Autolus Therapeutics plc

Ladies and gentlemen, thank you for standing by and welcome to the Autoless Therapeutics First Quarter 2022 Financial Results Conference Call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. If you require any further assistance, please press star 0. Thank you. I would now like to end the conference with your speaker today, Olivia Manser, Director of Investor Relations. Please go ahead, ma'am. Thank you, Wren.

Good morning or good afternoon, everyone, and thank you for joining us to take part in today's call on the operational highlights and financial results for the first quarter of 2022. I'm Olivia Manser, Director of Investor Relations, and with me today are Dr. Christian Eiten, 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, our discussion will contain forward-looking statements. Please make sure you're familiar with our disclaimer, which is on slide two of the presentation. On slide three, you'll see the agenda for today, which is as follows. Christian will provide an overview of our operational highlights for the first quarter of 2022. Lucinda will then discuss the company's financial results before Christian will conclude with upcoming milestones and any other concluding comments. Finally, of course, we will welcome your questions.

Thank you, Olivia, and good morning to you all. Thank you for joining us. It's my pleasure to review our progress for the first quarter of 2022. Please move to slide four. For those of you who are new to Otelus and as a fresher for those 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. Illustrating this approach are OviCell, with its focus on physiological engagement of leukemic cells, maximizing potency while improving safety and persistence, Auto4-5, with a unique targeting approach for T-cell lymphomas, and Auto6NG, a CAR-T product candidate building on a clinically validated CAR-2GD2, and adding programming modules to render the CAR-T cells insensitive to checkpoint and TGF beta inhibition while increasing CAR-T cell persistence. For manufacturing, we're using a common platform. We're using common platform and process design principles to generate products that are highly active and persisting in patients. Our current operations for clinical trial supply is working in four shifts, seven days a week, in what we are anticipating to be very close to our commercial manufacturing model. The commercial manufacturing facility designed for 2,000 products per year is under construction in the UK, about a mile away from our clinical trial manufacturing site, and expected to be ready for GMP supply by middle of 2023. Moving to slide five. We had a successful quarter with OVCell clearing the pre-planned futility analysis in the Felix trial and enrollment continuing to plan. In addition to the primary morphological cohort in the FELIX trial, we are expanding the MRD or minimal residual disease cohort to up to 50 patients. In clinical practice, patients get evaluated on a regular basis for recurrence of disease, typically using flow analysis of their bone marrow. Indication of MRD levels or minimal residual disease levels of leukemia triggers treatment of the patients rather than waiting for full-blown relapse before starting treatment. This additional cohort does not impact our client filing timelines as the primary data will be based on the data from the morphological cohort. With obtaining RMAT from the FDA, we have received preferred regulatory access for OB-Cell in all our key territories, the US, EU, and UK. In addition, the EU granted also orphan drug designation for OB-Cell, adding to the same designation we have received previously from the FDA. In the second quarter, we're looking forward to updates at EHA from our evaluation of OB-cell in non-Hodgkin's lymphoma and primary CNS lymphoma, and two oral presentations covering our initial evaluation of the dual-targeting OTO-1-22 in children with ALL who are ineligible for chemo therapy, and our dose escalation experience for OTO-4 in T-cell lymphoma. In addition, the clinical phase one evaluation for OTO-8 in relapsed refractory multiple myeloma started, and we are on track for Auto6NG to start a phase one in the second half of the year. Turning to slide six, here is a snapshot of our operational progress. As indicated, our new manufacturing facility in Stevenage is progressing well. During the quarter, Dr. Lucinda Crafty was appointed as chief financial officer of the retirement of Andrew Oakley, and as we prepare for the potential launch of OBSEL, Brent Rice was promoted to senior vice president and chief commercial officer. As well as clinical progress, we continue to innovate with our cell programming platform, and earlier this week, Otilus announced the online publication of three abstracts submitted to the American Society of Gene and Cell Therapy, ASGCT, to be held May 16 to 19 in Washington, D.C. The three abstracts focus on Otilus' modular approach to CAR-T cell programming. The abstracts involve, first, enhancing CAR-T cell persistence using a constitutively active cytokine receptor, Second, engineering of CAR T cells to express a fast CD40 protein to increase its persistence and antitumor activity. And three, developing a minocycling-mediated protein-protein displacement platform to make cell therapies untunable with a commercially available and safe small molecule in a dose-dependent and reversible manner. Slide seven, we're jumping over and go directly to slide number eight. The focus is here on OB cell. And just to remind you, OB cell 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 fastest engagement is based on the fast off rate of the cat binder and drives three key properties of OB cell. Very high clinical activity paired with minimal toxicity and excellent persistence. Moving to slide nine. There still remains a very high unmet medical need for adult ALL patients, with approximately 3,000 patients reaching the relapsed refractory stage of the disease that are residing in the U.S. and in the EU. While frontline high-dose combination chemotherapy enables about 90% of the adult patients to achieve complete remissions, only about 30% to 40% will achieve long-term remissions. Once patients are relapsed, they have a median overall survival of less than a year. The insight has become the standard of care for relapsed and refractory patients. However, most patients progress rapidly. More recently, the CARDS has been approved, showing a higher level of clinical activity, but also a significant increase in toxicity. When we look at slide number 10, this slide summarizes the key data we have shown to date for OB-CELL in ALL, which suggests that OB-CELL could be potentially a transformational therapy for adult patients with ALL. In the initial Felix Phase 1b data presented at ASH at the end of last year, OB-CELL showed a favorable safety and efficacy profile consistent with the data we have collected prior in the OLCAR19 study in the same patient population. We saw a high overall response rate, and the duration of response from the OLCAR19 study remained highly encouraging with morphological event-free survival for OB-cell of 46% at 24 months with a median follow-up of 29.3 months, and patients approaching up to 42 months of durability. We continue to see sustained OB-cell persistence in those patients as well. And to remind you, Obicel has been granted orphan drug designation by the FDA for ALL, prime designation by EMA, ILAC designation by NHRA, and most recently, RMAT designation by the FDA, and as well as orphan drug designation by EMA as well. Moving to slide 11, we're conducting the FELIX study with 100 patients in a morphological cohort, treating those patients at sites in the US, UK, and in Spain. We expect to be fully roamed as we go through the course of this year, and as mentioned, expect to have initial data starting in the second half of this year with full data in the first half of next year. Switching gears and moving to slide number 13. OB-cell's unique profile means it could be applicable to a broad range of B-cell malignancies. We are evaluating the product outside of ALL in mild Hodgkin's, B-cell lymphomas, including the typical follicular, DLD-CL, mantle cell, and CLL indications, and expect multiple clinical readouts during the course of 2022. The first clinical updates will be in June at EHA, where we have readouts from a Phase I study, an extension of the old CAR study in the non-Hodgkin's indications, as well as from a separate study, the so-called carousel study, in patients with primary CNS lymphoma. On slide 14, on the right-hand table, we provide a quick summary of the basic experience that we had to date with OB-cell in pediatric ALL patients in the so-called CARPAL study. The fundamental finding was that we have excellent activity without high-rate cytokine release syndrome, but we did see about half of the patients relapse due to antigen loss of CD19. That is why we went back and built on this favorable profile of OB-cell that we have seen in kids adding a highly potent CD22 CAR to create a product called OTA1-22. We will have an oral presentation at EHA of the Phase I data for OTA1-22 in pediatric ALL patients that were ineligible for chemorhyotherapy. Moving to slide 16 to talk more broadly about our technology base. Otolith has a wide range of technology covering mostly cell programming modules and product candidates. With over 100 patent families on the prosecution, we have a very significant technology treasure chest that we're building on. Three new cell programming approaches will be presented at ASGCT, the annual meeting in May, which showcase our industry-leading T-cell programming technologies. Key areas covered by our cell program model cover selective targeting of cancers, controlling CAR T-cell activity, shielding CAR T-cells from the cancer microenvironment as well as the patient's immune system, and enhancing CAR T-cell persistence as well as attracting the support of the patient's own immune system in the fight against the cancer. Moving to slide 17. Here we have tabulated next-generation programs alongside the progress in the clinic. Most advanced is Order 4, our program to address T-cell lymphomas. Order 5 is the sister program to Order 4 and following Order 4 into clinical development. Both programs are run internally. In collaboration with our academic partner, UCL, we have moved Auto-8 into the clinic in a phase one clinical study in multiple myeloma patients. And we're working on Auto-6-NG to get into the clinic second half of this year, targeting neuroblastoma, a solid tumor in children. Turning to slide 18, I'll give you further information about Auto-4. We're actively exploring T-cell lymphoma, which is an aggressive disease with very poor prognosis for patients. primary challenge has been to find a structure or target on the surface of T cells that would allow you to target the T cell lymphoma without at the same time targeting all T cells together. And of course, what that means is that you need to have a target that allows you to get the lymphoma, leaving the T cells behind and with that preserving immunity in these patients. Auto4 is targeting a structure called TRBC1, and it's just a program Auto4, a structure TRBC2. Both structures are related. They're part of the constant domain of the T cell receptor beta chain and are coming basically available in T cells in either one or the other isoform. Both targets are novel, and we obviously are planning to show first data in an oral presentation at EHA for Auto4 from our dose escalation experience in phase one. With that, I'd like to actually hand over into the financial section and hand over to Lucy, who's moving to slide number 20.