Autolus Therapeutics plc

Hello, ladies and gentlemen, and welcome to the Altalist Therapeutics call to discuss this third quarter 2024 financial results and business updates. At this time, all participants are in a 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 1 1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1 1 again. As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Olivia Mansour. Please go ahead.

Thanks, Jacinda. Good morning or good afternoon, everyone, and thanks for joining us on our Q3 2024 call today. With me today are Dr. Christian Eiten, our Chief Executive Officer, Rob Dolski, our Chief Financial Officer, and Chris Van, our Chief Operating Officer. So on to slide two, our disclaimers. As a reminder, 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 expected timing for the commercial launch of Orcatzel, Autoless manufacturing sales and marketing plans for Orcatzel, including potential refinements at the Nucleus, the market potential for Orcaxel and the status of clinical trials and development and or regulatory timelines for Obicel and our other product candidates. 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 on 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, which are both available on the investor section of our website. So on slide three, we have the agenda. As usual, Christian's going to give you an overview of our operational highlights. Rob will discuss the financial results, and we will then conclude with upcoming milestones and closing remarks and move on to Q&A. As I mentioned, we have Chris Fan, our Chief Operating Officer, also available for Q&A today. So with that, I will hand over to Christian.

Welcome, everybody, to our Q3 update. Obviously, the big news has been the approval of a capsule, which came in at the end of business day last week on Friday. Obviously, a huge step for the company, but I think also a very important step within the ALL field, providing patients with an additional option in the relapsed or refractory setting. What was very interesting to see and I think important with regards to a capsule is that this is the first CAR T program that was actually approved without a requirement for a REMS program by the FDA. And I believe this is obviously linked to the unusual mechanism of action that we have to combine the high level of activity together with a low level of immunological toxicity and in a together with the Tumor-verted guidance dosing that we have implemented for the program really provides a program that puts the physician in control of the therapy. We believe that's going to be very important to expand the CAR T use in the ALL indication. So, very excited about where we are. Obviously, this has been a long journey and, you know, fantastic to be here and, as you can imagine, a lot of activity at the company, obviously, to really get the program off and running and the product into the hands of physicians as we go through the next few weeks. So with that, I'd like to move to slide number five and just talk about some of the key elements that really drive the launch and are critical for the success of the launch. The first part is to actually deliver these types of therapies, the CAR-T therapies, you require actually quite a number of elements that have to be in place. The first one is that the centers obviously have to be ready and authorized to be able to deliver this type of a therapy. And that process is very involved. It takes a substantial amount of time. In fact, we started the onboarding process of the centers more than a year ago. We have currently about 60 centers at various stages of the onboarding process. and 30 of those centers are ready to be activated now. This gives us an opportunity to really launch from a broad base. Those 30 centers actually reach about 60 percent of the patients in the U.S. with relapsed or refractory ALL. As we go through the course of 2025, then, we're going to add the additional 30 centers, and with that, should be able to reach approximately 90 percent of the target population. So very involved process and obviously an area that requires not only obviously a lot of interaction, training, and support, but also a series of systems that have to be put in place to be able to deliver the product and support the centers appropriately. Now the other aspect, which is very important of course for CAR T therapies is that we have a personalized therapy. And so the manufacturing process, the reliability around it, the robustness of that manufacturing as well as the turnaround time are critical. And as you know, we have decided or had decided to build our own commercial manufacturing facility, which we call the nucleus located here in Stevenage in the UK. And this facility allows us to actually support the patients in this indication. The capacity that we have earmarked for the ALL patients is approximately 2,000 products a year. That will correspond to about two-thirds of the patients that are in the relapsed or refractory stage of their disease in the US or in Europe. We also target an attractive vein to release time of 16 days, which will obviously be improved over time, but it gives us a very robust platform to work from. And as we had conducted the pivotal study through the pandemic and also, frankly, built the facility through the pandemic, we have been able to pressure test pretty much every aspect of the product delivery route that we're going through, whether this is logistics, whether this is cell handling, whether this is the actual manufacturing process itself. Now, what's important to make this happen is that you have a very strong, experienced, dedicated team to actually have a successful launch. And the experience really comes from several sides. On the one hand, on the commercial team side, we have A lot of our team members who have actually in the past launched CAR-T products, but we also have team members that have been in prior launches in the ALL field, which gives us both a CAR-T experience within the team as well as an indication experience and relationships to the centers, which are very important. We're building on a strong scientific communication. You've seen us present over a series of medical conferences over the last 18 months, and obviously more data to come at the ASH meeting coming up within a few weeks' time. And we're also gearing up to obviously presenting and publishing the results in a peer-reviewed journal as well, which I think will be a next important step on sharing the information of this important trial. We also have been focused very much as we're setting up our systems and thought through the processes and how we engage with the centers to ensure that the way the centers can engage with us is as simple and straightforward as possible, moving as much work away from the center onto our side so that the centers actually can focus on what they need to focus on, which is treating the patients. And we're taking, obviously, the role and support to support both the centers, the reimbursement process, as well as the patients in the overall process. We've set the price for the product at $525,000. This is based on very extensive work on the value of the product, the clinical evidence, the differentiated safety profile, and also making sure that it is a price level that actually would allow us and allow the product to achieve broad coverage, and with that, access for patients. With that, I'd like to go to slide number six. On slide number six, just a few points of additional updates of activities that happened during the third quarter. Obviously, as you can imagine, the primary focus in the third quarter was really to get launch ready. And that actually has been certainly where the vast majority of the organization was focused on. Now, while we were doing that, obviously with a focus to launching in the U.S., we were also heavily engaged in the interactions with the regulatory authorities in Europe as well as the MHRA in the U.K. as we're working through the submissions that we have made to both of those authorities for OVCEL. We've also published or presented additional data from the FELIX study. One data set was at the Society for Hematologic Oncology, which was in August, and where we were really looking at the rationale and the impact of the tumor burden guided dosing. And then in October after the Q3 period, we also were presenting at the Lymphoma Leukemia Myeloma Congress And what we're really looking at was the impact of stem cell transplant after OB cell use, as well as the impact of reducing tumor burden prior to lymphodepletion on outcomes. Now, very important also on the operational side, I had an excellent new team member join us, Matthias Will, as the Chief Development Officer. And obviously, we continue to obviously expand both the commercial team as well as obviously driving the onboarding of the treatment centers. With that, we're going to slide number seven. This is just a brief outlook of what we're planning to present at ASH. There are four abstracts that were selected for either poster or oral presentation. The first one is looking at the impact of the depth of remission on outcome. You remember we already looked at the impact of persistence on outcome, which was the core theme for the presentation at ASCO this year. This now looks at the other key aspect, which is the ability to get very deep remissions. And as I'm sure you'll not be surprised, obviously the opportunity to have both a deep molecular remission and putting long-term pressure on the leukemia, we believe both of those are relevant to induce long-term outcomes in this very challenging patient population. The second question that we're looking at is really look at the impact of bridging therapies on both the performance of OB cell as well as the outcome that we're seeing for patients. The third area is looking at a very practical aspect from a clinical perspective, which is the healthcare resource utilization and costs associated with managing both cytokine belief syndrome and ICANNs. Those are obviously events that do require a lot of care, a lot of oversight for the respective patient. And they tie resources. And certainly for some of those events can tie resources for quite long periods of time. And we're looking at that impact and the impact of obviously having a product that has minimized both CRS and ICANNs from a practical perspective as you're looking at it from a clinic perspective here. And then finally, we're looking at the impact on outcomes and what are factors that are impacting outcomes that we're seeing in the patients. We have obviously already talked about the importance of the tumor burden and lymphodepletion. This was a core focus of the ASH presentation last year in 2023. What we're now looking at is actually whether there are any parameters that we can actually identify upfront at the time of screening the patient. that would actually give us a sense of how this patient will fare on an OB cell therapy. So that's going to be one of the key questions that will be looked at in the fourth presentation. So that kind of wraps up my actual update for the quarter, and I will now actually move over to just a quick outlook on the activities with OB cell moving to slide number nine. This is a slide that you've seen before, and it just highlights the fact that we're obviously are developing OB-GEL not in isolation as an individual product solely focused on ALL, but that we're also obviously are looking to explore the broader utility of the program. You're obviously aware of that we're conducting a study in pediatric patients with ALL, but we're also conducting a study in patients that are has systemic lupus, and that study is obviously ongoing as well. We're looking to broaden those activities as we go through the course of next year. And building on the properties that we have seen with OB cell, we devised two additional programs, OTO-122, a dual targeting approach. It's really designed to sort of capture the B cells very deeply and minimize the ability of either leukemic or lymphoma cells to escape recognition by the CD19 receptor by having a second receptor present, seeing a second antigen, and with that having an ability to minimize the chances for escape. This program, as you may remember, is part of the option agreement that we have with BioNTech. Secondly, the AutoA program, which is also a dual targeting program looking at both CD19 and BCMA. And this program, obviously, we've shown initial data in multiple myeloma patients, but we're also looking for additional uses that go beyond multiple myeloma for this program, and we'll update you also as we go into the first half of next year. Finally, just on slide number 10, obviously we're just ahead of the ACR meeting, which will take place in just a few days now. And we're obviously going to look for a lot of the updates that we're seeing in the field of what type of impact and what level of impact can we see removing the B cell compartment deeply, in particular removing the CD19 compartment, which also includes the And one of the areas that we certainly have been watching carefully as we went through the course of this year is the range of patients that are being treated and the impact that you can see, understanding there's going to be a tension between the inflammatory part of the process, which these therapies do impact directly, and the actual damage that the tissue actually may already have encountered, the fibrosis that patients may already have picked up. which obviously is the second component of the disease. And we're looking at the relationship between those two, and we're looking at the various outcomes, obviously, for the various modalities as we go forward. From our own perspective, we're obviously very keen on this approach. We think the product has a unique positioning in the space, also now with the approval for the product, but also having now commercial manufacturing available to the product, which is certainly a standalone feature at this point in time in the field, and building obviously on the excellent safety profile that we've seen in what certainly is the most challenging disease population to work with in ALL. So, we're looking forward to updating you on the phase one part of the systemic lupus program. with a first update towards the end of Q1 and then obviously a longer term update in the second half of next year. And also looking forward to sort of talking to you about the broadening of our activities from an indication perspective as well, which we're really excited about. But today is the focus on the approval, the focus on getting the launch off the ground and obviously a fantastic place to be and really looking forward to seeing that we can have a real impact in the lives of the ALL patients that we're looking to support here. With that, I'm actually moving to slide 11, and I'm handing over to Rob.