Autolus Therapeutics plc

Hello, ladies and gentlemen, and welcome to the Autolist Therapeutics Third Quarter 2022 Financial Results Conference Call. As a reminder, this conference call is being recorded, and I'd like to now turn the conference over to your host, Olivia Manson, Director of Investor Relations. Please go ahead.

Thanks, Brianna. Good morning or good afternoon, everyone, and thanks for joining us to take part in today's call on the Financial Results and Operational Highlights for the Third Quarter for Autolist. I'm Olivia Manser, Director of Investor Relations and with me on today's call as usual are Dr Christian Eichten our Chief Executive Officer and Dr Lucinda Crabtree our Chief Financial Officer. So before we begin I'd just like to remind you as usual that during today's call our discussion will contain forward-looking statements. Please make sure you're familiar with our disclaimer slide which is on slide two. And then turning to slide three, you'll see the agenda for today, which is as follows. So Christian will provide an update of our operational highlights for the third 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. And finally, we will of course welcome your questions. Over to you, Christian.

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 third quarter of 2022. Moving to slide four. We're really pleased with our strategic and operational progress during the third quarter of 2022, which is highlighted over the next two slides. Firstly, we remain on track to provide an update on our Pivotal Felix trial in Q4 2022, and we plan to present Felix Phase 2 data at a medical conference in the first half of 2023, most likely at ASCO. We're also likely, we're also looking forward to presenting longer follow-up data from our ALL patients in the old CAR-19 phase one trial at ASH and are planning a more in-depth look at the patients. Sorry. Looking forward at the patients that we've treated with non-Hodgkin's lymphoma. We're presenting further data at the three phase one trials at ASH in December 1st as indicated in the old CAR-19 phase one extension study for OB-CELL in BANHL, a CAR-PAL study, which is also a phase one trial with auto-122 in pediatric ALL, and from our LIBRA T1 phase one trial of auto-4 in peripheral T-cell lymphoma. The abstracts of these data updates will be online later this morning, so we won't be discussing them during this morning's call. In addition, the phase one McCarthy trial exploring auto-8 in multiple myeloma patients is progressing, And the phase one MCAR-TD2 trial exploring Oto6-NG is expected to start in the first half of 2023. Turning to slide five, we've made some great operational progress during the quarter and post-period end. We're very pleased to report on two technology deals in October 2022, which underscore the scientific capabilities and expertise at Otilus. We signed an agreement with Bristol-Myers Squibb, granting them access to our proprietary RQRA gritoximab-induced safety switch for incorporation into a set of selected cell therapy programs in return for a low to mid-single-digit million upfront payment with potential for near-term option exercise fees and development milestones plus royalties. Moderna exercised an option on one of the proprietary binders being developed against an undisclosed immune oncology target for the delivery of their messenger RNA therapeutics. in return for a low single-digit million upfront payment, as well as development and commercial milestone payments for each product successfully commercialized, plus royalties on net sales of all products commercialized under the agreement. The license option stems from the deal we signed with Moderna in August 2021. We also continue to make progress in our manufacturing and CMC operations. Phase one of the build of our Stevenage facility is on track for transfer to Odalus before the end of the year, to start the qualification and validation work of the facility and remains on track for good manufacturing practice operations commencing in the second half of 2023. We're also on track with the CMC workflow and report generation for the CMC package plan to support a BLA submission to the FDA. Cash and cash equivalents at the end of September were $163.1 million, not including the R&D tax credits for HMRC of $19.1 million received in October. Slide six. With that, let's talk about our primary focus, our lead product, Obicel, on slide seven now. Just to remind you, Obicel has a unique mechanism of action built on 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 Obicel. 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 of the CAR T cell, and improved engraftment and overall persistence. And those of you not familiar, I refer you to a paper by Sarah Garroshian at Nature Medicine published in 2019. Moving to slide eight. We show this slide as a reminder that there remains a very high unmet medical need for treatment of adult ALL patients with approximately 8,400 new cases diagnosed yearly on a worldwide basis in the last line setting. Approximately 3,000 of these cases reside in the US and the EU. And whilst a combination chemotherapy enables about 90% of the adult ALL patients to achieve complete remissions, only about 30% to 40% will achieve longer-term remission. Once relapsed, patients have a median overall survival of less than a year. Current approved therapies for adult patients are Blinsaito and Tecardis. Both therapies are highly active, but frequently followed by subsequent treatments, for example, allogeneic stem cell transplants. Blinsaito has a favorable safety profile with few patients experiencing severe CRS and ICANS, but with limitations on durability of effect and convenience due to the need for continuous IV infusion during its four-week treatment cycles. Tecardis is more challenging to manage and induces elevated levels of CRS, high levels of ICANNs, 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 subsequent allografts to achieve durability. Moving to slide nine. Many of you have seen this slide before, but it's a useful reminder of why we think OBSL is a potentially transformational therapy for adult ALL. Building on its unique mechanism of action, Obicel has shown a high overall response rate with a favorable tolerability profile and sustained event-free survival that tracks long-term persistence in those patients. Obicel has been granted orphan drug designation by the FDA and EMA for ALL and obtained prime designation by EMA for the EU, ILAP designation by MHRA for the UK, and most recently, RMAT designation by the FDA. Moving to slide 10. Based on what we believe is potentially transformational data from the old CAR study, we're conducting the pivotal Felix trial with approximately 90 patients with morphological disease, treating at 34 sites in the US, the UK, and Spain. We're on track with our previous guidance and expect to provide a qualitative update in Q4 2022, which we would expect to reference whether the primary endpoint has been met. We're planning on presenting data from the FELIX study at a medical conference in mid-2023. In order to maximize outcomes from the FELIX trial in parallel, we're also assessing OB-cell in additional cohort of up to 50 patients in second or later complete remission who have developed minimal residual disease. However, this additional cohort does not impact our planned filing timeline as the primary data will be based on the data from the morphological cohort. Moving to slide 12, OB cells unique profile means it could be applicable to a broad range of indications. We're consequently evaluating the product candidate outside of ALL in B-cell non-Hodgkin's lymphoma indications in an ongoing phase one clinical trial. As we said before, we have positive clinical readouts at the recent EHA Congress from the Phase 1 studies in B-cell non-Hodgkin's lymphoma and primary CNS lymphoma presented by way of the poster, as well as an oral presentation of the first Auto-1-22 Phase 1 data in pediatric ALL patients. And I'll cover these data in the upcoming slides. As I said, we'll be presenting additional data at ASH in December this year with abstracts due to go online later today. On slide 13, As a reminder, the academic All-Coron-19 study has been extended as a basket study where we are testing OB-cell in a number of B-cell malignancies. To date, we've treated 17 patients with follicular 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 diffuse large B-cell lymphoma patients, and three of three mantle cell lymphoma patients. We lost one patient to COVID and one MCL patient relapsed. Fourteen of the 16 patients that have responded remain in metabolic CR with a median follow-up of 9.2 months, the longest being 19.1 months as of the last reported data cut, and the data continues to mature. We've also started treating some CLL patients, and from the three patients that have reached the initial evaluation, as of the last data cutoff, two went into molecular CR in the bone marrow, but have some residual lymphadenopathy on CT scans. We're looking forward to presenting additional patients and longer follow-up data from this all-care extension study at ASH in December. Turning to slide 14, we're also exploring OV-cell and 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 particular poor prognosis. Initial treatment is often intensive, and outcomes for these patients tend to be poor. In the data we presented at DHA, we didn't see high-grade CRS. Two patients experienced neurotoxicity, grade 3 and 4. One patient improved with steroids and anakinra. The second patient had several neurological deficits consistent with progressive disease and didn't 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 15. Our initial experience with OB cell in children achieved a high level of sustained CRs without experiencing high-grade CRS. Those children who relapsed after treating with OB cell had, most of them had lost CD19 expression on their leukemic cells at the time of relapse. Here we're taking the next step in OB cell's life cycle with Auto-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 expressed on their surface. We evaluated all the 122 in an extension of the Carpal study in children who were ineligible for Kimraya. The children either relapsed after receiving Kimraya and could not be treated, or they had extramedullary disease, i.e., singular lesions in tissue without having disease in the bone marrow, the normal location of the leukemia. This is a very challenging group of patients to treat. Out of 14 children, four had prior Kimraya therapy, and three of them had lost CD19 expression. seven kids had extramedullary disease. Moving to slide 16, data were presented at EHA and showed that nine of the 11 patients achieved a molecular CR on day 28. On the one, 22 was well manageable with no patients experiencing high-grade CRS. No patient relapsed with antigen loss, and two of the CD19 negative patients achieved a molecular CR demonstrated the isolated activity of the CD22 CAR. We're continuing to follow the patients and we'll be presenting this data at ASH in the upcoming weeks. Slide 17 and moving straight to slide 18 on the pipeline. Here is a brief depiction of our broad-cell programming toolkit we have developed over the last few years and drove the deals with BMS and Moderna. All in, the technologies cover programming modules for targeting, control, shielding, and enhancing CAR T-cell activity. At Odalis, we have more than 100 patent families covering these products and cell programming technologies. Recent illustrations of three technology applications were shown at ASGCT, the annual meeting in May this year. Each of 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 19. This slide shows more of our next generation programs beyond OV-cell. A pipeline program we're particularly excited about is OTO4, which is a Phase 1 study in T-cell lymphoma. I'll give you a refresh of the data we presented at EHA in just a minute. OTO8 moved into the clinic earlier this year in a Phase 1 clinical study in patients with multiple myeloma, and we're now dosing patients. I also want to mention that our first solid tumor program, OTO6-NG in GD2-positive solid tumors, will be moving into the clinic in the first half of next year. Turning to slide 20, 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. Horvitz from the Department of Medicine Lymphoma Service Memorial 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 a clonal disease that either express TRBC1 or TRBC2. The T-cell receptor beta chain constant domain 1 or 2 are expressed on more than 95% of all T-cell lymphoma patients. Only gamma delta T-cell or NKT-cell derived lymphomas lack T-cell receptor beta chain constant domains 1 and 2. Auto4 targets TRBC1 and is the first product candidate to do so. Using next-generation sequencing, we identify patients with TRBC1 expressing T cell lymphoma, and then these TRBC1 positive patients are treated on the currently open Auto4 study. And in the future, we plan to open a study targeting TRBC2 positive patients with Auto5 as well. AutoIV 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 in that patient. Turning to slide 21, we presented data at EHA on the LIBRA T1 study evaluating AutoIV in patients with T cell lymphoma. We've seen encouraging activity and a favorable tolerability profile, indicating clinical proof of concept for the new approach for targeting T cell lymphoma. We're looking forward to presenting longer follow-up at ASH. So with that, we'd like to turn to slide 23. The manufacturing of cell therapies is complex, and we've developed a great deal of skill and experience manufacturing products throughout the pandemic and for a range of product candidates. We're building a new manufacturing facility in Stevenage in the UK. This location is about a mile away from our current clinical manufacturing operations at the Cell and Gene Therapy 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 commercial supply. As evidenced by our successful manufacture of CAR-T 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 otoliths with a capacity of approximately 2,000 cell therapy batches a year and with the ability to expand capacity further when needed. You can see on this slide a rendering of what the facility looks like once completed by the end of the year. In the middle, you can see the actual facility a few weeks ago when the large preassembled HVAC units were lifted onto the roof. I mentioned our progress earlier, Phase one of the BUILD project is scheduled to complete in the fourth quarter, and the equipment installations and qualifications for all of this is on track for GMP operations for the second half of next year. For our clinical supply operations, we currently operate with four shifts, seven days a week. Our commercial manufacturing model will continue with that pattern of a seven day a week throughout the year. So with that, I would like to turn to slide 25 and pass the call to Lucinda for our third quarter 2022 financial update. Lucy?