Autolus Therapeutics plc

Hello, ladies and gentlemen, and welcome to the Altalus Therapeutics First Quarter 2023 Financial Results Conference Call and Operational Progress. 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 11 on your telephone. You will then hear an automated message advising you that your hand is raised. To withdraw your questions, simply press star 11 again. As a reminder, today's conference is being recorded. I would now like to turn the conference over to your host, Alexandra Deschner, Investor Relations Consultant. Alexandra, please go ahead.

Thank you so much, Eric. Good morning or good afternoon, everyone. And thank you for joining us to take part in today's call for Autolis' first quarter 2023 financial results and operational highlights. I'm Alexandra Deschner, Investor Relations Consultant for AutoList. With me today are Dr. Christian Eisen, our Chief Executive Officer, and Dr. Lucinda Crabtree, 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 on 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 first quarter of 2023. Lucy will then discuss the company's first quarter 2023 financial results before Christian will conclude with upcoming milestones and any other concluding comments. Finally, we will, of course, welcome your questions. Over to you, Christian.

Thank you, Alexandra, and good morning to you all. Thank you for joining us. It's my pleasure to review our progress for the first quarter in 2023. Moving to slide number four. We're really pleased with our program and operational progress during the first quarter of 2023, which is highlighted over the next four slides. We're making good progress with our pipeline of CAR-T programs, particularly with our lead product, Obicel, in relapsed refractory adult ALL patients. You will recall that we announced in December that the phase two pivotal clinical trial of Obicel in this patient population have met its primary endpoint. based on a pre-planned interim analysis of 50 patients with morphological disease, and that's verified by an independent data monitoring committee. This positive data triggered a $35 million milestone for our partner Blackstone Life Sciences earlier than anticipated. We're looking forward to presenting the top-line data of the FELIX study in an oral presentation at the American Society of Clinical Oncology Annual Meeting on June 2nd in Chicago. and a second oral presentation at the European Hematology Association Congress being held from the 8th to the 11th of June in Frankfurt. Updates on longer follow-up and additional sub-analyses of the data are planned for the American Society of Hematology meeting at the end of 2023, as well as at medical conferences in the first half of 2024. Operationally, the key goal for OBCEL is the filing for a biologics license application to the U.S. Food and Drug Administration by the end of this year. In February, Dr. Claire Rohde from UCL presented long-term follow-up data from our adult ALL patients in the OLCAR19 Phase 1 study of OBCEL at the tandem meetings of ASTCT and CIBMTR. The data demonstrated that 35% of adult patients remained in complete remission without additional anti-leukemia therapy at a median follow-up of 36 months, with ranges from 24 to 48 months. We're now looking at the broader range of development options for Obicel and Auto-122 beyond adult patients with acute lymphoblastic leukemia. In the Olkar extension study, we have reported Obicel's high level of clinical activity and well-manageable safety profile across non-Hodgkin's lymphoma indications and chronic lymphocytic leukemia. We're completing enrollment in this study and expect to report final data in a peer-reviewed publication. In the Curricel study, we evaluate OB cell in peripheral CNS lymphoma, and we have completed enrollment and continue to see consistent and encouraging safety and efficacy. With adequate follow-up, we are planning to publish the full data in a peer-reviewed journal as well. We're following with interest the early and very encouraging results from the team of Georg Schett and Andreas Mackensen at the University of Erlangen in Germany in patients with refractory systemic lupus and related B-cell-mediated autoimmune diseases treated with an academic CD19 CAR-T product. Considering OB cells' excellent activity and safety profile and combined with our commercial manufacturing base, this set of indications may become an attractive additional opportunity for the program. In an oral presentation at the 49th European Bow Marrow and Transplant Meeting in April, our key investigators, Dr. Sarah Goroshian and Persis Amrolia from Great Ormond Street Hospital in London, presented updated data from Auto 122, our CD19 and CD22 dual-targeting CAR-T product candidates. Kymriah ineligible pediatric ALL patients 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 8.7 months. Included also were patients who had relapsed after chemariotherapy with CD19-negative disease. Additionally, data on the molecular design of Auto-122 and preclinical characterizations were published in molecular therapy in March and highlighted the state-of-the-art design of OTO-122 with its high sensitivity CD22 chimeric antigen receptor and the efficient core targeting leveraging OB cells CD19 chimeric antigen receptor. Turning to slide five and other pipeline updates. We're looking forward to updating the progress with the OTO-4 peripheral T cell lymphoma program in an oral presentation at the International Conference for Malignant Lymphoma in Lugano, Switzerland in June as well. Finally, we conclude, we continue to enroll patients into the McCarthy Phase I trial of Auto-8 in multiple myeloma and expect first data at the end of this year and expect to dose the first patient in the Phase I trial of Auto-6 NG in neuroblastoma this year as well. Turning now to slide number six, We've continued progress against our strategic and operational goals throughout the quarter. The company's new 70,000 square foot commercial manufacturing facility in Stevenage in the UK has continued to progress on track. Key equipment installation and validation were completed by Autolocin in the first quarter of 2023, enabling operational qualifications commencing now in the second quarter of 2023. This facility will have an initial capacity of up to 2,000 batteries per year sufficient to serve the global demand in adult ALL. Just 18 months from groundbreaking, we are now working on the qualification validation of the nucleus facility and remain on track for good manufacturing practice operations commencing in the second half of this year. We're also undertaking the development work and report generation for the CMC package planned to support a BLA submission to the FDA. Our industry-leading cell programming platform creates opportunities for collaboration and licensing. Through our relationships with BMS at Moderna, we added in Q1 a partnership with Cavaletta, granting them access to our proprietary RQR8 rituximab-induced safety switch, for incorporation into a set of selected cell therapy programs. In January, we also announced two changes to the board of directors. The company's non-executive chairman, John Johnson, who has held the role since September 21, will not stand for reelection at the ODLIS upcoming annual shareholder meeting. Additionally, at the end of February, Dr. Jay Brakstrom, who had served in ODLIS board of directors since August 2020, stepped down from the board after taking on a public CEO role at Scholar Rock. We also announced a change to our management team with Dr. Lucinda Crabtree, our CFO, also on the line today, stepping down or planning to step down in August 2023 to pursue a new opportunity. Searches for successes for these posts are underway. Finally, total cash and cash equivalents and restricted cash at the end of March were $343.4 million. We've had a diversified treasury approach in place, which served us well through well during the Silicon Valley Bank meltdown, and we continue to diligently monitor developments in the financial sector. Moving on to slide number seven, there are also several post-period events I'd like to bring to your attention. Last week, we announced that we had selected Cardinal Health as a core distributor for OVCell, giving us the platform and distribution capabilities required to commercialize a CAR T-cell therapy in the U.S. Cardinal Health's innovative depot model is intended to reduce delivery time by allowing for transit while product release is being finalized. Alongside this, we continue to build out Ottawa's own commercial infrastructure and are working towards onboarding the clinical centers over the course of this year. Also, last week, we held a virtual Capital Markets Day that presented the positioning and commercial opportunity for OB-Cell. The event started with Professor Laurie Muffley from Stanford University reviewing the disease, therapeutic options, and medical needs for adult patients with acute lymphoblastic leukemia. Professor Claire Rohde from UCL then introduced OB-Cell and the initial clinical experience in patients with ALL, followed by a video presentation of one of her patients and her experiences of living with ALL, with an ALL diagnosis, as well as her experience with the treatment regimen. With this deepened understanding of the physicians' and patients' view of this challenging disease, Dr. Matthew Gitlin talked about the ALL market and the perspective payers are taking. In particular, he looked at the cost of patient management and the impact on hospitals and payers, highlighting the substantial impact on cost of managing high-grade cytokine release syndromes and ICANNs. Finally, Chris Van Otelis is Chief Operating Officer Walk through the commercial roadmap for Obicel. We believe it was a very informative and well-attended event. And for anyone who missed it, a replay is on the event section of all of this website available to you. Finally, we recently announced the publication of two papers, the first of which included the publication of the preclinical data for auto 122 in molecular therapy, which I mentioned earlier. And the second, published in Molecular Therapy, Nucleic Acids, focused on a new set of cell programming modules based on novel FAS-TNF receptor kineras. This technology converts a threat to the CAR T cell into an activating or survival signal instead. We're borrowing here from a martial arts principle of taking an incoming blow and rolling with it. Slide eight, OV cell, moving to OV cell, with that, also moving forward to slide nine. OVCell 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, rapidly binding to the target, which delivers specificity, and paired with a fast off-rate for rapid disengagement from the target once the cell 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 in ALL and non-Hodgkin's lymphoma. Moving to slide 10. Our clinical experience with OB-cell in ALL shows a high overall response rate across all patient populations evaluated. In our prior All-Coron-19 study, we have 35% of patients in long-term remission at 36 months of median follow-up with a range of 24 to 48 months after receiving OB-cell and without receiving any further antileukemia therapy. The safety profile is well manageable with low levels of high-grade cytokine release syndrome and ICANs. The midsection of the slide shows the patients with long-term remissions have continued presence of CAR T cells over the entire observation period, pointing to CAR T cell persistence as an indicator for long-term outcomes. The program is developed under an RMAT, PRIME, and ILAP designation. Moving to slide 11. We've now completed the enrollment and dosing of our pivotal study, which we call the FELIX study, in adult patients with relapsed refractory ALL. As I mentioned, we announced in December that we had met the primary endpoint based on the overall response rate at an interim analysis on the first 50 patients followed for at least three months. Clinical benefits. in ALL will be assessed based on patients remaining in a sustained complete remission. We conducted this study in 34 centers, 24 centers in the US, seven centers in the UK, and three centers in Spain, enrolling patients from July 2021 to November 2022 during the peak infection period of the pandemic. It's important to realize that relapsed refractory adult ALL patients are highly immune suppressed the pandemic posed a significant added risk to them. Moreover, due to access restrictions and various other pandemic rules and regulations, we could actually not access our clinical trial sites for the most part of the FELIX study. This is about as difficult a population to work with as you can imagine, particularly in an environment where there is a high risk of infection, and indeed, we did lose a few patients to COVID. In many ways, This was more of a real-world study conducted under difficult circumstances. In addition to patient safety, every aspect of product delivery and logistics were pressure tested during the trial, with massively reduced air traffic and other impacts of the pandemic in our manufacturing teams. Remarkably, manufacturing for all patients from our facility in the UK turned out to be an asset also for US delivery, as the long-haul flights from the US to the UK have priority over domestic flights. We're pleased that we got it done under such challenging circumstances, and credits to our patients and their caregivers, clinical collaborators, and the whole ODELIS team for this achievement. As mentioned earlier, next key data is planned in oral presentations at ASCO and EHA in early June 2023. Moving to slide number 12. This slide summarizes the announcement we made in December regarding the pre-specified interim analyses of the first 50 out of 90 patients dosed that had reached at least three months of follow-up. The primary endpoint is based on overall remission rate, which includes patients in complete remission and patients in complete remission with incomplete bone marrow recovery, or CR and CRI. The ORR was 70 percent. All recent programs in ALL have used ORR as the primary endpoint in their respective studies. Safety analysis was conducted on a larger 92-patient data set and showed an excellent profile with high-grade cytokine release experienced in less than 3% of patients and high-grade ICANNs in less than 8%. ICANNs were fully reversible, and less than 25% of patients had any grade of neurotoxicity. In contrast, to prove T-cell or T-cell-engaging therapies, a very unusual profile in this patient population. And as I mentioned earlier, the data triggered a $35 million milestone from Blackstone. Moving to slide 13. This slide summarizes our current experience with OVCell across ALL. As you can see, the data are highly consistent across the various studies, both on safety and efficacy. Worth noting is that Carpal and Olkar were conducted prior to the pandemic, while both parts of the Felix study were conducted during the pandemic. Both the CAR-PAL and all CAR-19 studies were conducted in the UK, while the FELIX study was largely conducted in the US. What we did pick up is that the patients in the FELIX study were more advanced in their disease based on tumor burden and increased presence of so-called extramedullary disease. This is, in essence, again a function of leukemia that allows it to leave the bone marrow and successfully settle and grow in other organs. Patients with extramedullary disease respond poorly to antileukemia therapies. Moving to slide 14 to look at further into the data we presented at ASH from the old CAR-19 study. When we look into the outcome or long-term observation from the old CAR-19 study where we have up to four years of follow-up, you can see quite an unusual profile. We could see the clinical benefit in these patients is the ability to convert patients into complete remission, sustain them over time without additional therapy. And as you can see, obviously, a substantial proportion of the patients are indeed in sustained therapy. So if you go from bottom up, you can see at the bottom patients that obviously did not respond. We have then a group of patients that did respond but relapsed quickly, including patients that had lost a CD19 antigen. We have then a group of patients that actually relapsed with CD19-positive disease. Those are patients that have lost persistence of the CAR-T product. And then there is the top group with the long green survival lines where you can see patients that actually have continued remission. And in fact, those are also patients that have continued presence or persistence of CAR T cells. Overall, obviously, it gives us a lot of confidence in terms of the consistency of data, the data understanding the reasons when patients actually do relapse and what the causes for that relapse are. and obviously the proportion of patients that are in ongoing remission without any additional therapeutic need. Turning to slide 15, I thought it might help here to give you an overview of the ALL treatment landscape as it stands. The figure on the right represents the NCCN guidelines for the treatment of relapsed refractory ALL, and you can see it is sort of has two main arms. The lower arm actually looks at T-cell lymphoma which is a subset and relatively small group of patients. And the upper two arms actually include B-cell lymphoma, sorry, B-cell acute lymphoblastic leukemia. And with that, the disease setting that we're focusing on. We can also see that we see three novel therapeutics that are being incorporated into that scheme over the past 10 years. The first is Blenatumumab or Blencyto. This is a bispecific T-cell engaging anti-CD19 therapeutic antibody. It's given as a continuous intravenous infusion for 28 days at a cycle. These cycles can be repeated with two weeks of intervals in between the cycles. The patient starts at the hospital and eventually are discharged from the hospital with a container or a bag that actually contains the product that is continuously delivered through a central port. over the entirety of a treatment cycle. These bags are being changed typically once weekly and by a nurse that actually usually visits the patients at home to sort of support the therapy. These cycles can be repeated, but obviously the patient needs to be in a remission for a continued cycle or a next cycle to be received. The product is obviously very active. And it's particularly active in patients that have low disease burden. Now, unfortunately, like with all therapeutic options today available for adult patients with ALL, while the product is very active, it does not actually lead to long-term remissions. And that is one of the fundamental challenges that we have in the field is that we have active therapies, but we have a hard time converting those effects and responses into long-term remissions. The next therapeutic that we're looking at is inotuzumab or bisponza. This is an antibody-conjugated drug therapy. It is directed to CD22, which is expressed on most B cells that conform ALL. And this drug is also associated with a very high response rate, but also, like Blincyto, is not curative and, in fact, is usually used as a bridge to transplant. Finally, the newest product that is available is Brexacel or Tecardis, which is approved in 2021, which is the first CAR T-cell therapy approved for adult ALL patients. Both Blinsito and Tecardis, which are leveraging or utilizing T-cells, do show similar types of immunological toxicities, which are CRS and ICANS, whereas Besponza can cause liver toxicity. Overall, we do have, obviously, a view that if you have a product that has a high level of clinical activity with a well-manageable safety profile, obviously, it's very attractive for patients with the ALL. And if that product actually can translate into at least a proportion of the patients in long-term remission, I think that would represent a big step forward. Moving to slide 16 to look at the data from these programs in the space. Plencyto, as I mentioned, is a T-cell-engaging CD19-targeting monoclonal bispecific antibody that has become the standard of care in relapsed refractory ALL over the last few years. Key to its success have been the well-manageable safety profile. Key focus from a patient management perspective is the monitoring of ICANs, which impact about two-thirds of the patients. And in contrast, if you look at OB-cell, obviously substantially more patients do experience ICANNs. As I mentioned before, we've seen about 25% of the patients experiencing ICANNs with OB-cell. High-grade CRS for Blink-Syto is relatively low at around 5% level. And OB-cell seems to be similar, potentially slightly better in terms of the high-grade cytokine release syndrome level. Now, in contrast to BlinCyto, the CARTUS induces high-grade CRS in a substantially higher proportion of patients, in 26% of the patients, and high-grade neurotoxicity reaches about 35%, while 87% experience of patients experience neurotoxicity of any grade. Forty percent of patients receive vasopressors. This is a challenging safety profile to manage and often requires access to ICU. When we look at inutuzumab, while obviously active, the program has liver toxicity and is primarily used to bridge to transplant. None of the therapies established long-term remissions without subsequent stem cell transplant. Moving to slide 17. The market opportunity in ALL is unchanged, obviously as a consequence of the fact that we didn't actually see any significant move with regards to patients having long-term remissions. And so we still see, as we've seen about 10 years ago, 3,000 patients in high medical need for therapy between the U.S., Europe, and Japan. Moving to slide 18, when we look at the actual size of the market, we always look for good surrogates, and we believe that the sales of Blinzaiter are actually a good surrogate for our product. Firstly, in that Blinzaiter has obviously got a very similar mechanism of action, being CD19 T-cell engaging agents. Secondly, it's used largely in the same indication as a similar, albeit somewhat higher, CRS and ICANN level. So around 80% of the Blinzaito cells come from adult ALL, and around 20% of the cells from pediatric ALL. And very importantly, it's got a similar type of toxicity profile to OB cell as just reviewed above. The safety profile allows use of Blinzaito in a broad range of centers, not just in the academic transplant centers. And indeed, BlinkSight has had a record quarter in Q1, growing 41% year-over-year, with sales of 194 million reached in the first quarter. If we were to prudently assume quarterly sales remain constant and do not grow any further, we estimate that full-year sales could reach approximately 800 million, which corresponds to year-over-year growth of about 33%. This development highlights the meaningful commercial opportunity in adult ALL, which is driven by the well-manageable safety profile of Blincyto. Amgen reports a key driver for the increase is attributable to an expansion of the number of treatment centers where Blincyto is being used. We're also seeing that many CAR T centers are now also expanding their capacity for delivering CAR T cell therapy. So both Blincyto and ultimately Obicel have the potential to be used in a broader range of hospitals. Prices for CAR T therapy in the U.S. are in the range of $450,000 to about $500,000. Moving to slide 19. When we look at the steps forward, first of all, we're planning to disclose Felix data in an oral presentation at ASCO and also DHA. Long-term follow-up and additional sub-analysis are planned for ASH. We're targeting the BLA submission for the program towards the end of this year, MAA filing towards the end of the first quarter in 2024, and the U.K. filing in the second quarter of next year. That sets up very nicely for the key territories that we expect to be initially active in. In addition to the mature clinical data, the submission will also require data from the validation of our commercial manufacturing site. This work has been a key focus throughout the first half of 2023 and will do so into the third quarter. Importantly, our commercial manufacturing facility is set up to cover supply for approximately two-thirds of the estimated market from the start. We've talked about selecting Cardinal Health as our U.S. distribution partner, which is an important step. As we're moving through 2023, we need to prepare the key areas for commercialization. We're creating awareness for the program through a focused medical affairs program, and alongside this, we're establishing the value proposition for payers in our HTA dossiers, and finally, preparing for and starting center onboarding, a process that will take between nine to 15 months, to get each center ready to deliver CAR-T therapy. Slide 20. Moving to slide 21 to talk about the broader opportunity that we see with Obicel. As part of the old CAR extension study, we've been evaluating Obicel in relapsed refractory non-Hodgkin's lymphoma in CLL patients. We see consistently very high response rates combined with a very attractive safety profile suitable for outpatient use. That data will form the basis for the selection of the second indication after ALL. In terms of the life cycle, we're working on the next-generation version of OviCell with Auto-122. What we're looking to minimize CD19 antigen loss during relapses with this dual targeting approach. Building on OviCell, we are adding a highly potent CD22 CAR that can recognize very low amounts of CD22 on the surface of leukemia cells. This program was initially evaluated in children who had failed Kymriah or were not eligible for Kymriah therapy. In this very challenging population, we saw 83% molecular response rate, and this included also patients who had CD19-negative disease, demonstrating the efficacy of the CD22 CAR in isolation. Crucially, amongst the responding patients with a median follow-up of 8.7 months, where there have been no cases of leukemic relapse or emergence of MRD-related antigen escape. Together, these data indicate that combining our optimized CT22 CAR design with the CT19 CAR used in OV-Cell may be effective in preventing antigen loss-driven B-lapse in pediatric BALL. We're working on further streamlining the manufacturing process for Auto-122, knowing that we have an attractive lifecycle option. Timing of investment decisions in Auto-122 will be balanced with additional investments for OV-Cell. Switching gears and headed to slide 23. Our technology platform allows us to engineer a range of properties into T-cells that drive specificity of recognition, resilience against negative signals used by tumors to evade T-cell attack, and provide survival signals for T-cells. Our strength in T-cell engineering drives our pipeline and is also at the heart of the three collaborations that I've mentioned, which were reported on in 2022 and early 2023 with Moderna, BMS, and Cavaletta. On slide 24, we have a quick summary of the earlier stage programs in T cell lymphoma with auto 4-5, auto 6-NG in neuroblastoma, and auto 8 in multiple myeloma. Auto 4 and auto 8 are in phase 1 clinical studies, and auto 6-NG is expected to start during the course of the year. Moving to slide 25. T cell lymphoma is a very high medical need, similar to BALL. In fact, when you look at the NCCN guideline, it basically says that once you're through the frontline therapy and you relapse, you have to look for a clinical trial. Moving to slide 26. With its unique targeting approach, all of four starts to show meaningful clinical impact at the higher dose levels that we have explored. The first metabolic CRs are reaching one year post-treatment, and we continue to follow the patients. In addition, we have streamlined the manufacturing process and are exploring the activity in an additional cohort, and we're planning to report data at the ICML conference in June. Moving to slide 28 to talk about manufacturing. Cell manufacturing is obviously at the core of any autologous cell therapy. Developing a highly reliable, robust, and economical process is critical for the success of any program. In addition, we have to be able to deliver product at scale and matching capacity to the size of the medical need, which is important for a successful rollout of any therapy. Building on the robust and very well-characterized process used to manufacture for the Felix clinical study, we're standing up our commercial cell manufacturing facility called the Nucleus about a mile away from the clinical trial manufacturing site. This proximity is important as we will be able to move our entire staff to the facility, the new facility, and many, in fact, of our employees are already in the process of validating the Nucleus facility. Capacity of the Nucleus and its initial setup reaches 2,000 patient patches per year, or about two-thirds of the adult ALL market size. The Nucleus has been a fantastic project to realize with innovative design and about 75% off-site building to accelerate the building while maximizing the quality of the build. Moving to slide 29, which is the interest slide to the financial section, and with that, I would like to turn to slide 30, and pass the call over to Lucy for our Q1 2023 financial update. Lucy?