Autolus Therapeutics plc

Hello, ladies and gentlemen, and welcome to the Autoless Therapeutics Third Quarter 2021 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 Crabtree, Vice President, Business Strategy. Please go ahead.

Thank you, Daniel. 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 Third Quarter 2021. I am Lucinda Crabtree, Vice President of Business Planning and Strategy. With me today are Dr. Christian Eytton, our Chief Executive Officer, Christopher Vann, our Chief Operating 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 4, 2021, 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, November 3rd, 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 obligations 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 subsequent date, to today. Please be advised that today's call is being recorded and webcast. So on slide three, you will see the agenda for today, and it is as follows. Christopher will provide an overview of our operational results for the third quarter of 2021. Andrew will then discuss the company's financial results before Christian will conclude with upcoming milestones and any other concluding comments. Finally, we will, of course, welcome your questions following our remarks. Let's turn to Christopher.

Thank you, Lucinda, and good morning to you all. Thank you for joining us. It's my pleasure to review our operating progress for the third quarter 2021. If we move to slide five, I'd like to give a quick update on the key pipeline activities. And first of all, our multi-center Felix study for our lead program, OBSEL, which is progressing very well. Enrollment in the phase two portion of the study is on track. And consequently, we are reiterating our guidance that the primary endpoint data will be delivered in the middle of next year, with the full pivotal data available by the end of 2022. Furthermore, we are pleased to be in the position to update you that the initial observations from the 16 patients in the phase 1b running portion of this multicenter Felix study where we observed the one-month complete response rate and safety data are so far consistent with the data reported from the academic all-caste study of oversell in relapsed refractory adult acute lymphoblastic leukemia. Clearly, this is very encouraging, and we plan to present this early data from the Phase 1b cohort later this year at ASH. In addition, we also expect to update you, Ash, on additional data from the All-CAR-19 Extension Study of OberCell in indolent B-cell non-Hodgkin's lymphoma indications, as well as the first early clinical data from the CAR-PEL Extension Study, which is evaluating our next generation product, Auto-1-22, in pediatric ALM. In addition to the OberCell news flow, We also plan to provide an update on our phase one trial of auto four in peripheral T cell lymphoma in the first half of 2022. If we move to slide six, we'd like to walk you through a general corporate updates from the third quarter. Firstly, during this period, we were delighted to announce the appointment of John H. Johnson as non-executive chairman. John brings a wealth of commercial oncology and business experience to Autolus, and is a recognized leader in the biopharmaceutical industry, having held a number of executive, operational, and commercial leadership roles. His experience will clearly be invaluable as we look towards the commercial launch of Oberson. We're also very pleased to announce that in September, planning approval was granted to build the company's new manufacturing facility in Stevenage, UK. This 70,000 square foot facility will be leased to Autolus and is another important step for Autolus on our journey to becoming a fully integrated commercial company. We anticipate that this will meet the global demand for initial indications for oversell, and as it will be built for a capacity of approximately 2,000 GMP batches a year, it will also have a further scope to expand beyond that if needed. In terms of other updates, we promoted Chris Williams to Senior Vice President of Corporate Development and Alec Swan to Senior Vice President of Human Resources. This follows the departure of Mateus Older, our Chief Business Officer, and we're extremely grateful to Mateus for his service to Totalus and wish him all of the best for the future. We are delighted to welcome Chris and Alec to the Senior Leadership Team. as part of the Q2 earnings as post-period events, we were very pleased to also announce the appointment of Dr. Edgar Brendel, who has now joined us as the new Chief Development Officer of the company, as well as Wolfram Brugger, who joined us as the new Head of Clinical Development. Finally, we announced an option and license agreement with Moderna where we granted Moderna an exclusive license to develop and commercialize mRNA therapeutics incorporating autolysis proprietary binders for up to four immuno-oncology targets. This is further tangible recognition of the technology base that we have developed within the company. With that, let's move on to the next slide, slide seven. What we'd like to do is to provide a brief overview with regards to OberCell. which is on track to be the first product commercially launched by Autolus. As you remember, our focus for the company is on delivering the Felix study in adult patients with relapsed refractory ALL, with the study enrolling patients who are both post-blendotumormab and inotuzumab, as well as patients that are just progressing in the relapse setting but have not, or may not have yet, received inotuzumab and blendotumormab. As we mentioned earlier, we're also exploring the activity of OBSEL beyond ALL in the context of the ORCAR19 extension study, and we expect to provide further updates in Q4 2021 to the data already released at EHA in June of this year. In addition to the updates in follicular lymphoma and mantle cell patients, we will also include data on patients with DLBCL and CLL. In addition, we're also now treating pediatric patients with Auto-122, which is a newer product that builds upon the oversell backbone by adding a novel CD22 antigen receptor. As mentioned previously, we also expect to share some of the initial clinical data on this product also in Q4 2021. Next slide, please. Slide eight. Focusing specifically on adult acute lymphoblastic bulimia, it's worth remembering what are the key features of a successful CAR cell therapy for this indication. Boba Cell was specifically designed to tackle the underlying biology of adult ALL, and that's why we believe it's uniquely placed to address the current limitations of therapy in this indication. One of the core challenges with this disease is that it's fast-proliferating disease, being stem cell-like in nature. And another challenge is that patients often present in very poor condition. The fast off-rate binder of oversell, whereby the cell interacts with its target and releases more quickly, means that the cells experience less exhaustion and hence better engrossment and persistence. Then, at the same time, Because of the quicker and more efficient interaction with the target, we would also expect to see less inflammation and lower levels of toxicity. Please move to slide nine. Let me remind you there still remains a very high unmet medical need for adult ALL with approximately 8,400 new cases diagnosed yearly worldwide in the last line setting. Approximately 3,000 of these cases reside in the US and EU. Whilst combination chemotherapy enables 90% of adult ALL patients to achieve CRs, only about 30% to 40% will achieve longer-term remission. Once relapsed, patients have a median overall survival of less than a year. The approved products include linatumumab, and inatuzumab for this indication, and in some countries, CARTUS is in the process of being launched. We believe, however, there remains a real opportunity for a product candidate with Obercel's profile in this setting, and to remind you all, Obercel has been granted orphan drug designation by the FDA for ALL, crime designation by EMA, and ILAP designation by MHRA. Moving on to slide 10. So let's just take a moment to recap on the data presented to date. Key new data were recently presented at EHA for the Orcas study, notably an update on durability of response as measured by event-free survival. As we've already communicated, and as you would expect of a CAR-T cell product in this indication, OvaCell has high levels of initial response. However, as the patients go out post-treatment, what we're seeing now is that the event-free survival is maintained in the Kaplan-Meier curve, with it stabilizing over time. This emerging evidence gives us a level of confidence that oversell has the potential to get a good proportion of these patients into long-term remission. So turning to slide 11, to our knowledge, This is the first time that such a plateau of long-term response has been seen in this disease setting. Furthermore, it provides a degree of validation for the basic design premise of OberCell, since this long response is correlated with the exceptional persistence that we're seeing with the product. Not only do we see about a tenfold increase in the maximum number of CAR T cells that have been reported in other programs, that the level of CAR T cells is maintained over time, and it's our belief that persistence is actually a prerequisite to be able to translate a molecular response into a long-term remission in this indication, and the emerging data seems to support this. On the right-hand side of the slide, you'll also see the adverse event profile, and as reported previously, we haven't seen high-grade cytokine release syndrome Furthermore, this was achieved without prospective intervention and with only limited use of supportive care, such as tocilizumab and steroids, and no vasopressor use in these patients. So again, as would be anticipated based upon the design hypothesis for the product, Oversell has a very good safety profile, which should render the product more easily manageable in the clinic. In conclusion, the data is very encouraging, the Vobacil having a potentially unique efficacy and safety profile in this clinical setting. So moving on to slide 12. To put this data into context with the data published for the other products used in this space, I'd like to first compare it to the existing standard of care and the data sets that were the foundation for the approvals of Blenatumumab and Inotuzumab. Overall, as you can see, the available data for Obersel thus far stacks up very well against both of these programs, particularly in respect of offering potential for high levels of activity with a more sustained response. Turning to slide 13, Tocatus was recently approved in adult patients with relapsed refractory ALR. The data supporting this approval shows a 24% high-grade CRS, neurotoxicity of 87% in patients experiencing any grade neurotoxicity in the label. And on the efficacy side, I would like to point you to Oversell's complete response rate and compare it with the excellent persistence and event-free survival observed in the Orcas study. In conclusion, taken in context, we believe all CAR-19 data is very encouraging, with oversell having a potentially unique efficacy and safety profile in this clinical setting, and we feel we have a very nicely differentiated product for this high medical need patient population based on both durability of response and overall safety profile. Slide 14, please. Moving on to the oversell registration study, FELIX. This is a 100-patient study in relapsed refractory adult ALL patients. It has two subpopulations, relapsed refractory post-exposure patients to Blinner and Inertuzumab, as well as patients inexperienced with regards to previously receiving Blinner Tumormab or Inertuzumab. The primary endpoint of the study is complete response rate, and the secondary endpoints include molecular responses as well as event-free survival and duration of response. So let us turn to the market size and the current market size in slide 15, please. I touched upon the opportunity in ALL in an earlier slide in terms of patients, but what I'd like to just highlight is the sales performance of the current standard of care. Blyn Saito, always known as Blyn the Tumor Man. Amgen reported yesterday sales growth of 40% in the third quarter, sorry, 40% growth in the third quarter on a year-by-year basis as compared to third quarter last year. As you can see, if we look at the first half sales in 2020 and 2021, there were cells of 187 million and 215 million with a growth in the region of around 20%. If we apply publicly available information on the proportion of use in pediatric and adult patients, and by using a very simple extrapolation that patients typically receive on average about two cycles of this product, This provides further evidence and translates to approximately 2,000 patients currently receiving this commercial product globally in 2021. Amgen has stated that one of the underlying key drivers for sales increase has been the expansion to the community hospital segment in the U.S. beyond academic transplant centers. While Blencerta in ALL is moving to non-academic centers, we also expect the launch of Brianzi, in DLBCL to also establish CAR T experience in those centers. Both of these developments bode well for a product with the properties of oversell. Slide 16, please. Slide 16 summarizes the current situation for oversell in ALL. From the All CAR-19 study, we have observed a subset of patients with a high level of sustained CR achieved without subsequent stem cell transplant and durability of remissions that are highly encouraging with 50% EFS at 12 and 24 months. Oversell is well tolerated despite being used in a heavily pre-treated patient pool with high disease burden. We observed no grade three or higher CRS, and in the 20% patients experiencing any grade ICANNs, these resolved swiftly. Overall, we're very excited about the opportunity for oversell in a sizable market with clear unmet medical need. Now taking a different track and moving on to other indications, please move on to slide 12. At EHA in June, we shared data from the all-car extension phase. In this fluid plot, all of the nine patients that were dosed achieved a metabolic complete response. And in this small population, the safety profile was consistent with that observed in ALL, with no patients experiencing high-grade CRS. Furthermore, none of the patients experienced any form of neurotoxicity. One of the patients, unfortunately, contracted COVID and died as a consequence of COVID-related AEs. The patient, however, died in complete metabolic remission. There was one further patient who developed a single lesion in the skin which could be removed surgically, but obviously that event was also considered a progression. No other patients progressed and all other patients were in remission. Moving on to slide 18. Given Oversell's mechanism of action and profile, we're also evaluating its use in other B-cell malignancies. Non-Hodgkin's lymphoma patients as well as CLL patients are being evaluated as part of the extension in the ORCAR19 study. We're also conducting, in collaboration with our academic partners at UCL, in the CARICEL study, the use in primary CNS lymphoma and aggressive lymphoma similar to DL-BCL that is exclusively localized in the brain. In addition, as already mentioned, we're conducting an extension of the CARPEL study with auto-122 in pediatric patients. These programs taken together will give us a very good overview of the activity of oversell across the spectrum of CD19 positive malignancies. Moving on, on slide 19, a brief reminder of the broad and exciting technology toolkit that we have developed in Autolus, particularly as it relates to the suite of next generation programs, some of which you will recall we showcased at AACR last year. We're looking to move these programs forward into the clinic through 2021 and into 2022, including in our first solid tumor programs. It's worth also reiterating the deal we recently signed with Moderna, which highlights the highly skilled in-house binder discovery team we have here in Autolus and the applicability of our work to other potential modalities. Finally, on slide 20, you can see that we have tabulated these next generation programs alongside expected phase one start dates. You will note, as discussed, we started the pediatric ALL clinical trial of Auto 1-22 in Q4 2020. We also expect the Auto 6-NG study in GD2 positive solid tumors to start enrolling in the first half of 2022. Auto 4 is also likely to move into the clinic in first half of 2022. And finally, Auto 8, our next generation multiple myeloma product, will move into the clinic in Q4 2021. With that, I'd just like to turn over to slide 21 and turn over the call to Andrew. Thank you.