and Ravi Rao, who's an expert in autoimmune diseases and inflammatory diseases.

So broadening of the skill set on the board and obviously a sort of a next step in terms of the evolution both from a movement towards commercialization, which is obviously robotic bodies background is obviously very strong, but also an expansion from a medical perspective into adjacent indications outside of oncology, which clearly we'd rather own feedstock at a particular experience, is extremely valuable.

Now, in addition, obviously, we've been driving to a remarkable amount of growth and maturation of the organization as we're setting up our commercial manufacturing capabilities, again through first regulatory filings and keep pushing through that process and are preparing for commercialization.

And there is a group of very talented leaders within the company that have really risen to the challenge and has done a fantastic job and in recognition of their work and their leadership, I have been promoted to Senior Vice Presidents within the organization.

And this includes , Brian, on the regulatory side, risk-weight Site Head for Stevenage, Markus Gruell on quality, quality immersive. There's really operations of the from the manufacturing technical operations side, but also actually in a broader role in that.

And then Dilip Patel, who's looking into market access and obviously, we did a fantastic job on that side as well. So great to see this group of leaders really grow up and within the organization and having to make substantial contributions that we expect to see a lot of important contributions going forward to the business.

Moving to slide number 6, I would like to just briefly remind you of some of the key data that we did update on at ASCO as well as EHA. Both meetings happened during the course of June out of this year. What we did focus on is actually look at the totality of the data from the FELIX study. And as I remember, FELIX study has reports, my by far, the largest cohort of patients that have a relapse of their proper relapsed refractory disease with morphological disease for more than 5% tumor burden and this is the vast majority of the patients that we have treated.

We have also had two small cohort in addition that we have included in this study, a small cohort for patients that may have isolated extramedullary disease. That's typically a cohort that actually gets excluded from clinical trials because of the difficult nature of the disease and the challenges of managing those patients, but also a small cohort of patients that have minimal residual disease.

So disease burden below 5%, but off at a 10 to the minus 3. So very sporadically now reporting over of MRD, MRD-positive disease. So that's the group. We actually analyze the totality of that data. And as you can see this is a total of 127 infused patients.

And what we're starting to see is incredibly encouraging in terms of the patients that actually are in ongoing remission without subsequent stem cell transplant or other therapy. And that is, I think, really important because that 40% of the patients that are to continue in remission without any need for additional therapy. And we also have the smaller subgroup that also referred to now the next slide, then received a subsequent stem cell transplanters, taking patients that received this transplant while being in complete remission, not only complete remission, but also being MRD-negative.

So no signs of measurable disease in these patients at the time of transplant. And then obviously, we had also a group of patients that are losing to other therapies or have relapse and died. So that's the status with a median follow-up of 21 months, which was the data cut that we were using for the ASCO at EHA presentations.

Moving on slide number 7, we're looking actually at the event-free survival of the patients. And as you can see, the event-free survival and we're looking here at the two curves with and without attempting to stem cell transplant. But both curves you can see are stabilizing and actually are starting to form a plateau, which is very indicative of a substantial portion of these patients remain in continued remission, which is also extremely encouraging in this very difficult group of patients has a very aggressive form of disease.

When you see the curve actually for patients that have includes the stem cell transplant, that's the green curve. The blue curve of the patients where we sensitized patients that went on to stem cell transplant. What you see when you look at those two curves is actually a picture, which is the opposite of what you would normally observed in these studies, normally would have observed that patients that actually with a stem cell transplant would do better.

I would actually give you a better event free survival. What we're seeing here, it looks like inverse certainly not doing better, possibly doing a bit worse if they actually receive a stem cell transplant after receiving obe-cel.

Now when we look at the slide number 8 at the overall survival, we see a similar picture. Certainly no evidence that a patient receiving a transplant provided them the survival benefit. And so very interesting in the sense that clearly the product of its own appears to be able to deliver a longer-term outcome.

It may actually be able to serve as a stand-alone therapy for a subset of the patients. So these are two of the key findings that we were presenting at ASCO at EHA which we move on to slide number 9, what we're evaluating that on the left-hand side is the impact of the of CAR T persistence in event-free survival in the patients where you can see on the blue curve on the top where patients that had actually ongoing CAR T persistence.

And you can see that these tend to do very well, again with the stabilization of event-free survival. Patients that lose CAR T our presence at 12 months, you can see that the median curve, the green curve and patients that would lose CAR T persistence over the six months, its the red curve are tracking, it's tracking below.

Indicating that indeed, longer persistence of the CAR T cells appears to be associated with a better performance on that true survival. And just as other surrogate to look at that so that the impact we're looking at B-cell aplasia and you can see also there the same type of stagger, but less differentiation between the patient. So persistence seems to be a better readout and a more reliable readout if you want to understand the potential impact for longer-term outcome.

Now in summary, on slide number 10, a quick takeaways from this pooled analysis. First of all, 40% of the responders are in ongoing remission without any subsequent therapy. And this is now with a median follow-up of 21.5 months.

We clearly see evidence of a plateau forming within event-free survival as well as in overall survival and it does not appear that stem cell transplant based consolidation provides an advantage for the patients and does not appear to improve event-free survival or overall survival, which is certainly an important outcome consistent with the effects we're seeing, but certainly unusual in the field so far.

And clearly, we do see an interesting correlation between online persistence and improved event-free survival in these patients. With that, what I'd like to do is actually move to sort of more the operational side to the getting to commercial launch readiness and move to slide number 12.

As you remember, we sort of have been already very active in the preparatory steps to get ready for commercialization for quite an extended period of time already. And a lot of that obviously was really focused on a key area of activities, clearly creating awareness around the medical affairs activities as you would expect building the value stories for a full market access of the product.

But then what's variable is certainly the onboarding of the treatment centers. And that onboarding process is very involved, not only from a company, but also from a center perspective. That's a real effort that actually has to be putting that goes across quite a wide range of activities that we need to sort of integrating, whether it's related to FRECs to the actual delivery of the product, the handling product of the product at the center as well as additional support that we're looking to provide both data centers on this, thanks to the active patients as well.

There's quite an involved process, including everything related to sell journey from the collection of the cells at the center to the manufacturing process and back and the IT systems required to really be able to track the core that ensure that we are have a very clear chain of identity throughout the entirety of the process.

So very substantial amount of work that's ongoing there. We're on track to have between 30 and 36 centers ready for activation by the time of approval. And are going to move once we are and we're getting to that point, would expect to be within the 1st year of launch at a level of about 60 centers onboarded and active with the product. So we're moving here in a very significant way, as well as a significant number of centers even for the initial start-up phase.

Now what we're particularly focusing on at where we are at this point in time is really looking at the integration of the workings and testing, frankly, of all the systems required to deliver the product. So there's a lot of activity going on and making sure that all the interfaces as well are working between the different processes, different systems. And that's a very involved process that we're actually engaging in the third quarter and leading into the fourth quarter to make sure that all elements required to deliver this therapy are fully operational and tested out and actually have achieved the level of robustness required for a commercial operation.

Now on the next slide is just a brief view on kind of where we are and what some of those activities are that we actually need to think about at the time point when we actually do get to an approval. Obviously, we talked about the path there on the prior slide. We eventually get to a point where hopefully around the target date, we do receive an approval for the product.

Once that happens, there are several activities that need to take place on our side and driven from the company side is really kind of the activities that are defined by the label itself. And there are certain aspects of training and activity that only can actually be finalized and run through at the time when the label is fully set and determined.

And that actually has to do with a set of trainings that are -- that have to be consistent, obviously with the approved label. As well as obviously administering a REMS strategy and training that needs to actually be implemented at that point in time.

So those are elements that from a company perspective, you'll be able to complete once the approval is in. Now data centers themselves need to run through quite a range of activities at that point in time that really make sure that they're internally ready to be able to actually manage this type of therapy, both from an administrative perspective as well as from an actual physical operational perspective. And you see quite a set of those activities that sort of will actually have to be worked through on the center and the inside of the center. And you can see that at the right-hand side spelled out in a bit more detail.

Now when we think about what that means from an overall timing perspective, you can see the blue curve or blue arrow, there is actually quite a range of time that we actually see. Where from that time point where the center actually can't get activated until it actually would enroll the first patient. And we will see certainly the variability amongst centers in terms of the time it will take to be onboard FDA enrolling patients.

To look at that in a bit more detail, we'll go to the next slide and just look at sort of in a relatively simple way of what are some of those key activities and time lines. So completing the site accreditation we expect will take anywhere from 2 to 12 weeks with the centers that we have prepared for the -- through the onboarding process. For their now from the time point where you can actually initiate the site activation will have take anywhere between 2 and 12 weeks.

Obviously patient screening leukapheresis scheduled and having that completed anywhere from one to two weeks at that point in time. And then obviously the anticipated relative delivery time of 16 days. So when you think about that and you think about a target date PDUFA target date of middle of November and as well as for the year end holidays, it is reasonable to assume that the first patient dosed will be happening in the early part of 2025. If we're operating on those time lines.

So I think that's sort of -- I think hopefully gives you a sense for what it means to start-up and whatever sort of reasonable assumptions around when to expect kind of first patients dosed. And then obviously, that would gear up from there, as we go through the course of the year.

Now with that, what I'd like to do is switch gears and just briefly talk about sort of the Obe-cell product family, on slide 16, franchise opportunities. This is the slide you've seen before. Also continued to work not only on the current activity in the [B-ALL] side, but also are working on the pediatric side as well as the autoimmune side with Obe-cell.

And we'll continue to actually work on AUTO1/22 as well as AUTO8. AUTO1/22 on the pediatric ALL side, where we do additional work with the [UCL] and GOSH, our partners for that program for a long period of time. And we're also obviously, with AUTO8 continue to work on the multiple myeloma type of also looking to expand the opportunity for that program going forward as well. And we'll update you as we go forward and initiate next studies with that program and when that actually happens.

So with that, just a quick word on the environment on the autoimmune side of the state that many of you have watched carefully. We have one major conference that happened in Q2 which is the EULAR conference interesting datasets presented during the course of the conference.

I think what we're starting to see some differences that appear between programs still early days in terms of understanding what is contributing to some of the differences that are being observed to what extent are those product driven? To what extent are those on track to variability in the patients that are being treated. But certainly very interesting development that we're seeing but also overall, I think also very nice cooperation of the initial observations that we had seen with [Garrett and EULAR] that indeed, there is very profound impact that can be had in those patients using CAR-T approaches.

When we look at the next slide, just to remind you obviously that we have a program that has a remarkable set of similarity in terms of the clinical properties to the program that's used in EULAR. We have -- but also not only do we have a high degree of similarity in terms of the efficacy the persistence of the pediatric ALL side where we can compare the programs directly.

But also, obviously, we do have a very substantial amount of safety data and which also is an area where we can see differentiation to the program in EULAR, but also obviously differentiation to any of the other CAR-T programs that are currently commercially available and what you see is just a summary there on the right and the table on the various key outcomes that we have seen across the various studies that we've conducted with Obe-cells. And I think gives you a very good view on the level of activity that we're seeing and the ability to achieve those levels of activity with a very attractive safety profile.

Now this study on slide 19, the CARLYSLE study, our Phase 1 study in SLE, as I indicated, the study, I would say -- start off happened in the during the latter part of Q1 and into Q2. First, patient dosed in Q2, and we're continuing to enroll in the study. We're planning six patients at a 50 million cell dose level, which obviously is a level that we know to be highly active in pediatric ALL, giving us molecular, complete responses.

And also a level of dose that is also highly active in the adult patient population where, as a reminder, we're using as little as 10 million cells to induce complete remissions in patients with high tumor burden in that setting.

So overall, I think we're a very interesting stage, we're starting to see the sort of get first insights from a data perspective, and we'll continue to collect that data with a plan to have an additional update on clinical data later in the year.

Now other pipeline programs ,on slide 21. As you remember, there's a number of other programs we're working on, I think with regards to AUTO1 indicated that we're looking at the potential expanding the program into additional indications. So that's something that's ongoing. And we'll update certainly by the end of the year, early next year on sort of the trajectory we're going to be on.

And then just as a quick highlight, because we have actually talked about that in a of AUTO6NG. That program also obviously is enrolling patients and first patient actually has been treated as well in the second quarter. As part of the progress that we were making during the quarter. So overall progressing well. And we also expect additional publications to come out during the second half of the year related to our clinical programs that we've been conducting.

With that, I'd like to hand over to Rob, who will lead you through the financial results.

Thanks, Christian, and good morning or good afternoon to everyone. It's my pleasure to review our financial results for the second quarter of 2024. So I am on slide 23, where we see at the top our cash and cash equivalents at the end of June 2024 totaled $705.9 million that's compared to $239.6 million at the end of last year December 31.

Our total net operating expenses for the three months ended June 30, 2024, were $58.9 million as compared to $44.4 million for the same period of 2023. For research and development, these expenses increased from $33.2 million to $36.6 million for the three months ended June 30, 2024 compared to the same period in 2023.

This change was primarily driven by increases in operating costs related to our new manufacturing facility. Employee salaries and related costs in Obe-cell clinical trial and manufacturing costs. These were partially offset by a more favorable UK R&D tax credit reimbursement for the period as well.

General administrative expenses increased from $11.1 million to $21.9 million for the three months ended June 30, 2024 compared to the same period last year. This increase was primarily due to salaries and other employment related costs driven by increased headcount supporting our overall pre-commercialization activities.

And finally, for the company, net loss was $58.3 million for the three months ended June 30 compared to $45.6 million for the same period of 2023. Autolus estimates that with current cash and cash equivalents we are well capitalized to drive the full launch and commercialization of Obe-cell in relapsed refractory adult ALL, as well as to advance its pipeline development plans, including runway to date in the first pivotal study of Obe-cell in autoimmune disease.

I'll now hand things back to Christian to wrap up with a brief outlook on milestones. Christian?

Okay. Let me -- I'll jump in here. We're waiting for Christian. Maybe moving to slide 25. Just again to hit on some of the anticipated anticipated milestones through the year end, we've got the target action date on the FDA side with the PDUFA, as Christian mentioned, that's November 16, 2024, and we'll have updates certainly at the end of ASH, you've seen some of those with the ASCO data and EHA that will be further advanced in and presented towards the end of the year.

And then as Christian mentioned on the SLE Phase 1 study. We expect initial data from that program later in the year.

So Rob, thanks a lot for jumping in. I had my headset was basically give up. So that I actually wanted to say in addition to the news flow is really that we're going to be obviously later-focused on getting the program through the registration for first approval and getting the launch off the ground with the product that will be the primary focus of the company looking forward to the data update. Absolutely. But operationally, that is what we're really going to be having our eye on and that we will look forward to keeping you updated on the progress there.

And now we're happy to actually go to Q&A.

(Operator Instructions)

Gil Blum, Needham & Company.

Good morning, everyone, and thanks for taking our questions. So first one, as it relates to the launch, if I'm thinking here, maybe something of a rolling launch would we see sites coming on. Over time basically?

Hi, Gil. That's actually not what it is. What we're trying to do is just explain that the actual activation at the centers is ultimately a decision or frankly process that's governed by the centers. And the time line that we're seeing anywhere from 2 weeks to 12 weeks is pretty much what we see across the space with centers that are ready to actually get activated and then the actual time of activation. A lot of time, it is actually also driven in your centers by a [factor] of patients there they need a therapy. And that usually actually accelerates the process and the final stretch of the activation.

This is not a rolling launch by any stretch of the imagination and being able to be out of the gate in that 30 to 36 centers ready to activate it at that point, which has been all the internal target centers. That compares very favorably to almost all launches that actually have been done in our space.

Could you go from there to 60 centers within a year? Will give us more than 90% access -- patient access in this indication, which is obviously a very, very rapid build, a much more rapid than I think we've seen across the competitive programs.

Thank you for the clarification. And maybe moving to the autoimmune data. So probably then the top question is what level of data disclosure should we expect at the center and [co-marketing] safety? Or will there be some follow up to suggest that efficacy as well?

I think the most of the update will clearly be on safety and short-term impact or shorter-term impact of therapy, as I indicated, treated the first patient in Q2. So that gives you the massive observation time that you will have. And obviously the rest of the patients will be at a shorter time period than obviously Q2 the end of the year time line. So there's going to be some initial data that will indicate activity that obviously will not be a substantially item follow up for most of the patients.

Okay. And maybe a bit of a in the [weeds] question. So we saw data updates for CAR-T that include 4-1BB , co-stim, versus, CD28 co-stim. And historically, people have talked about how CD28 tends to, how very high ramp up in cells, but also leads to maybe higher toxicities and 4-1BB linked to really longer aplasia, maybe there AID autoimmune indications that are more amenable to one versus the other probing your thoughts here?

So what you basically referring to is that the customer maturity may have sort of a impact on the initial activity that we see. [Oftentimes], in particular, the cell expansion of the CAR T cells that we're seeing, and that is circulating generically true that most programs we show faster of the migration of the CAR-Ts with CD28, a somewhat slower 4-1BB ligand 4-1BB would give you a longer assistance. CD28 can be a typically gives you very little perceptions.

And that also then has an impact, obviously on the longer term, you know, B-cell aplasia attaching [CPC] factoring markets, you have no active agent indicates you have activation. I think it's worthwhile remembering certainly for Obe-cell said, actually the peak expansion that we're seeing with our product exceeds that of the CD28 CAR.

So the story certainly is a bit more complex than just co-stimulation. So we actually see have an exact level of in terms of natural expansion of the CAR-Ts, which are beyond the what the CD28 comes we're able to do and that combined inhibition have a very long positions. So that may be very, I think unique set of properties that we do have with Obe-cell that is quite different from the rest of the commercially available CAR-T programs.

Now in terms of the type of activity you may need depending on the indication? That's an interesting question, and I think I will probably answer it from a position of what is the mechanism of action. And the mechanism of action, obviously that we have is the removal of B-cell CD19 positive cells and also plasma class.

In the case of autoimmune disease, where you have to get beat up typically are our clones that are cells that actually drives the autoreactive antibodies until you need to actually have a complete depletion of those cells. If you want to get to reset the disease. And that I think so there should be the expected outcome for CAR-T therapy, which is obviously very monotherapy for this type of disease.

So that mechanism is shared across the board. And I think what you need to ask is what are the properties that we need to have to achieve that goal? And in my view, but you need to have is because it's a cell-based mechanism, you obviously need to have an ability to actually have proper sales of engagements. In other words, your CAR-T cells have to plant those particular sales that drive autoimmunity and then actually have to be able to take them out because at the cell-based process, you need to have to go through cell migration, distribution, et cetera.

To do that and you need to get all of those sales eliminated that (technical difficulty) drive volume reaction. And that means there's a certain amount of time required to actually do that. What we do not know is we did not know what's the minimal amount of time to actually achieve that goal. What we do know is that the time that actually the program has been the airline study was sufficient to do that.

So the importance of the message that I was looking to gave before in the prepared remarks, was that our product actually shares all of those properties in terms of presence, better of cutting to the B-cell compartment and sufficient persistence to actually achieve that goal shares that would be a loan program but have a better safety profile.

So that's I think the way I would answer the question, how short you can go that, frankly, I think that none of us knows at this point because we haven't seen enough data from other programs with different profiles from being along for our product to get a feel when something else might also work. But what we do know is that profile that we achieved in our long dose work.

All right, that's very helpful, Christian, and thanks for taking our questions today.

Thanks, Gil.

Asthika Goonewardene, Truist.

Thanks. Good morning -- Good afternoon, guys. Thanks for taking the question. So congrats on the progress as well. Christian, I'm going to add on to your questions on the centers here. I may be asking something related share. Among the 60 centers targeted, how many centers require an approval in hand to even begin the qualification process?

And just to give us some color here. All in, how long does it take percentage to become an agency, including the whole qualification process and site activation acquired? And then I've got a couple of quick follow-ups.

So there's two steps to that. First of all that the center has to be obviously interested to actually onboard the product. That's the first hurdle we have to take. We had remarkable success in having centers interested in actually taking the fall off on board. It's the very bullish guidance that we're giving of 30 to 36 centers ready to be activated at a time -- at a time of approval.

So that's a very significant goal, which is to put any numbers that is those centers to cover about 65% to 70% of the AOL population in the US. So that's kind of the magnitude we're talking about. That's right out of the gate.

So that -- the level of interest to actually even engage in that first few -- second is, you need to actually go through all the preparatory steps so that you can get when you go to the left, you can actually activate the center. That can take anywhere from six to 12 months, so that is a very involved process that has a lot to do on the IT side as contractual pieces that we have to put in place and so on.

So it's a very involved process and typically takes in that order of magnitude of six to 12 months. This is why we've been working on these for an extended period of time. Many of the centers that we expect to get ready for activation after approvals in, are already now in the onboarding process, just to be clear.

So that's a continuous process and most of the centers actually are in ongoing in terms of process already at this stage. So those are kind of the key things. That then the final bit is obviously, we can go with these 30, 36 centers as far as I want to go. But there are obviously the final steps do require the actual label in hand, and that is sort of the final destination step that actually gets you to that -- into that they were booked between two weeks and 12 weeks max time to actually get the centers fully activated and enrolling pensions.

So that's sort of that that stretch. And obviously, the vast majority of the centers are working with obviously have made a decision to actually put all their work into the onboarding process ahead of actually having the label in hand, there are some policy that would actually want to wait until the label is here and will act with sort of actually engaged in more higher workload of the activity later on.

But those obviously will be owned 36 centers that will be add that in. But the overall majority of centers actually has been remarkably engaged and willing to actually proactively work on the actuation.

Thank you, Christian. That's really helpful. Then maybe bigger picture with the recent deal with BioNTech and the raise. You've got a good nice pot of cash that you can kind of dispense clinical development here. We see a lot of obviously -- a lot of prioritization done for and commercializing Obe-cell as well as doing the on the autoimmune and at the study. Make sure you can it's a good time to also revisit, what comes next, what's next on your really high on the priority list after these these top-two priority items?

Right. So look, we're very keen, I'll say on -- as committed to the next pivotal study. So this is very much workflow that is in full swing at the company. And obviously, at the same time, we will build on this track from what we need to do now, which is a very heavy lift for any organization going through the first time, through an approval and launch.

So we want to be mindful that, the one hand that we're having the focus required to execute, execute with what we hope to get asset class launch. At the same time, obviously, we're preparing for that significant engagements and into next pivotal study.

So that's what we're working on. And we'll see, we'll update the data from a public perspective at the right time to write that but that's healthy where there's a lot of activity. And we're also very excited about the interaction we're having with BioNTech, as -- really great chemistry between the teams on micro-irrigation and product discussions that are going on.

And I think that political scarcity or other key activity that people didn't have yet that level of visibility in terms of news flow that it's an area. I'm very excited about that, I think will create additional opportunities as well, that are not necessarily visible at this point from them and overall company perspective.

So I'm excited about those next steps. But first things first, get the approval, get the launch of the brand, get into the next pivotal study. And then we're kind of we're going to move from there. But very excited about kind of what the end of the year and then also the achievable plan.

Great. Thanks so much for taking my questions.

Thanks a lot.

Kelly Shi, Jefferies.

Congrats on the progress, and thanks for taking my question. As we're very close to the first launch of Autolus. Curious just a quick question, maybe -- it's too early to comment on the price of Obe-cel, but I'm curious if this play to dosing regimen would add additional cost to compare to singled -- single-dose of the cell therapy?

Hi, Kelly. Really good question. The -- first of all, I'll say on price, you're right, that would be too early to actually give any specific guidance. I think we can only remind sort of the current price levels that we see with the [CAR T], which is around four 62 in the US And which is combined, which is around [82]. There's an overlap. There is often a range where we have Phoenix settled on study goes from 18 of years, onwards, when you look at the labels for the two commercial products what obviously goes up to 25 years, which is Kymriah and the second one thick [harvest goes] above 25 and older. So that's the range that's currently in the market. And I think we can give more guidance than that. (inaudible) And just actually basically point to the references that I referenced sizes that we have here in the space.

In terms of the cost or the added cost related to dosing, what we do, obviously, with Obe-cel is we do a tumor burden adjusted dosing, and that actually has proven to give us an enormous amount of robustness in terms of the safety data, which has driven over the long half of the design, but also takes into account also to a burden.

And remember, these are very sick of the older patients tend to be fairly frail patients and a lot of these patients certainly caused a lot of issues with earlier. Our key programs make to actually treatment related mortality. We see that in some of the real-world data as well that being a real issue.

As you may remember, our median age in that study actually was about 10 years older than some of the other studies that were done to space. So despite we did that whole thing through the pandemic, we adjusted aggravated, the safety related challenges for it.

So the dosing that we have in combination with obviously (inaudible) from a business, a very substantially improved safety profile. The primary costs that actually you see for the delivery of the CAR-T is not the delivery itself. It's not the administration because that's pretty uneventful that's literally in infusion and that statins that tend to be very short infusions, we're talking maybe 15 minutes or something like that.

It's a very short infusion that doesn't actually add a significant amount of burden, but actually expert and what really drives costs is related to the management of the patients, but they actually do experience high-grade CRS, 40 years, hybrid IT and in fact, the eye cancer almost worse because they tend to take substantially longer period of time.

If you actually get out of control and all too often are associated also with long-term steroid use in combination can lead to sepsis and treatment-related mortality. So that's where the real cost actually comes in, to be able to reduce the number of events massively, but also shorten the recovery time, which is both at both elements we have seen with Obe-cel of the FELIX study, actually reducing massively the cost and it is actually one of the key attractive element as for onboarding the product, which is the product actually will be less intense to manage because it's less intense to manage actually the profitability goes up for the centers.

And that actually is one of the key drivers that from a financial perspective is attractive for the centers. Why the onboarding also is growing as well as it does and what is also recognized, not just as a clinical improvement as well as the longer term outcome, but also an immediate financial improvement that I think is visible at the private along should within the centers that were engaging.

Super helpful. And thanks very much. And also have follow-up on auto new follow that -- follow your comments from opening remarks.

So although we saw better tolerability of CD19 CAR T cell therapy in autoimmune indications when compared to [him on ClinTrials] from Dr. Chess Pioneer work. We still receiving neurotox from other ongoing trials in lupus.

So curious if you could share your insights on if the patient had a baseline difference as more like a dominating factor all CAR design or maybe other reasons regarding the impact on safety. And also another important question here is how Obe-cel achieved much better neurotox control in the hem oncology indications generally speaking and also whether this is a transferable to autoimmune trials, your opinion? Thank you very much.

Yeah, very good question, Kelly. So the -- what we're also seeing is in general, what we're seeing is there's several parameters that drive immunological (inaudible) and this is both actually CRS and neurotox. And the parameters on the one hand are the number of target cells that you have to be taken and have to be reduced.

Obviously, that means -- that defines the number of CAR T cells that get activated and with that depending on the type of CAR T cells gives you a baseline of activity, potential cytokine release and also the recent logical toxicity. So that's one element. So it's the number of cells that, when we look at the logic of your own communication, we do expect to see significant validation in terms of the number of cells and have to be removed.

These are patients that had overall immune system. They have are lucky in the sense that they have individual clones that recognize structures and in the body and drive autoimmunity as a consequence of it. But it is not a proliferative disease as we would see inventory marketing.

So we see a pretty steady level, pretty much a normal level of details and plasma blasts that need to be (inaudible). So that's what it basically becomes a constant, but then actually it becomes a variable. And that's a second element that can drive consistency through the design of the CAR T product.

The two key components there. We already talked in, I think, costi mentioning that before, which is the cost of inventory elements and the impact that the costimulatory element can have, they do have an impact in terms of how quickly the cells proliferate and kind of cytokine release. They actually view that as an element that is sort of in part coming from the co-stimulatory domain.

But what we have proven with Obe-cel is really the primary driver. And probably the most important parameter that we're dealing with is actually the way that the CAR T cells physically engages with the target cell.

And what have you to remember about the design of Obe-cel is what we're looking to do with Obe-cel creative product that behaves as physiological as possible while also being a primary [message and] receptive to trying to be as close to a normal piece of engagement.

And what's characteristic for a normal T cell engagement is that litigation is short-lived. So T-cell actually recognize the target cell. (inaudible)So for some time, as the liver society policy concept, which tries to sell at or at [Republic] process into the target cell and then actually disengage it magnitude. We're talking minutes in terms of litigation Max.

And that short engagement is really characteristic of a normal physiological engagement and it is that engagement that actually is clearly different for the first generation of CD19 CAR T programs in the space, but also that will be true for most of the products currently being developed immune disease.

And that is that the most of those designs use antibodies fragments to CD19. There are high affinity in nature, which means that have a cash burn rate at a very slow off-rate. And net-net, if you then think about thousands of CAR and the size of the CAR T cell side and the CD19 molecules or the type of target cell.

You do basically an enormous amount of high-affinity interaction between the cell, very, very long interactions between them. Those low long interactions do not actually have the kill that already happens within a minute or so, for what they do is they drive an overactivation of the CAR T cell that overactivation drives the cytokine release as well as actually drives exhaustion of sales and ultimately is beta contributing in a very significant way to toxicity. And that toxicity is unrelated and unnecessary to get the activity until what we designed with what we said is really obviously a product that has the ability to be specific, but disengage rapidly after delivering the kill. And we do that by having about a hundredfold faster operate from the target than any of the other products out there. And that gives us a very different behavior of the CAR T cells and fundamentally changes the toxicity profile. That difference is will be relevant in any setting and will give you a substantially better safety profile in a setting you would actually apply the CAR T cell.

Really appreciate all insights. Thanks, Christian.

Thanks a lot, Kelly.

James Shin, Deutsche Bank.

Good morning, guys. I had a question on the onboarding activity. The range of two to 12 weeks for accreditation, the sites that would fall into the two week range centers that have existing CAR T programs and those that fall in the 12 week range are centers that are CAR T naive. That's question number one and I have a follow-up.

Okay. Hi, James. Good way to think about it. It's suggested that could be the case. That anything actually, that's true. I think you have a lot more to do with the workflow at the centers and their contract, probably four to five programs for many of the centers that they're onboarding.

So there is a very involved process for many of the centres there is a capacity component, and I think all of it will be very much driven by rapid patient needs as well. So I think that's going to be a big driver of actually how quickly that final stretch on the activation will occur.

I think there's a lot more to do with that. Most of these centers also rapid CAR T centers we're talking about at the top centers in the US, which frankly, all of them has attempt have multiple CAR T programs already on board.

Appreciate that. And then on the P&L side, are we pretty much at full commercial run rate for the commercial activity. on the small side. That is.

Hi, James. It's Rob. Yes, so -- we are still going to be building towards the end of the year. We haven't fully built out the team yet in the US. So I wouldn't necessarily project kind of a flat run rate from Q2.

Thank you very much.

Thanks a lot, James.

Matthew Phipps, William Blair.

Hey, Christian, thanks for the update and taking my questions.

Following on a little bit, what Kelly asked earlier but with Cabela's reporting a great four I can this morning from their lupus trial, they so they're implementing some protocol modifications, including some seizure prophylaxis. Wondering if that's something that you guys have used or thought about using? And then I realize you are very early in your trial [front of me], but maybe you can just give any kind of comment on how the safety profile is reflecting a kind of Felix and other experience with of those health so far?

Yeah. Good to have you on that, and thanks for the question. So I think probably the best surrogate here. Also, we've kind of indicated we're early on -- in our Phase 1 study. So not seeing something in that early stage doesn't really get you -- to give you a clear-cut answer, I think the better part of looking at the way we're looking at is really the ALLCAR 19 infection model study where we had about 40 patients with the various pools in the Hodgkin's lymphoma.

And what we did observe in those patients is that without prophylaxis, so just normal conditioning at dosing prophylaxis and also no steroid prophylaxis and no seizure prophylaxis in these patients. We actually did not observe neurological toxicities in these patients. (inaudible) which I think is giving us a lot of confidence around the overall product property.

And similarly, also the patient with low disease burden in ALL also had a very limited neurological activity and in fact, no Grade threes even those settings. So overall, I think the product profile is also a really different here. For Obe-cel and what we know from our product is that clearly that we would have a different behavior in that we're seeing.

As we're based on the non Hodgkin's data, which is probably a good way of sort of comparing, although we do have some localized high tumor burden in these patients. There's not a lot of bone marrow burden is attempted, density very low or normal and normal circulating T-cells getting that's ending up to be half that we have not seen neurological toxicity in the patients. So it gives us a lot of confidence that we are obviously in a good space, but it's early days in autoimmune, and I think there's a lot of people.

And one quick follow-up. I don't think you discussed this but and when do we get an announcement on, I guess, the next autoimmune disease beyond lupus that you guys might explore?

I think we're also -- we're going to go through kind of the launch process. I think kind of the next trajectory and update, we're probably going to providing key well. In terms of next steps and that's what we're working towards. But it is probably the key focus where we think it needs to be, which is really on getting through the regulatory process and getting into its way through the launch before we done everything in a broad array they were in focus.

Good. Thanks, Christian.

Yanan Zhu, Wells Fargo.

Great. Thanks for taking our questions. On the autoimmune side, I was wondering, you mentioned the three centers are enrolling in UK and Spain. I just wondering. Are all these centers also Felix centers and have you enrolled patients, SLE patients at all of the three centers?

The other question related to autoimmune is wondering about your thoughts on the recent sale publication regarding allogeneic CAR T and demonstrating some efficacy in some autoimmune indications, like as you look into that data, what is the learnings and takeaways with the regarding the prospects of [AlloCAR T or EBU] Thanks.

First off with regards to the centers the assets, all three centers happy Felix centers, service experience at all centers at the rollable. So that's I think the first part of your question, the second part of your question was related to just different modalities that could be giving you deep, deep remissions of deep responses in the resale and copper brass compartment.

And obviously, there's three basic categories under investigation. You have the ortholicist CAR T cells which is what we talked about mostly on the call, we have averaged a CAR T cells, which is what the question is and then also their bispecific T-cell engagers, which is in the three categories of T cell-mediated approaches to reset the B-cell compartment.

What we do know at this point is obviously that with the autologous programs that we do get very deep responses we looked at. I hope that the original data in [narrow] and I think indicative that we can get the transformational outcomes will be no pediatric ALL or the ALL that can be extremely deep responses being MRD negative at a level of the under ten to the minus six is the most strange way has been tested and development capacity is get patients into long-term remission in those settings, which I'll say is what we have seen.

with our product and what we see with that Raia a pediatric ALL as well. So clearly those are called the most patient tests. You can run to evaluate the activity of these products. We do know that the alternate programs can make a cut into the compartment to date, all the data we have on the oncology side is indicative of the fact that [there's not competition this] week or as consistent.

I think that is certainly going to be a true and I think also in the autoimmune setting, but you do expect that when you do make accounting the compartment, any ceiling tile and even if you do have even much less of a of a cost as we've seen in the compassionate use work with [title] in the trials that are earlier in a year, you could see that actually at least temporarily you can actually have a reduction of detailed plans are in those patients and see an improvement in clinical improvement in those patients.

It doesn't appear to be on action sustainable, but you would see an improvement, I think what we've seen so far is consistent. I think with what we know what these products can do the fundamental question is connectivity. Is it going to be a differentiation between a design phase and other generic programs and do either one of those actually get into a place where you can sustain them to come.

And I think you just don't know at this point in time, I think we have a pretty good feel that if those programs if any will have probably the best chance without revealing the transformation. I think that's sort of where we are at this point. Also be interesting to see how these other programs evolve over time. And that were simply we'll be carefully watching the space.

Great. On the oncology side, I was just wondering, your confidence about delivering the 16 day range to delivery time and also your sense of manufacturing failure rate and how do these compare with trocars because that's something when we talk to some experts, these aspect of it reliable delivery seems to be one of the factors that could drive the shift from one product to the other?

Yeah, really good question. So this is a patient population, where you need to deliver a unique therapy to actually deliver these patients don't have extra time. There's another we do typically possible. So you have to have very high levels of reliability of delivery will be able to show in our clinical study.

If you compare to the clinical studies with each other remind we get ours through the pandemic with a lot of other indications, we actually have higher level of intensity, that you'll see that in the prior study were 84%. And that clearly was that was a very good outcome overall on intensity.

So we can show if you look at it from that perspective, we can look at it from the perspective of the our expect range, which is around 6% is a Felix study, which is very low. And we were at 21 days across the Felix study and one of things that we have included and sort of implemented through the course of the Felix study incentive, faster analytical methods that would allow that actually allowed us to accelerate the release of the product.

So big chunk of the time you actually have to make a living time non-demand factors that you'd actually be out [April] testing as to sort of achieve the release. And the final part is related to logistics and one of the things that were being were implemented for the commercial delivery. This is part of the collaboration, the deal that we have with Cardinal Health is that we are shipping a product before the releases completed two units so that the product is already close to the site on higher costs and will that actually be released once the product releases through.

But what that does is it basically takes that element of the turnaround time out of the equation. So between the logistics element as well as the faster analytics, we're able to Carbonite six days IOP of a delivery time. And so what we're guiding is currently 16 days at time of launch with an opportunity to reduce the net times pretty much in line with what the best competitor data looks like.

Very helpful. Thanks, Christian.

That's a lot Yanan.

Sebastiaan Van Der Shoot, Van Lanschot Kempen.

This is [Karen on the rhodium] on behalf of Sebastian. Congrats on the progress. Thank you for taking my question. So I was wondering whether you could provide your thoughts or some insights on the recent approval of Blincyto in the consolidation phase of the multi phase chemotherapy of the first-line ALL.

So what do you anticipate the effect will be on the number of patients in the relapsed refractory setting of this disease.

So this is a question related to the recent approval of Blincyto in the front-line consolidation. Obviously, this is data that there has been first of all, known about for quite awhile presented at last at two to three years on voting consolidation of the MRD-positive as well as patients as well as patients that are altering the initial induction and initial consolidation with chemo immunotherapy that you're setting those aspects, those actively cycle.

What is very interesting about that part of the data is that when you look at the data more carefully realized, there's a subset of patients with acute benefit. There's another subset that does not appear to benefit from that consolidation. And the group that did not appear to benefit actually were patients that were a bit older.

And that's a very interesting kind of observation, I think is certainly something that I think we're in a nice neat can follow up and I think better understanding, but it was clearly certain patients that they actually benefit, whereas others actually departmental goals.

And so that's, I think, interesting to us when we looked at that at that part of the data. Overall, we think that most of the impact actually of this done has already been pretty much in the space, given that the data actually be well, not only with the cost savings is a large number of centers involved a lot of patients that actually will be managed in the in sort of using please type in the frontline setting.

In fact, there's also safety and you can see that also when you looked at the trajectory of Blincyto sales, is that clearly the sales upswing actually went ahead of the approvals, although it was trailing off exactly that data that was driving and actually ultimately was the basis for the approval.

So you think most of that is actually baked in. And we do not expect to actually have a major impact of the relapse refractory setting. And certainly would expect that there's some delay or some of the patients actually becoming refractory so buying some time. But we also believe that a lot of that actually already starts to be realized that many of these patients actually start to get back to the point to relapse given that the consolidation has actually been use for a period of time, certainly in the US.

Okay. Thank you. Very helpful.

And this concludes the question and answer session. I would now like to turn it back to Christian for closing remarks.

Well, thank you very much for joining. A real pleasure to have you all along and looking forward to keeping you updated in the I'll obviously, as we said, all focus on getting to the final stretch and hopefully get to approval later in the year and then be in a position where we can get this product to patients, which is really something that we've been working towards for many years now and I think would be fantastic to be able to transition as we get to the end of the year to that stage. Thank you very much and looking forward to keeping you updated.

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.