Autolus Therapeutics plc

Hello, ladies and gentlemen, and welcome to the Autoless Therapeutics call to discuss the full year 2023 financial results and business updates. At this time, all participants are in listen-only mode. After the speaker's remarks, there will be a question and answer session. To ask a question at that time, please press star 1-1 on your touchtone telephone. As a reminder, this conference call is being recorded. I would like to turn the conference over to your host, Olivia Mansour. Please go ahead.

Thanks, Michelle. Good morning or good afternoon, everyone. Thanks for joining us on today's call. With me are Dr. Christian Aitken, our Chief Executive Officer, and Rob Dolski, our Chief Financial Officer. So on slide two, before we begin, I'd just like to remind you 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 or 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 assume 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 three, you'll see the agenda. As usual, Christian will provide an overview of our operational highlights. Rob will then discuss the financial results before Christian will conclude with upcoming milestones and closing remarks, and we will then take questions. Over to you, Christian.

Thanks a lot, Olivia, and welcome everybody to our full year update. Obviously, it's been a very successful year for us, and we're going to go through the accomplishments during the course of last year, particularly with our lead program, OBSEL, on the following slide. But what we'd like to start out with is obviously the important transactions that we've been able to complete in February this year, obviously post the reporting period. Obviously, there are two transactions we conducted. One was the strategic collaboration with BioNTech, which I think sets us up in a very interesting and attractive way going forward with a very strong partner, and I think a lot of opportunity to realize synergies between the two companies. The focus of this collaboration has been sort of on three key platforms that we have developed. is providing access to BioNTech to our manufacturing platform. Obviously, at the core of that being the nucleus manufacturing facility, but also, of course, all the systems surrounding the product supply platform. Secondly, the commercial platform that we've been setting up and obviously are in the midst of preparing the company for a potential launch at the end of this year for OBSEL. Obviously, the systems we set up, the procedures, the presence of the centers we're building up, All obviously can be leveraged beyond just OB-Cell, and I think there's significant opportunity there for additional programs to be served through that platform. And then also, obviously, the access to two of our product candidates, Auto 122 and Auto 6NG, in co-development and co-commercialization options that we have granted to do both of those programs. and I think will allow us to accelerate some of our pipeline programs, and obviously looking forward to the collaboration here with our partner. We also have additional support to launch and to expand OBSEL into additional indications, and so between all of those components, we were looking at an upfront a contribution of $200 million through an equity investment and $50 million in cash from BioNTech, and then an additional $582 million in further option exercise and milestone payments. So this obviously is a key transaction for us, I think, with a very attractive partner that has a very similar view on how we want to approach oncology, what the challenges are, the opportunities are. and we're really excited to working with BioNTech on a number of opportunities and products going forward. Now, what we also did in parallel or right in sequence to executing the agreement with BioNTech is to run a financing transaction which has yielded gross proceeds of an additional 350 million. So between the two transactions and the year-end cash position of 240 million, We're looking at a beginning of the year cash position on a performer basis of around $800 million plus, which also sets us up in a very strong position to execute the plans that we have discussed with you leading up to these transactions as well. Moving to slide number five, what I'd like to do on this slide is really kind of highlight some of the key activities that we've been engaged in with OBSEL during the course of last year, but also have progressed in the first quarter now, as well in 2024. First of all, we've given obviously two key updates during the course of last year on the Felix data for Obicel, providing the first data presentation at ASCO, which was focused on the morphological cohort of the Felix study. This included about 94 patients that we reported on, and we presented the overall outcome of the study. What we then did actually at the ASH time point in December, early December last year, is to look at the entire Felix study, which included two additional cohorts, one cohort with patients that had minimal residual disease, so less than 5% tumor burden at time of inclusion, and also patients that have isolated extramedullary disease, which is a patient group that typically gets excluded from clinical trials due to the challenging nature of the disease and the very high bar and challenges to actually get meaningful results in these patients. So we're provided at ASH actually the totality of the data and we believe that is important because that actually reflects the continuum of tuber burden and risk categories that physicians are facing when dealing with adult ALL patients and in that regard reflect a proper cross-section of the patient population And obviously, as you may remember, and we'll talk about a bit in further detail in upcoming slides, obviously, we've shown very significant, very meaningful clinical activity combined with an excellent safety profile across all of these categories of risk in the patients treated in Felix study. What we also did is we provided an update on patients where we do actually have longer follow-up, and these come from the old CAR-19 study as well as the Felix-1B study. In fact, between the patients that we had actually in that analysis had more than three years of median follow-up, and that gives us a very good understanding of what to expect longer term in terms of outcomes from the study, and we'll briefly talk about that as well in the upcoming part of the presentation. Now, what's absolutely critical in this space is your ability to deliver product, and that's certainly been the most challenging part if we think about the path that we've taken with OBCEL, with the company, is to establish our own capability of delivering product. And obviously at the core of that is the Nucleus facility, which is located here in the UK in Stevenage. And what we managed to do during the course of last year is really get that facility, not just get the build finalized, but also taking the facility into operation, qualify and fully validate the facility. And all of that data is is key data that actually did flow into the BLA filing. Just as a reminder, from the time point when we actually broke ground for this facility, which is a four-story industrial build, a greenfield build, we took exactly 24 months to actually get the facility fully validated, everything written up, and into the BLA to the BLA filing. Overall, in terms of generating all the reports and the data sets, it was 22 months. So that's an exceptionally short period of time and it required us to frankly take very different approaches from the build, the design, the build, but then also the operational model to be able to achieve this. So what we also have obviously since reported is that we just went through the full inspection cycle with the MHRA. One of the prerequisites that you have if you operate with manufacturing facilities in Europe or in the UK is that you actually do need licenses for those facilities to supply product, not just for clinical trials or for supply within the country, but also to be able to export product. So if we think about U.S. patients, obviously we're also exporting back to the U.S. the final produced product here in the U.K., and that actually required a specific license. So we have obtained this license. And they're now actually in a position that we have fulfilled the first major step here to get the facility in a position where it can actually support patients from the UK. Now, the second, obviously, key step is, obviously, the regulatory review coming that we're in the midst of the process of. We filed the BLA at the end of last year. And during the course of November, we got by mid-January the filing accepted for review by the FDA with a PDUFA date of November 16 this year. Meanwhile, we also actually have filed with the European Medicines Agency, an MAA. And with that, obviously, we have now filings into the two major jurisdictions, from a commercial perspective for this product. We're also going to be in conversation with the MHRA on the approach here to a registration path, and that's going to be the third jurisdiction we're looking to actually get the product approved as well. When we look in terms of the commercial readiness, obviously one of the key activities that you have to involve in is not only creating awareness for the product, which is mostly the medical affairs teams job to drive that, but also to make sure that we're in a position to deliver the product. And for that, obviously, the centers need to be accredited. We're in the midst of the process of getting centers ready for commercial use of the product. And those activities are all on track with an expectation that we will have 30 centers ready at the time of launch for ready-to-use OBSEL once an approval is in. So those are kind of the key updates that we ran through from an OB cell perspective during the course of last year. It was a very heavy lift to get to a place where we had both the clinical data as well as the manufacturing capability. And now the focus this year is obviously to drive through the regulatory process and prepare the organization for launch. Moving to slide number six, when we look beyond the OB cell opportunity within ALL, As we had indicated, we also are going to be moving into the autoimmune segment. And in fact, the first study is open for enrollment. It's called the Carlyle Study. What is important about where we are with the program is obviously that we're setting up and spacing our program on the very strong foundation that we have built for OB-Cells in the adult ALL setting, which gives us a lot of safety data. It gives us, obviously, the regulatory packages, which are absolutely relevant. It gives us the commercial supply capability and presence in the centers. These points, we believe, are very critical to be able to deliver effectively in the autoimmune settings. And obviously, what we have shown over the last several years is that we have an exceptional profile from both an activity and a safety perspective with OB-SEL. Looking at programs beyond OB-cell, we did update on two programs. We updated on auto-8 at an oral presentation of the McCarty study at ASH, where we could show very high levels of clinical activity and we believe very nice cellular dynamics that we were seeing beyond just the clinical activity, but also cellular dynamics of the product. It looked very interesting and seemed to benefit from the dual targeting approach that we're choosing, and we've chosen for auto A-tier targeting both BCMA and CD19. And then the auto 6NG study in neuroblastoma, the Magneto study, also is open for enrollment as of the end of last year. So that's actually very nice progress on those products, not on this slide. We also published the pediatric ALL data from auto 122 in the journal blood also in the September timeframe last year. Moving to slide number seven and looking at some of the organizational changes that we ran through. First of all, I'd like to congratulate Chris Williams as well as Alex Strix to their promotions. Chris obviously has been instrumental in the various transactions that we have done over the years and obviously most recently the BioNTech transaction. And Chris has been promoted to Chief Business Officer and Alex Strix has been promoted to senior vice president for legal affairs and obviously continue as the general counsel of the company. We also have a transition within the executive team. Edgar Brandly will step down as chief development officer to pursue other opportunities. Edgar will continue to advise the company through the regulatory process for the BLA and MMA through the completion and approval of these and getting to approvals in those two processes. And obviously we'd like to thank Edgar for the fantastic job. Edgar joined in the middle of 21, right at the start of phase two of the pivotal sections at Felix study. Obviously a very challenging starting point managed to with the team to get the study obviously conducted to very successful outcome as well as obviously then translate in record time this data set as well as the data set coming from Dave's team. on the manufacturing side into the BLA filing and the M&A filing, which was an enormous achievement in a very limited amount of time. So fantastic outcome. A lot of gratitude there and wish Edgar well with his next endeavor. And what we're internally will have Miranda Neville take over from Edgar. She's running the OB-Cell program and has been for quite a while. and she will also continue to run the development team, so we have a nice level of continuity and drive forward. As we go through the course of this year, we will obviously expand also our team more also into the autoimmune segment, and there will be certainly announcements during the course of this year with sort of the build-out of the development team in that direction as well. And finally, we have strengthened our board of directors. We had two recent appointments. Liz Leiderman joined us, as well as Bob Azelby. Both of them obviously bringing very significant level of experience. Liz obviously with a strong financial and transactions background, and Bob with a very strong background in commercializations, both on the oncology side, on the CAR T side, but also on the rheumatology side. So very relevant backgrounds, very significant opportunity for contributions as we go forward, and also we're excited to have both of them now part of the board of directors. Now with that, I'd like to move to slide number nine, and just briefly remind you obviously of the unique mechanism of action at the heart of the features that we see in the clinical properties we see with OB-Cell. And this is all about driving a product that can physiologically engage with target cells, which means it can engage rapidly, it can deliver the kill, and it can then disengage rapidly as well so that you do not have over activation of the CAR T cell in the process. And as a consequence, you'll maximize, on the one hand, the activity because the product and the cells get recycled back into action much more quickly. So you have actually more active agent available at any given point in time. But also you avoid the toxicity that is seen with overactivation of the T cells and obviously is at the core for the reduced cytokine release syndrome. and in general as well the immunological toxicities related to neurological toxicities are usually referred to as ICANNs. So in the feature that's at the core is this very different way of engaging the target antigen and obviously as you remember has resulted in very different profile for the product. What I'd like to do on the next slide which is going to be slide 11 is really talk about a few aspects of the Felix study that we have presented in terms of the pooled analysis at the ASH meeting at the end of last year. I think what's important here is to understand, and I sort of already alluded to that when I was briefly talking about the time point when Edgar actually joined us, we conducted this study in the midst of the pandemic. And that is important because obviously we're dealing here with patients that are highly immune compromised, patients that are very high risk of infection. In fact, many of these patients do pass away as a consequence of sepsis in general as a major cause of death. And as you can imagine, being in the midst of the pandemic with travel restrictions and lots of concerns around the safety for patients, This has been a really challenging study to conduct, and in essence, what it resulted in is actually a study that is pretty much a real-world study that we conducted here. Now, what is also important to understand is that as you're operating in this type of an environment, you also have to actually make sure that the way that the physicians can manage the patients gives them a very significant level of or a degree of freedom to frankly make the right choices and deal with the circumstances and challenges that they may also have experienced at the respective sites during that period. One of the key aspects there is actually the bridging therapy. Most clinical studies conducted in the space actually do restrict the type of bridging therapy you can use, which is the therapy between collection of the cells and actually dosing of the cells. And by restricting those, therapeutic options for the bridging therapy, obviously it helps you select the patients that can manage with a certain type of bridging therapy. But at the same time, if you imagine this situation in the midst of the pandemic, it also would have been very, very challenging if we had actually basically put that in place. So different from studies in the past, we actually allowed any type of bridging other than Blinzaito, so CD19-targeting T-cell engager, but any other therapeutic actually was allowed in the bridging therapy. And we did do that because we needed to make sure the physicians had every possibility to manage the patients, given the unforeseen nature and the challenges that many of these institutions were facing, and with that actually making sure you can keep the patients safe and properly manage the patients. So that's a key element. And of course, what that also means is that the data we're seeing is very much a reflection of the real-world setting. The same is true, obviously, in terms of the types of patients included. I mentioned that before, where you have very low disease burden, or you have extremely high disease burden, or you have disease in areas outside of the bone marrow where the disease tends to be very challenging to manage. In all of those cases is where the patients present, and you need to understand, actually, what the product does in those patients. And one of the strengths of the FELIX study is it actually provides data for all of these risk categories and with that gives valuable information to the physicians on what to expect with a particular patient and manifestation of the disease in that patient. Slide number 12, we did actually look at sort of the change in disease burden in these patients as we are comparing the disease burden at screening versus the disease burden at lymphodepletion. And of course, this is an impact, what you see here, also of bridging therapy. And what's quite remarkable is that from every level of tumor burden at bridging, you get to every other level of tumor burden at lymphodepletion. So you can go from very low tumor burden of less than 5%, being in minimal residual disease, you can go all the way up to 75% tumor burden. But also the reverse, you can have more than 75% tumor burden at screening, and you can go below 5% at lymphodepletion. And it shows the variability of the disease and the dynamic nature of this disease and the impact of actual bridging therapy here for these patients. What was very striking to us, and this is what's summarized on the next two slides, is when we then actually look at the outcome of these patients, dependent on the level of tumor burden at lymphodepletion. And what's quite striking when you look on slide number 13 is that going from the top line in blue, where you have below 5% tumor burden, to the middle line in green, which is between 5% and 75% tumor burden, to the red line, which is above 75% tumor burden at lymphodepletion, you see there's a profound impact on the event-free survival, as you would expect, because there's obviously very different amounts of tumor cells that have to be removed in these patients to drive outcome. Now, we see very clear differentiation, but remarkably, patients that are below 75% tumor burden tend to actually reach a plateau on the EFS, which is very encouraging when you think about the potential for long-term outcomes in these patients. Now, if we go to slide number 14, we also see an impact on the tumor burden on the actual adverse event profile, particularly with regards to immunological toxicities. And what you can see on the left-hand side is a view on the cytokine release syndrome and ICANS in all patients. And you can see we had a very attractive profile having high-grade CRS in 2% of the patients and high-grade ICANS in 7% of the patients. This is very low. This is lower even than what was observed in these types of patients with products like Blimcyto. Now, when we look at the CRS by the BLAST count, the level of tumor burden at the time of lymphodepletion, you can see that there is clearly quite an interesting behavior here. We see overall, as tumor burden increases, we see an increase in the overall adverse events with cytokine release syndrome of any grade going from 47% to 88%. However, we do see that consistently across the board, the high grade percentage for cytokine release syndrome is low. It's in the 3% to 4% range between 5% and close to 100% tumor burden. But in patients that have mineral residual disease, we actually have not observed any high grade cytokine release syndrome in these patients. Now, very similar when we look at ICANs. First of all, I think it's important to realize that the overall level of ICANs is relatively low, also compared to other T-cell engaging or CAR-T approaches. But what we also do see here is the same picture that as tumor burden and lymphodepletion increases, we do see an increase in overall ICANs levels in these patients, going from 8% to 43%. But even in the extreme high tumor burden patients who have more than 75% tumor burden, the high-grade ICANNs is at 15%, which is comparable to a T-cell engager. Now, what's also important, and this goes back to also the view that we had on the CRS, if we look at patients that have less than 5% tumor burden, we do not observe high-grade ICANNs in these patients. In fact, the overall ICANNs level is very low with 8% overall. So it points to an impact of tumor burden and lymphodepletion both on the outcome from a clinical activity perspective, both on an ORR perspective as well as on an EFS perspective, but also see very clear differentiation with regards to immunological toxicity and the risk of these patients experiencing immunological toxicity as a consequence of the therapy. So this gives you actually an ability to anticipate for the physicians and plan accordingly for these patients. Moving to the sort of the sentinel view based on the Olkar-19 and the Felix Phase 1b data. And this is going to get us to slide 16. And so what we're looking at here on the left-hand side is the event-free survival. And we do see that the event-free survival with or without censoring for stem cell transplant or gives us a plateau that's somewhere in the range of 35 to close to 45% here. And that also gives us a very attractive proposition because it suggests that indeed a significant proportion of the patients manage to get into a long-term remission. In these patients, you can see the longest observation with time we have with these patients is at 60 months or five years. When we look at the median overall survival or just the overall survival curve per se, what you do see, the median obviously gets crossed at around 16 months. But the actual story is the fact that we see a tail building. And we have around 40% of the patients that are surviving. And it looks like the curve, as we've seen at EFS, is stabilizing, suggesting that indeed we have long-term benefit for a proportion of the patients. which is very encouraging and something that, unfortunately, we have not been able to see with other therapeutic modalities in the past in this indication and at this stage of the disease. Moving to slide 17, this is just a slightly different look where you just look at swim plots here, and you see the coral area as well, as we just looked at, also depicted in a slightly different way. Now, if we look at the commercial launch readiness, which is sort of the key activity that we're engaged in during the course of this year while we're working with the agencies through the review process for the product, obviously we have just updated you on the fact that we had this week that we got the MHRA inspection and approval for the nucleus facility, and we filed the MAA in Europe as well. We expect to file an MAA in the UK with the MHRA as well. Timing's still to be defined, but it's going to be as soon as we can. And then, obviously, we have the FDA PDUFA date on November 16. So this sets us up for very significant, very tangible, obviously, progress through the course of this year for OB-Cell and also planned data updates for OB-Cell and additional follow-up data on the Felix study in the mid-year section, so the ASCO EHA timeframe, and then also at the end of the year at ASH. So when we then think about sort of the possibility and the opportunities for expanding OB-cell into additional indications, there's sort of two fundamental paths we can think about. One is to move more broadly into the oncology arena with different forms of B-cell malignancies, and alternatively also look at the opportunity in autoimmune disease where we know that the driving factor for those autoimmune diseases are autoreactive antibodies, obviously driven by B cells and corresponding plasma cells. In this, from this approach perspective, obviously when we think about the lifecycle management for OB cell, it goes into two directions. There's OB cell itself. And then, obviously, auto-122, which is the dual targeting approach that we explored in pediatric patients, which gives us opportunity, particularly in those indications where we have established loss of CD19 antigen as a right of escape. And that's certainly shown in ALL. It's clearly shown in the BCL. So those are very clear kind of directions for that type of a product. And with auto-8, a combination of BCMA targeting with CD19, And I would say DAC is an option for both moving towards the multiple myeloma segment or related diseases, as well as plasma cell and B-cell-mediated autoimmune diseases. Now, I did mention earlier here on slide 22 that we have opened the CAR-Live study and we're enrolling patients. This is really a dose confirmation study, and as a backdrop, I think it's important to understand that the product that is sort of referenced and really has opened up the opportunity for CD19 CAR-T products in autoimmune disease at the University of Erlangen, which is a study that was done by Georg Schett and Andreas Muckensen, actually comes from a product that was initially set up for patients with pediatric ALLs. And the product has a lot of similarity in its structure, if you look at the chimeric antigen receptor with Chimriah and Brianzi, as a different manufacturing process compared to both of those commercial products. The properties of the product actually are quite well known, and it has allowed us to actually compare our pediatric data to the pediatric data that was obtained at the University of Erlangen, and we do see a very nice match in terms of the overall data, as we had seen with Kimraya, as you may remember, in the CAR-PAL study. So very high levels of molecular CRs, comparable, superimposable, very similar levels of long-term outcome, very comparable levels of long-term persistence. So the product in Erlangin is a long-term persisting CAR-T product, which in pediatric patients also has persistence of two to three years or longer, very similar to what we've seen with OB-Cells. And of course, as we had seen with Kimraya before, obviously the safety profile that we have with OB-Cell obviously is better because of the different way of engaging the CD19 antigen. All of this is done at the exact same dose level that was used with OB-Cell in the pediatric studies, which is one million cells per kilogram. So we know that our profile is absolutely overlapping on actual clinical data in pediatric ALL patients with the product that was actually ultimately then used in the autoimmune patients in airline. Now, the additional point I think here is that because we obviously know what the dose is and we have a lot of safety data obviously from our product at that level, what we're doing now is moving the product into a single dose rather than actually have a fixed dose, rather than having a weight-based dosing, which is a million cells per kilogram, which you have to do in children because of the wide range body size that you actually have between one-year-olds and young adults. Obviously, here in autoimmune diseases, we're dealing typically with young adults or adults in general. And so we can actually pick a fixed dose, which simplifies the operation at the clinical center, and it reduces any possible dosing errors that could happen as a consequence of a variable dosing regimen. So we're exploring, therefore, and confirming the fixed dose here at 50 million cells in six patients. And with that, we believe we're actually well set to then take the next step and move this product forward and towards a pivotal study. So this is a quick update on the study and what we're intending to do with it. But also I think the reference to how it sort of relates to the original data that was generated in the field I think is important also to understand that we do not have to speculate whether our profile of our product is appropriate for these patients. We know it's exactly the same profile from an efficacy perspective. So when we then look into other pipeline programs and technologies, obviously you'll remember there's a number of programs that are ongoing. And we keep on, we'll keep updating you on these programs as they progress in their early clinical studies, particularly obviously also Auto 6 and G. Auto 9 will be transitioning into a clinical study as well during the course of this year. So with that, I'd like to hand over for the financial results to Rob.