Autolus Therapeutics plc (AUTL) Earnings Call Transcript & Summary

Good morning, and thanks for joining the 40th Annual JPMorgan Healthcare Conference. I'm Eric Joseph, senior biotech analyst with the firm. And our next presenting company is Autolus. And here to talk to us a little bit about the company is CEO, Christian Itin. There is a Q&A session after the presentation. So just click the icon and I'll work in questions where appropriate. With that, Christian, thanks so much for sharing some of your time with us this week.

Well, thank you very much. Thanks, Eric, for having us at the conference. I'm looking forward to giving you an update on where we are with Autolus and give you an outlook on the activities planned for this year and into next year. So we're a company focused on the development of CAR T therapies. We're listed on NASDAQ. If you go on Slide 2, please have a look at our SEC filings for a full set of disclosures and also the risk factors. Moving to Slide 3, and then 4, we're focusing on the development of our lead asset lead program called obe-cel, which are developing in patients with acute lymphoblastic leukemia, in particular, the adult patient population. This is a very significant opportunity as we'll walk through during the course of this presentation. We're conducting a pivotal study, which is called the FELIX study, and we're expecting data in the second half of the year and in the early part of next year. The program, obviously, is not only designed for the treatment of acute leukemia, but also has potential applications with the broader set of non-Hodgkin's lymphoma indications. And we're in the process of evaluating the profile of our product in those indications as we're going through the course of this year, we're having our planning updates at the middle of the year as well as towards the end of the year as well. In addition, we're working on the next-generation program as part of life-cycle management for obe-cel where we're adding a highly potent CD22 CAR on top of the CD19 CAR that is sort of the foundation for the obe-cel program. And this program is currently being evaluated in pediatric patients, and we also are having data updates during the course of the year. In addition, we're working on other indications, including T-cell lymphoma, and we're preparing clinical trials for neuroblastoma and multiple myeloma as well. Overall, we have a broad set of technologies and also a very strong manufacturing base for our products. Moving on to the description and an introduction to acute lymphoblastic leukemia, particularly again, the focus on the adult patient population. I'm moving to Slide #6. There's a very high unmet medical need for adult patients with ALL. ALL is a very challenging disease. It actually resides in the bone marrow, and it actually formed and driven by cells that are very, very close to actual stem cells. So they have an enormous proliferative potential, and they're very challenging to manage. Because they reside in the marrow and they dry that marrow, the patients tend to become, as a consequence of the disease, quite significantly immunosuppressed. Now the standard of care that we're using in this space is that we are treating the patients with high-dose combination chemotherapies, which are intervals of treatment, short recovery times, other treatment interval drug recovery time, and we're doing this in repeat cycles. It's a quite a horrendous type of treatment that the patients are going through. The outcome, though, is positive from a response perspective. In fact, 90% of the patients do achieve a complete remission. The challenge, however, is that most of those remissions are short-lived and the patients do relapse. In fact, only about 30% of the patients see longer-term benefit after the initial line of therapy. Once you relapse, the outlook actually is rather poor for the patients and the disease tends to progress rapidly. Normal course of action is that the patients get back on high-dose chemotherapy followed by stem cell transplant. And for patients that are breaking through that again, which is the majority of the patients, the patients then have the option of a set of targeted therapies, which include Blincyto, Besponsa and Tecartus. Overall, the challenge has been with these patients that they are prone to have immunological toxicities, particularly if you use immune-based therapeutic approaches like Blincyto or Tecartus. And that has been one of the challenges overall that the patients are rather fragile and have a lot of comorbidities. And you need to have a therapeutic approach that is, on the one hand, highly potent, but on the other hand, well tolerated. And that's quite a tall order to sort of combine those different sets of properties into a single product. We believe that is exactly what we're doing with obe-cel, and we've been able to manage to obtain orphan drug designations as well as designations for accelerated reviews with various regulators. Moving on to the next slide. What we have on Slide #7 is a quick summary of the 3 products that have more recently been approved, all targeted therapies, Blincyto targeting CD19, inotuzumab targeting CD22 and Tecartus for CD19 CAR. What we're seeing with all of these products is a high degree of activity in terms of the complete remission rates that can be achieved at a range between the 40s to up to the 80% range. However, the fundamental challenge has been with all the therapies that actually to get sustained responses that, that still remains elusive. And as we're seeing, if we're looking at 18 months of event-free survival, those numbers are relatively low. They're about 10% for Blincyto, which is the market-leading product. And they go up to about 25% for Tecartus. Now the toxicities that we're seeing with these agents are typical immune type of toxicity or neurological toxicities in the case of Blincyto with cytokine release syndrome and neurotoxicity. However, the severe versions or forms of those toxicities are limited with Blincyto. With inotuzumab, it's mostly toxicities related to hepatic toxicities that are -- need to be considered. And with Tecartus, it's a typical CAR T type toxicities that you've seen across a number of indications when you do see that they tend to be quite a bit enhanced in the context of ALL with a high-grade of the patients actually having -- almost all patients experience CRS or neurotox. And when we look at severe grades of CRS, about 25% of the patients experiencing high-grade CRS and about 35% of the patients experience high-grade neurotoxicity. So overall, a high level of activity challenges to make it sustained and certainly significant levels of toxicity. So what we were doing when we're designing obe-cel and starting with -- moving to Slide 8, is we're looking to create a product that actually would act as physiologically as possible, which means that the T cells should behave like they normally would engage a target cell, which means having a very [ aggressive ] engagement, delivery of the kill but avoiding high degree of overstimulation. And in order to avoid that high degree of overstimulation and cytokine release, what you have to have is a product and actually engage with the target cell only for a short period of time and then actually dissociates from that target cell and can actually be used again in other kills and consider to continue to contribute to the clinical activity without adding and producing a lot of cytokines. Technically, the way to do that is to actually creating a product that has a fast on rate, which means it has a very high degree of specificity, but also a fast off rate so it can get away and off the target very quickly. And that is fundamental to the design of the product. So it's a unique mechanism of action that we designed here. And the premise was that we should see improvements in activity, we should see improvement in persistence and we also should see improvement with regards to the long-term as a consequence of that. Now, we have the opportunity and summarized on Slide 9 to evaluate the product at this point in 3 Phase I clinical trials. They do cover quite a range of patients in ALL. We're having -- started actually with the program in pediatric patients, moving then to an adult patient population that we treated in the U.K. and then the running for the pivotal study where most of the patients actually were recruited in the U.S. Now, what we see across these 3 pivotal -- at these 3 Phase I studies is a very consistent outcome. None of the patients that we have treated in these studies, which was a total of 50 patients, have experienced any form of high-grade cytokine release syndrome. They also experienced only limited high-grade neurotoxicity that was rapidly reversible with a steroid intervention. And as you can see in the adult population, actually, when you look at the any [ grade ] line for neurotoxicity, it is actually fairly low. It's between 13% and 20%, far off from the close to 90% that we're seeing with the currently approved product in this space. Now, we're seeing this consistent outcome despite, obviously, a huge difference in the underlying patient conditions that we had in these trials, starting with children with a median age of 9 years, going to adults with a median age of 42, a wide range of tumor burden going from 21% higher amounts of tumor burden to 75% of the patients having higher amounts of tumor burden and also a varying degree of pretreatment with Blincyto as well. So what is very encouraging is the fact that the data is highly consistent across this wide range of outcomes -- in the patient population. Now, moving on to Slide 10. What we've been able to show, and this is now data from the ALLCAR study, and there's very similar data that we could show and actually have published on the pediatric study, the CARPALL study, is that we have exceptional persistence. What you see on the left-hand side is, in fact, the median persistence of the CAR T cells now looked up to a time point of 24 months of follow-up and we'll obviously continue to observe these patients. But what is important is this is not just a faint signal that you pick up by a genetic marker. This is actually looking at cells in circulation using facts analysis to actually determine the presence of the CAR T cells. These CAR T cells are active, so we can see continued B-cell aplasia in these patients as well. And what that translates to is what you can see on the right-hand side. On the right-hand side, you see the event free survival of these patients and looking at patients in morphological complete remission. As you can see, as the patients reach 12 months of follow-up, the event-free survival stabilizes and actually stabilizes at around 46% and actually stays flat up till 2 years and out to 3 years. In other words, we have been able to actually get these patients while there were initial relapses to then actually stabilize and the patients that made it beyond 12 months stayed in remission. That is very encouraging and very different. Remember, I quoted before that Blincyto 18 months is at 10% and Tecartus is at about 25%, right? 46% and we continue to stay there whereas and all the currently approved programs continue to deteriorate. So with that, in summary, on Slide 11, we believe that the profile of the product actually has the potential to be transformational for adult patients. We're building on a unique mechanism of action with a very high level of complete remission rate that shows and translates with excellent persistence into long-term event free survival in these patients now, obviously, with a median follow-up of close to 30 months. We combine this very favorable profile with a very favorable safety profile with no high-grade cytokine release syndrome and very limited neurotoxicity. Moving to Slide 12 and a quick look at the market as it currently presents itself. And as I indicated, the leading product in the space is Blincyto. And you can see the product has been doing well and continually adding market share actually as we're looking at the last few years. We expect the product to reach this year about 2,000 adult patients. This is based on an average treatment price of about $180,000 per patient. As you remember, the CAR T price that we have between the various approved products now in this space range from about $400,000 to just shy of $500,000 in the current environment. Now, what we also see is that a lot of centers gaining experience with CAR T therapy, a lot of it in the DLBCL segment. But also now, a certain number of centers are gaining experience either through our own clinical trial or then through the activities on Tecartus with ALL patients. Overall, the adverse event profile that needs to be managed for obe-cel is very, very similar to that of Blincyto, which is very encouraging because it means that a lot of that experience base within the hospitals are directly applicable for our therapy as well and bode well in terms of the ability to actually manage the product adequately. Moving to Slide 13, and we're obviously conducting a pivotal study at this point in time. It's a 100-patient single-arm study. We expect to be fully enrolled as we go into the course of this year and expect to have initial data starting in the second half of this year. Moving on to Slide 14. As I indicated, we're also evaluating the product outside of ALL, in non-Hodgkin's indications as well as obviously expanding into the dual targeting approach AUTO1/22. And this is what we're going to be looking at next on Slide 16. There's a quick summary on the right-hand table of the basic experience that we had with the program in pediatric patients. I think the fundamental finding was that we had excellent activity, no tox cytokine release related toxicity that was significant, but we did see about half of the kids relapse due to antigen loss in CD19. And that's why we went back and basically built on this very favorable profile that we'll be selling kids and adding a highly potent CD22 CAR. We're able to show a high degree of activity on Slide 17. This was shown also on ASH a few weeks ago. So a highly potent approach, more potent in those models than obe-cel was on its own and certainly active against leukemias that are CD19 negative as shown at the [indiscernible]. Overall, we're excited about the program as on slide -- summarized on Slide 15, with an ongoing exploration in a Phase I clinical trial with pediatric patients, and we expect to provide an update middle of the year and then a longer-term follow-up by the end of the year. Moving to B-NHL on Slide 20. We have explored started the exploration of the product in those indications. We so far have a remarkably positive safety profile, no high-grade cytokine release syndrome and no patient experienced any form of neurotoxicity. Moving to Slide 21. We translated -- as we've seen in ALL in this program into a very high level of persistence that the CAR T cells actually behave very similar to what we've seen in the ALL patients. I'm moving to Slide 22, resulting into very high levels of clinical activity. All non-Hodgkin's lymphoma patients achieved a metabolic complete remission that were evaluable at the time with data cut. We had 1 CLL patient in addition to the non-Hodgkin's patients that did have a partial response with a complete minimal residual disease negative condition in the bone marrow. Now all in, obviously, very encouraging. We see initial good durability in the follicular patients and no relapse in that patient population. Now in summary, I think, very favorable starting point that we have. We'll obviously explore in a larger patient group. We expand the cohorts. And we obviously want to have extended follow-up from these patients to understand the profile and then to support the decision-making around further clinical development in those indications. We go to the pipeline on Slide 25. Obviously, we're active in T-cell lymphoma. The AUTO4 program is in clinical exploration. We expect to provide an update midyear. And then when we look at technology, we obviously have a wide range of technology, 99 patent families under prosecution obviously, a very significant technology treasure that we're building on. And when we look on Slide 27, a series of programs that use that technology in various forms. I just want to highlight our first solid tumor program, which is getting into clinical middle of the year, AUTO6NG, which has multiple programming modules actually included. Then getting towards the end of the presentation, a quick look at the announcement that we made at the end of last year. We have the opportunity to collaborate with Blackstone Life Sciences, who've committed to invest up to $250 million into the development of obe-cel in adult ALL and supporting the full development of the program towards commercialization. This obviously gives us a very strong opportunity to really drive the program as we sort of need to do that at this point and build off commercial manufacturing capacity, et cetera. And obviously, this transaction has obviously strengthened our balance sheet, provides us capital and runway into 2024. So finally, our next steps. We believe we have an interesting year ahead of us here with obe-cel obviously running through the pivotal study, developing delivering first clinical data on the pivotal study. We have updates on AUTO1/22 in pediatric patients, progress across the pipeline and overall, a strong cash balance, which is starting the year with more than $300 million in cash. With that, I'm happy to take questions. Thank you very much.

Good. Thanks, Christian. Maybe just picking up on the FELIX study to start. I would just be curious to get a sense of how accrual -- how enrollment of that trial has been progressing. And really, if you're really how accruals weathered some of the -- where you've seen experience any impact from spiking cases of COVID in the pandemic. And yes, we'll do the first question there.

Yes. So the accrual into the study is going well, obviously, for patients with a very high medical need. But I think it is absolutely important to understand the challenges that I think many of the clinical centers, not just in the U.S. but across the globe are having -- with dealing with the COVID infections. And there's sort of 2 challenges, I think, there are 2 levels that the centers are facing. One challenge is that many of the centers lost nursing staff. And we're looking at 20%, 25% loss of nursing staff in many of the institutions. We're talking top centers in the U.S. and Europe. So that's been a very significant issue kind of a consequence of, frankly, burnout during a very high, highly intense and challenging period for hospital staff. So the centers are facing significant challenges that they're working through. We're obviously with a patient population that is -- had a very high medical need were less impacted than I think would be in other indications. But it's an objectively a very significant challenge for the centers. Certainly, in certain areas within the U.S. right now the centers are having a hard time actually conducting clinical trials because they're completely swamped. And we're talking really the developments over the last few weeks, with the Omicron variant really taking over and going into overdrive.

Okay. Okay. It seems as though because of all this, there's a little bit of a slip in time line from what we -- from when you're now anticipating to read that initial data from, from the Phase II portion of FELIX. Can you just sort of speak to what that initial readout might comprise? Initially, we've been kind of thinking about an early look, including response rate data and a follow -- a subsequent follow-up looking at event-free survival. Is that still the expectation? The expected sequence of readouts just right shifted a little bit? Or should we be thinking about things a little differently, perhaps a more comprehensive presentation in the second half, comprehensive readout in the second half?

So the way the study is set up is -- the primary endpoint of the study is complete remission rate, and that is actually achievable, will be done after 2 months at the last patient dose. So that's a relatively short observation to get to the actual CR rate within the trial, which is the primary endpoint. The secondary endpoints, which are also actually the critical ones from an approval perspective is the ability to sustain those CRs over time. And so there's event-free survival, duration of response, which was a secondary endpoint. So what we expect to be able in terms of data releases, we expected to circulate a top line data related to the primary endpoint. But then the full readout, we expect to become available in the first part of 2023 in terms of target and endpoints.

Yes. Okay, okay, okay. Great. And in terms of just the sequence in terms of the registration strategy, the filing strategy, just kind of walk us through the sequence of events. I guess do you expect to -- assuming positive data kind of file on global, both U.S. and European basis or kind of focus in one geography first versus others?

Yes. I think if you look at the filing strategy, we can look at pretty much all the CAR T programs. There's -- the initial filing is likely going to be the U.S. filing, followed by European filings. And what you also see then in terms of the actual review time lines, we see reasonably consistent review time lines in the U.S. around CAR T programs and at the same time, sort of an extended review time line for all of these programs actually in Europe. So from a sequence perspective, we expect the U.S. market to come first and then actually the European market to follow [indiscernible].

Okay. Okay. With respect to the pediatric program, the pediatric trial with AUTO1/22, there, again, I would also be curious to get a sense of enrollment progress and as well as how patient characteristics in that trial compare with those in the studies with obe-cel so far, including the patients in the CARPALL study.

Right. So within -- on the pediatric side, the patient characteristics are similar to kind of what we had involved in the first place. So these are relapsed/refractory kids or has obviously changed to the original part of the trial is that some of the kids obviously have experienced Kymriah and have been relapsing from Kymriah. We also included, initially, kids that had actually no access to CAR T therapy because of comorbidities or because of tumor presentation that were basically outside the main compartments. And so that's sort of the -- so there's a slightly wider range that we initially included. At this point, we're basically having all comers come in. But it's a small Phase I study as we'd expect for initial exploration.

Okay. Okay. Great. And as looking beyond the pediatric ALL population, just I guess, how should we be thinking about expanded development of that asset for other NHL indications? Do you kind of view it as the kind of the next core product for B-cell after for obe-cel? Or I guess at some point, perhaps there's a decision point between whether to -- whether obe-cel or AUTO1/22 is kind of better positioned for the broader set of B-cell indications. Can you just kind of talk about the decision framework there?

Yes. No, that's absolutely a relevant question now. The answer is literally, it's data-driven. So what we need to see is with AUTO1/22 in pediatric patients is a reduction in kids relapsing due to antigen loss. So that's the premise of what we're aiming for and what the product is designed to do. The other data point that will be important on the adult side is, well, what is the percentage of patients on the adult side that relapsed due to antigen loss. It clearly seems less based on our initial experience. But I think we need to have sort of larger data set to have a really good read on what contribution antigen loss is making to the relapses that we're seeing in the adult patients. So those are 2 key data points. The other data points, obviously, when you think about the broader application in the non-Hodgkin's indications is, again, the overall level of activity, the safety profile and the impact of antigen loss in the respective indication, and that's going to be a critical part of the evaluation as we're making the decisions around the programs. But the beauty is we're going to be building very nice data sets that actually allow us to make decisions based on actual clinical information and basically pick and choose our indications accordingly.

Okay. Okay. Great. A question coming in here in the portal. With respect to AUTO8, it's to be designed as a bispecific for BCMA and CD19. Can you speak to the rationale for targeting CD19 to multiple myeloma?

Well, it's interesting when you look at the space and particularly at the cells that are driving multiple myeloma, there's been quite a wide range of work that was done to kind of look at the cells and the sort of slightly different ways of thought. But there's certainly one avenue would suggest that there is sort of an earlier form of differentiation that actually contributes to the driving of the disease, which appears to actually have earlier markers like CD19 on it. So that's one of the observations. I think the other observations in terms of design of the product, what the product is really designed to do is, on the one hand, to have a very high level of activity on the BCMA side that's really optimized on the BCMA side for a high level of potency. But at the same time, what we're looking to achieve is an improved level of persistence, which has been sort of more challenging for the CAR T programs in that space. Overall, obviously, we're exploring the profile in the clinic. And again, we're going to be setting as I indicated in the past, a pretty high level of activity as a requirement to progress the program forward in the multiple myeloma setting. But the exploration obviously is getting under way, and we're looking forward to the data.

Okay. Okay. Got it. And with respect to AUTO4 and peripheral T cell lymphoma, maybe you can just sort of frame expectations a little bit there, looking to the initial -- the interim readout in terms of patient numbers and what a meaningful activity signal would be in that population -- in those patients?

What we're doing is it's a completely new approach with a novel target that actually haven't been explored before. So what the trial is designed to do is really a classical dose escalation across quite a range of cell doses. And what we really want to see at the higher cell dose is good evidence of clinical activity. And I think that is sort of what we're aiming for at this point in time, and that is the basis for any additional decisions to move forward.

Okay. Okay. All right. All right. I think we'll leave it there for now. So Christian, thanks so much for your time this morning. We really appreciate it. And thanks, everybody, for tuning into this session.

Thanks for having us.