Autolus Therapeutics plc (AUTL) Earnings Call Transcript & Summary

Okay. Good morning, and thanks again for joining us at the JPMorgan Healthcare Conference. I'm Eric Joseph, senior biotech analyst. Our next presenting company this morning is Autolus, and it's my pleasure to welcome CEO, Christian Itin, to tell us a little bit about the company. [Operator Instructions] With that, Christian, thanks again for sharing some of your time with us.

Well, thank you very much for having us. And to be included in this year's presentation at the conference. Welcome, everybody. We'd like to first actually go on Slide 2. Please remember, have a look at our SEC filings, periodic filings, risk factors, look at our forward-looking statements in there, et cetera. And make sure that you're adequately informed. So with that, I'd like to move to our lead programs and go to Slide #4. And obviously, we're focusing on our AUTO1 program in a disease setting in acute lymphoblastic leukemia, at the outpatient -- adult patient population, which is a truly underserved area and certainly, one of the areas where we still have a very dire outlook for the patients. This program is now moving into its pivotal stage. I'm very excited about the program, and we'll talk through some of the data that we just presented at the end of last year. We're also exploring beyond adult ALL additional indications. In particular, we're looking into the utility of the product also across the broader range of non-Hodgkin's indications. And we're also including an exploratory trial in primary CNS lymphoma, one of the quite neglected areas of lymphoma usually excluded actually from clinical development. So we're excited about that opportunity, and we'll expect data on all of those exploratory studies towards the end of this year. In addition, obviously, we've been very active and been reporting a lot on our AUTO3 program in DLBCL. I'll talk about it a bit later as well. And we expect additional programs to start actually delivering data, in particular, our programs in T-cell lymphoma called AUTO4 as well as the next-generation program in pediatric ALL. And there's a few additional programs that will actually start clinical development during the course of this year. So with that, I'd like to actually move on, just a brief summary on Slide #5 of the various activities and indications that we're active in. And with that, we'd like to actually move to the AUTO1 opportunity. And first, I'd like to talk about adult ALL, and we're going to Slide #7. I think it's important to understand that within that indication, we actually have no approved CAR T therapy at this point in time. The only redirected T cell therapy that is approved is Blincyto or blinatumomab, and in terms of other targeted therapies, we also obviously have inotuzumab, CD22 targeting ADC. Now the normal course that the patients actually are experiencing is first actually a very heavy, very challenging high-dose chemotherapy regimen that they get exposed to. In fact, the vast majority of the patients do respond to that initial therapy. The problem is that only 30% to maximally 40% of the patients benefit long term. Which means that the mass majority of those patients actually progress and become relapsed/refractory patients. When you actually reach this stage of actually having relapsed at the front line, your life expectancy is very short. The median survival is less than a year in that population. And it is actually a very challenging situation with regards to the availability of therapeutic options. When we look at the general challenges with that population, it is that they actually have a very poor -- or they're typically in quite poor condition. And that is actually a consequence of both the disease as well as the high-dose chemotherapy that they receive in the first-line therapy. The disease itself crowds out the bone marrow, and that has an enormous impact on the immune system and the capability of the immune system to regenerate to the patients. And these patients become severely immune suppressed as a consequence of the disease itself. Put on top high dose chemotherapy, obviously, that makes things worse. So a lot of these patients are highly prone to actually succumb or be infected, and a lot of them actually do die of sepsis in the late stages of that -- of their journey. Now when we think about the overall opportunity, it is a very sizable opportunity, and it is a very high medical need indication. Now as we're going to the next slide, Slide #8. The basic design principle that we applied for AUTO1 was actually to create a product that is -- behaves as physiologically as possible, have a short engagement with the target cell, the leukemic cell, deliver the kill very quickly and then disengage very rapidly so that the CAR T cell wouldn't actually get overstimulated, and as a consequence, will be very active. It would avoid the high level of toxicity that we've seen with many of the initial CAR T exploratory work that was done in adult ALL patients. Now we think the benefit of this type of physiological behavior is that we would actually get better persistence which means gives us an ability to put pressure long-term onto the disease, which is critical to get actual long-term outcome in adult leukemia. But it also actually will improve the overall tolerability of the program and actually give us a much better safety profile. So that's the design principle that we've actually built into the program. So in technical term, it's a product that actually has a very fast on rate onto the target cell and a very fast off rate again after the kill has been delivered into the target cell. Next slide is going to be Slide #9. Now we believe that the product actually has quite remarkable opportunity here because what we have been able to see, and I'll show you some of the data on the next slides, is that we can actually get patients into long-term complete remissions, in fact, long-term molecular complete remissions, and we've seen that our event-free survival with 16.9 months of follow-up is reaching 52% at 12 months. That is quite an unusual outcome. Because, as I mentioned in the introduction, most of the patients actually are already dead within a year's time after being relapsed refractory. We have seen that the product is very well tolerated, and we're actually conducting a pivotal study, which gives us, obviously, the key activity and is the key focus of the organization. On the next slide is a quick summary of our adverse event profile, and I'd like to highlight just a few points here. First, when we look at cytokine release syndrome, which is a typical adverse event related to the activity of the CAR T therapy, what we do see is that we have 50% of the patients experience -- experiencing cytokine release, but only Grade 1 and Grade 2. We have no patient that actually has experienced a Grade 3 or Grade 4 cytokine release syndrome. That is important because in the -- if you avoid high-grade cytokine release syndrome, you also avoid the need to manage the patients in ICU, which is obviously one of the challenges that a lot of the initial exploration in the field actually was sort of dealing with. Secondly, when we look into the neurotoxicity, which is the second known adverse event that is associated with CAR T therapy, typically, we see that only 20% of the patients have experienced neurotoxicity. And in fact, those are patients that have very high tumor burden of more than 50% leukemic cell blasts in their marrow. What we could see is that as these patients develop their adverse events, they intervene with a steroid and the patient actually normalized between 1 and 3 days. So it's very well manageable, and it is basically an adverse event impacting only a small proportion of the patients. Overall, we had 7 of the 20 patients we treated who died. We have 2 patients dying of progressive disease, and 1 actually has the consequences of a second stem cell transplant that the patient had received. 4 patients died of infection, which is, as I mentioned before, a typical course of event of events. In fact, those patients had either fungal or bacterial infections that had led to sepsis. Moving on to the next slide, what you can see here is a swim plot where we look at the individual patients that were treated [ patients ]. I would like to point out at the x-axis, and you can see that we have patients that are reaching 24 months in molecular complete remission without receiving a [ stem cell transplant ]. So this is the single-agent activity that we're looking at. And as you can see, only a small portion of patients, in fact, 3 patients did receive a stem cell transplant while being in remission. So the activity here is an activity that is induced and sustained by AUTO1 on its own. As mentioned before, our event-free survival at 6 months is 69% and our event-free survival at 12 months is 52%, and this is with 16.9 months of follow-up in the median. Looking on to the next slide. Here, we do see that the patients, obviously, the data stacks up well on Slide 12 compared to the data from the standard of care. And I want to highlight here, in particular, blinatumomab, which captures about 50% of the patients in that indication. What you can see is if you look at the CR rate of event-free survival, that we are approximately twice as active as blinatumomab. And in fact, in this patient population that we have treated, 70% of the patients have either received prior blinatumomab or prior inotuzumab and failed on those therapies before entering the AUTO1 trial. Now what's important to see as well is that our cytokine release syndrome and our neurotoxicity data that we have is very comparable to that of blinatumomab. So in a very simple way, we're looking at a program that has at least twice the level of clinical activity to blinatumomab standard of care, as -- at the same time, the program has a comparable safety profile to the standard of care. We believe that is a very good starting point to move this program into a registration study. When we look at the commercial opportunity, we see that approximately 3,000 patients between the U.S., the top 5 European countries and Japan are experiencing relapsed/refractory ALL. And obviously, as we move up the lines, that number gets substantially bigger. And when we also look at the pediatric patient population, we see that, that population in the relapsed/refractory setting is about 1/3 of the adult population, approximately 1,000 patients in the same period [and lines ] combined. Now as we move to Slide 14, just a quick view on 2 of the key programs and products that are approved in the space. We're looking at the Blincyto and Besponsa. As you can see, Blincyto has reached annual sale in up to September 2020 of $350 million. Typically, the patients experience or receive 1.7 cycles of the product, which results in approximately 1,400 to 1,800 patients that were treated with a commercial product. That also ties to about a 50% market share in this 3,000-patient opportunity in the space. What we also see here is, obviously, a differential pricing approach that was used by Novartis in this space, where, for Kymriah, the price tag in the pediatric ALL setting was set at $475,000, whereas DLBCL price tag was around $375,000. So with that, I'd like to move on to the Slide #15. And just a brief outlook in terms of our next steps that we're engaging in. First off, obviously, the program at this point is in motion, in a Phase Ib/II pivotal study. It's called the AUTO1-AL1 study or the FELIX study. This program is ongoing and will recruit through the course of this year, not the least because of the significant COVID impact that we've seen both in the U.S. and in Europe. We expect that enrollment will be increased, and we can increase enrollment as we get to the middle and second half of the year. When we look at the study design, it's a single-arm study, approximately 100 patients with relapsed/refractory disease. The primary endpoint is the overall complete response rate. Secondary endpoints include molecular responses as well as event-free survival and duration of response. Slide 16 now looks at the additional studies that we are conducting to explore the activity of AUTO1 beyond the adult ALL population. That includes activity in indolent lymphoma, particularly mantle cell and non-Hodgkin's and follicular lymphoma as well as in DLBCL and then also initial explanation in CLL. As mentioned earlier, we also are exploring the activity in primary CNS lymphoma, which is typically a neglected indication and one that we think the program is quite likely well suited for. We also started in December, a next-generation version of the AUTO1 program that looks at minimizing the large number of relapses that were seen in all programs in pediatric ALL, driven by antigen loss of CD19. So we designed a novel highly active CD22 chimeric antigen receptor that we're adding to the AUTO1 product. And this product now has gone back and it's labeled AUTO1/22 into the clinic, and we expect data at the end of next year from that trial as well. Moving to our next program, AUTO3 diffuse large B-cell lymphoma. For this program, obviously, we have presented quite a significant amount of data updates during the course of last year. The last update was also at ASH in an oral presentation. This is a dual targeting approach targeting CD19 and CD22. The 2 chimeric antigen receptors are delivered with a retroviral vector system as a single vector. So each cell that gets transduced carries both of the receptors. When we look at the outcomes that we had in the study, and we go to Slide 19, look first at the safety. We had reported on 49 patients treated to date with the AUTO3 product. Obviously, we've run through dose escalation in this trial, and we also explore different regimens with regards to pembrolizumab either a single dose or 3 doses of pembrolizumab. Overall, we did see a very good safety profile. We had a relatively low level of cytokine release syndrome. Predominantly, our cytokine release syndrome grade 1 and grade 2. And also, when we look at neurotoxicity, we had a remarkable outcome with regards to Neurotox, where the vast majority of the patients did not experience any type of neurotoxicity. And in fact, the patients that did experience neurotox, which are 3 out of the 49, were all patients in progressive disease with no obvious CAR T activity visible or measurable in those patients. When we go on to Slide 20, where we look at the overall activity. And you can see here that overall, the patients have responded well to the therapy. The overall response rate from a complete remission rate perspective is 51% because all the various dose cohorts and permutations that we have tested. We also, when we look at the actual doses administered, we did see that the dose levels went up as we look at higher doses administered, where the level of complete remission rate is 73% out of the 15 patients that did receive 450 million cell dose. So a very consistent level of activity and a high level of activity that we were observing across this trial. When we look in summary at the program, it's been a very informative Phase I experience. We did see overall, obviously, a high complete remission rate. We see what we believe to be a best-in-class safety profile with very limited high-grade cytokine release syndrome and very low levels of neurotoxicity. We've been able to show that we can safely administer the product in a combination of either single or 3 doses of pembrolizumab, that was well tolerated. And we also did see that having the 3 doses of pembrolizumab did actually give us sustained CRs in those patients having not observed any relapses in patients that received 3 doses of pembro. Now what was also important was one of the key updates that we've given at the ASH meeting is actually our experience in a 20-patient cohort of patients that were treated in outpatient setting and we could demonstrate that we could actually do this safely that, in fact, when we look also at the readmission rate of patients, it was low, it was 38%. And in fact, the reasons for admission was development of fever in these patients which obviously requires you to admit them because the concern is that they might actually have an infection. The patients were obviously tested for the presence of pathogens. They have no infection and normalized quickly in terms of the elevated temperature and quickly released after that. None of the patients required any form of intensive management. Now the path forward for the program. Obviously, we're looking to -- at opportunities for this program in the relapsed/refractory setting. There are several opportunities here that we can look at. What we look at in terms of the general information that we can get from the Phase I portion of the study gives us a very clear understanding of the dose range to take forward as well as, obviously, the use of pembrolizumab going forward as well. Fundamentally, when we look at the program, this is a significant opportunity, particularly because of the opportunity to reach a large proportion of the patients which are not actually treated in the academic centers or in in-patient setting. Most of the third-line relapsed/refractory patients in the U.S. are treated in outpatient setting, which ultimate at this point in time, is untapped by the current therapies that are approved and on the market. We do intend to partner this program, and we'll obviously keep you updated as we go through the course of this year. Now a quick look at the pipeline. I would like to go to Slide 23. Just a brief word on the way we program our cells. We do actually program them by using a small protein modules that actually can refer certain sets of properties to the cells. Obviously, a particular set of properties relates to the targeting itself and the activation, which is typically done by chimeric antigen receptors. We have included control elements that allow us to either transiently or permanently control the activity of the product. We then, in particular, focusing on enhancing activity. In essence, those are activities that actually give the CAR T cell resilience in the context of complex tumor environments, and allow the cells to survive and continue to be active in those settings. And there is also activity directed at driving towards more broadly usable cell populations as well indeed towards the allogeneic side. Now just looking at the pipeline of the early programs, the 2 programs that are active in clinic at this point. This is AUTO4, our T-cell lymphoma program, which we expect to have a good clinical update by the end of the year, actually have a good understanding of the clinical profile of this product by then. We also are expecting data from our next-generation work on AUTO1 for the pediatric setting. As mentioned, that program has started with first patient dosed in December last year. And then there are several programs that are gearing up to be started in terms of clinical development during the course of 2021. And some of them, like AUTO7, will be ready for clinical activity and clinical exploration in 2022. Finally, Slide 25. Obviously, we believe we're at a very interesting point with the company. We're obviously embarking on our first pivotal program building on a data set that we believe has the potential to be transformational in a high medical need setting in patients with relapsed/refractory -- adult patients with ALL. We're expecting data for that program in 2022. The pediatric program, I already mentioned, we expect data by the end of the year. And then obviously, we also will have approximately 30 patients in terms of the exploration of AUTO1 in non-Hodgkin's indications as well as obviously first information on the primary CNS lymphoma indication as well. All of that expected -- is expected during the course of this year, with obviously an emphasis on the end of the year. The -- when we look at AUTO3, obviously, as mentioned, this is a program we're looking to partner and collaborate on. AUTO4, we expect to have a clinical profile for this program by the end of the year as well. And then obviously, several candidates that we'll start to move into clinical development. In terms of the cash position of the company at the end of September, our cash position was at $178 million with the guidance that this gives us a cash runway into 2022. With that, I think I'm concluding the presentation and happy to take questions.

Okay. Great. Thanks, Christian, for that presentation and overview.

So first question here coming in the portal. Just to share some of your thoughts on the decision to kind of shift the path forward with AUTO3 to make it partnership dependent. What are you looking for, in particular, when it comes to potential partnering candidate? And I guess, are you looking beyond AUTO3 in potential partnering opportunities within the pipeline?

So as we were getting into last year, obviously, we had -- we're building on the AUTO1 data that we had and decided to move forward because we did see that the program, obviously, had a very significant opportunity in that rather underserved disease setting. As regarding -- we're getting towards the end of last year with the update, we just went through that was presented at ASH. We're now at a place where we believe that we actually have a high probability of actually looking at a truly transformational program in this disease setting. So that is the type of situation where you absolutely have to double down and really make sure that, that program actually gets pushed through the pivotal stage and gets ready to actually move forward towards the market. So that is where our core focus is at this point in time, making sure we deliver that product and deliver that type of benefit that we see the product can actually deliver to patients. With AUTO3, obviously, we had a very interesting set of data that we presented at the end of last year. What is very interesting about it is not only the fact that it's a high level of activity that we see, but it's the ability to actually give this product in a patient setting. When you think about that, that is clearly an opportunity that's significant because currently, the CAR T therapies in DLBCL capture just about 10% of the market opportunity confined to literally the inpatient segment of the academic centers, which is 10% of total of the opportunity. So AUTO3 with its profile, I believe, has a very significant opportunity to go substantially beyond that. But it also means, of course, that you'll be -- from a commercial perspective, you'll be looking into a wide range of centers that you actually will have to target, very different from ALL, where it's a very focused delivery with very small number of centers that treat the majority of patients. We believe that is really the profile that is very well suitable to collaborate on. And those are some of the key things we're looking for is obviously the ability of our potential partners with the program. And obviously, also the support, not only the operational side, but also, obviously, on the funding side for the program.

Okay. Great. Coming back to AUTO1. How -- I guess, in terms of patient disease burden and prior treatment history, how reflective are -- is the adult ALL population in ALLCAR1 of sort of the real world, market opportunity? And is the safety profile seen within the ALLCAR19 study something physicians can basically expect in the real-world setting?

It's a very good question. And one of the tough things about this disease setting is that it's obviously enormously rapidly progressing patients at that stage of the disease. When you look at the nature of the patients that we've included in the ALLCAR study, these are patients that are -- 70% have received stem cell transplant and relapsed from it. And then also about 70% of the patients had, had treatment with blinatumomab or inotuzumab and failed on those treatments. That is a very good reflection of what we expect the "real-world" situation will look like. I did mention before that blinatumomab captures currently about 50% of the market in relapsed/refractory. Obviously, the -- as you could see also from the sales numbers that the inotuzumab or Besponsa, obviously, is substantially smaller in terms of opportunity than blinatumomab. So the 70% number is actually, we believe, is quite relevant for the space and quite a good reflection. The rate of sort of failure after patients receiving transplant and failing on it is also very much in line with what you would expect for these patients. Because obviously, some of the patients cannot receive either do not actually have a donor at the right time or for some other reasons, are not in terms of comorbidities, cannot actually receive a stem cell transplant. So we believe it's a very accurate reflection of what we expect going forward. And it's also, frankly, very similar to the original patient population that, in fact, we've dealt with in the context of the development of blinatumomab as well in my previous life. So we believe this is highly relevant. Now the patient population that we're including in the pivotal study is actually the same population. So we allow blinatumomab prior therapy, inotuzumab prior therapy. The only thing we exclude is CAR T therapy. But frankly, there is no approved CAR T in the space, and there are very, very few patients to even have a chance of accessing CAR T therapy in any sort of clinical trial at this point. So that is not a real limitation. And it's nothing with regards to the real world that you should be shifting on. So we believe it is a very accurate reflection. The safety profile, we believe, is important. And it is relevant in terms of the patient population. It's also corroborated by our experience in the pediatric population, where we see the same profile in kids as well. And remember in those -- just to give you some flavor in the -- for the approval study for Kymriah, we had about 50% of the children developing high-grade cytokine release syndrome. And in fact, more than 50% of the kids ended up in ICU. None of that happened with AUTO1.

Is it the expectation that, if approved, you would essentially be sort of listed in the compendia to be used after or post blinatumomab or inotuzumab? Is there opportunity to perhaps move ahead in the treatment paradigm short of conducting another study. Would you -- yes, would you have to conduct other trial to reach that patient population? How are you sort of thinking about that based on physician feedback?

So the inclusion criteria allow, actually, the enrollment of patients that are post blina or inotuzumab as well as patients that have not yet received blina or inotuzumab. So we'll actually have data both of kind of the parallel setting as well as the post setting. And we believe that having those 2 data points should actually help us give -- or basically provide the database to justify the use of the product actually instead of rather than just post those 2 therapies.

The pivotal study would be for full approval or is it conditional? Is there sort of a confirmatory study that need to be conducted after AL1?

Well, typically, what you see in the space, and this is looking more broadly, not just in the CAR T space. Typically, you do have actually a follow-up obligation when you go for sort of an accelerated approval path. And we've seen that with blinatumomab that had -- was approved based on Phase II data and then had a commitment for a Phase III program as well. I would expect that we're seeing similar type of approach here as well.

Got it. And maybe just shifting to other CD19-driven opportunities, you kind of highlight the primary CNS lymphoma market. How should we be thinking about the size of the opportunity there? And it being an underserved indication, is that because it's sort of more challenging than adult ALL? Is there a proof of concept, I guess, with other CD19 modalities that give you comfort than being active in that disease subtype?

I think starting out, I think it's probably worthwhile stating that primary CNS lymphoma is typically a disease that gets excluded from clinical trial conduct. As an example, we would -- in our DLBCL study, we would exclude primary CNS lymphoma. And that is true for most people who actually do develop in non-Hodgkin's and DLBCL. The disease itself is sort of similar to DLBCL in terms of its aggressiveness and the cellular features. But of course, the localization is different. The localization is actually in brain, typically. And the concern, of course, when you do actually treat in the brain is that you obviously want to make sure that the adverse event profile is reasonable, and you wouldn't actually get a significant amount of adverse event. So when we look at our own program, we believe that we have, obviously, a very good safety profile, and demonstrated that. And we had some limited information in terms of the activity of the product from experience in children who developed leukemic relapses in the CNS and that were treated with AUTO1, and where we could show clearance of the disease in the brain as well as a reasonable safety profile. In addition, obviously, when we look in patients in the CSF, we do also find very significant levels of AUTO1 CAR T cells in the CSF. In other words, the product gets where it needs to be active. Now in terms of proxies from other programs, there is actually very, very little data. Because frankly, as I mentioned, mostly everybody excluded that indication from therapy and the standard of care. In essence, it's high-dose chemotherapy regimens that are being used, at times intrathecal delivery directly into the brain as part of the therapy. So it's truly one of those neglected almost orphan-type of ultra-orphan type of cancer indications.

Okay. Okay. Another question related to this strategic update on AUTO3. I guess, does the change in planning their impact -- how you're thinking about the buildout of the manufacturing facility? Yes, that'll be the question there.

So the way that we've always been thinking about the manufacturing infrastructure required to support the programs is really to build it in a modular way so that you can actually adjust to the ramp, that you're actually going to go through the expected ramp for these programs. And that gives you a lot of flexibility. So in a very simplistic way, think of it as a shell with a set of modules in it and you can basically, through the number of modules, adjust the level of capacity that you need. And you can also, with that, actually operate at a level that is sensible and also sensible from a capital expenditure perspective.

Okay. On AUTO4, I guess, how should we be thinking about sort of the updates, the type of data that we could see over the course of 2021 from that program just based on sort of what you're seeing in terms of patient accrual, patient numbers, [ types of ] treatment, those kind of metrics?

So AUTO4 is in a Phase I dose escalation trial. So this is going to be sort of a limited number of patients because you go through classical 3-plus-3 design through dose escalation, which obviously has DLT periods and review points as you increase the dose levels. This program is enrolling well, and we're very happy to sort of be back actually in full swing with the program. It was actually one of the programs that got pretty severely hit last year due to COVID. We're active predominantly in the U.K. and in Spain. And obviously, both countries were very significantly impacted and led to a delay with that program, but we're all back on track. Enrollment looks good, and we're treating patients.

Okay. All right. All right. And perhaps just coming back to the pivotal program. You've kind of -- it's adopting a 2-stage component design to it rather than a Phase Ib ahead of Phase II. Just maybe just help us with the rationale for structuring the trial in that fashion rather than just sort of proceeding to a Phase II only study. I guess what sort of learnings or sort of needs to be established in the Phase I -- Phase Ib running portion?

Right. So there are 2 things basically in this. First off, obviously, we went into what ultimate will also be the commercial environment for manufacturing. So it was a transition into a different environment, still using the same type of equipment. But obviously, with some small adjustments in the manufacturing process. Secondly, we were moving to, but it will be the commercial source of the viral vector used for the manufacturing process. And so that transition and adjustment of the manufacturing process also obviously required comparability work and the transition in that sense. And that was one of the key reasons for including a Phase Ib component into the program. The second aspect is that we were obviously going from a single country, a relatively small number of centers trial to an international trial with actually the majority of the centers in the U.S. And one of the key things that we wanted to make sure we can really iron out, we really have adequately derisked, is around -- and it's been around the logistics, which is obviously an area that's been significantly impacted by the pandemic with the massive reduction in flights as well as obviously, additional logistics impact that we've seen across both the U.S. as well as many European countries. So those were kind of the key questions that we wanted to actually address, make sure they're properly tested out and de-risked before we start actually enrolling into the pivotal start of the program. And what we couldn't assume, obviously, when we did that planning is, actually, we didn't even think anywhere close to what we're seeing right now in terms of the impact we're seeing on the centers in the U.K. and centers in the U.S. But clearly, a transition to get to those adjustments in the manufacturing process and the logistics.

Okay. Great. Great. Maybe final question here for Andrew. Really, just to update us on the cash position of the company and what that presents in terms of runway?

Yes. Thanks, Eric. I mean the guidance really hasn't changed. Christian don't mind that the cash runway is into 2022. That's what we see that where we are at the moment, hasn't changed.

All right. Great. All right, guys. Well, we'll have to leave there for the time. Thanks again for joining us this morning, and thanks, everyone, for tuning in to the webcast today.

Thank you.

Thanks, Eric. Thank you very much.

Thank you. Thank you.