Autolus Therapeutics plc

Hello, ladies and gentlemen, and welcome to the Autoless Therapeutics Fourth Quarter 2020 Financial Results Conference Call. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Dr. Lucinda Krajci, Vice President, Investor Relations. Please go ahead.

Thank you. Good morning or good afternoon, everyone, and thank you for taking part in today's call on the financial results and operational highlights for the fourth quarter 2020. I am Lucinda Crabtree, Vice President of Investor Relations. With me today are Dr. Christian Eytton, our Chairman and Chief Executive Officer, and Andrew Oakley, 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. All statements other than statements of historical facts on this call are forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the section titled Risk Factors in our annual report on Form 20F filed with the Securities and Exchange Commission on March 3, 2020, which can be accessed on the EDGAR database at www.sec.gov and in subsequent filings we make with the SEC from time to time. The forward-looking statements on this call reflect the company's views as of today, March 4th, 2021, regarding future events and should not be relied upon as representing the speakers or the company's views as of any subsequent date. While the company may elect to update these forward-looking statements at some future point, the company specifically disclaims any obligation to do so even if the company's views change. These forward-looking statements should not be relied upon as representing the company's views as of any date subsequent to today. Please be advised that today's call is being recorded and webcast. On slide three, you will see the agenda for today, and it is as follows. Christian will provide a brief introduction, and that will be followed by our operational highlights for the fourth quarter of 2020. Andrew will next discuss the company's financial results, and then Christian will conclude with upcoming milestones and other concluding comments. And of course, we will welcome your questions following our remarks. So with that, I'd like to now turn the call over to Christian.

Thank you, Lucinda, and good morning to all of you, and thank you for joining us. I'm pleased to review our progress for the fourth quarter 2020. First, on slide five, I would like to provide an update in our programs. We have now entered into a more stable period post the initial COVID peaks last year, and our programs remain on track. We have not seen any further disruption in the fourth quarter last year. We continue to work hard with our supply chain and logistics teams, as well as our clinical centers, to ensure timely continental and transatlantic deliveries of leukophoresates, final products, and samples for analysis in order to support our clinical trials and ensure timely data availability and integrity. We continue to monitor developments very carefully with a particular focus on patient safety. In Q4, and indeed the full year, we provided data updates from our Phase I all-car study of Auto I at EHA in June and also at ASH in December 2020. The pivotal program, Auto 1 AL1, which we now can also refer to as the Felix study, remains on track with data expected in 2022. We also provided an update from the Alexander study of Auto 3 in DLBCL at EHA and also ASH last year. I will touch on Auto 3 a little later. In addition, our academic partners published data from a Phase 1 study of Auto 6 in the journal Science Translational Medicine, and we're looking forward to moving Auto 6 NG into clinical development. In January this year, we provided a business outlook where we guided on a renewed focus on the Auto 1 program. As part of this outlook, we announced our intention to partner our DLDCL program, Auto 3. Finally, in January and February 21, we strengthened our balance sheet with the sale of ADSs under our ATM facility for net proceeds of approximately $15 million, And also, public offering of ADS is raising approximately $108 million in net proceeds. More detailed updates will follow on the next slides. So moving on to slide six. We're focusing our Auto I program on addressing the high unmet medical need in adult acute lymphoblastic leukemia, which is a truly underserved area with limited treatment options in development. The FELIX study is designed to address the relapsed refractory population with data expected next year, building on the unique profile of Auto-1. We're also exploring its utility in relapsed refractory, BNHL indications, and in primary CNS lymphoma. In addition, the next-generation program, Auto-1-22, is being explored in pediatric patients. We expect data updates for these programs in the fourth quarter of 2021. Beyond data in B-cell malignancies, we expect clinical data from auto-4 in peripheral T-cell lymphoma in the fourth quarter, and are moving our next-generation programs forward into clinical development in collaboration with our academic partners. Moving to slide 7. Focusing on our lead program in adult ALL, I think it's important to understand that with this indication, we have no approved CAR-T therapy at this point in time. The only approved redirected T-cell therapy is blincyto or blinatumumab, And in terms of other targeted therapies, there is also inotuzumab, a CD22-targeting antibody drug conjugate. Frontline therapy is very intense, based on very intense high-dose chemotherapy regimens. Most patients do respond to that initial therapy. The challenge, however, is that only 30% to 40% of the patients benefit long-term, while the majority of those patients relapse. Once relapsed, life expectancy is very short, with a median survival of less than one year. The relapsed patients, when they're fitted off, will receive a high-dose chemotherapy followed by an allogeneic stem cell transplant with a small proportion of patients achieving a long-term benefit. Patients not eligible for stem cell transplant or relapsing post-transplant may receive additional chemotherapy, linatumumab, or inotuzumab. However, none of these therapies drive long-term benefit at that stage of the disease. This is a very challenging situation for patients and their treating physicians. At this stage, these patients are typically in quite poor condition, both from the immunosuppressive nature of their underlying disease and as a consequence of the often multiple courses of high-dose, very toxic chemotherapy. As a consequence, a lot of these patients are highly prone to infection, and a lot of them do die of sepsis as the primary cause of death. The core of relapsed, refractory adult patients in the U.S., EU, and Japan are approximately 3,000 patients with high unmet medical need and very limited new therapeutic options in development. Turning to slide number eight, we've pulled together a funnel to illustrate the treatment journey for patients diagnosed with adult ALL. Unlike pediatric ALL, high relapse rates are common in adult ALL despite favorable initial responses, and therefore opening the door for a product like AutoOne. The significant unmet need in relapsed refractory adult ALL necessitates new innovation, which can offer improved durability, safety, and curative intent. We will initially look to target those patients post-receiving Blina or inotuzumab, but also expect to capture some patients prior to having been exposed to these standard of care agents. The initial indication represents approximately 3,000 patients, And we expect data in the last line setting will drive interest to move the program into earlier lines of therapy. On the next slide, number nine, we summarize the key features of a successful CAR-T cell therapy for adult ALL. The basic disease challenges involve very fast proliferating leukemic cells with almost stem cell-like proliferative potential in patients who are in overall poor condition as a consequence of their underlying disease and also the toxicity of prior treatments. So the product needs to combine very high levels of sustained anti-leukemic activity with a good tolerability profile. The technical solution for CAR-T for the CAR-T product Auto-One is its highly specific but transient engagement of the leukemic cells, maximizing its activity and persistence while minimizing cytokine release and neurotoxicity. The result is a high molecular response rate and event-free survival combined with a manageable safety profile. Moving to slide 10, we would like to highlight some of the key data presented in December at ASH. The event-free survival at six months was 69, and at 12 months, 52%. Overall, we showed a median follow-up of the patients of 16.9 months, and first patients without receiving a second transplant passed 24 months in sustained molecular complete remission with persisting CAR T cells. This profile gives us a lot of hope that the program can drive long-term remissions in a proportion of patients. We're now conducting the Felix study to confirm these results. On the next slide, number 11, we're looking to put the Auto-1 data in the perspective of the standard of care. The primary treatment option for patients is Blinitumumab, while Inotuzumab may typically be used as a bridging therapy. If you look at the event-free survival, we're approximately twice as active as splenotumor MAP at six months. And even at 12 months, where we are seeing a value of 52% event-free survival for auto one, we see a substantial exceeding data compared to the six months value for the tumor MAP of just 31%. When looking at the Auto-1 data, it is important to realize that 70% of the patients had either received prior blinitumumab or prior inotuzumab and failed on those therapies before entering the Auto-1 trial. Despite the elevated Auto-1 activity compared to blinitumumab, cytokine release syndrome and neurotoxicity are very comparable. In a very simple way put, with Auto-1, we're looking at a program that has at least twice the level of clinical activity of blinitumumab which is the current standard of care with a comparable safety profile. We believe that the data is a very good foundation to move this product into a potential registrational study. Moving to slide 12, just another quick view on two of the key programs and products that are approved in the space, but from a commercial perspective. We're looking at Blinsight or Blinitumab and Besponsa or Inotuzumab. As you can see, Blinsight has reached in 2020 annual sales of 379 million. Typically, patients receive an average of two cycles of the product, which translates to approximately 2,100 patients treated with this commercial product globally. Note that the majority of patients receiving the product are adults. We understand the key driver for sales accelerating into the fourth quarter was the expansion to community hospitals segment in the U.S. beyond the initial academic transplant centers, which were where the product started its journey. While Blinzite and ALL is moving to non-academic centers, we also expect the launch of Brianzi in DLBCL to establish party experience in those centers. Both developments bode well for a product with the properties of AutoOne. Let's now turn to slide 13. First off, obviously the Auto-1 program at this point is in motion in the Felix Phase 1b2 Pivotal Study. It is a single-arm study with approximately 100 patients with relapsed refractory disease. The primary endpoint is overall complete response rate. Secondary endpoints include molecular responses as well as event-free survival and duration of response. This program is ongoing and will recruit through the course of this year. As I've mentioned, we're also conducting some clinical additional studies to explore the activity of Auto1 beyond the adult ALL population. That includes indolent lymphomas and CLL. As mentioned earlier, we're also exploring the activity in primary CNS lymphoma, which is typically a neglected indication. In December, we also started a next-generation version of the Auto1 program that looks at minimizing the relapse rate in pediatric ALL driven by CD19 antigen loss. The program is called Auto1-22 and builds an Auto1 with its unique properties and adds a novel, highly active CD22 chimeric antigen receptor. Data presentation is planned for Q4 in 2021. In summary, we believe there's a significant commercial opportunity to build an Auto1 franchise anchored in ALL, both with adult and pediatric patients, and also expanding into additional B-cell non-Hodgkin's lymphoma indications. Turning to slide 14. Moving to our next program, auto three, and diffuse large B-cell lymphoma. We provided updates and oral presentations of the Alexander study at ASCO, EHA, ESMO, and ASH last year. The program has shown a high level of clinical activity paired with a very favorable safety profile. Two regimens of Pembrolizumab were tested and shown to be safe. And building on what we believe is a best-in-class safety profile, we tested Auto3 in outpatient setting and demonstrated feasibility. Of the patients administered in the outpatient setting, 38% were admitted with fever due to concerns of a potential infection, and all were discharged after the risk was cleared. Patients were all well-managed, manageable without need for intensive care. We're planning to partner the program considering the broad commercial footprint required to serve the outpatient setting. So let us turn to slide 15. Auto IV is our T-cell lymphoma program currently active in the clinic and we expect to have a clinical update at the end of the year and expect a good understanding of the clinical profile of this product by then. The sister program, Auto V, is prepared for an IND towards the end of 2021. The medical need in T-cell lymphoma is high, with very limited available treatment options for patients once they relapse after frontline therapy. Moving to slide 16. Always good to remind you all of the technology toolkit we've developed at Odalis, particularly as it relates to the suite of next-generation programs, some of which you will recall we showcased at AACR in 2020. We're looking to move several programs into the clinic through 2021 and into 2022, including our first cell tumor programs, which we are very excited to be progressing. Our cell programming modules are designed to provide T cells with a high degree of specificity and activity against cancer cells, while strengthening the T cell's resilience to withstand the hostile environment cancer cells create to fend off T cell attack. Slide 17. You can see we have tabulated these next-gen programs alongside the expected phase one start dates. As you will note, and as discussed, we started the pediatric ALL clinical trial of AUTO1-22 in Q4 last year. We haven't yet mentioned, of course, AUTO6-NG. We expect to move into a study of GD2-positive solid tumors, particularly neuroblastoma, second half of this year. AUTO7 in prostate cancer is due to enter the clinic next year. And finally, auto aid will move into the clinic in the first half of 21 in multiple myeloma. All programs will initially be explored clinically in collaboration with our academic partners. Now, with that, I would like to turn to slide 18 to tell you about a project we incubated with our research team in 2020. This is a program we will look to actively partner in 2021. As we started to learn about the SARS-CoV-2 virus in Q1 last year, we got concerned about two areas that did not feature at the time in many of the discussions on the virus. The first was the risk of mutational drift, which was known for coronaviruses in general, but at the time not well established for SARS-CoV-2. And the second were the challenges this viral infection could pose for our patients with B-cell malignancies and with multiple myeloma, who would likely only have limited ability to benefit from future vaccines. We considered that vaccine approaches as well as antibody-based therapeutic approaches may not work well for our patients and more generally could be outsmarted by the virus. The approach we wanted to focus on should remain active even if the virus were to undergo mutational drift and could be used as a universal decoy against not only SARS-CoV-2 and its variants, but ideally against all coronaviruses using the same human receptors to infect cells. What we developed is an ACE2-FX fusion molecule combining an enzymatically inactive form of the extracellular domain of ACE2 and a mutated constant domain from an IgG to avoid unwanted immune activation. This molecule can efficiently neutralize the virus by acting as a receptor decoy for the spike protein SARS-CoV-2. The FC domain has been introduced to confer an extended half-life to the molecule and improve effectiveness of the product. The product candidate has been tested in vitro and in vivo against SARS-CoV-2. We have now demonstrated in in vitro models the efficacy of this product candidate against the UK B.1.7 and the South African B.1.351 variants using lentiviral vector pseudotype to address the SARS-CoV-2 spike protein. In addition, we also tested the ability of the product to neutralize SARS-CoV-1 to further highlight the potential utility against a wider range of ACE2 tropic viruses. As you can see, only the ACE2-FX neutralizes all SARS-CoV-2 variants, whereas therapeutic antibodies lose activity against SARS-CoV-2 variants and are inactive against SARS-CoV-1, whereas obviously the product candidate is active against SARS-CoV-1. We're very encouraged by this early data and the opportunity to develop a potentially universally neutralizing agent against SARS-CoV-2. As indicated, we're looking to partner the program for clinical development. With that, I will turn over the call to Andrew for our fourth quarter 2020 financial update. Andrew?