Autolus Therapeutics plc

Hello, ladies and gentlemen, and welcome to the Autolist Therapeutics Third Quarter 2023 Financial Results Conference Call and Business Update. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to turn the conference over to your host, Julia Wilson. Please go ahead.

Thank you. Good morning or good afternoon, everyone. And thank you for joining us to take part in today's call for Autolis' third quarter 2023 financial results and business update. I'm Julia Wilson, communications consultant for Autolis. With me today are Dr. Christian Eytin, our chief executive officer, and Rob Dolski, our chief financial officer. Before we begin, I would 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 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 in the investor section of our website. On slide three, you will see the agenda for today's call, which is as follows. Christian will provide an overview of our operational highlights for the third quarter of 2023. Rob will then discuss the company's third quarter 2023 financial results before Christian will conclude with upcoming milestones and closing remarks. Finally, we will, of course, welcome your questions. Over to you, Christian.

Thank you, Julia, and good morning to you all. Thank you for joining us. It's my pleasure to review our progress for the third quarter in 2023. Moving to slide number four. We'll give you here a quick summary of the progress we've made with OBCL during the third quarter. Key focus has been on preparing the BLA filing, which is on track for a filing by the end of the year. Building on the data we presented at ASCO and EHA early in the year for our pivotal Felix study in adult patients with relapsed refractory acute lymphoblastic leukemia, we look forward to presenting longer follow-up and subgroup analyses at ASH in December. The ASH abstract embargo has just lifted, and we have an oral presentation giving longer follow-up data from the FELIX study on Saturday, December 9. In addition, we will, in a poster presentation, provide long-term follow-up data from our prior OCAR19 study and the FELIX1B study. On both OCAR19 and FELIX1B, we're approaching up to five years and up to three years of follow-up, respectively. I'd also like to highlight that before the end of the year, we'll be initiating a pediatric phase one study of OB cell to support our filing with the European Medicines Agency, which is expected to start in the first half of 2020. So it will be filed in the first half of 2024. Critical for the successful outcome of the Felix study was our robust product delivery platform with high manufacturing success rate, short range of delivery time, and high percentage of patients dosed with OV-cell. During the third quarter, we successfully completed the process performance qualification at the nucleus manufacturing facility, set up for commercial supply, and are on track to support a biologics license application with the FDA by the end of 2023, and a market authorization application with EMA in the first half of 2024. Importantly, we'll be presenting more detail about the OV-cell manufacturing performance also at the ASH meeting in December in a poster presentation. As the program is progressing through the regulatory review, we're actively preparing OBCEL for a potential U.S. launch with critical activities underway in medical affairs, completion of value dossiers, and or boarding of CAR T centers. Moving to slide five. Here is a quick overview of the pipeline progress during the third quarter. First, we continue to expand the OBCEL opportunity, and we are progressing the development of OBCEL in autoimmune diseases, starting with a phase one dose confirmation study in SLE patients which we expect to start early in 2024. We held an analyst and investor event last week where we discussed this in more detail, and a replay of this presentation can be found on the events section of the ODLIS website. In summary, we believe that the excellent clinical profile we've seen for OB-cell will translate well into B-cell-mediated autoimmune diseases. The differentiated mechanism of action, regulatory package, clinical validation in ALL, substantial safety database, and commercial manufacturing and delivery base will provide a differentiated opportunity for OB-cell in autoimmune disease. Data presented at ASH last year demonstrated the potential investing class profile of OB-cell supported by the data observed from the old CAR extension study in B-cell non-Hodgkin's lymphoma. with continued high levels of clinical activity paired with an encouraging tolerability profile across diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia. We expect to complete enrollment in the Olkar Extension Study by the end of the year and to publish the data in a peer-reviewed journal, as well as update data at the upcoming ASH conference this year as well. Together with Dr. Sarah Gorashian from Great Ormond Street Hospital, We published the phase one experience with auto 122 in pediatric ALL patients in blood. The study showed that patients who were not eligible for commercial CAR T therapy showed a high level of clinical activity and good tolerability with over 80% of patients achieving a molecular complete remission with no antigen negative relapses seen with a median follow-up of up to 8.7 months. Included also were patients who had relapsed after chemariotherapy with CD19 negative disease. Our final pipeline updates during the quarter include AUTO8 and AUTO6-NG, both in collaboration with UCL. AUTO8 is progressing well in the phase one study in multiple myeloma patients called the McCarty study, and I'll give you more information shortly on the anticipated study data at ASH. With AUTO6-NG, we expect the first patient to be dosed in the neuroblastoma phase one study by the end of the year. Moving to slide number six. as well as from there, going straight to slide number several, focusing on OB cell. As you remember, OB cell has a unique mechanism of action. What's fundamentally different about our product candidate is that it has an ability to engage physiologically with the target cell. What this allows us is to actually have a product that can rapidly bind the target cell, which delivers specificity, paired with a fast off-rate for rapid disengagement from the target cell once the kill has been delivered. This unique engagement drives maximal activity while minimizing toxicity and is at the heart of the differentiated clinical profile we are observing for OB cell and ALL, and we believe provides a great platform for future indication expansions in oncology and autoimmune diseases. Moving to slide number eight. On this slide, you can see a summary of the Felix data we presented at ASCO and EHA earlier this year. What we've characterized to date and what we continue to hear from KOLs as we share the Felix data is that we enrolled a study and studied a patient population, our Felix trial, that is highly representative of a real-world clinical setting. Remember, we did this study during the pandemic, obviously, where patient flow was very challenging, particularly given the challenges with access to centers and a lot of patients only being moved to centers when there was an absolute need for them to actually move to the next therapy. Felix patients were refractory to multiple lines of therapy, including stem cell transplants, presented with high disease burden with medium bone marrow blast of 50% at screening, and extramedullary disease was present in 19% of the patients. Despite this challenging population with high disease burden, lots of risk features, overall older than was studied in prior programs, Obicel delivered complete responses in 76% of patients, and of those responders, 97% actually had deep MRD-negative responses. The tolerability is remarkable. Obicel had 3% high-grade CRS as well as patients with ICANN-grade 3 ICANNs in the range of 7%. So both of these numbers are very low compared to any other trial conducted in this type of indication, and also obviously allows for a very good level of control of these patients. Most of these events, particularly the higher-grade ICANNs, occurred in patients that had more than 75% tumor burden ad lib for depletion. And as you know, we're providing longer-term follow-up from this study as well as further subgroup analysis at the ASH meetings. Regarding the manufacturing process, irrespective of disease burden and adverse prognostic factors, the manufacturing was robust and reliable. The majority of patients for whom leukapheresis was achieved had a released product with a median vane to delivery time of 21 days. Eighty-four percent of the enrolled patients were also dosed. CAR T-cell engraftment and persistence looked consistent with our prior observations in the all-CAR9 team study. where we showed that all patients with long-term outcome had also long-term persistent CAR T cells. Moving to slide number nine. As I've mentioned, the ASH abstracts were released this morning and are available online via the ASH conference platform. And we just would like to briefly highlight the presentations at the conference. We have had four abstracts accepted, two oral presentations, and two poster presentations. In an oral presentation on Saturday afternoon, December 9, Professor Claire Rohde will present the pooled safety and efficacy, as well as longer follow-up data from the FELIX study, including subgroup analysis in addition. Data from all patients treated in the FELIX study continued to demonstrate high rates of overall responses, CRs and CRIs, and a very favorable safety profile. Additionally, data suggests better outcomes in a subgroup of patients with low leukemia burden at screening and lymphodepletion. Data presentation will be based on a median follow-up of approximately 15 months versus nine months at ASCO earlier this year. And we look forward to sharing more details, obviously, at the actual presentation. Second, in a post-m presentation, we'll look, in addition, at data from a pooled analysis of relapsed refractory adult ALL patients that were treated in the Olkar-19 study, as well as the Felix Phase 1b study. So this was the precursor, the running part of the study before we conducted the pivotal study. After a median follow-up of more than three years between those two studies, we approximately have 30% of patients that remain in remission without subsequent transplant or other anti-leukemia therapy. indicating that we have a proportion of patients that are likely to experience a long-term benefit. When we then look into the CLL and NHL cohorts of the all COVID-19 extension study, we have there more than two years of follow-up at this point in time. And the study also shows durable responses and the low incidence of serious infections, as well as a very good overall safety profile. which gives us, I think, a very strong, I think, rationale for moving over time into these additional disease settings. Continuing on with the OB cell abstracts, we'll also be presenting data on our manufacturing capabilities in a poster presentation. Data gathered in the Felix study successfully demonstrated the robust operability of OB cell manufacturing. All apheresis starting materials were successfully processed despite the multitude of constraints posed by the COVID-19 pandemic. and many patients that had very high levels of leukocytes and cancer cells, frankly, collected in the leukophoresates. Further optimization improvements were made during the startup of the study and increased reliability, consistency, and precision of the manufacturing process, as well as improved analytics helped to minimize turnaround time and supported development of, obviously, the nucleus as well as our our new OB cell manufacturing facility. Shifting gears to our dual BCMA-CD19 targeting CAR-T program, auto-aid for multiple myeloma. In an oral presentation, we'll be sharing preliminary data from the ongoing phase one McCarty study at ASH. All patients treated achieved a response, and doses were well tolerated with no ICANS or CRS larger than grade three with a median follow-up of 4.5 months at the time of the abstract. With that, we're transitioning to slide number 11, and we're looking at the preparation for commercial launch of OBZelle. As you can see on slide number 11, we are well on track with the activities as we have laid out. Key, obviously, is getting the manufacturing supply all set up, and that obviously has progressed very well. I'll spend a little bit on the next slide on that as well. Remember, what we designed the facility for is for a capacity that will allow us to actually address and support two-thirds of the total market in the U.S. and Europe for relapsed refractory ALL patients. So we have an initial capacity set for 2,000 batches a year. The full capacity of the facility actually exceeds that level. Secondly, obviously we're working towards the filing of the BLA. The target is to get the filing in before year end, and we're on track of delivering that important milestone for the program and the company. We then also will, as we go through the early part of next year, obviously we'll go through a set of inspections of the facility. We will certainly have one from the MHRA, which we expect in the early part of next year. as well as in the context of a BLA review, obviously additional inspections that are expected during that process. The filing for a EU registration is expected in the first half of next year and is also conducted under a prime designation similar to the RMAT designation that we have with the FDA. From a commercial perspective, there's been a significant amount of activities this year, particularly in the medical affairs side, where we obviously are very active sharing the data, running medical education, et cetera. The second key area that we're working on is really working through the value proposition for the program and the value dossiers. So that's a key set of activity that we're well on track with and exactly where we expect it to be at this point in time. And third, obviously, we have started the onboarding of clinical centers for OVCell, which is a process, as we had indicated in the past, it typically takes somewhere between about just between probably nine and probably 15 months, depending on the center, to actually get fully onboarded and registered. When we look into next year, obviously, we'll start to build up towards U.S. launch preparation. And that obviously will be one of the key activities that we're really going to get seriously focused on in terms of buildup as we're after we have filed the BLA and we're in the review process of the application. So with that, we're going to slide number 12. And this is a brief overview of the Nucleus facility. As you remember, this is a very compact facility, quite unusual in its design. has a total square footage of 70,000 square feet. It's a four-story building, industrial height. And in order to actually get this building off the ground and operationally ready in a very, very short period of time, we have taken on an approach that was based on a high degree of offsite building of the facility. In fact, we had about 70% of the facility built offsite. move to the actual construction site and they're actually assembled. By taking this approach and then also taking an unusual startup approach in order to get the facility up and running and qualified, we're actually able to go from November 8th to 2021 with the groundbreaking in less than two years or actually to the full qualification of the facility, which is complete at this point in time. And obviously, if we look at the timing for the BLA filing, we've been just around a little bit above probably two years of time to go from groundbreaking to a full package that is submittable in its complete form. So that's an exceptionally fast process that we're able to run through. It had a lot to do with the innovation that we're applying to both the design as well as the buildup. And the design was not just chosen for The reason of actually being fast and be able to actually set up this facility in probably less than half the time than anyone actually had done it in space so far. But also because it gives us an ability to replicate the facility with increased demand elsewhere and also be able to do that with relatively short timelines from decision making to operational activity. That is going to be important because there's a big impact on the risk profile of investments and the timing of investments. What you then see on the right-hand side is the actual inside of the initial operating suite. This is a suite that's designed to deliver about 700 products a year. And what you see here is this suite actually at full activity level during the capacity challenge. The manufacturing process, as you remember, is highly automated, and that gives us an ability to really run relatively large number of products in parallel within the same environment and in fact what you see here is in fact a picture that comes from the actual capacity challenge where we pushed the output of that particular clean room to its limits and obviously with the the key objective to be able to demonstrate sustained control throughout that level of pressure and be able to deliver high quality products during this period So a key aspect actually also of data that goes into a BLA filing as well. When we look beyond the ALL opportunity of moving to slide 14, what you see summarized on slide 14 is basically the evolution of the OBSL program as we see it currently. First of all, as you've seen, OSIL with its anchor indication in ALL gives us a very unique product with an exceptional level of activity combined with a remarkable level of safety. And that creates a unique opportunity, not only for the development of the product in patients with acute lymphoblastic leukemia, but also, obviously, for indication sets in non-Hodgkin's lymphoma, as well as in autoimmune disease. So that's the core opportunity we see with OB-Cell, and obviously we're active on all those fronts with the program. When we think about the next steps of the program and building on the unique features of the CD19 card that's utilized in OVCell, we developed, obviously, two next-stage products. One is Auto 122 that I mentioned before, where we published the data in blood from our Phase 1 initial clinical trial, which is a dual-targeting approach with the aim to minimize the risk of patients relapsing with CD19-negative disease, which is one of the major drivers for relapse in acute lymphoblastic leukemia, both in children as well as in adult patients. This product obviously gives us sort of a next leg up. It builds on the unique properties on the CD19 targeting, utilizing the same CD19 CAR as Ovisel does, but actually adds a highly potent a CD22 card that was designed to recognize cells that express very low levels of CD22 on their surface, which is one of the known escape mechanisms for CD22. So this is the next generation program for OVCell, which is really designed for oncology indications as sort of the primary area of opportunity. The second program, Auto8, I mentioned before, we're going to be presenting an oral presentation on the initial phase one data that we generated together with our colleagues at UCL. This program, again, builds on the CD19 CAR from OpiCell, and it adds a highly potent BCMA CAR, in this case as well, optimized for recognizing very low levels of BCMA on the surface of target cells. This is a known challenge with BCMA targeting, is that you do have that the target is selective, but the target is often expressed at copy numbers that are maybe as low as 10 or 20 molecules on the cell surface for multi-myeloma cells. And as you can imagine, that creates somewhat of a challenge to actually efficiently recognizing these cells and making sure you can really get at all the cells and not just the higher level expressing multi-myeloma or plasma cells. So this program obviously is, again, as with auto on 22, a dual targeting program, and so that starts opening up opportunities that could go both on the oncology as well as the autoimmune side, and depending on the development of the data, we'll make decisions in which direction we think we're gonna be taking this program. Moving to slide 15, this is just a slide that we have shown last week and explained and sort of walked through in more detail, Fundamentally, we believe we're in a very good position with our program. Given that we do obviously have a substantial amount of clinical validation, we have a large data set and an incredibly difficult-to-treat patient population where we show sort of a best-in-class benefit-risk ratio for sure across this indication, but also a highly attractive profile in the non-Hodgkin's lymphoma settings as well. This gives us a lot of confidence around the product. What you need to do is you need to, obviously, in these autoimmune diseases, make a very deep cut into the B-cell compartment. This is what we've demonstrated, obviously, in all of these patients driving or where we can demonstrate and show that, indeed, these patients do experience B-cell aplasia. But I think much more stringently, we can demonstrate that we also get the patients that have leukemia into a MRD negative state, which gives us a much higher level of resolution and a much more stringent measure of removal of all CD19 positive cells in these patients. So it gives us a strong amount of information about the quality of the clinical activity that we can see in these patients and obviously combined with an exceptional safety profile. Safety matters a lot in autoimmune disease. It's more important, actually, than in oncology. And one of the advantages that we have with OB-Cell is that we always have a substantial safety database now that we have generated in the development leading up to the imminent filing for patients with ALL. This safety data becomes important, particularly when you think about the opportunity that we have seen from the work that was done by Georg Schett and Andreas Mackensen in inducing deep responses in SLE patients. And in fact, by now actually have shown that indeed those responses are sustainable at least for a year to two years, which is the observation time that's currently available for those initial patients treated. with their own CD19 CAR-T therapy, which they manufactured on the academic side. Now, this level of activity creates also an interesting opportunity with regards to the development path you can take in SLE, which is a much more aggressive, much more compact development path, as you would normally have seen with the standard add-on trial designs that have been used for the various monoclonal antibodies that have developed for the space, which tend to do sort of a limited or can show a limited improvement over the standard of care and obviously require very large patient numbers to demonstrate the effect as a consequence of it. Here we believe that if that level of activity can actually be confirmed, that was originally seen in the airline study, that you would be able to actually run relatively compact studies that you would then actually have to supplement with safety information from other studies to actually discharge the safety risks for the product. We believe this puts us in a very strong position because obviously we do have a substantial amount of data from our current development. We also obviously do have a very significant level of de-risking from a manufacturing perspective, from a regulatory perspective, as well as from a commercial perspective. And I think one point I want to just highlight is that we believe it's going to be important in this indication to also have an ability to deliver product with a good cost of goods. as we think that the range of prices that ultimately will be realized will be similar but may not exceed what we're seeing on the oncology side. And clearly that requires you to actually have attractive cost of goods to actually maintain profitability across these indications. And that's going to be very difficult to actually generate if you have to, for an example, utilize a CDMO on the way there. So this is a few considerations here for why we think we're exceptionally well positioned. Obviously, we're going to be starting with the dose confirmation study early next year. And with data from that study, we'll then discuss the pivotal study designs and take it from there. But we believe that this is obviously with all the work that we've done and enabling work and infrastructure pieces we have in place puts OVCell in a very, very strong position. Moving to slide number 16, this is just a quick overview in terms of the competitive environment where we have either companies that have significant presence in the CAR T field, but have changed the manufacturing process to a point where the products, as far as we can tell, will not be comparable to what they have used in the past in the oncology setting. At that point, you do lose the ability to actually utilize the safety information that you generated on the oncology side, and you need to actually generate more clinical data to discharge the safety risk. There's also, obviously, investment required to sort of adjust manufacturing, et cetera, to the new manufacturing process, which we do not have to do. And then, obviously, we have additional new programs coming in which lack clinical data as well as infrastructure. which obviously will require very substantial investments to be in a competitive place going forward. And it will be interesting to see over time what potential allogeneic approaches might do. At this point, obviously, there's still a lack of data and obviously needs to be built, frankly, across the board in terms of capabilities. So with that, I'll move on to just a quick update on the pipeline. We touched on most of the programs. What I briefly want to just highlight is that we're in the process of writing up the clinical experience with Auto4, which we are expected to publish in a peer-reviewed journal, as well as with regards to Auto6NG, our neuroblastoma program, where we expect to dose our first patient during the fourth quarter now as well. We're excited about, as we're sort of included in that program, quite a range of cell programming technologies developed over the last few years, and they're now basically bringing together in this indication, solid tumor indication. So with that, I'd like to actually hand over to Rob, and we're moving to slide number 19.