Autolus Therapeutics plc

Hello, ladies and gentlemen, and welcome to the Autoless Therapeutics Second Quarter 2021 Financial Results Conference Call. As a reminder, this conference call has been 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. Good morning or good afternoon, everyone, and thank you for taking this call on the Financial Results I am Lucinda Crabtree, Vice President of Business Planning and Strategy. With me today are Dr. Christian Eyton, our Chief Executive Officer, and Andrew Obey. 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 4th, 2021, which can be accessed on the EDGAR database at www.sec.gov and in subsequent filings that we make with the SEC from time to time. The forward-looking statements on this call reflect the company's views as of today, August 5th, 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. So 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 original highlights for the second quarter of 2021. Andrew will discuss the company's financial results, and then Christian will conclude with upcoming milestones and any other comments. And of course, we will welcome your questions following our remarks. So with that, I'd like to turn the call over to Christian. Thank you.

Thank you, Lucy, and welcome everybody to our second quarter call. First off, I'd like to briefly go back to kind of where we started also the Q1 call, which is have a quick look at the state of the COVID epidemic that we're going through and the impact it will have or has on our business. As you may remember, we did guide in Q1 that we were hopeful that by the middle of the year, we should reach a level of stabilization due to increased levels of vaccination, but also a substantial number of people actually having recovered from COVID infection that we should get into an overall more stable environment so that the fluctuations that we see in terms of the cycles of COVID or the waves of COVID should actually start to ebb up and get us to a place where we have overall more stability and a more predictable environment for our patients that we're obviously enrolling into our trials. And we also did guide that we're expecting to be able to actually ramp up enrollment by middle of this year. We're very pleased to say that indeed what we were hoping for actually is a reality today. I think we do have reach now between vaccinated people as well as people who've recovered from infection as a level of about 70% in the U.S. and the same actually in the U.K. And that gives us actually a base level of stability that I think is very helpful in terms of the conduct of the clinical studies. Now, we obviously all have seen the impact of the Delta variant, but we also do see very nicely that, indeed, while there are surges in certain places, that, in fact, they seem to be curved much, much more quickly than what we had seen earlier in the year, and I think are a nice reflection of the fact that the vaccines are doing actually a great job, and we are. You know, as we were hoping, that also actually did allow us to increase and ramp up the enrollment rate into our trials. And obviously, this is obviously very good news and I think will allow us to actually keep on track and on the timelines that we were given with regards to our key studies. If we go to slide number five, A quick update on just the key activities on the pipeline. First off, obviously, the activities on ObieCell. Our Felix study, it's progressing well, and we're reiterating our guidance of pivotal data that we will deliver during the course of next year. Now, in this quarter, we have an opportunity to update additional experiences with ObieCell in patients, not only in ALL, but also in non-Hodgkin's lymphoma. In ALL, we were able to actually look at now a quite extended observation time of the patients of now more than two years. And what we were able to see is that, indeed, the event-free survival in this trial actually was stabilizing at 12 months, just above 50%, and actually that level was sustained over 24 months. This is very good news because it really gives us the first clear hint that indeed we may have a transformational therapy for this patient population and frankly suggestive of a durable effect in at least a subset of the patients that we've been treating. So that's obviously very good news. It's now the data starts to actually mature to a point where I think the data actually has a level of validity that really matters in terms of our own view as well of the program. In addition, we also obviously did look or did present data on patients with non-Hodgkin's lymphoma, particularly follicular lymphoma, mantle cell lymphoma, and were able to show very high levels of metabolic CR rates. In fact, all patients achieved metabolic CRs. and also combined with a very good safety profile. Now, in addition to, obviously, that key data update, the DHA, we also had a publication in Nature Cancer looking at some of the product features that may be associated with this longer ability of effect that we're starting to see in DLL patients. Now, Moving to the regulatory side, I think there are two key events that were happening in the second quarter. First, we did receive a so-called prime designation from the European Medicines Agency, which really gives us an ability for a preferred engagement with the key regulatory body in Europe, and which should be very helpful in the actual review process for the program as we're moving this program through pivotal stage and then further towards an approval. When we look into the second designation that we did receive was a so-called ILAP designation from the UK Medicines and Healthcare Agency, MHRA. And what we did actually, and what that allows us to do is quite similarly to the prime designation, it gives you a preferred access to the regulatory body but it actually goes beyond that. It also actually allows you to engage with the National Health Service as well as with NICE and gives you an ability to really approach with innovative therapies the key players in the UK that not only actually get you through the regulatory process but also, frankly, ultimately to the patients. So those developments, we believe, actually are very important because it gives us a very good projection and the path that we can take with the program and are a reflection of the data that we obviously were able to generate so far. As I've indicated initially, also reiterating our guidance to have the pivotal data during the course of 2022 as we have guided before. As indicated, the OVCEL data on relapsed refractory obviously is very encouraging. And I think that gives us, obviously, an opportunity for additional data flowing later part of the year. And finally, on auto four, we did also receive an ILAP designation from the NHRA, again, giving us that preferred access that we believe will be helpful to the program going forward. Moving to slide six. Just a quick update on the corporate side. First off, we had... sold about 2 million ADSS under the Open Markets and Sales Agreement during the course of the quarter, which netted $14.3 million in additional capital into the company. We had a change of the chairman role. Martin Murphy has taken over as non-executive chairman during the course of the quarter. And when we look at the post-period updates, we're very excited to announce, and actually that happened just in July now, the appointment of Dr. Edgar Brandley, who has joined us as the new chief development officer of the company. Edgar has a tremendous amount of development experience in a range of companies, including, I would say, a very long stay and very significant levels of activities that he had in the context of Narwarkis' R&D organization as well. In addition, Wolfram Brugger joined us as the new head of clinical development. Wolfram joined us from morphosis, where he was running the clinical programs and particularly focused, obviously, on the Monjuvi program or tefacitumab program that was recently, obviously, improved in a subset of diffuse large B-cell lymphoma patients. And then finally, we did announce early in the week an option and licensing agreement with Moderna, Actually, we're kind of a nice recognition of the technology base that we've developed at the company. This is particularly related to our capabilities of engineering binders with very unique properties, and those types of binders are considered to be used, obviously, in the context of the RNA approaches, platform approaches that Moderna is working on. With that, I think we're good to move to slide number seven. And what I'd like to do is to switch gears, briefly reset sort of our thoughts with regards to ALL. As you remember, obviously our key focus is on delivering the FELIX study in adult patients with relapsed refractory ALL, which includes patients that are both post-blenatumumab as well as inotuzumab. but as well as patients that actually are just in that relapse setting but have not yet experienced inotuzumab or linotuzumab. So we have two subpopulations that we're actually looking at in this particular trial. As we just mentioned, we're exploring the activity of the program of OB-cell then beyond ALL, and we do that in the context of the OLCAR19 study with additional cohorts. And in addition to the data that we just released on first follicular and mantle cell patients, We will also actually include patients with ELD cell and CLL, and we are planning for an additional update towards the end of the year. And then as an evolution of the OB cell or Auto 1 program, we are now actually treating children with Auto 1-22, which is building on the Auto1 or OV cell backbone, but adds a novel CB22 chimeric antigen receptor where we're evaluating that product in pediatric patients with ALL. So with that, I'd like to move to slide number eight. And on slide number eight, it's just some of the key, I think, features that are important with regards to ALL as an indication and the standard and status of care that we currently see in this indication. First off, I think it's important to realize that particularly in the adult population with ALL, only a smaller percentage of the patients actually have an ability to achieve a long-term benefit. We're looking at somewhere between 30% to 40% of the patients. This is despite the fact that most of the patients, about 90% actually will achieve a complete remission in frontline therapy. However, for most of these patients that complete remission actually does not translate into a long-term remission. So when patients do relapse after obviously having gone through a very intense high-dose chemotherapy, induction, and then consolidation, after they get through that and eventually relapse, many of them would actually go on additional cycles of high-dose chemotherapy followed by stem cell transplant. However, although there is a certain chance of cure with the stem cell transplant, still the majority of the patients getting onto transplant will actually relapse again. And that gets us to the patient population that's really in a very, very difficult spot with a very, very limited time that indeed, on average, these patients still have available. What we are currently looking at in this field is that the standard of care, particularly in the U.S., is really starting to concentrate on glenotumor map We see about 60% or so of the patients receiving Blinitumumab in the U.S. However, although Blinitumumab is active, it does not actually convey long-term remissions in the patients in the relapsed refractory setting. So when we then look on the CAR-T side, I think obviously a very challenging start that we have seen the CAR-T approaches in general getting into the adult population in ALL with a a lot of challenging in managing actually the adverse events that were induced by the therapy itself. And we're now at a point where obviously we're starting to see first programs moving. We believe that we have a highly attractive set of properties with our program. And obviously there is an opportunity when we think about the progression and the positioning of the product to ultimately move this type of therapy up the line where we believe is actually the best place from a benefit-risk perspective that I think that we can get with this type of a therapy. We just talked about the fact that we did receive, obviously, a set of regulatory designations. Slide number nine. Key update that we presented at EHA is really around event-free survival. We already had communicated, obviously, that we have very high levels of responses, that we have a good safety profile, But what we're seeing now is, as we're seeing looking at this event-free survival, is that indeed that curve is stabilizing over time. And that gives us actually a very good sense that indeed we have a chance of getting a proportion of these patients into long-term remissions. Moving to slide number 10, I think I want to make the point that the fact that we do see this stabilization of event-free survival, which to our knowledge hasn't been shown before in this disease setting, is actually correlated with the exceptional persistence that we're seeing with the product. Not only do we see about a tenfold increase in the maximal number of CAR T cells that have been reported in other programs, but we also are able to actually maintain the level of CAR T cells over time. And we believe that that is actually a prerequisite to be able to actually translate a molecular response into a long-term remission. And clearly, the data from the OLCAR study are quite unique, both in the actual absolute amount of CAR T cells formed in the patient, which is as indicated about tenfold over other programs, but also the sustained level of CAR T cells over time. On the right-hand side, you see basically the adverse event profile as we had reported it earlier, I think what's important is obviously we haven't seen high-grade cytokine belief syndrome. And related to that, when you look actually at the treatment that was used to sort of manage the adverse events related to the CAR T therapy, quite often you see with CAR T therapies the need for vasopressors to stabilize the patients, and it's important to note that none of the patients receive vasopressors. And what that also tells you is that these patients didn't actually have to go into ICU to be managed. So it's a very good safety profile. It's very well manageable. And it gives us a very unique efficacy profile. Moving to slide number 11. This is just a quick look at some of the data that we see now in the space. We have obviously the data sets that were the foundation for the approvals for blinitumab and inotuzumab. And we also now have, as presented at ASCO and then published as well, right at the same time, the data from Tecardis, also in the laboratory factory at Alt-ALL, also the basis of a DLA filing that the company made. So when we look at overall at these data sets, we do see that the data from OBSEL does stack up very well against all of these programs. And certainly when it comes to safety as well as to the long-term impact we see of end-free survival, that we have a very advantageous end-free survival profile, which we believe will actually give us overall a very nicely differentiated product in this space. Moving to slide number 12. I did mention before, obviously, the FELIX study. This study is about a 100-patient study. Relapsed refractory patients, as indicated, two subpopulations that we're looking at, relapsed refractory post-exposure tubulina and or inotuzumab, as well as patients who are inexperienced with regards to tubulina or inotuzumab. The primary endpoint of the study is overall complete response rates. And the secondary endpoints include molecular responses as well as eventually survival and duration of response. Quick word onto the data that I referenced before in the non-Hodgkin's lymphoma patients. This is a swim plot of the nine patients that were dosed and were the subject of the presentation at EHA. As you can see, all of these patients achieved a metabolic complete remission. The safety profile was very positive. Nobody had a high-grade CRS. None of the patients experienced any form of neurotoxicity. One of the patients, unfortunately, actually contracted COVID and died as a consequence of COVID. The patient died in metabolic complete remission, which was a very sad event, as well as one patient who developed a lesion in the skin, which could be basically removed surgically, but obviously that lesion is a progression event in that patient and will have to be recorded that way. Now, slide number 14, just a quick word on the activities ongoing now that sort of actually round out the exploration of the activity of OB cell across a range of indications. As I indicated to you before, we do evaluate the activity in non-Hodgkin's lymphoma patients as well as CLL patients as part of the extension of the OLCAR19 study. We're also conducting, in collaboration with our academic partners, the CARUSEL study, which is a study in patients that have primary CNS lymphoma which is in essence an aggressive lymphoma similar to DLBCL that is exclusively localized in the brain. And then, as already mentioned, we're conducting an extension of the CAR-CAL study with auto-122 in pediatric ALL patients, and obviously all of these programs will give us a very good overview over the range of activity that we see across the range of CD19-positive malignancies. Moving to slide 15, on the T-cell lymphoma side, we continue to dose escalate the AutoIV program. We expect the data will be, the first update on the data will be in the first half of 2022. and we'll provide that update, obviously, at one of the conferences in the first part of next year. And alongside the progress on the Auto 4 program, we're also going to time the study entry for the Auto 5 program, which we expect to occur in the same period of time. Now, on slide 16, just a quick reminder that the company has a very strong technology base with probably one of the largest IP estates in the business. And what you obviously did see on the Moderna side is that aspects of this technology now used in a different setting. This is now obviously the case of the Moderna collaboration related to binder technology. That is obviously one of the key elements that we're using in all our products as one of the key elements of differentiation. And you do remember But obviously, Obicel, the key feature in Obicel is a very unique type of binder with a very unique set of properties, which really gives us that differentiated overall clinical outcome, both in efficacy, on persistence, but also on safety. Now, moving to slide 17. So the broader program here, obviously, I indicated already the Auto-122 and Auto-5 program. Auto 6NG is moving forward. We expect to be able to have an academic trial up and running with this quite advanced programmed product in the early part of 2022. And then obviously, as we had guided before, Auto 8 is obviously in the clinics this half of 21, and we're preparing also the Auto 7 programs. Now, with that, I'd like to actually hand over to Andrew, who will lead you through our financial results. Thank you.