Autolus Therapeutics - Q1 2024

Transcript

Operator (participant)

Hello, ladies and gentlemen, and welcome to the Autolus Therapeutics call to discuss its first quarter 2024 financial results and business update. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Olivia Manser. Please go ahead.

Olivia Manser (Director of Investor Relations)

Thanks, Tanya. Good morning or good afternoon, everyone. Thanks for joining us on today's call. With me today are Dr. Christian Itin, our CEO, and Rob Dolski, our CFO. On slide two, before we begin, just like to remind you as usual, that during today's call, we will make statements related to our business that are forward-looking under federal securities laws and the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These may include, but are not limited to, statements regarding the status of clinical trials and development and/or regulatory timelines for our product candidates and our expectations regarding our cash runway. These statements are subject to a variety of risks and uncertainties that could cause actual results to differ materially from expectations and reflect our views only as of today. We assume no obligation to update any such forward-looking statements.

For a discussion of the material risks and uncertainties that could affect our actual results, please refer to the risks identified in today's press release and our SEC filings, both available on the investor section of our website. Moving on to slide three, you're going to see the agenda for today's call, which is similar to usual. Christian's going to provide an overview of our operational highlights. Rob will then take you through the financial results, and Christian will conclude with upcoming milestones, and we'll then hand over for questions. With that, I will hand over to Christian.

Christian Itin (CEO)

Well, thank you very much, Olivia, and welcome everybody to our first quarter call. It's been a very successful quarter, and obviously with a lot of activity related to obe-cel, but also obviously quite a lot of overall corporate updates as well. I'll start out with obe-cel. We started the year with the acceptance of our BLA filing, which obviously was an important event and also set the target date for the PDUFA, which is expected now for November 16, 2024. We also managed, towards the end of the quarter, to get the European filing accepted. So we have now both major jurisdictions with filings under review.

What was very important because it led to also the overall preparedness of the company towards commercialization was the inspection that we had of the Nucleus facility by the MHRA. That was very successful and resulted in a license for both clinical and commercial supply from the Nucleus facility. What's important to understand is that this is actually a prerequisite for us to actually be able to commercially deliver product, and that is a necessary license that we actually need to hold. So getting through that first full inspection and successfully completing that, obviously was a huge accomplishment and sets us up very well for the ongoing interactions in the review process, both with the FDA as well as with the European Agency.

We also obviously started the phase I dose confirmation study in SLE during the quarter, and also involved there our first patients. Now, when you think about data updates, the important next updates are going to be at ASCO and at EHA, which are at the end of May and the beginning or middle of June. At both meetings, we have now confirmation that we have an oral presentation of the updated FELIX results, with a particular focus on longer follow-up for the study, the impact of stem cell transplant that patients may have received, as well as the impact of persistence on outcome. Now, in addition at EHA, we have two further analyses that will be presented in the form of posters.

One looks at the impact of inotuzumab-based bridging regimens in the trial, and the second is on sensitive methodologies to determine the presence of CAR-T cells, to measure persistence, and obviously also linking that then to outcome in the study. So very significant amount of update, a lot of accomplishments through the course of this year, which sets us up very well for the further review of the program, both by the FDA and the European Agency, and also sets us and on a very good trajectory for the target PDUFA date as well in the middle of November. Now, on the operational corporate side, obviously, there was a lot of activity leading into this year, which resulted in the early February timeframe in two announcements.

The first was the announcement of the strategic collaboration with BioNTech, which obviously is an important cornerstone in terms of our relationships that we're building. There is a significant set of options are part of this collaboration. There are options related to access that BioNTech will have for the lead program to the Nucleus manufacturing facility to support the launch of their lead CAR-T program. That's one area that we were looking at very closely, including support on the commercial launch side. We then have obviously an area of activities around access to two of our pipeline programs. That's AUTO1/22 and AUTO6NG. Both of those have option exercise time points that are before the start of the pivotal study in each one of these programs....

We then look and in addition to those key areas, then also on the technology side, providing access to technology we've developed, particularly for the use with in vivo cell therapy approaches, but also for certain applications, also in the context of other treatment modalities as well. So it's a very comprehensive relationship that we're building, and we're very excited about the relationship and the interactions that we're having with BioNTech. Now, in parallel to the transaction with BioNTech, or just following the transaction, we also did a capital markets transaction and added additional capital.

Between the two transactions, we added $600 million to our balance sheet, which obviously sets us up well to deliver on the launch of obe-cel, but also gives us the ability to expand the footprint of indications, particularly for obe-cel. And that also gives us a very significant opportunity for future growth and expansion for the business. Now, we also have, as we're transitioning the company from a development stage to a commercial stage, have also actually had transitions at the level of the board that sort of actually go alongside that transformation of the company. We had, at the end of last year, Liz Leiderman and Bob Azelby join. Obviously, both with very strong capital markets experience and operating experience, as well as a very strong commercial experience.

And then we had, in addition, this quarter, joined Mike Bonney, who's taken over as the chair of the company, from John Johnson, and Ravi Rao also joined, who's an expert on particularly, immunology and the autoimmune diseases, and kind of rounds out that level and that aspect, in terms of the experience base of the board. So very important part of the transition that we're making sure we're sort of getting the company very well set up and forward-looking, to becoming a commercial stage company, and also a company that starts expanding into a broader set of indications. Now, with that, moving to, the, slide number six.

What I'd like to start out with obe-cel is actually answer one of the or illustrate one of the questions we're getting quite a bit, which is, "Well, you guys are, you know, built up this manufacturing facility, the Nucleus in the U.K., and but how do you actually ensure that you can actually deliver product and this, that, is it even possible to do that within the U.S. as well as outside of the U.S.?" And what I thought might be actually helpful is just to look at actually back at our FELIX study and actually kind of just remember on what kind of environment we actually did the FELIX study in.

So what you see is basically a timeline that goes from 2019 to 2023, and the actual study was conducted from the middle of 2020 towards the end of 2020 to 2022, in terms of the involvement of the study. Obviously, that sort of coincides with, you know, the majority or the entire of the key period for the COVID-19 pandemic. As you can see in the blue shaded area, you see all the various types of infection peaks that we've seen over times that were reported across the globe. Now, what you also see on the green line is actually the number of international flights that basically have gone in and out of the US during that entire period. This is data from the US government.

As you can see, this was a very challenging period from a logistics perspective, because clearly you have huge variability in the number of available flights internationally. Clearly, you know, being based in the U.K. for manufacturing makes us obviously highly reliant on international flights actually taking place and the ability to really reach every site in the U.S., as well as elsewhere, from our manufacturing site. Now, what was quite remarkable is when you then actually look on the small fever curve in the middle. This is actually the actual range of delivery time over that entire period for the phase II conduct. You see that for the ranges at the low end, it's 15-30 days on the upper end.

You see kind of literally every one of these products actually have plotted on that particular jagged line. But what it means is that despite all the variability, the challenges with infections, the shutdowns of clinical centers, the shutdown of flights, and so on, so forth, all the limitations we had in that terms of access, moving people and so on, had actually virtually no impact on our range of delivery time. And in fact, we were able to deliver on time for every single product. And one of the things that we obviously learned, that many of you do know, given that many of you are traveling internationally quite a bit, is one of the things that we obviously have in our favor is that international flights have priority. That's where the airlines make most of their money, and those flights go on time.

That actually has been a huge asset through the pandemic, and actually gave us not only a good ability to serve, but an actual advantage in terms of the robustness and stability of our logistics. This is not what you would have expected based going into the pandemic, but that's the actual reality that we have been able to see. Also, obviously, gives us a lot of confidence that the systems that we have put in place have been pressure tested in an extreme way and have actually delivered throughout this challenging period.

Now, if we go to the next slide, slide seven, just as a brief reminder, of the FELIX study and what we're actually looking to do with the study, and I think the first thing I want to point out is that this is a study that actually included all risk categories of patients that have relapsed refractory disease, acute lymphoblastic leukemia. And what we have in there is obviously the largest group, which is the cohort A, which are patients that have disease burden that range somewhere between 5% of cells in the marrow, all the way up to close to 100%. So we have this entire bucket of disease.

We also have in the middle with the cohort C, patients that have very low levels of disease, so-called minimal residual disease, where disease levels you can pick up by flow analysis, by PCR or by NGS sequencing. But it's important because it's basically just actually catching the relapse a little bit earlier before the standard methodology starts to pick it up. And then the last group of patients in cohort C were patients that actually didn't have a relapse in the marrow, which is normally the place where you find the disease and where you typically also have the relapses. But these are patients that have isolated extramedullary disease, which is basically the disease that almost had a gain of function, could actually escape the marrow, settle in another tissue, and grow out.

These are particularly difficult to treat patients, because obviously the disease has managed to actually morph, to a certain extent and actually gain this ability to survive and succeed in a very different environment. So having all of these different groups is actually important when you think about it from a treating physician's perspective, because what it basically gives you, it gives you an ability to see the patients that will actually walk into your practice, the patients you care for, you'll see them represented in the study. And that doesn't often happen in clinical studies. Often, clinical studies are quite selective. They're quite protected to make sure the outcome is as maximal as possible. And often with that, you actually do not have a representation of the real world.

What we have with this study is a remarkable representation of the real-world setting and the experience that the physicians are actually having, and this is also why this study resonates as well as it does. Now, a few things just to point out, tying to the prior part of the conversation on supply, logistics, and delivery. We actually managed to get 83% of all of the patients across the entirety of the study treated with the product. And that actually is a number that's higher than what we've seen in studies that were conducted prior to the pandemic, where you had every level of control of the patients, the selection of the patients, and every aspect on logistics. So it just tells you something about robustness and delivery alongside the study.

So with that, moving to slide number eight, what we're looking at here is the event-free survival across the entirety of the experience. As you can see, we see a stabilization of that curve. It looks like the curve starts to go horizontal after a certain period of time, indicative that indeed we may have a group of patients that actually have a chance for long-term outcome. Now, this is the snapshot, the data snapshot, that underpins the ASH presentation. This is where this slide is from. Obviously, the next update that we're gonna have at ASCO EHA will be somewhere between 5 and 6 months additional follow-up, and obviously gives us much more stability in the outer part of that curve, in the part of the curve where we actually are starting to see this stabilization.

And so we believe the update, middle of this year will be important because it will give us a very good understanding whether indeed we have this robustness in the data, also in the later time points as well. Now, as you may remember, one of the things we looked at, and we have pointed out, in several types of conversations and presentations, is that we did find that the level of disease burden the patients have prior to lymphodepletion, actually was giving you a pretty good predictor of what to expect, these patients will experience, on the one hand, from an efficacy perspective, but also from a safety perspective. I'll start with the efficacy side, and again, we're now looking at these event-free survival curves, but we look at it by the leukemic burden prior to lymphodepletion, before we actually do the intervention.

As you can see on the blue line, these are patients that have less than 5% tumor burden, and you can see that these patients do exceptionally well. Low tumor burden not only does give us a very high, overall, you know, response rate, but it also gives us obviously a very, attractive, long-term outcome in that patient group. Below that, in the green curve, we see the patients that are in the range, of about 5%-75% tumor burden. That's a wide range of tumor burden in these patients, but it's not going to the very extreme, of tumor burden in the marrow. As you can see, these patients still do remarkably well, and you see a stabilization, also in the green curve, which is very encouraging.

Where you see that the patients struggle more is in that group, in the orange curve, where you have patients that have more than 75% disease burden at lymphodepletion, which are clearly the ones that could not be controlled by bridging therapy. They're, you know, have almost a by definition, refractory nature of the disease. You do see that these patients obviously struggle a lot more than the other groups of patients. Now, the outcome here is still substantially different to what you would have seen as an overall picture for Blincyto. So it gives you a very good sense in terms of the actual power of the therapy, even in the worst patients that we have been treating.

But it also tells you that obviously, finding ways to actually reduce disease burden in these patients before you treat them actually has a very significant impact on outcome. Now, it's not only on the side of efficacy, but also when you look on the next slide, slide 10. There's also a difference that we see in the safety signals. Now, the left-hand side, we see the totality of the data across all patients, and you see that what's standing out is the dark blue areas, which are obviously very small, and these are the high-grade cytokine release syndrome patients or the high-grade ICANS patients. So the levels are low. They're 2% and 7%, which is substantially below any of the other T-cell engaging or CAR-T type therapies in the space. So again, a very attractive overall profile.

But when we then look at the impact of disease burden, we can see that the patients that have actually less than 5% disease burden have lymphodepletion, both for CRS in the middle or for ICANS on the right-hand side. None of these patients had a high-grade event, immunological toxicity event, where no high-grade ICANS, no high-grade CRS. If you then look at the middle group, the middle group does still remarkably well. It has actually now you see some of the patients that actually do experience high-grade cytokine release syndrome, and ICANS, but it's still at a relatively low level.

But what you do see is you do see somewhat of an increase, actually, to a level which is, you know, similar maybe to what an overall cytokine population would look like in terms of CRS and ICANS, if you're above 75% tumor burden after bridging therapy at the time of lymphodepletion. So also there, not only do you see differences in the outcome from event-free survival perspective, but you also see differences in the risk of safety signals.

Now, clearly, when you look at the data, it looks that patients that obviously are on the low disease burden side look to be very well manageable and very predictable, both in terms of the efficacy as well as the safety outcome, which I think will be an important factor and feature that we'll see, actually, worked on going forward, but I think will be an important part also in terms of the positioning of the product and where to treat the patients. Now, in terms of commercial launch readiness, moving to slide number 12, obviously, we have been talked about briefly about the trajectory here on from a regulatory milestone perspective. Obviously, we're in full swing of making sure we're adequately prepared for launch. There are quite a wide range of activities.

You see, the left-hand side, basically, the four key areas that we're sort of working with, in terms of preparation, how we manage the regions within the US. It's basically a regional view. That's kind of the way we sort of also are overlaying our organization across those. When we look in terms of the areas that we're particularly focused on, first of all, obviously, in terms of communication, creating awareness, and supporting, frankly, every activity, whether it's with engagement with centers, with payers, et cetera, is through the medical affairs team. So very focused amount of activity that's going on, a lot of efforts, a lot of direct engagement, and also, of course, a lot of work and support in the context of the onboarding of the centers.

So that's a very significant amount of activities. A lot of that will be quite visible because it will result in presence at conferences, et cetera, and presentations and publications. There's obviously a very significant work stream around demonstrating the value of the therapy, so there's a lot of activity going on on that side. And we're looking at, obviously, a number of parameters. Important here, when you think about value, there's the obvious, you know, how much long-term benefit can you induce? You know, what is sort of the overall safety profile, et cetera. But there's also much more nuanced elements there.

The fact that we have such a reduction in high-grade CRS and in high-grade ICANS, and substantially shorter events when we have high-grade events, that has a huge impact on the resource utilization at the hospitals, and a huge impact on costs, on patient management. And when you think also about the ability to sort of actually have an understanding of what to expect based on the disease burden at lymphodepletion, also more predictability. There's more plannable. These treatments are more plannable, and there's a way to anticipate what's going to happen to the patient and what type of support do you need to actually prepare for. That is very important because all of those are important cost drivers. That's value.

But those are really important aspects that we have to not only describe from a clinical perspective, but then also translate that into an economic description from an operating perspective at a hospital, but also for a payer. So there's a lot of activity that's going on in that segment, I think we're relevant on those conversations, and also a key element in terms of preparing the market that we're looking to get into. The onboarding of the centers is probably the single biggest work stream that we have, which requires us also to make sure that the product can be appropriately handled, whether it is from a cell collection, handling perspective, delivery perspective, safety management, long-term outcome management. There's a lot of training involved.

There is a lot of interaction and support involved. And all of that actually has a corollary in terms of systems that we are holding on our side in support of the centers, and are managed through a center coordinator that really is the triaging point to support the centers in whatever the need is and the support required is. So getting the centers onboarded, accredited, is absolutely crucial. This is a very involved activity, also involved from the center. It takes a commitment from the center, it takes time, and we're very pleased to see the resonance that the product has and the interest and willingness of the centers to onboard the product. So that preparation is all ongoing and very well on track. And then we already talked about supply chain logistics.

There's obviously a lot of implementation of testing as well that we do. What you also have seen is that we have, I mentioned before, closed the transaction with Cardinal Health. That's an important transaction for us because it actually complements some of the backbone infrastructure pieces that we want to have in place and need to have in place. It also gives us an element on the logistics, which allows us to actually ship product during the release process, and with that, also take some of the time out of the batch delivery time, which is important from a patient perspective and physician perspective as well. So this is kind of the preparation work that we're doing.

Obviously, very engaged, very involved, fantastic team on the ground, very experienced team. And we're seeing a very nice resonance and good dynamic there. Moving to the next slide, and just briefly talk about the commercial manufacturing facility, the Nucleus. So the image in the middle, actually, I took a week ago. It was one of the few sunny days we had the last few weeks in the U.K., so this was the opportunity. So this is a true industrial setup for the production of cell therapy products. It's a 70,000 sq ft facility, and a facility that we really went from groundbreaking to MHRA approval within about 27 months.

So this is a remarkable delivery actually, of this facility, with very different approaches that we took in terms of the design, the setup of the facility, but also the taking into operation and validation of the facility. We did in a very different mode than I think mostly, most of our colleagues in the industry would do, but it allowed us to actually massively reduce the time to get a fully functioning, fully validated, inspected facility ready. And with that, obviously put us in a very strong position to be in, in a very good, a very good starting point with good level of capacity to support a future launch. So with that, just moving to slide 15.

It's a slide you've seen before, really looking at sort of the opportunities in terms of the obe-cel family of products. There's obe-cel itself, with opportunities both in hem-oncology as well as in autoimmune disease. And then there are obviously the two daughters of obe-cel, AUTO1/22 and AUTO8 that allow us to actually give us sort of a next layer into the respective disease areas with a dual targeting approach. Now, if we move to slide 16, maybe just a few words on kind of the dynamics that we're seeing in the space, particularly when it comes to autoimmune disease. So obviously a hugely active space.

There's a lot of communication happening, and every time there is a paper coming out, I tend to get, and we tend to get, obviously, pings from some of you and to, to you know, how to interpret the data and how to think about it. I think in general, I think what's important to keep in mind is that almost all data points that we look at today are based on compassionate use, not clinical trials. So while the data is very impressive and quite compelling, given that we've seen long-term outcomes in patients that frankly, it was not possible to actually get reversal of disease and certainly no long-term outcome in these patients. So very impressive outcomes, but obviously still very low patient numbers and very limited observation.

Most of what we know is from a Kymriah-like product. So this has a receptor that's identical to the Kymriah CAR, with a modified manufacturing process, which is somewhat closer to the way we manufacture it. But that product is really what all, almost all the information is based on, particularly when we look at longer term observation. Of all the patients that were treated, be it in SLE, in vasculitis, in scleroderma, et cetera, there's 1 patient so far that's been reported to actually have relapse. That relapse happened after 18 months. Patient is still a lot better than, obviously, where the patient was, but there's clearly a recurrence of antibodies that was visible in that patient.

And what we're starting to see is obviously that we're starting to learn where maybe the limitations are of some of these approaches, where the opportunities are, but we're still in a phase where there's a lot of learning going on. I think with that, I think it's important to, you know, keep basically look at the data with certainly a grain of salt and remind ourselves that it is still very limited amount of data, very exciting, but limited amount of data. We've also seen now, in addition to this initial work that was done at the University of Erlangen, we've seen now first work with blinatumomab, also part in Erlangen, part of Munich, to explore the use in RA patients and in single,

sclerosis patient, indicating that there was a bit, an ability to induce an improvement in these patients without actually showing a reset of the B-cell compartment and a lack of clarity whether these activities would actually be sustainable. What was interesting is that Georg Schett gave a recent interview, and which was actually published by one of your colleagues, at Cantor, and was actually asked about the data, which obviously was taken also at the University of Erlangen with the rheumatoid arthritis patients. And he indicated clearly that he would see clearly was obviously seeing good deep responses, which seemed to be, you know, meaningful, giving meaningful clinical outcomes.

But at the same time, obviously there is a lot to be learned, and it's unclear whether there would be an ability to see longer-term outcomes in these- in this approach. So there's a lot of movement, and one of the things that certainly will be interesting to see as we're sort of thinking going forward is how many shots do we actually have in an autoimmune patient with a very active immune system to actually redose the patient? And that's certainly an area where I think we start to learn, I think, as more mechanisms get in. But it's highly likely gonna be one of the areas where there's gonna be probably more variability introduced in outcomes.

Now, on the next slide, what I'd like to do is just briefly, sort of show kind of the relationship between obe-cel and the product that was used at the University of Erlangen, for their work. I think it's important, as I pointed out, that the product is very similar to Kymriah. And it was designed and actually used initially for the treatment of pediatric ALL patients. So there's actually quite a good set of data available, from that product in peds. And not surprisingly, the data was very similar to the data we knew from Kymriah's original trials.

So high level of activity, long persistence, 2-3 years persistence in these patients, and, you know, giving you in the 85% give or take rate of molecular complete remission, as was seen with Kymriah. You see the reference on the right-hand, lower side, the ELIANA study, which is what the summary of the data from the original study with Kymriah. The initial data from the pediatric experience with the Erlangen, CAR actually was published at the... or presented at the ASH meeting in 2021, and there's likely gonna be a publication at some point with a fuller dataset. Now, what I'd like to sort of remind you of is that the key difference, obviously, between that product and our product is really in the design of the targeting domain to CD19.

Rather than having the high-affinity character, which is a fast on-rate with a very slow off-rate, as you can see in the blue box called FMC63, which is the binder used in that particular product. The CAT19 binder in green, that's actually the property that we see for our product, for obe-cel, and what you can see is that we have the same on-rate, which gives you the same specificity, but about a hundredfold faster off-rate. With that, obviously, having that differentiation that you heard us talk about quite a bit, which gives us this difference in terms of toxicity and a much more significant reduction in immunological toxicity, but also overall an increased level of activity that the product has.

And, overall, we see very similar properties of the product in, in ALL from an activity perspective. We see differences in toxicity, as you can also delineate from the comparison between our experience with obe-cel in the light blue columns and the dark blue column, the experience with Kymriah and the ELIANA study. Now, the remarkable thing is, obviously, we have this similarity, we have a better safety profile, and with that we believe we're in a very attractive position to obviously move into the autoimmune space. One of the things that I'd like to highlight is that this long persisting product in pediatric ALL had a much shorter persistence in the autoimmune patients. In fact, it went from two to three years in pediatric ALL to about three months, maximally six months, in autoimmune patients.

This is not a difference based on amount of target available or target cells available, which some folks were thinking about it. That's not what the difference is, because that long persistence is also true if you have MRD-positive patients or patients with extreme low levels of target cells, you still get 2-3 years of persistence in leukemia. Now, the difference between those two settings is predominantly the ability of the immune system to mount a response. And we actually assume that the key driver for the difference in persistence is, in fact, the ability of the patients with autoimmune disease, of their immune system, to recognize the cells eventually and clear them.

And that also was corroborated by the myositis patients I mentioned before, that was actually an attempt done to actually retreat with CD19 CAR, and in fact, the cells were cleared very rapidly. Consistent with the fact that indeed, the patients actually had built up over time an immunological reaction and rejection. Now, quite similarly, if you think about subcu-delivered products and antibodies, there's also pretty significant risk there that you might actually induce as well some immunogenicity, and that certainly has been seen with a number of products, also T-cell engagers in the past.

So that's an area to watch that could actually have an impact in terms of the profiles of some of the approaches over time or the ability to redose, which certainly for some approaches seems more important than others.... All right, so with that, going to slide 18. The phase I study obviously is open for enrollment. We had our first center open during the course of Q1. We have now 2 patients enrolled, and we're well on track for the initial data that we have guided you to towards the end of the year. Just to remind you, this is a dose confirmation study.

We're basically translate the pediatric ALL dose in a fixed dose for adults, which is a 50 million cell dose. We don't need to do DLT periods or any of those types of restrictions within the enrollment, but we can actually enroll patients as they come without limitations of that nature. All right, so with that, just a last sort of view in terms of the pipeline. A big broad view. Obviously, we're inactive with additional programs. Certainly there's more activity on the AUTO8 program, the AUTO6NG program, and obviously both of those we're looking forward for additional data. And we're also enrolling additional patients with AUTO1/22 as well. All right, so with that, I'd like to actually transition.

We go to financial results, and I'll hand over to Rob.

Rob Dolski (CFO)

Thanks, Christian, and good morning or good afternoon to everyone. It's my pleasure to review our financial results for the first quarter of 2024, and I'll be on slide 22 of the presentation. As you saw from our press release and Form 10-Q that we filed with the SEC earlier this week, we delayed this call by a few days, and I'd like to provide some additional color around that decision. As Christian highlighted in February, we completed a license and option agreement with BioNTech, as well as the underwritten registered direct equity financing, that in part enables the company to accelerate our expansion of obe-cel into autoimmune diseases. The BioNTech deal was a complex transaction, with, as noted, a number of different components to it.

We required additional time to evaluate certain technical accounting matters related to the BioNTech deal, as well as the projected impact of the autoimmune opportunity on our existing Blackstone liability valuation, each of which impacted our financial statements for the quarter. So as a result, we needed that time to complete our financial statements and have our accountants complete their quarterly review for us to be able to file our 10-Q with the SEC. The Form 12b-25 gave us a 5-day extension on the 10-Q filing, which would otherwise have been due, this past Wednesday. We plan to file the Form 10-Q later today.

So to now summarize our results for the quarter, cash and cash equivalents at March 31, 2024, totaled $758.5 million, as compared to $239.6 million at December 31, 2023. Our total operating loss for the three months ended March 31, 2024, was $38.8 million, as compared to $39.1 million for the same period in 2023. On the operating expense side, our research and development expenses increased from $27.4 million-$30.7 million for the three quarters ended March 31, 2024, compared to that same period in 2023. This change was primarily due to increases in operating costs related to our new commercial manufacturing facility, employee salaries and related costs, obe-cel clinical trial costs, and a decrease in our UK reimbursable R&D tax credit.

These were partly offset by decreases in professional services and consulting fees, obe-cel clinical material supply costs, and some other general admin fees and expenses. Our general admin expense increased from $9.3 million-$18.2 million for the three months ending March 31, 2024, compared to that same period in 2023. This increase was primarily due to salaries and other employment-related costs, driven by an increase in general and administrative headcount, supporting the overall growth of the business and primarily related to commercialization activities. Our net loss was $52.7 million for the three months ending March 31, 2024, compared to $39.8 million for the same period again in 2023.

Autolus estimates that with its current cash and cash equivalents and the proceeds received from the strategic alliance with BioNTech and our equity financing, that we are well capitalized to drive the full launch and commercialization of obe-cel in relapsed refractory adult ALL, as well as advance our pipeline development plans, which includes providing runway to data in our first pivotal study of obe-cel in autoimmune disease. I'll now hand things back to Christian to wrap up with a brief outlook on expected milestones for the rest of the year. Christian, back to you.

Christian Itin (CEO)

Thanks, Rob. Obviously, the next key event that we're looking forward to is really the midyear conferences with ASCO and EHA, the oral presentations and the update in the posters at the EHA in addition. Obviously, looking forward to seeing you, hopefully there and connecting at that point as well, hopefully in person. We're also gearing up, particularly during the second half of the year, for the full reviews on the regulatory side, getting towards the November 16, 2024 PDUFA date in the FDA review, but also expect to have quite an involved process with the European agency. Our process is a bit different than the way it's operated under the FDA.

We're also planning to obviously initiate and drive the process in the UK as well as we go through the second half of the year. In parallel, we'll keep you posted on our startup activities towards our next pivotal study. Also excited to keep you posted on that, and looking forward to your questions.

Operator (participant)

As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again, and please stand by while we compile our Q&A roster. Our first question will be coming from... Excuse me, Kelly Shi of Jefferies, your line is open.

Kelly Shi (SVP and Senior Research Analyst)

Congrats on the great progress made, and thank you for taking my question. The first question on adult ALL, Christian, do you expect AdCom meetings based on the prior communications with both regulatory agencies in the U.S. and Europe, and also have follow-up? Thank you.

Christian Itin (CEO)

Well, thanks a lot for joining, Kelly. The agency did not expect to hold an AdCom meeting. They did communicate as much at the acceptance of the filing, and there's been no other communication to the contrary of that. So we don't expect an AdCom for this product.

Kelly Shi (SVP and Senior Research Analyst)

Terrific. And also for the SLE program, and, you mentioned that two patients have been enrolled. Could you also add more color in terms of, patient baseline characteristics? Do we expect, similar to the trials from, Dr. Schett's team? And, also, for the year-end, the data, disclosure, do we expect, from all six patients? And on top of that, you also mentioned, T-cell engagers, comparison to like a CAR-T for tackling autoimmune, and, you talk about, the efficacy, prediction. But I'm curious, given that your rich experience with, Blincyto, how do you think about, its safety profile in autoimmune indications, given the prior, clinical profile shown in hem-oncology indications? Thank you very much. I know there's a lot of questions in one.

Christian Itin (CEO)

Yeah, I'll try to sort of go through that. So, first of all, in terms of the types of patients that we're enrolling in this trial, they're very close in terms of the characteristics as you've seen in the ELIANA study. Tend to be younger patients initially, certainly that have, you know, very severe forms of disease, very significant impact on their outlook on life. Obviously, organ involvement is one of the parameters that I think all of these patients do share, typically at least one to two organs that are impacted.

So it's a very advanced, very involved state of the disease, and in that sense, very similar to the patients that have been treated and described in the initial ELIANA evaluation. So that's the first thing. The second thing point was around the enrollment and what we expect to sort of for the end of the year. So our expectation is that we should be able to enroll the patients and get them treated. We'll probably have all patients treated, but we expect to have obviously variable follow-up with these patients. And so that's sort of what the current expectation is, that is, what we're seeing in the trial, the progress we're seeing in the trial.

So that's our current expectation in that regard, in terms of what to expect, which is initial data understanding, initial activity, and safety. You then asked about additional modalities, treatment modalities that could enter, like T-cell engagers. I think what you see in the publications that were made on sclerosis patients and SLE patients is that clearly both teams were taking a very cautious approach to dosing. Both the duration of the dosing as well as the level of dose that was used. And also very careful in terms of managing the patients, and a lot of that certainly has to do with concerns around safety signals. And we'll need to see kinda how that obviously evolves going forward.

But also what we did see is also that the level of T-cell depletion was limited in these patients, but at the same time, also inducing some clinical benefit, in all the patients that were treated. So I think it's early days, but certainly, not an easy profile if you look at it from a good side or perspective with continuous high efficacy in these patients. Not an easy way to go, and for sub-Q, the challenge would be, would have to be very frequent. And in that setting, certainly on the oncology side, the toxicity has gone up quite substantially. So those are certainly some of the considerations there, but all early days, and I think premature to have a firm view on how that might develop.

Kelly Shi (SVP and Senior Research Analyst)

Thank you very much.

Operator (participant)

One moment. One moment for our next question. Our next question will come from James Shin of Deutsche Bank. Your line's open.

James Shin (Director and Senior Equity Research Analyst)

Reception is a little poor, so I apologize. Hi, can you hear me?

Christian Itin (CEO)

Yes, we can.

James Shin (Director and Senior Equity Research Analyst)

I apologize, Christian. My reception is a little poor. Thank you for contextualizing the manufacturing and logistics hurdles that you went through during FELIX. You now have Cardinal support for the ALL launch. Can you help us understand or quantify Cardinal's benefit to obe-cel's delivery, logistics, and day delivery times? And then I'll have a follow-up.

Christian Itin (CEO)

Yeah, really good question, James. So the opportunity we have with Cardinal's presence across the U.S. and the presence of centers that we can basically hold product in gives us an ability to ship product while in parallel with completing the final steps of the quality control and release process. Now, in practical terms, what this allows us to do is take approximately three days out in the return time of the product, because it allows us to get the product close to the centers, to the respective center already before we're fully signed off, and then as soon as the product is signed off, the product obviously can then be shipped.

We basically say, all the, almost all of the logistics are grounded, and it's literally, typically, it's a truck drive from the particular holding spot to the center. So it's about 3 days that we expect, all in between the element here on the from the holding step that we have, together with the faster analytics that we introduced in the second half of the pivotal study, will give us actually a reduction of the delivery time from about 21 days to 60 days at time of launch. So it has a very significant impact between the 2 measures that we took and improvements that we introduced in the process, and puts us in a very competitive pocket.

James Shin (Director and Senior Equity Research Analyst)

Fantastic. And then for autoimmune, Christian, you nicely walked through the rapidly moving field. You have bispecific CAR-Ts, and there's probably going to be more B-cell approaches. I mean, BTKs are also being looked at. My question is: Do you see this autoimmune field becoming a zero-sum clinical or commercial environment, or is it just going to be more of like a medical evolution, where patients possibly cycle through these regimens?

Christian Itin (CEO)

Well, it's a really interesting question, and it's one we're speculating in the absence of; it's almost a void of data we're speculating in. Obviously, the excitement comes from the observation that with a CAR-T approach, you appear to have the possibility to get to a very deep, and for most patients, lasting remission. That's a quality of outcome that no other therapy actually today has actually been able to get anywhere close to. So it's a new quality, and I think that's where the excitement really is, and that's what the opportunity is. Now, using or impacting B cells, that's obviously not entirely a new story. That goes back to the late 1980s, into the 1990s, and got for the first time valuable with the availability of rituximab.

So that story is old, and we've been looking, and the field's been looking for better ways to sort of actually, you know, drive into the B-cell compartment itself, most of the ways in CD20 approaches. Well, what the exciting aspect here in terms of the biology and the thing that, or the element really, that, Georg and Andreas' data was opening up, is the revelation that indeed the majority or maybe most, of the autoantibodies appear to be produced, by early forms of plasma cells, so-called plasmablasts, and not by mature plasma cells. And the plasmablasts, different from plasma cells, still carry CD19 on the surface, which makes them targetable with the CD19 CAR.

With that, we do not only have an ability to remove the memory of the autoreactivity or autoimmunity, but you also have the ability to remove the factory of the autoreactive antibodies. And that actually gave you two things. It gave you a very fast, with a very deep and lasting effect, that's the memory removal, but it also has a fast effect, and that was the removal of the plasmablast. And I think that's really where the remarkable part of the biology is. Now, the question is: What mechanisms can you actually deploy that give you that level of depth of an outcome?

BTKI is not very likely to be able to do that, will impact B cells, but it will not impact the plasmablasts in that way, and with that, may have an effect similar to a rituximab antibody, which has some activity in some of the indications, and then some others, it doesn't have much of an impact. So that may not actually be getting you where you need to go. If you have a monoclonal to CD19, you may also not have enough, frankly, power in your therapeutic approach to be able to really make that escape and really get to these compartments, where those particular cells reside. And, you know, we've seen that from an oncology perspective, very clearly played out.

If you then go to the ADCs, we see it played out, we see it also with T-cell engagement, and with all of those modalities, we see quite a differential when you look at sort of the completeness of the removal of B cells. We see the differential clearly in oncology settings quite dramatically in terms of long-term outcomes, et cetera, et cetera, what you can do, where you really need to get to resets. So there are differences in performance, and, depending on that difference on performance, you may be able to actually get a lasting effect, you get a temporary effect. And I think what we'll be seeing is that, what I think I would expect is that agents that give you sort of a temporary effect, probably are agents that you would use in a more broader range.

If they're very safe, if they're very benign in their safety profile, you could use them more broadly and in early settings, and you could sort of, you know, add it on to the current standard of care, which is mostly steroid-based and, as well as a few other agents on top. But if you really want to get a reset, you're gonna get a fundamental change, and particularly those patients develop very severe forms of disease and where you don't have time to mess around, or you have a condition you really cannot afford to mess around.

That's where you would go in with a therapy that has the ability to really get a proper reset and get these patients back to, hopefully, firm footing, in a state where they are not dealing with these very horrific conditions that they're frankly dealing with and they're handicapped with.

James Shin (Director and Senior Equity Research Analyst)

Thank you.

Christian Itin (CEO)

Thanks, James.

Operator (participant)

One moment. For our next question. Our next question will be coming from Asthika Goonewardene of Truist. Your line is open.

Asthika Goonewardene (Managing Director and Senior Biotechnology Equity Research Analyst)

Hey, good afternoon, guys, and thanks for taking our questions. So, Christian, I wanted to ask about the updates coming down to the FELIX study at ASCO and EHA. Obviously, long-term event-free survival is going to be a key focus there, but how much weight do you think physicians will place on maybe the patient's transplant-free rate or transplant-free survival?

Christian Itin (CEO)

It's a really good question, Asthika, and thanks for joining. You know, one of the questions that, you know, you, you have when you look at a, at a cell-based therapy is that whenever you have a cell-based therapy and you follow after that with a stem cell transplant, you have to go through a step where you frankly kill the cell-based therapy and then replace it with a stem cell transplant. And the problem with that is, is you-- if your, if your therapy was still active at that point, your cell therapy was still active, you also would take that out and replace it, with, with another, with, with basically, normal cells and try to reset the, the, the bone marrow compartment. But it's a very tricky trade-off.

Now, in some instances, we've seen that actually happen, particularly if you have a product with a short persistence, so where the cells, basically, the CAR-T cells disappear quickly. If you then, after that, come in with a transplant, you know, in that setting, you would expect to actually see, at least have a chance for improvement in outcome of the patient. In the case of obe-cel, obviously one of the questions is, well, you know, does that actually hold for obe-cel, which we know to have long persistence? And we also see, you know, that clearly the patients that have, based on our ALL CAR-19 study, the patient have long-term outcome, also tend to have long-persistent CAR-T cells.

So in that setting, if you were to actually intervene with a stem cell transplant, you kill the CAR-T cells off, and then you actually put a new marrow in, basically. And also at that point, you know, it's a real question: Is that then gonna be beneficial or not? And so one of the things that we're looking to do is at least give a first view of the answer based on the experience that we had in the study. And it's certainly an area that is of a lot of interest for the treating physicians. So that's a, I think, an element, a key focus of the presentation.

Asthika Goonewardene (Managing Director and Senior Biotechnology Equity Research Analyst)

So, Christian, can you maybe give us a little bit of color on what you think is the threshold that you think that the physician community will feel this is differentiated from Kymriah's? I know Zuma-3 doesn't give you the right kind of data to make that kind of comparison, but perhaps you can comment on some of the real-world data that's out there that sets the bar to beat.

Christian Itin (CEO)

So, first of all, you know, the data is gonna be limited because certainly in our trial, we had a very limited number of patients that were receiving a transplant after receiving obe-cel. So there is the limitation of a small number. But it certainly will give you a view on whether there is a likely improvement of outcome or not. That certainly will answer that question for sure. And I think you sort of indicated it of kind of what to expect. The other flip side of that is also the analysis of persistence and whether longer-term persistence correlates with longer-term outcome, which is sort of the other side of that story.

And we're gonna be actually really walking through both of those and we'll present analyses to both of those. So it really depends, I think, on the experience of the physician in the field. You know, what happened, what they have in their hands, frankly, in terms of products. What is interesting when you look at some of the real-world experiences, there was a clear conclusion, basically, at the ASH. Well, certainly for the competitive program, it is that the competitive product should be consolidated with another therapy, which typically would be a stem cell transplant. So that was an interesting conclusion in its own right, and it'll be, I think it'll be interesting to see our data at ASCO EHA.

Actually, I think you get a pretty good view on the difference between the programs in that regard.

Asthika Goonewardene (Managing Director and Senior Biotechnology Equity Research Analyst)

... Got it. And then I got two quick questions on autoimmune, of course, Christian. The two patients that were recruited, was that from a single site, or was that kind of one apiece from the UK and the Spanish site? And then-

Christian Itin (CEO)

Both of those. So the answer to that, the first question is, both were recruited in the UK at different sites.

Asthika Goonewardene (Managing Director and Senior Biotechnology Equity Research Analyst)

Got it. Okay. And then also to meet the target recruitment of about six patients with data by year-end, expected we should see the recruitment rate step up, maybe around a patient a month. So what needs to happen to get that kind of recruitment rate? And then do you see the... Is there any potential for it to exceed that?

Christian Itin (CEO)

Well, first of all, you know, every time that, you know, physicians use a modality for the first time, you know, you want to make sure you really pick, you know, the perfect patient for that first, for that first dose. So that's true for every, I think, every agent you test and every site that is a first site, with that type of an agent and an indication. So the first patients are always the most challenging ones because, you know, that's where you have no experience. Once you see the therapy work, you see the impact, that's where you see clearly confidence build nicely, and then you see actually things kind of start moving at that point.

We've seen it, in fact, even with, you know, across the various Hodgkin's indications, where the first patient was always the biggest hurdle, where you wanted to make sure you get everything right. And then, actually after that, confidence starts to build, and then the recruitment is starting to pick up at that point in time. That's very normal, and I think you see it pretty much across all studies, with, you know, very active substances in patients with a severe disease.

Asthika Goonewardene (Managing Director and Senior Biotechnology Equity Research Analyst)

Great. Thanks for taking my questions, guys, and congrats on the progress.

Christian Itin (CEO)

All right. Thanks, Asthika.

Operator (participant)

One moment for our next question. Our next question will come from Matthew Phipps of Blair. Your line is open.

Matthew Phipps (Partner and Group Head of Biotechnology Equity Research)

Hi, Christian. Thanks for taking my question. Sorry for some airport noise. Curious if you've had discussions yet with the FDA on how they will treat patients that are in morphological disease versus those that are MRD in the label.

Christian Itin (CEO)

So just thanks, Matt, for joining. The analysis, the primary analysis the FDA will do, is based on patients that have morphological disease. That's the primary focus of the analysis. And that's actually in terms of analysis, both at the time point of inclusion as well as the time point of intensification.

In Europe, the difference will be is that it will be the patients actually at the time of inclusion with measurable disease, and then basically, and the fact that they intend to treat approach in terms of the analysis, which is sort of the difference in the view, where the European take the view of the treating physician and make a decision, and then you want to know what the outcome is, or what outcome to expect, and, with the FDA, which is more, more kind of looking at from a scientific perspective and actually, looking at the individual patients, and in terms of response assessment to a defined time point.

So there's some differences there in terms of the analysis, but we're looking at patients with morphological disease as the primary group for the analysis. But the experience typically tends to be reflected more broadly in the label. So we'll see where we end up on that.

Matthew Phipps (Partner and Group Head of Biotechnology Equity Research)

Thanks, Christian. And then one quick one on multiple myeloma, actually. You know, obviously now we have Carvykti approved and second line, and just kind of curious how you're thinking about where AUTO8 development path can be. But just like, would you ever consider treating a patient who had prior BCMA CAR-T and failed?

Christian Itin (CEO)

Yeah. So that's a really good question. Obviously, the multiple myeloma field is sort of, you know, filling up with a number of agents at various lines of therapy. And so we're looking at that kind of very carefully, and we're looking both at multiple myeloma and related diseases. So we've taken a pretty broad look at the plasma cell disease areas and are evaluating kind of the various path there. But too early to actually give you a very clear steer on that. But I agree with you, there is a level of competition that's building up, that you want to pick your battle very carefully.

Matthew Phipps (Partner and Group Head of Biotechnology Equity Research)

Okay. Thanks for taking my questions.

Christian Itin (CEO)

Okay. Thank you.

Operator (participant)

Our last question will be coming from Gil Blum of Needham & Company. Gil, your line is open.

Gil Blum (Senior Biotech Analyst)

Hi, everyone, and good morning and good afternoon. Just a couple of questions from us. So, first one on the commercial launch, potential commercial launch for obe-cel. Do you expect the treatment to be initially provided mostly in centers that already provide other CAR-Ts?

Christian Itin (CEO)

I think what you find is that the centers that actually treat an ALL outpatient tend to be the highly specialized academic centers. So certainly, a high focus and aggregation of the patients in those centers, given the high intensity of support that these patients tend to require. So a lot of these centers do actually have already multiple CAR-Ts available that they're actually delivering in various disease settings. And in that sense, are some of the most experienced centers across, I think across the US for CAR-T delivery. And that's certainly true, and also obviously matches the very high degree of overlap, the clinical centers that participated in the FELIX study.

Gil Blum (Senior Biotech Analyst)

Okay, that makes sense. And maybe an open-ended one. So given it took about 18 months to see a relapse from one of the Schett patients, what in your view would be a good leading indicator for sustained efficacy, and is there even something like that? Thanks.

Christian Itin (CEO)

A really good question, Gil. One of the things that's interesting about that myositis patient is that that's one of the very to my knowledge, probably was the only patient in Georg's dataset that actually had a low amount of autoreactive antibodies left that were not removed in the therapy. So in other words, there were actually autoantibodies visible in that patient even early on, although the clinical symptoms were all clear, but there was sort of a remnant of autoantibodies that remained detectable in the patient. And that also, obviously, you know, if you think about early indicators, certainly in this case, you would consider to be the early indicator because it would be also very directly linked to the outcome and the underlying disease. And so that's probably a very good one to follow.

Other than that, I think it's very difficult to actually develop one. First of all, we don't have another event that we can look at, but certainly the event we can look at, we have certainly evidence of sustained low-level presence of an autoantibody that just wasn't cleared in full.

Gil Blum (Senior Biotech Analyst)

All right. Thank you very much, and, congrats on all the progress.

Christian Itin (CEO)

Thanks a lot, Gil.

Operator (participant)

I would now like to turn the call back to Christian for closing remarks.

Christian Itin (CEO)

All right. Well, first of all, thanks a lot, guys, for joining today. Obviously, a very successful quarter for us. We're looking forward to obviously the data updates in a few weeks' time. Hope to see most of you at one of the meetings or conferences that are so alongside. We'll keep you updated, and certainly an exciting year as we're getting into the second leg here towards the, hopefully, approval of obe-cel in the U.S., and then our next steps in Europe and the U.K. All right, with that, thank you very much and have a fantastic day. Thank you.

Operator (participant)

This concludes today's conference call. Thank you for participating. You may now disconnect.