Autolus Therapeutics PLC

NASDAQ:AUTL

Earnings Call Transcript 2024-Q1

[Operator]

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, executive]

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. So on Slide 2, 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 time lines for our product candidates and our expectations regarding our cash runway.

These statements are subject to a variety of written 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 Investors section of our website. So moving on to Slide 3, you're going to see the agenda for today's call, which is similar to usual. So Christian is 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.

So with that, I will hand over to Christian.

[Christian Itin, executive]

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 the -- with obe-cel. We started the year at least 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. We also managed by the -- towards the end of the quarter to get the European filing accepted. So we have now both major jurisdictions or 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 facility -- 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 there 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 in our first patients. Now the -- when you think about data updates, the important next updates are going to be at ASCO and EHA, which are at the end of May at 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 and outcome. Now in addition, at EHA, we have 2 further analysis 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 sensitive methodologies to determine the presence of CAR T cells to measure persistence and 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 it sets us 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 time frame in 2 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 2 of our pipeline programs. It'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 in addition to those key areas and also on the technology side, providing access to technology we've developed, particularly for the use with 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 2 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 the ability to expand the footprint of indications, particularly for obe-cel. And that obviously 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 transitioned at the level of the Board that sort of actually go alongside that the transformation of the company. We had, at the end of last year, Lis Leiderman and Bob Azelby joined, 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 autoimmune diseases and kind of advertise that level and that aspect in terms of the experience base of the Board. So a 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 #6. 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 built up this manufacturing facility in Nucleus in the U.K. and -- but how do you actually ensure that you can actually deliver product and this at least 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 with FELIX study in. And so what you see is basically a time line that goes from 2019 to 2023, and the actual study was conducted from the middle of 2020 towards the end of 2022 in terms of the enrollment of the study. I would say that, so the coincides with the majority of 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 time 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 U.S. during that entire period. This is data from the U.S. government. And 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. And clearly, 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 side.

Now it was quite remarkable is when you then actually look on the small fever curve in the middle, this is actually the actual wait to delivery time over that entire period for the Phase II conduct, and you see that for the ranges at the low end is 15 days, 30 days on the upper end and 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, to shut down of flights and so on so forth, all the limitations we have 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. And 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 base going into the pandemic, but that's the actual reality that we have been able to see, but also obviously gives us a lot of confidence that the systems that we have put in place have to be pressure tested in an extreme way. And have actually delivered throughout this challenging period. Now if we go to the next slide, Slide 7, just as a brief reminder of the FELIX study and what we're actually were 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 sales in the matter all the way up to close to 100%. So we have this entire bucket of very high levels of disease. We also have, in the middle with the cohort B patients that have very low levels of disease so called minimal residual disease, 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 did have a relapse in the marrow, which is normally the place where you fight 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 visibility to survive and succeed in a very different environment. So having all of these different groups is actually important when you think about this from a treating physicians perspective because what it basically gives you, it gives you an ability to see the patients that will actually walk in your -- to your practice to patients you care for, you'll see them represented in the stuff. And that doesn't often happen in clinical studies. Often clinical studies are quite selective. They're quite protected to make sure that the outcome is as maximize 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 gave 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 #8. What we're looking at here is the event-free survival across the entirety of the experience. And as you can see, is that 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 strong. Obviously, the next update that we're going to have at ASCO EHA will be somewhere between 5 and 6 months additional follow-up and also gives us much more stability out of part of that curve in the part of the curve where we actually are starting to see the 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. And 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. So low tumor burden not only does give us a very high overall 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 the right 5% to up to 75% to a -- such a wide range of tumor burden in these patients. but it's not going to the very extreme of tumor burden in the marrow.

But as you can see, these patients still do remarkably well, as 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 have almost by definition, refractory nature of the disease. And you do see that these patients already 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 on 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 we get 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 at lymphodepletion, both for CRS in the middle or for ICANS on the right-hand side, none of these patients had a high-grade event hematological 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 similar maybe to what an overall inside 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 an 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 #12. Obviously, we have been talked about briefly about the trajectory here 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 on the left-hand side, basically the 4 key areas that we're sort of working with in terms of preparation, how we manage the regions within the U.S., 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 airports, a lot of direct engagements 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 on that side. And looking at also a number of parameters important here when you think about value, there's the obvious how much long-term benefit can you induce, what is sort of the overall safety profile, et cetera. But there's also much more new and old 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 higher grade events. That has a huge impact on the resource utilization at the hospitals and a huge impact on cost 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 is 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 valued. 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 and 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's just 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 into the board 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 of the product has and the interest and willingness of the centers to onboard 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 mentioned before, close to 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 of the logistics, which allows us to actually ship products during the release process and with that, also take some of the time out of the bank's 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 residence 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 in the last few weeks in the U.K. So this was the opportunity. So this is a true industrial setup for the production of several therapy products. It's a 70,000 square foot facility and 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 be taken 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 a very good -- have a very good starting point with good level of capacity to support a future launch. So with that, just moving to Slide 15, the slide you've seen before, really looking at sort of the opportunities in terms of the obe-cel family of products with obe-cel itself with opportunities both in human oncology as well as in autoimmune disease. And then there are obviously the 2 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 a hugely active space has a lot of communication happening. And every time there is a paper coming out I tend to get and we tend to get obviously things from some of you and to 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 in 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. But that product is really what all -- almost all the information is based on particular ones when we look at longer-term observation.

Of all the patients that were treated, be it in SLE, in myositis, in scleroderma, et cetera. There's one patient so far has been reported to actually have relapsed, that relapse happened after 18 months. Patient is still a lot better than obviously 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 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 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 also have seen now in addition to the initial work that was done at the University of Erlangen, we've seen the first work with inotuzumab, also part in Erlangen, part of Munich to explore the use in our 8 patients and in single sclerosis patients, indicating that there was 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 University of Erlangen with various patients. And he indicated clearly that we would see clearly was -- obviously, good deep responses, which seem to be meaningful, given 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 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 shops 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 going to be one of the areas where there's going to be probably more variability introduced in outcomes.

Now on the next slide, what I'd like to do is just briefly to 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, is 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 for that product in piece. And not surprisingly, the data was very similar to the data we knew from Kymriah's original trials. Some high level of activity, long persistence, 2 to 3 years persistence in these patients. And giving you in the 85%, give or take rate of molecular complete remissions, 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 ALLCAR actually was published at the -- or presented at the ASH Meeting in 2021. And there's likely going to be a publication at some point with the fuller data set. 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 delay to CD19. And 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. What you can see is that we have the same on rate, which gives you the same specificity but about 100-fold faster off-rate. And 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 much 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 ALL. From an activity perspective, we see differences in toxicity as you could also alleviate from the comparison between our experience obe-cel in the light blue columns and the dark blue column, the experience with Kymriah, the ELIANA study. Now the remarkable thing is, obviously, we have the 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 2 to 3 years in pediatric ALL to about 3 months, maximum 6 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. 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 to 3 years of persistence in leukemia. Now the difference between those 2 settings is predominantly the ability of immune system to map the response. And we actually assume that the key driver for the difference in persistence is, in fact, the different -- the ability of the patients with autoimmune disease or 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 -- it was an attempt on to actually retreat with CD19 CAR. And in fact, the sales were cleared very rapidly, consistent with the fact that indeed, the patients actually have built up a retirement immunological reaction and the rejection. Now quite similarly, if you think about top 2 delivered products and antibodies is also a pretty significant risk there that you might actually induce as well some immunogenicity and that certainly has been through 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 opened in the -- 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 fast -- a last sort of view in terms of the pipeline. They brought a few -- obviously, we're active 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 also are 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.

[Robert Dolski, executive]

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 12b-25 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's 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 20 -- 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 3 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 to $30.7 million for the 3 quarters ended March 31, 2024, compared to that same period in '23. 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 U.K. 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 to $18.2 million for the 3 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 head counting supporting the overall growth of the business and primarily related to commercialization activities. Our net loss was $52.7 million for the 3 months ending March 31, 2024, compared to $39.8 million for the same period again in 2023. Autolus estimates 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, executive]

Thanks, Rob. Obviously, the next key event that we're looking forward to is where the midyear conferences with ASCO and EHA, the oral presentations and the update in the posters at the EHA inhibition. 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 PDUFA date in the FDA review but also expect to have quite an involved process with the European agency cost it's a bit different than the way it's operated under the FDA. And we're also planning to obviously initiate and drive the process in the U.K. 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 and also excited to keep you posted on that.

And looking forward to your questions.

[Operator]

[Operator Instructions] And our first question will be coming from Kelly Shi of Jefferies.

[Dingding Shi, analyst]

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

[Christian Itin, executive]

Well, thanks a lot for joining, Kelly. The agency did not expect to up held 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.

[Dingding Shi, analyst]

Terrific. And also for the SLE program and you mentioned that 2 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 and team. And also for the year-end data disclosure, do we expect from all 6 patients. And on top of that, you also mentioned T cell engagers comparison to like a CAR T for taking autoimmune and you talk about the efficacy prediction. But I'm curious, given that your characteristics with Blincyto. How do you think about its safety profile in autoimmune indications given the prior clinical profile show in oncology indications. I know there's a lot of questions in one.

[Christian Itin, executive]

Yes, 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 you've seen in the Erlangen study. Tend to be younger patients initially certainly that have very severe core to disease, very significant impact on their life. Obviously, organ involvement is one of the parameters that all of these patients do share typically at least 1 to 2 organs that are impacted. So it's a very advanced, very involved state on disease and in that sense, very similar to the patients that have been treated and prescribed in the emission Erlangen evaluation. So that's the first thing.

The second thing point was around the enrollment then what we expect to sort of for the end of the year. So our expectation is that we should be able to enroll patients and get them treated, we'll probably have variable 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 some -- what we're seeing in the trial and the progress received 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 prevent like T Cell engagers. I think what you see in the publications that were made on sclerosis patients and the RA patients is that clearly both teams for 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, we're 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 kind of how that obviously evolves going forward. But also, what we did see is obviously 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 who have treated. So I think it's early days. But certainly, not an easy profile, if you look at it from Blincyto perspective, with continuous have infusion in these patients. Not an easy way to go and for subcu the challenge where people have to be very frequent. And that said, it 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, I think have, I think for a view on how that might develop.

[Operator]

Our next question will come from James Shin of Deutsche Bank.

[James Shin, 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 B-ALL launch. Can you help us understand or quantify Cardinal's benefit to obe-cel's delivery logistics and bank delivery times? And then I'll have a follow-up.

[Christian Itin, executive]

Yes. 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, this is an ability to ship product, while in parallel, we're completing the final steps of the quality control and release process. Now in practical terms, what this allows us to do is take approximately 3 days out in the return in time of the product because it allows us to get the product close to the centers to the respective center already before were fully signed off. And then as soon as the product is signed off, the product obviously will then be shift. And we basically say all the -- almost all of the logistics part around it, and it's literally typically it's a tough drive from the particular holding spot the center. So it's about 3 days that we expect all in between the element here on -- 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 delivery time for about 21 days to 16 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 bucket.

[James Shin, analyst]

Fantastic. And then for autoimmune, Christian, you nicely walked through the rapidly moving field. You have bispecifics, 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 this going to be more of like a medical evolution where patients possibly cycle through these regimens?

[Christian Itin, executive]

Well, it's a really interesting question, and it's one we're speculating in the absence, I think is almost avoid if they were speculated in. Also 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 the quality of outcome that no other therapy actually today has been ever -- have 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 '80s into the '90s and got the first time evaluable with the availability of inotuzumab. So that story is whole that we've been looking and feels been looking for better ways to sort of actually drive into the B cell compartment in itself, most debating CD20 approaches. What was the sounding aspect here in terms of the biology and the thing that where the element created at the Georg and Andreas' data was opening up is the regulation that majority or maybe most of the AUTO antibodies appear to be produced by early forms of plasma circles so-called plasma blasts, not by mature plasma cells. And the plasma blast is different from plasma cells still carry CD19 on the surface, which makes them targetable with the CD19 CAR. And with that, we do have the ability to remove the memory of the autoreactive and autoimmune but they also have an ability to remove the factory of the autoreactive antibodies. And that actually gave you 2 things that gave you a very fast, with a very deep and lasting effect. That's the memory removal. But it also a test effect and now the removal of the plasma blast. And I think that's really where the remarkable part of biology is. Now the question is what mechanisms do you -- can you actually deploy that give you that level of step of an outcome. BTKi is not very likely to be able to do that will impact B Cells, but it will not, either not impact the plasma blast in that way. And with that, may have an effect similar to a toxin antibody, which has some activity in some of the indications and then some others, it doesn't have much to do. So that may not be actually getting where it needs to go. If you have a monoclonal to CD19, you may also not have enough currently power in your therapeutic approach to be able to really make that and really get to these compartments where those particular cells reside. And we've seen that from an oncology perspective very clearly played out. If you then go to the ADCs, we see a put, we see also with T Cell engager. 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, what you can do where you really need to get to these. So there are different phases 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 I think I would expect is that agents that give you sort of a temporary effect probably are agents that would use in a more broader range if they're very safe, very benign in their safety profile. You could use them more broadly and in the early settings and you consider adding on to the current standard of care, which is mostly tariff-based and as well as a few other agents on top.

But if you really want to get a reset, you're going to get a fundamental change, and particularly those patients develop the severe form of disease where you don't have time to mess around or you have a condition you really cannot afford to mess around. That's where we're going with a therapy that has an ability to really get a proper reset and get these patients back to, hopefully, for our footing in a state where they are not dealing with these very horrific conditions that they're frankly dealing with or they handicapped.

[Operator]

Our next question will be coming from Asthika Goonewardene of Truist.

[Asthika Goonewardene, analyst]

So Christian, I wanted to ask about the updates coming on 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 patients transplant-free rate or transplant-free survival.

[Christian Itin, executive]

It's a really good question, Asthika, and thanks for joining. A lot of the questions that you have when you look at it a cell-based therapy is that whether we have a cell-based therapy and you follow after that with a stem cell transplant, you have to go through a step where we frankly kill the cell-based therapy and then replace it with a same cell transplant. And the problem with that is 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 another with basically a normal cell and try to reset the bone marrow compartment. But it's a very tricky trade-offs now -- in some instances, we've seen that actually happen, particularly in 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, that saying, you would expect to actually see -- at least have a chance for improvement in modification. In the case of obe-cel, obviously, one of the questions is, well, that's not actually hold for obe-cel, which we know could have long persistence. And we also see that clearly the patients that have based on our ALLCAR19 study, the patient have long-term outcome, also tend to have long persistence CAR T cells. So that said, if you were to actually intervene with a stem cell transplant, you kill the CAR T cells off and then you actually put the new marrow in basically. And obviously, at that point, it's a real question is that any going to 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 clearance that we had in the study. And it's certainly an area that is of a lot of interest for the treatment position. So that's, I think, an element of the key focus of the presentation.

[Asthika Goonewardene, 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 Tecartus. 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, executive]

So first of all, the data is going to be limited because certainly in our trial, we had a very limited number of patients that we're receiving a transplant after receiving obe-cel. So there is the indication of a small number. But in terms of a view on whether there is a likely improvement of outcome or not, that certainly we'll answer that question for sure. And I think sort of dig at it of kind of what to expect. The other flick side of that is also the analysis of persistence and whether longer-term persistence correlates with longer-term outcome, which is on the other side of that story. And we're going to be actually really working through both of those and we'll present analysis to both of those. So it really depends, I think, on the experience of the physicians in the field, what happened -- what they had in their hands actually in terms of products. What is interesting when you look at the -- some of the real growth experiences there was a clear conclusion basically we have at the ASH, we'll certainly for the competitive program and 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 it's own way. And it will be -- I think it will be interesting to see our data at ASCO EHA. And actually, I think you get a pretty good view on the difference between the programs and margin.

[Asthika Goonewardene, analyst]

Got it. And then I got 2 quick questions on autoimmune, of course, Christian. The 2 patients in recruited, was that from a single size? Or was that kind of 1 piece from the U.K. and the Spanish side?

[Christian Itin, executive]

Both of those -- sorry, the answer to that first question is it was -- both were recruited in the U.K. at this insight.

[Asthika Goonewardene, analyst]

Got it. Okay. And then also to meet the target recruitment of about 6 patients with data by year-end. We 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 that -- is there any potential for it to exceed that.

[Christian Itin, executive]

Well, first of all, every time that physicians use a modality for the first time, you want to make sure you wait take the perfect patient for that first dose. So that's true for every -- I think every agency test and every site that is the first side with that type of an agent and an indication. So the first patients are always the most challenging ones because that's where no experience once you see the therapy work, you see the impact that's where you see clearly, confidence rising and then you see actually things kind of start moving at that point. We've seen it at even with across the areas of hospice indications where the first patient was always the biggest hurdle where we wanted to make sure you get everything right and then have a lot of 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 very accurate substances in patients that have severe disease.

[Asthika Goonewardene, analyst]

Congrats on the progress.

[Operator]

And our next question will come from Matthew Phipps of Blair.

[Matthew Phipps, analyst]

Curious if you've had discussions with the FDA on how they will treat patients that are in morphological disease versus those that are MRD in the label?

[Christian Itin, executive]

So thanks, Matt for joining. The analysis, the primary analysis, the FDA will do is based on patients that have morphological reviews. That's the primary focus for the analysis. And that's actually in terms of analysis, both at a time point of inclusion as well as the time point of interaction. In Europe, the difference will be is that it will be the patient actually at the time of inclusion with measurable disease and then basically the fact to treat approach in terms of the analysis, which is sort of the difference in the view where the European tech if you are treating physician and make a decision.

And then you want to know what the outcome is or what outcome do you expect with the FDA, which is more kind of looking at from a scientific perspective and actually kind of looking at the individual patients in terms of result assessment to the defined time on. So there's some differences there in terms of the analysis, but we're looking at patients with morphological diseases, the primary group for the analysis. But the experience significant has to be attracted more broadly in the label. So we'll see where we end up on that.

[Matthew Phipps, analyst]

And then one quick one on multiple myeloma actually. Obviously, now we have purposely approved in second line. And just kind of curious how you're thinking about where AUTO8 development path can be? Is this telling would you ever consider treating patients who had prior BCMA CAR T instead.

[Christian Itin, executive]

Yes. So that's a really good question. Obviously, the multiple myeloma field is sort of filling up with a number of agents at various lines of therapy. And so we're looking at that very carefully, and we're looking both at both myloma and related diseases. So we're taking a pretty broad look as to 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 that you there is a level of competition that's building up that you want to think about that very carefully.

[Operator]

And our last question will be coming from Gil Blum of Needham & Company.

[Gil Blum, analyst]

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, executive]

I think what you find is that the centers that actually treat adult ALL patients 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 U.S. 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, 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?

[Christian Itin, executive]

Really good question, Gil. One of the things that's interesting about that myositis patient is that, monitors patient as Georg stated that actually had a low amount of autoreactive antibodies less that were not removed in the therapy. So in other words, that we're actually autoantibodies visible in that patient even early on, although the clinical sentences were all clear, but there was sort of a remnant of other antibodies that remain detectable in the patient. And that also, obviously, if you think about early indicators, certainly, in this case, you would consider to be the early indicator because it would be obviously 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 on. 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, analyst]

Congrats on all the progress.

[Operator]

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

[Christian Itin, executive]

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 update in a few weeks' time. I hope to see most of you at one of the meetings or conferences that are is alongside. And we'll keep you updated and certainly an exciting year as we're getting into the second layer 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]

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