OptimumBank Q1 2024 Earnings Call Transcript

Quartr
Provided by Quartr
May 17, 2024

There are 9 speakers on the call.

Operator

Hello, ladies and gentlemen, and welcome to the Autolus Therapeutics call to discuss its 1st 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.

Speaker 1

Thanks, Tanya. Good morning or good afternoon, everyone. Thanks for joining us on today's call. With me today are Doctor. Christian Itin, our CEO and Rob Dolsky, our CFO.

Speaker 1

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 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 Investors section of our website.

Speaker 1

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 will then hand over for questions. So with that, I will hand over to Christian.

Speaker 2

Well, thank you very much, Olivia, and welcome everybody to our Q1 call. It's been a very successful quarter and obviously with a lot of activity related to OV Cell, but also obviously quite a lot of overall corporate updates as well. I'll start out with the with obicel. 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 2016. We also managed by the towards the end of the quarter to get the European filing accepted.

Speaker 2

So we have now both major jurisdictions to 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 nuclear 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 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 set the sales 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.

Speaker 2

Now the when you think about data updates, the important next updates are going to be at ASCO and at 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 on outcome. Now in additional at EHA, we have 2 further analysis that will be presented in the form of posters. One looks at the impact of inatumumab 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 also linking that then to outcome in the study.

Speaker 2

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 European Agency and also assess 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 timeframe 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 Belemtec will have for the lead program to the nucleus manufacturing facility to support the launch of their lead CAR T program.

Speaker 2

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, AUTO-one hundred and twenty two and AUTO-six mg. 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.

Speaker 2

Now in parallel to the transaction with Velvetech or just following the transaction, we also did a capital markets transaction and added capital. Between the two transactions, we added $600,000,000 to our balance sheet, which obviously sets us up well to deliver on the launch of OV Cell, but also gives us the ability to expand the footprint of indications, particularly for OV Cell. 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 Leiterman and Bob Aitelby join, obviously both a very strong Capital Markets experience and operating experience as well as a very strong commercial experience.

Speaker 2

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 Vaho also joined, who's an expert on particularly immunology and autoimmune diseases and kind of ramps out at 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 6. I'd like to start out with OV Cell. It's 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, a nucleus in the UK, but how do you actually ensure that you can actually deliver product and is that even possible to do that within the U.

Speaker 2

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 just remember on what kind of environment we actually did the Felix study in. And 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 2022 in terms of the enrollment of the study.

Speaker 2

Obviously that sort of coincides with the majority of the entire of the key period for the COVID-nineteen 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 U. S. During that entire period.

Speaker 2

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 UK for manufacturing makes us obviously highly reliant on the international flights actually taking place and the ability to really reach every site in the U.

Speaker 2

S. As well as elsewhere from our manufacturing side. 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 and you see that for the ranges at the low end, it's 15 days, 30 days on the upper end and you see literally every one of these products actually applauded on that particular jacket 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 and so forth, all the limitations we have in 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.

Speaker 2

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 based 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 been 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 looking to do with this study.

Speaker 2

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 very high levels of disease. We also have in the middle with the cohort D patients that have very low levels of disease, so called minimal residual disease. But at these levels, you can pick up by flow analysis, by TCR or by NGS sequencing.

Speaker 2

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 also 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 this 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.

Speaker 2

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 maximized 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.

Speaker 2

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 of logistics. So it just tells you something about robustness and delivery alongside the study. So with that, moving to Slide number 8, what we're looking at here is the ventral survival across the entirety of the experience.

Speaker 2

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 from. Obviously, the next update that we're going to have at ASCO EHA will be somewhere between 5 6 months additional follow-up and also 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.

Speaker 2

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.

Speaker 2

And you 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 about 5% to up to 75% tumor burden. So 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. But as you can see, these patients still do remarkably well and you see stabilization also in the green curve, which is very encouraging.

Speaker 2

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 and 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 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 diverse patients that we have treating.

Speaker 2

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 are 2% 7%, which is substantially below any other T cell engaging or CAR T type therapies in the space.

Speaker 2

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 less than 5% disease burden had lymphodepletion, both for CRS in the middle or for ICAMS on the right hand side, none of these patients have high grade event immunological toxicity event. We have 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 Tythe belief syndrome and ICANN, but it's still at a relatively low level.

Speaker 2

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 PINKSYSER population would look like in terms of CLS 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 number 12. Obviously, we have been talked about briefly about the trajectory here from a regulatory milestone perspective.

Speaker 2

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 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.

Speaker 2

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, 1st of all, obviously in terms of communication, creating awareness and supporting, frankly, every activity, whether it's with engagement with centers, with payers, etcetera 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, etcetera, and presentations and publications.

Speaker 2

There is obviously a very significant work stream around demonstrating the value of the therapy. So there's a lot of activity going on that side. And we're looking at obviously 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, etcetera. But there's also much more nuanced elements there.

Speaker 2

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, has 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 planable. These treatments are more planable and there's a way to anticipate what's going to happen to the patients and what type of support do you need to actually put care for.

Speaker 2

That is very important because all of those are important cost drivers, sets 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 well advanced 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.

Speaker 2

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 a triaging point to support the centers in whatever the need is and the support required is. So getting the centers onboarded, accredited, absolutely crucial. This is a very involved activity, also involved from the center. It takes a commitment from the center, it takes time.

Speaker 2

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 mentioned before closed the transaction with Cardinal Health.

Speaker 2

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. They also give 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 veins 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. I would say 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.

Speaker 2

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 UK. So this was the opportunity. So this is a true industrial setup for the production of cell therapy products. It's a 70,000 square foot facility and a facility that we really went from ground breaking to MHRA approval within about 27 months.

Speaker 2

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 a very good and 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 omicelle family of products with omicelle itself with opportunities both in human oncology as well as in autoimmune disease. And then there are obviously the $2 of Aubicell AUTO1 hundred and twenty two and AUTO8 that allows 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 dynamic that we're seeing in the space, particularly when it comes to autoimmune disease.

Speaker 2

So obviously, a hugely active space, 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 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.

Speaker 2

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 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 Vicitis, in scleroderma, etcetera, There's one patient so far that's been reported to actually have relapse. That relapse happened after 18 months.

Speaker 2

Patient is still a lot better than not was, but there's clearly 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 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 this initial work that was done at the University of Erlangen, we've seen that first work with lenetuzumab, also part in Air Lung, part of Munich to explore the use in RA patients and in single sclerosis patient, 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 Georges said gave a recent interview and which was actually published by one of your colleagues at Cantor and was actually asked about the data which was taken also at University of Erlang with the rheumatoid arthritis patients.

Speaker 2

And he indicated clearly that he would see clearly was obviously seeing 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 sort of think it going forward is how many shots do we actually have in 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.

Speaker 2

But it's highly likely going to be one of the areas where there's going to 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 Ovisell and the product that was used at the University of Wehrlungen 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 is actually quite a good set of data available from that product in PEATs. And not surprisingly, the data was very similar to the data we knew from Kymriah's original trials.

Speaker 2

So high level of activity, long persistence, 2 to 3 years persistence in these patients and giving you in the 85 percent give or take rate of molecular complete remission as we're seeing with Kymriah. You see the reference on the right hand lower side, the ILLIANA study, which is what the summary of the data from the original study with Kymriah. The initial data from the pediatric experience with the airline car 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 a 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 domain 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.

Speaker 2

The CAT19 binder in green, that's actually the property that we see for our product for obicela. 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. With that, obviously, having that differentiation that you heard us talk about it 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 with OVYCELL in the light blue columns and the dark blue column, the experience with Kymriah and the ILLIANA study.

Speaker 2

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 2 to 3 years in pediatric ALL to about 3 months, maximally 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.

Speaker 2

That's not what the difference is because that lung persistence is also true if you have MRD positive patients, so patients with extreme low levels of target cells, you still get 2 to 3 years of persistence in leukemia. Now the difference between those two settings is predominantly the ability of the immune system to map the response. And we actually assume that the key driver for the difference in precision is in fact the different 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 it was an attempt done 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 rejection.

Speaker 2

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 involvement. We had our first center open in the during the course of Q1.

Speaker 2

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 basically translate the pediatric ALL dose in a fixed dose for adults, which is a 50,000,000 cell dose. We don't need to do DLT periods or any of those types of restrictions within the enrollment, but we can actually involve patients as they come without limitations of that nature. All right.

Speaker 2

So with that, just a fast a last sort of view in terms of the pipeline, a bit broader view. Obviously, we're active with additional programs. Certainly, there's more activity on the AUTO8 program, the AUTO6 MG program and also both of those, we're looking forward for additional data and we're also are enrolling additional patients with AUTO1 hundred and twenty two as well. All right. So with that, I'd like to actually transition.

Speaker 2

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

Speaker 3

Thanks, Christian, and good morning or good afternoon to everyone. It's my pleasure to review our financial results for the Q1 of 2024, and I'll be on Slide 22 of the presentation. As you saw from our press release and Form 12b-twenty 5 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 OBLY Cell into autoimmune diseases. The BioNTech deal was a complex transaction, with as noted a number of different components to it.

Speaker 3

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 2012b-twenty 5 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 758,000,000 dollars 58,500,000 as compared to $239,600,000 at December 31, 2023.

Speaker 3

Our total operating loss for the 3 months ended March 31, 2024 was $38,800,000 as compared to $39,100,000 for the same period in 2023. On the operating expense side, our research and development expenses increased from $27,400,000 to $30,700,000 for the 3 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, obicel clinical trial costs and a decrease in our UK reimbursable R and D tax credit. These were partly offset by decreases in professional services and consulting fees, obicel clinical material supply costs and some other general admin fees and expenses. Our general admin expense increased from $9,300,000 to $18,200,000 for the 3 months ending March 31, 2024, compared to that same period in 2023.

Speaker 3

This increase was primarily due to salaries and other employment related costs, driven by an increase in general and administrative headcounting, supporting the overall growth of the business and primarily related to commercialization activities. Our net loss was $52,700,000 for the 3 months ending March 31, 2024, compared to $39,800,000 for the same period again in 2023. Autolist estimates that with the 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 OBL cell in relapsedrefractory adult ALL, as well as advance our pipeline development plans, which includes providing runway to data in our first pivotal study of obicel 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.

Speaker 2

Thanks, Walt. Obviously, the next key event that we're looking forward to is really the mid year conferences with ASCO and the oral presentations and the update in the posters at 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 PDUFA date in the FDA review, but also expect to have quite an involved process with the European agency. Process is a bit different than the way it's operated under the FDA.

Speaker 2

And 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 start up activities towards our next pivotal study And also excited to keep you posted on that and are looking forward to your questions.

Operator

And our first question will be coming from Kelly Shai of Jefferies. Your line is open.

Speaker 4

Congrats on the great progress made and thank you for taking my questions. The first question on the for adult ALL. Christian, do you expect ADCOM meetings based on the prior communications with both regulatory agencies in the U. S. And Europe?

Speaker 4

And I also have a follow-up. Thank you.

Speaker 2

Well, thanks a lot for joining, Kelly. The agency did not expect to hold an outcome 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.

Speaker 4

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 Doctor. Sha's team?

Speaker 4

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 tackling autoimmune and you talk about the efficacy prediction. But I'm curious given that your risk experience with BLINK Cyto, how do you think about its safety profile in autoimmune indications given the prior clinical profile show in hem oncology indications? Thank you very much. I know there's a lot of questions in one.

Speaker 2

Yes. I'll try to sort of go through that. So first of all, in terms of the types of patients that we're involving in this trial, they're very close in terms of the characteristics that you've seen in the ALONAV study tend to be younger patients initially, certainly, that have very severe forms of disease, very significant impact on their outlook of life. Obviously, organ involvement is one of the parameters that in 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 of the disease and in that sense very similar to the patients that have been treated described in the initial air lung evaluation.

Speaker 2

So that's the first thing. The second thing point was already 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 variable all patients treated, but we expect to have obviously variable follow-up in these patients. And so that's sort of what the current expectation is that is some what we're seeing at the trial, the progress we're seeing at the trial.

Speaker 2

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 diesel engagers. I think what you see in the publications that were made on sclerosis patients at the RA 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, 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.

Speaker 2

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 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 perspective with contiguous IV infusion in these patients. Not an easy way to go. And for subcu, the challenge would be we would have to be very frequent. And in that setting, certainly on the oncology side, toxicity has gone up quite substantially.

Speaker 2

So those are certainly some of the considerations there, but all early days and I think premature to I think have a I think a thorough view on how that might develop.

Speaker 4

Thank you very much.

Operator

And one moment for our next question. And our next question will come from James Hsin of Deutsche Bank. Your line is open.

Speaker 5

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

Speaker 2

Yes, we can.

Speaker 5

I apologize, Christian. My reception is a little poor. Thank you for contextualizing the manufacturing and logistics hurdle that you went through during Felix. You now have Cardinal support for the V ALL launch. Can you help us understand or quantify Cardinal's benefit to Oviso's delivery logistics and data delivery times?

Speaker 5

And then I'll have a follow-up.

Speaker 2

Yes, really good question, James. So the opportunity we have with cardinals present across the U. S. And the presence of centers that we can basically hold product in. This is an ability to ship product, but in parallel we're completing the final steps of the quality control and release process.

Speaker 2

Now in practical terms, what this allows us to do is take approximately 3 days out in the return time of the product. 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. And we basically say all the almost all of the logistics are around it 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 basically refined for about 21 days to 60 days at time of launch.

Speaker 2

So it has a very significant impact between the two measures that we took and improvements that we introduced in the process and puts us in a very competitive pocket.

Speaker 5

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, BTKs are also being looked at. My question is, do you see this autoimmune field becoming a zero sum clinical or commercial environment?

Speaker 5

Or is it just going to be more of like a medical evolution where patients possibly cycle through these regimens?

Speaker 2

Well, it's a really interesting question and it's one where we're speculating in the absence in almost a void of data we're speculating 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 a quality of outcome that no other therapy actually today has been ever 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.

Speaker 2

That goes back to the late 80s into the 90s and got the first time evaluable with the availability of ribotoximab. So that story is all that we've been looking and the field has been looking for better ways to sort of actually drive into the B cell compartment itself, most of the base in CD20 approaches. But what's the astounding aspect here in terms of the biology and the thing that the element really that Gerhard and Andreas' data was opening up his regulation that indeed the majority or maybe most of the auto antibodies appear to be produced by early forms of plasma cells, so called plasma blasts, not by mature plasma cells. And the plasma blast different from plasma cells still carry CD19 on the surface, which makes them targetable with the CD19 CAR. And with that, you do have the ability to remove the memory of the auto reactivity or auto reactivity, but you also have the ability to remove the factory of the auto reactive antibodies.

Speaker 2

And that actually gave you 2 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 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 depth of an outcome?

Speaker 2

BTKI is not very likely to be able to do that, will impact B cells, but will not highlight it not impact the plasma blasts in that way. And with that, may have an effect similar to our epoximab antibody, which has some activity in some of the indications and some others it doesn't have much of an impact. So that may not be actually 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 leap count and really get to these compartments where those particular cells reside. And we've seen that from an oncology perspective very clearly played out.

Speaker 2

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 T cells. We see the differential clearly in oncology settings quite dramatically in terms of long term outcomes, etcetera, or you can do radio really to get to these sets. So there are differences in performance.

Speaker 2

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 you would use in a more broader range if they're very safe and they're very benign in their safety profile. You could use them more broadly and in early settings and you could sort of 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 going to get a fundamental change and particularly those patients develop very severe forms of disease that where you don't have time to mess around or you have a condition you really don't 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 for a footing in state where they are not dealing with these very horrific conditions that they're frankly dealing with and they're handicapped with.

Speaker 5

Thank you.

Speaker 2

Thanks, James.

Operator

Thanks for our next question. Our next question will be coming from Aftikha Goonewardene of Truist. Your line is open.

Speaker 6

Hey, good afternoon guys and thanks for taking our questions. So Christian, I wanted to ask about the updates coming down to the FEELIX 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?

Speaker 2

It's a really good question, Asthika. Thanks for joining. One of the questions that you have when you look at a cell based therapy is that, but having 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. 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 normal cells and try to reset the bone marrow environment. But it's a very tricky trade off.

Speaker 2

Now in some instances, we've seen that actually happen, particularly if you have a product with a short persistence, so where the cells you would you would expect to actually see at least have a chance for improvement in our final comment of patients. In the case of OV cell, obviously one of the questions is, well, does that actually hold for OV cell, which we know to have long persistence? And we also see that clearly the patients that have based on our oral CAR T19 study, the patient have long term outcome also tend to have long persistent 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 marrow in basically. And also at that point, it's a real question, is that going to be beneficial or not.

Speaker 2

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 physician. So that's an element of key focus of the presentation.

Speaker 6

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 TECARIS? 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 outside that sets the bar to beat.

Speaker 2

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 were receiving a transplant after receiving OV cell. So there is the limitation of a small number. But in terms of what gives 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 have David, 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.

Speaker 2

And we're going to be actually really walking through both of those and will present analysis to both of those. So it really depends I think on the experience of the physician in the field, what happened what they have in their hands actually in terms of products. What is interesting when you look at the some of the real world experiences is it was a clear conclusion basically at ASH? Well, certainly for the competitive program, the competitive rollout should be consolidated with another therapy, which typically would be a stem cell transplant. So that was an interesting conclusion in its own right.

Speaker 2

And it will be I think it will be interesting to see our data at ASCO DHA and actually I think you get a pretty good view on the difference between the programs in that regard.

Speaker 6

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

Speaker 2

And then Both of those so the answer to that first question is it was both were recruited in the UK at different sites.

Speaker 6

Got it. Okay. And then also to meet the target recruitment of about 6 patients with data by year end, expected we should see recruitment rates 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 there is any potential for it to exceed that?

Speaker 2

Well, first of all, every time that physicians use a modality for the first time, you would want to make sure you really pick the perfect patient for that first dose. So that's true for every I think every agent who tests 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 that's where no experience. Once you see the therapy work, you see the impact, That's where you see clearly confidence built nicely and then you see actually things kind of start moving at that point. We see it in fact even with across the various of 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, customers starts to build and then the recruitment is starting to pick up that debt at that point in time.

Speaker 2

That's very normal. I think you see it pretty much across all the studies with very active substances in patients that have severe disease.

Speaker 6

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

Speaker 2

All right. Thanks, Asthika.

Operator

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

Speaker 7

open. Hi, Krish. Thanks for taking my questions. So for some important noise. I'm 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?

Speaker 2

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 length of the patient. In Europe, the difference will be that it will be the patients actually at time of inclusion with measurable disease.

Speaker 2

And then basically the fact that they tend to treat the approach in terms of the analysis, which is sort of the difference in the view where the European state that you're treating physician and made a decision and then you want to know what the outcome is, what outcome do you expect with the FDA, which is more kind of looking at from scientific perspective and actually looking at the individual patients in terms of response assessment to the very 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.

Speaker 7

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

Speaker 2

Yes. So that's a really good question. Obviously, the plasma field is sort of filling up with a number of patients at various lines of therapy. And so we're looking at that kind of very carefully and we're looking both at both myeloma related diseases. So we're taking a pretty broad look at that as to the plasma cell disease areas and are evaluating kind of where it's at there.

Speaker 2

But too early to actually give you a very clear steer of that. But I agree to you, there is a level of competition that's building up that you want to pick your battle very carefully.

Speaker 7

Okay. Thanks for taking the questions.

Speaker 2

Okay. Thank you.

Operator

And our last question will be coming from Gil Blum of Needham and Company. Gil, your line is open.

Speaker 8

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

Speaker 2

I think what you find is that the centers that actually treat adult ALD patients tend to be the highly specialized academic centers. So certainly, a high focus and aggregation of the patients in those centers, just 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.

Speaker 2

For CAR T delivery. And that's certainly true and also, obviously, matches the with a very high degree of overlap, the clinical centers that participated in the Pfenex study.

Speaker 8

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 SHET patients, what in your view would be a good leading indicator for sustained efficacy and is there even something like that? Thanks.

Speaker 2

Really good question, Gail. One of the things that's interesting about that myositis patient is that that's one of the benefits my notion, the only patient in Georges dataset that actually had lower amount of auto reactive 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 remain detectable in the patient. And that also 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.

Speaker 2

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.

Speaker 8

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

Speaker 2

Thanks a lot, Gail.

Operator

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

Speaker 2

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 also the data updates in a few weeks' time. Hope to see most of you at one of the meetings or conferences that are also alongside.

Speaker 2

And we'll keep you updated and certainly an exciting year as we're getting to the second layer here towards the hopefully approval of OV Cell in the U. S. And then our next steps in Europe and the U. K. All right.

Speaker 2

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.

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Earnings Conference Call
OptimumBank Q1 2024
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