Autolus Therapeutics plc

Hello, ladies and gentlemen. Welcome to the Autolist Therapeutics Second Quarter 2022 Financial Results Conference Call. As a reminder, this conference call is being recorded. Towards the end of the call, we will have a Q&A portion. If you would like to be put in the queue, first come, first serve, press star 1-1, and at that time, you will be called upon to ask your question. Without further ado, I would like now to turn the conference over to your host, Olivia Mansour. Director, Investor Relations. Olivia, thanks.

Thanks, Corey. Good morning or good afternoon, everyone, and thank you for joining us to take part in today's call on the financial results and operational highlights for the second quarter of 2022. I'm Olivia Mansour, Director of Investor Relations, and with me on the call are Dr. Christian Eysen, our Chief Executive Officer, and Dr. Lucinda Crabtree, our Chief Financial Officer. So on slide two, before we begin, I would just like to remind you that during today's call, our discussion will contain forward-looking statements. Please make sure you are familiar with this disclosure slide. On slide three, you should see the agenda for today, which is as follows. Christian will provide an overview of our operational highlights for the second quarter of 2022. Lucinda will then discuss the company's financial results before Christian will conclude with the upcoming milestones and any other concluding comments.

we'll then turn over for q a i'll now hand over to christian to begin the presentation thank you olivia and good morning to you all and thank you for joining us it's my pleasure to review our progress for the second quarter in 2022. please move to slide number four for those who are new to auto lists and as a refresher for those of you who know as well we're building a fully integrated car t company Building on our broad platform of cell programming technologies, we're generating CAR-T products that are tailored to the specific tumor setting we're addressing. We had a successful quarter with multiple readouts from our clinical programs at the European Hematology Association Congress in Vienna in June, which give us a great confidence in the inherent value of our pipeline and the progress achieved. We continue to enroll patients into the Pivotal Felix trial, where we're investigating OB cell for the treatment of relapsed refractory and acute lymphoblastic leukemia patients. And in April, we obtained a regenerative medicine advanced therapy or RMAT designation from the FDA. As a consequence, we now have preferred regulatory access for OB cell in all key territories, the US, Europe, and the UK, and have met with the FDA in the context of a Type B meeting to discuss the regulatory pathway going forward. We're on track to announce the initial results for the FELIX trial in Q4 2022, which will be provided by way of a press release, and we're planning on presenting the full dataset at a medical conference in mid-2023, most likely at ASCO. As previously announced, in addition to the primary morphological cohort, in the FELIX trial, we have expanded the MRD cohort to enroll up to 50 patients. In clinical practice, patients get evaluated on a regular basis for recurrence of disease, typically using flow analysis or PCR of their bone marrow samples. Indication of minimal residual disease levels of leukemia triggers treatment of the patients rather than waiting for full-blown morphological relapse to occur. This additional cohort does not impact our plan filing timelines as the primary data will be based on the data from the morphological cohort. However, we do believe the MRD cohort will broaden the data set across the full range of tumor burden and align with current clinical practice. We remain fully focused on generating the data package needed to file for BLA approval for OB cells for the treatment of adult patients with acute lymphoblastic leukemia. and remain confident in OV-cell's potential to be a best-in-class treatment in a growing market. As I mentioned, EHA was a very busy meeting for us with data readouts from multiple clinical programs, and I'll go into more detail about the specific data later in this presentation. But in summary, OV-cell continues to show what we believe to be best-in-class activity with a high level of sustained complete remissions in BNHL patients, without inducing severe cytokine release syndrome or any neurotoxicity. In addition, we have now seen first activity in primary CNS lymphoma patients. Beyond Dovizel, we've seen first and promising results from the dual-targeting OTO1-22 program in children with acute lymphoblastic leukemia who are ineligible for chemoriotherapy. The data presented at EHA, we believe, are demonstrating clinical proof of concept with a high level of activity and a well-manageable safety profile. We're particularly excited about ORO4 reaching clinical proof of concept in patients with peripheral T-cell lymphoma, reaching metabolic CRs while maintaining a well-manageable safety profile. This data validates a novel targeting approach, which is very important given the high unmet need and difficult to treat patient populations. With two new programs reaching clinical proof of concept, our pipeline beyond OV cell is advancing well, and we're pleased with how it's shaping up. Finally, we're pleased in the quarter to dose our first patient in the phase one study, auto eight, for the treatment of patients with relapsed refractory multiple myeloma, and are also on track for auto six NG, our first solid tumor program, to start a phase one in the second half of the year. The build of our commercial manufacturing facility in Stevenage is progressing on track and within schedule, and I'll cover that in more detail later in the presentation. Moving to slide five. With that, let's focus on our lead product, Obicel, and move to slide six. Just to remind you, Obicel has a unique mechanism of action built on a highly specific engagement of CD19, coupled with a fast release from CD19 once the kill of the leukemic cell has been initiated. This fast disengagement is based on the fast off rate of the cat binder and drives three key properties of OB cell. Reduction of the amount of cytokine release per target cell encounter, which in turn will reduce the amount of immunotoxicity in the patients, reduced exhaustion in the CAR T cell, and improved engraftment and overall persistence of the product. And those of you not familiar, I refer you to a paper by Sarah Garroshian at Nature Medicine in 2019. Moving to slide seven, there still remains a very high unmet medical need for adult ALL patients with approximately 8,400 new cases diagnosed yearly worldwide in the last line setting. Approximately 3,000 patients of these cases reside in the U.S. and Europe. While its combination chemotherapy enables 90% of adult ALL patients to achieve CRS, to achieve CRs, complete remissions, only 30% to 40% will achieve long-term remission. Once relapsed, patients have a median overall survival of less than a year. Current approved therapies for adult patients are Blincyto and Ticardis. Ticardis is currently approved in the U.S. and has received a favorable CHMP opinion in Europe, and it's expected to be approved in Europe later in the year. Both therapies are highly active, but frequently followed by subsequent treatments, typically including allostem cell transplants. Blinzaito has a favorable safety profile with few patients experiencing severe cytokine release syndrome and ICANS, but with limitations on convenience due to the need for continuous IV infusion during its four-week treatment cycles. Descartes is more challenging to manage and induces elevated levels of severe CRS, high level of ICANS or neurotoxicity, and requires steroids and vasopressors for many patients to manage adverse events. Both therapies have been shown to be highly active. However, most patients progress rapidly and require a subsequent allograft to achieve durability. Moving to slide eight. Building on its unique mechanism of action, Obicel has shown a high overall response rate with a favorable safety profile and sustained event-free survival that tracks long-term persistence in those patients. As mentioned before, Obicel has been granted orphan drug designation by the FDA and EMA for ALL and obtained prime designation by EMA for the EU, ILAC designation by the MHRA for the UK, and most recently, RMAT designation by the FDA for the US. Moving to slide nine. Based on what we believe is potentially a transformational data from the Olkar study, we are a treating patient, we're conducting the pivotal Felix study trial with approximately 90 patients in the so-called morphological cohort. We're treating currently patients at 34 sites across the U.S., the U.K., and Spain. We're on track with our previous guidance and expect to announce initial results in the fourth quarter this year, which will be in the shape of a press release. We're planning on presenting full data at a medical conference in the first half of 2023, as indicated, currently thinking about ASCO. In order to maximize outcomes from the FELIX trial, in parallel, we've initiated an initial cohort of up to 50 patients in the second related complete remission, and in second or later complete remission, we have minimal residual disease, so-called MRD-positive patients. However, this additional cohort does not impact our planned filing timelines, as the primary data will be based on the data from the morphological cohort. Moving to slide 10, and switching gears as we move into slide 11. OBSEL's unique profile means it could be applicable to a broad range of indications. We're consequently evaluating the product outside of acute lymphoblastic lipidia in B-cell non-Hodgkin's lymphomas in a set of ongoing phase one clinical studies. As I mentioned, we have positive clinical readouts at the recent IHA Congress from phase one studies in B-cell non-Hodgkin's lymphoma and primary CNS lymphoma presented by way of a poster each as well as an oral presentation of the first auto 122 phase one data in pediatric ALL patients at that event. And I'll cover these data in the upcoming slides. Slide 12. As a reminder, the academic OLCAR19 study has been extended as a basket study where we're testing OV-cell in a variety of B-cell malignancies. To date, we've treated 17 patients with follicular, DLB lymphoma, DLBCL, and mantle cell lymphoma. And no patient experienced high-grade CRS, and none had any grade of neurotoxicity. Of the 17 patients dosed, 16 achieved a metabolic complete remission, seven of seven follicular lymphoma patients, six of seven BLBCR patients, and three of three mantle cell lymphoma patients. We lost one patient to COVID and one mantle cell lymphoma patient relapsed. Fourteen of the 16 patients remain in metabolic CR with a median follow-up of 9.2 months, the longest being 19.1 months in follow-up, at the last data cut, and obviously the data will continue to mature and will give us more insights as we go forward. We've also started treating some CLL patients, and from the three patients that have reached initial evaluation, two went into molecular CR in the bone marrow, but have some residual lymphadenopathy on CT scan. We expect to have follow-up data from this Olkar extension study again in the second half of this year. Turning to slide 13. We're also exploring OB cell in primary CNS lymphoma in our academic carousel study. This is a type of aggressive B cell lymphoma, but because of its anatomical location, it has a particularly poor prognosis. Initial treatment is often intensive, and outcomes for these patients tends to be poor. In the data we presented at EHA, we didn't see high-grade cytokine release syndrome. Two patients experienced neurotoxicity, grade three and grade four, respectively. One patient improved for steroids and anakinra. The second patient had several neurological deficits consistent with progressive disease and did not respond to steroids and anakinra. Overall, you can see on the right-hand side of this slide that despite these patients having no disease outside of the CNS and having had lots of rituximab treatment, we still see really nice expansion of OB cell in peripheral blood, and we expect to provide more data from this study in 2023. Moving to slide 14. Our initial experience with OB cell in children achieved a high level of sustained complete remissions while without experiencing high-grade cytokine release syndrome. For those children who relapsed, most had lost CD19 expression of their leukemic cells at the time of relapse. Here, we're taking the next step in OB cells' life cycle with OTO-122, a dual-targeting product building an OB cell and adding a highly potent CD22-targeting chimeric antigen receptor. The CD22 CAR was designed to be active against leukemic cells with low levels of CD22 expression on their surface. We evaluated ODO-122 in an extension of the CAR-PAL study in children who were ineligible for chemriya. The children either relapsed after receiving chemriya and could not be retreated, or they had extramedullary disease, i.e., single lesions in tissue without having disease in the bone marrow, the normal location of acute leukemia. This is a very challenging group of patients to treat. Out of 11 children, four had prior chemoriotherapy, and three of them had lost CD19 expression. Seven of the children had extramedullary disease. Moving to slide 15. Data were presented at EHA in an oral presentation and showed that nine of the 11 patients achieved a molecular CR on day 28. Auto-122 was well manageable with no patients experienced high-grade cytokine release syndrome. No patient relapsed with antigen loss, and two of the CD19 negative patients achieved a molecular complete remission, demonstrating the isolated activity of the CD22 CAR. We will continue to follow the patients and will update you later in the year. Moving to slide 17. Here is a brief depiction of our broad cell programming toolkit we developed over the last few years. All in, the technologies cover programming modules for targeting, control, shielding, and enhancing CAR-T cell activity. More than 100 patent families cover our products and cell programming technologies. Recent illustrations of three technology applications were shown at ASGCT annual meeting in May. Each one of our product candidates applies one or several of the technologies to maximize its impact on the specific cancer it is designed to tackle. Moving to slide 18. This slide shows more of our next generation programs beyond ObieCell. A program we're excited about is Auto4, which is in phase one study in T cell lymphoma. I'll give you an update of the data we presented at EHA in just a minute. During the first quarter, as I mentioned, Auto-8 moved into the clinic in a phase one clinical study, multiple myeloma patients, and we're now dosing patients. I also want to reiterate our first solid tumor program, Auto-6-NG in GD2 positive solid tumors, will be moving into the clinic second half of this year. This program has a clinically de-risked chimeric antigen receptor to GD2 and contains multiple programming modules to enhance its activity. Turning to slide 19. We're actively exploring T-cell lymphoma, which is an aggressive disease with a very poor prognosis for patients. You might recall our EHA analyst call where Dr. Horwitz from the Department of Medicine Lymphoma Service at Memorial Sloan Kettering Cancer Center talked about the majority of patients being either refractory or relapsing after initial treatment. Standard of care is variable and often based on intensive chemotherapy treatment. Median survival for patients with relapsed or refractory disease is less than six months. T-cell lymphomas are clonal diseases that either express TRBC1 or TRBC2. The T-cell receptor beta chain constant domain 1 or 2, or short, TRBC1 or TRBC2, are expressed on more than 95% of all T-cell lymphoma subtypes. Only lymphomas derived from gamma delta T cells or NKT cells lack TRBC1 or TRBC2. Auto4 targets TRBC1, and it is the first product candidate to do so. Using next-generation sequencing, we identify patients with TRBC1-expressing T cell lymphoma. These TRBC1-positive patients are then treated on the currently open Auto4 study, and in the future, we plan to open a study targeting TRBC2-positive patients with auto 5 as well. Auto 4 is designed to selectively kill lymphoma cells in a manner that we believe will preserve a portion of the patient's normal healthy T cells to maintain immunity. Turning to slide 20. To date, we've treated 10 patients with increasing doses of auto 4 in the so-called Libra T1 study. We evaluated four dose levels ranging from 25 million cells to 450 million cells. and have seen no dose-limiting toxicities and only mild cytopenias. In terms of cytokine release syndrome, we just saw one grade three cytokine release syndrome at the highest dose level, so the four was generally very well tolerated. We've seen metabolic complete remissions in five of the seven evaluable patients, with three of three patients at 450 million cell dose achieving a metabolic CR. Two of the complete remissions at 450 million cell level are ongoing at three and six months. And we expect to have longer follow up on these patients in the second half of this year. Moving to slide 22. The manufacturing of cell therapies is complex and requires a great deal of skill and experience. We're building a new manufacturing facility in Stevenage in the UK. This location is about a mile from our current clinical manufacturing operations at the so-called CGT facility and will allow us to transition our entire operation, including our experienced staff, to the new facility in an expeditious and efficient way, both minimizing startup risks and costs for the commercial supply. As evidenced by our successful manufacturing of CAR-T's products for the Pivotal Study with centers across the U.S. and Europe, The location is well suited for global supply with easy access to several international airports, including London Heathrow. The new 70,000 square foot facility will provide all of us with a capacity of approximately 2,000 cell therapy batches a year with the ability to expand further when needed. You can see on this slide a rendering of what the facility will look like once completed by the end of the year. We're on track to commence GMP operations in mid 2023. For our clinical supply operations, we currently operate with four shifts, seven days a week. Our commercial manufacturing model will continue the seven-day-a-week pattern for the 365 days a year. With that, we're moving to slide 24, and I'd like to pass over to Lucinda for our second quarter 2022 financial update. Lucinda?