Autolus Therapeutics plc

Ladies and gentlemen, thank you for standing by and welcome to the Autolus Therapeutics first quarter 2020 financial results and operation highlights conference call. At this time, all participants are in a listen only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one on your telephone. Please be advised that today's conference has been recorded. If you require any further assistance, please press star zero. I will now like to hand your conference over to your speaker today, Dr. Lucinda Crabtree, Vice President of Investor Relations. Thank you. Please go ahead, ma'am.

Thank you, Cara. 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 first quarter of 2020. I am Lucinda Crabtree, Vice President of Investor Relations. With me today are Dr. Christian Itin, our Chairman and Chief Executive Officer, and Andrew Oakley, our Chief Financial Officer. Before we begin, I would like to remind you that during this call we will be making forward-looking statements. All statements other than statements of historical facts contained in this presentation are forward-looking statements. Our actual results, performance or achievements may be materially different from those expressed or implied by the forward-looking statements. For a discussion of the risks and uncertainties relating to our business and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, please see the section titled Risk Factors in our annual report on Form 20F filed on March 3, 2020, as well as discussions of potential risks, uncertainties and other important factors in our other periodic filings with the SEC. The forward-looking statements contained in this presentation reflect the company's views as of the date of this presentation regarding future events. and the company does not assume any obligation to update any forward-looking statements. You should therefore not rely on these forward-looking statements as representing the company's views as of any date subsequent to the date of this presentation. So with that 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 first 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 welcome your questions following our remarks. So with that, I'd like to now turn the call over to Christian. Thank you.

Thank you, Lucinda, and welcome to all of you and thank you for joining us. I'm pleased to review our progress for the first quarter in 2020. We are pleased to report in a very productive first quarter. We remain on track with our clinical programs despite the challenges of COVID-19. As an organization, we have quickly adapted to this challenging environment, ensuring business continuity. Our focus has been on ensuring our clinical B-cell programs, Auto 1 and Auto 3, continue to progress, and we remain on track with recruitment ongoing and manufacturing operations uninterrupted. As such, we expect to deliver data in the timelines that we have previously guided. While some of our participating clinical centers have been infection hotspots and had to pause enrollment for a few weeks, others could continue to work unimpacted. We expect infections will continue throughout the year with flare-ups in places that were hit by the first wave of infections, while areas spared for now may see a rise in infections at some point in the upcoming months. What is important to remember is that the patients we enroll in our trials have a very high medical need, no different from a severe COVID-19 patient, and the drive for centers to continue to treat these cancer patients is very high. Typically, if a center gets under heavy pressure from COVID-19 infections, stem cell transplants and CAR T therapy are among the last procedures to be stopped and are among the first to resume post-peak infection. As many of you have analyzed, the time from establishing social distancing and stronger measures to reaching the other side of the first infection peak has in all impacted areas taken approximately eight weeks, irrespective of whether the measures were taken early or late relative to the rise of infections. The consistency of this infection pattern is helpful to anticipate the time of impact on a given center and catchment area. We expect the increasing levels of preparedness and adjustments underway in the various healthcare systems and the continued implementation of social distancing measures will allow for continued treatment of these severely ill patients throughout the year. We expect that the adjustments we made for clinical trial operations and in our supply chain will remain relevant and in place for the duration of this infection cycle plus the vital operational adjustments we made to minimize risk of infection and exposure as well as increase resilience towards the risk of business interruptions will also remain in place and if necessary will be adjusted. With regards to our earlier stage programs we are monitoring potential impact. At this point we may see up to a quarter of delay depending on the program and the impact COVID-19 had on our respective academic or business partners. With that, and remaining on slides live, let me give you an overview of our corporate highlights. We announced in April that the FDA accepted the IND application for Auto-1, our lead CAR-T product candidate, for the treatment of adult patients with acute lymphoblastic leukemia, which allows us to initiate clinical sites in the company's first pivotal study, Auto-1, AL-1, in the US. This followed the opening of the first site in the UK in March of this year, having received approval of the clinical trial applications by the MHRA earlier in the quarter. We expect to initiate dosing of our first patient in this study this quarter and remain on track to provide full data by the end of 2021. With regards to our lead product candidate for the treatment of DLBCL auto three, the phase one two Alexander study is ongoing. The timing of the program remains on track and we will update on decision for phase two in mid 2020 as previously guided. We're excited about our DLDCL program and its broader market potential following the positive data update we provided at the EHA-EBMT CAR T-cell meeting in February 2020. Our Chief Scientific Officer, Dr. Martin Pule, presented early encouraging signs of sustained complete responses achieved with low toxicity and minimal patient management required. We're now planning to add a 20-patient cohort to the ongoing Alexander study in second half of this year with patients treated in an outpatient setting which I will explain and expand on a little later in this call. The last item I wish to touch on in this slide is our forthcoming clinical data updates expected through May and June. For order one in adult ALL, we plan to present updated data at the virtual EHA meeting in June with approximately six months of additional follow-up post our ASH 2019 data cut. For order three, we're planning to present updated data at ASCO in an oral session. We will also follow up with a similar presentation at the EHA meeting two weeks later. We plan to present both sets of data to investors in calls shortly following these virtual conferences. Moving to slide six. In addition to our two lead clinical candidates, we're planning a series of preclinical data updates on some of our pipeline programs at AACR2 in late June. We have been invited to make an oral presentation on our prostate cancer program auto seven and also have poster presentations planned for both Auto 6 and G in small cell lung cancer as well as Auto 5, the sister program to Auto 4 in T cell lymphoma. Much like ASCO and DHA, we're planning an investor call that will shortly follow these presentations at AACR2. Finally, I would like to thank our partners at the Cell Therapy Catapult and the GSK site organization in Stevenage for their continued support that enabled us to maintain operations throughout the peak infection and support the critically ill patients in our trials. Moving to slide seven, I wanted to spend a brief moment recapping on our lead program model one in adult ALL. Relapsed refractory adult ALL is a challenging disease and often impacted in elderly patients. A lot of these patients have significant comorbidities making them a fragile patient group to treat. The indication is approximately three times the size of relapsed refractory pediatric ALL and represents an attractive market opportunity. Within the US and the top five European countries, approximately 3,000 patients every year are at an end stage of treatment having failed chemo and transplant and therefore requiring other options. At this point, there's no CAR T therapy approved for adult ALL. Obviously, there are a number of programs that are being tested However, all of them have experienced significant challenges with the management of the toxicities. What we created with Auto1 is a product that is designed to behave physiologically and engages target cells like a normal T cell would. First generation CAR-T products share the identical binder to CD19. This is true for Chimriah, Triscarta, and Lysa cell. This binder has a slow off rate from the CD19 target. and as a consequence, once the CAR-T cell binds to the leukemia cell and has delivered the toxic payload, it has difficulty letting go from the target cell and gets stuck. When you have CAR-T cells getting stuck to target cells, they continue to be activated, which drives cytokine release and thus adverse events. In addition to leading to cytokine release syndrome, this continued activation of the CAR-T cells can drive exhaustion, which negatively impacts persistence. So there's a fundamental challenge with that type of engagement. In contrast, what we created with Auto1 is a CAR-T product that mimics the behavior and the binding kinetics of a physiological T cell with a very fast off rate and an ability to disengage relatively rapidly after delivering the kill. The result is reduced cytokine release and also an increase in target cell killing as the CAR-T cells are freed up more quickly and can re-engage new leukemia cells. In addition, CAR-T cells can expand more readily leading to more active CAR-T cells in the patient's body capable of fighting the leukemia. Now turning to slide eight, what we show on the left hand side is the data for Blina-2 imabrable in cyto which is the current standard of care in this disease setting. What is important to understand is that the patients that we have treated on our trial and what we highlighted at ASH is that the patients have mostly undergone and failed stem cell transplants. In addition, approximately 60% of patients have been on inotuzumab or blenatumumab and failed. So our data is based on a patient population with more advanced disease compared to the data shown for blenatumumab. However, what you see in the blenatumumab results is that the CR rate in that population is about 40% with an event-free survival of about 30% at six months, and in fact, most patients relapse within less than a year. When we look at the safety profile, Blincyto shows a good safety profile overall, and in fact, the product is typically delivered in an outpatient setting. Now, when we look at our own data for order one, if you look at the total data set of 16 patients, you have an overall CR rate of 87%, and then have an event-free survival of 68% at six months. So in a simple way, We have around twice the activity that was reported with Blenatumumab with a comparable safety profile. We have had no patients with high-grade cytokine release syndrome. We had 19% of the patients with high-grade neurotoxicity. All patients with high-grade neurotoxicity had a very high tumor burden in the marrow of more than 50%. Going forward, we will manage these patients when the neurotoxicity starts to build to minimize high-grade adverse events. Finally, I just wanted to touch on the subset of patients that were treated with the closed commercial manufacturing process. You can see that the data, if anything, looks somewhat better than the total overall, which includes patients that were treated with product that was manufactured by hand with a conventional manufacturing process. So based on this data, on turning to slide nine, we decided to move the program forward into a pivotal study. The CTA was filed in the UK and cleared in Q1 and we're rolling currently in the UK. The USID also is now open and we're opening up centers in the US with the aim of enrolling patients in the second quarter. As a reminder, this is a single arm 100 patient study with relapsed refractory patients. The primary endpoint is CR rate and secondary endpoints include molecular CRs, rent-free survival, and duration of response. We remain on track to complete enrollment in the first half of next year. To what extent we may be impacted by the COVID-19 situation going forwards, we'll have to see, but we currently expect the impact to be limited. Our plans to deliver data by the end of 2021 remain on track. Let's now turn to slide 10, where I would like to switch gears and talk about Auto3, a program that is designed for the treatment of patients with diffuse large B-cell lymphoma. Thirdline DLBCL is about four times bigger an indication than relapsed refractory adult ALL and a setting with already two approved CAR-T therapy products with Giscard and Kimraya plus Lysazel or JCAR17 expected to be approved later this year or beginning of next year. We know this is a large opportunity with approximately 10,000 patients on the back end of the disease, which is a sizable population with a very significant medical need. In terms of the outlook for those patients, they have typically run through a series of chemotherapy combinations often with a monoclonal antibody and may also have received a transplant if they were eligible for it. If not, they go directly to salvage therapy. CAR-T therapies are approved in the third-liner salvage therapy setting with trials ongoing in patients in second-line setting. There are two things that we see as being really important for successful treatment and commercial uptake in DLD-CL. First, you have to induce complete remissions that are lasting. This is a disease setting where you aim for cure. Second is that you actually have to have a therapy that can be administered where the patients are situated. Today, in the US, approximately 80% of the patients are treated outside of university hospitals, and only about 10% of the patients are treated as university hospital inpatients. It is this population that is primarily treated with CAR T therapies. The key challenge for treatment centers is the need for intense patient management, which has limited the use of CAR T outside of the university hospital inpatient setting. What we're looking for in auto three is a high level of sustained complete remissions. In addition, we're looking for a safety profile that can be managed in non-academic outpatient settings to reach the majority of patients. Moving to slide 11, across the CAR T programs in DLBCL, We observe a fairly high overall response rate, yet the sustained complete response rate is limited. It is somewhere between 30% and 40%, depending on the program and the subset of indications that were treated or included in the respective trials. Roughly a third of the complete responses are lost early on, typically within the first three to six months. There are two key mechanisms reported that are likely driving relapse. Loss of CD19 antigen in about 30 to 50 percent of the patients at time of relapse and PD-L1 checkpoint upregulation in about two-thirds of the patients at time of relapse. Looking at safety, with the commercial CD19 cars there is a significant amount of management of those patients required to address severe cytokine release syndrome and in particular as well as the severe neurotoxicity. Typically, these toxicities have an early onset and require intense patient management and monitoring, meaning patients are largely confined to a classical hospital inpatient setting. We designed a program with a dual targeting approach, having two independent receptors in each CAR-T cells, individually designed and optimized for the respective target antigen to minimize the impact of CD19 antigen loss. We also countered the PD-L1 upregulation and checkpoint-based escape of lymphoma cells with a single dose of pembrolizumab on the day before infusion of order 3, providing the cover to achieve a CR and sustain it. Order 3 has shown a high level of CRs in the dose escalation phase of the current study and we will present a further update at ASCO. It is worthwhile noting that the high level of complete remissions were obtained without inducing high-grade CRS, or cytokine release syndrome, and no neurotoxicity of any grade in the patient's dose at 150 to 450 million cell doses. This is a very unusual finding. When you compare this profile to the Chescarita, Chimraya and JCR17 data, the contrast is remarkable. What is also important to note is that with Auto3, we have not managed the patients actively for adverse events. Now to talk about the extent of the total addressable market this profile enables us to potentially reach, let's continue to slide 12. Currently, approved products are only tapping into a proportion of substantially less than 20% of the market opportunity, which is managed by the academic centers. There's very little to no penetration to the remaining 80% of the market, which comprises settings that cannot deal with the intensity of patient management required for the current CAR T products. We believe this creates an enormous opportunity for the profile of a product that we're seeing with Auto3 and as such we believe that the program has a unique potential going forward. We expect to provide an updated ask on the clinical profile of the program. So let us turn to slide 13 where I would like to outline how we continue to build on this potential patient profile. Given the highly differentiated clinical and safety profile we have reported so far, we see an attractive opportunity for Auto3 as an in and outpatient solution for patients with DL-BCL, therefore maximizing the commercial potential of CAR-T products across all settings of care in this disease. As such, we're planning to add a 20-patient cohort to our ongoing Phase 1-2 Alexander study in the second half of this year with patients treated in an outpatient setting in order to broaden our understanding of the feasibility of outpatient administration. With that, I will turn over the call to Andrew for our first quarter 2020 financial update. Andrew?