Q1 2024 Autolus Therapeutics plc Earnings Call
Operator: Hello, ladies and gentlemen, and welcome to the Autolus Therapeutics call to discuss its first quarter 2024 financial results and business updates. 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.
Hello, Ladies and gentlemen, and welcome to the ATA list 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 Mann Sir. Please go ahead.
Olivia Manser: Thanks, Tanya. Good morning or good afternoon, everyone.
Thanks, Tania and good morning, Oleg afternoon, everyone. Thanks for joining us on today's call with me today are Dr. Christian <unk>, our CEO and Rob Dulski Asti.
Olivia Manser: 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 two, before we begin, just like to remind you, as usual, that during today's call, we will make statements related to our business that are forward-looking under federal securities laws and the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These may include, but are not limited to, statements regarding the status of clinical trials and development and or regulatory timelines for our product candidates and our expectations regarding our cash runway.
Speaker Change: So on slide two before we begin just like to remind you as usual that during today's call. We will make statements related to tell a business that are forward looking under federal securities laws on the Safe Harbor provisions of the private Securities Litigation Reform Act of 1995.
Speaker Change: These may include but are not limited to statements regarding the status of clinical trials and development and regulatory timelines for our product candidates and our expectations regarding our cash runway is.
Olivia Manser: These statements are subject to a variety of risks and uncertainties that could cause actual results to differ materially from expectations and reflect our views only as of today. We assume no obligation to update any such forward-looking statements. For a discussion of the material risks and uncertainties that could affect our actual results, please refer to the risks identified in today's press release and our SEC filings, both available on the investor section of our website.
Speaker Change: Shipments are subject to a variety of restaurant uncertainty that could cause actual results to differ materially from expectations and reflect our views only as of today.
Speaker Change: No obligation to update any such forward looking statements for a discussion of the material risks and uncertainties that could affect our actual results.
Speaker Change: Please refer to the risks identified in today's press release, and our S. T SEC filings available on the investors section of our website.
Olivia Manser: Moving on to slide three, you're going to see the agenda for today's call, which is similar to usual. So Christian's going to provide an overview of our operational highlights. Rob will then take you through the financial results, and Christian will conclude with upcoming milestones and will then hand over to questions. So with that, I will hand over to Christian.
On slide three you can see the agenda for today's call, which is similar to usual. So my question is going to provide an overview of our operational highlights Ross will then take you through the financial result, and Christian will conclude with upcoming milestones and will then hand over for questions. So with that I will hand over to Christian.
Christian Martin Itin: Well, thank you very much, Olivia, and welcome, everybody, to our first quarterly call. It's been a very successful quarter, and obviously, with a lot of activity related to OVCell, but also, obviously, quite a lot of overall corporate updates as well. I'll start out with OVCell.
Olivia: Well, thank you very much Olivia and welcome everybody to our first quarter call.
Speaker Change: It's been a very successful quarter.
Christian: And obviously with a lot of activity related to what we sell but also obviously quite a lot of overall corporate updates as well I'll start out with the with all B cell.
Christian Martin Itin: We started the year with the acceptance of our VLA filing, which obviously was an important event, and also set the target date for the PDUFA, which is expected now on November 16th. We also managed, towards the end of the quarter, to get the European filing accepted, so we now have both major jurisdictions, so filings under review. What was very important because it led to the overall preparedness of the company towards commercialization was the inspection that we had of the nucleus facility by the MHRA, which was very successful and resulted in a license for both clinical and commercial supply from the facility. What's important to understand is that this is actually a prerequisite for us to actually be able to commercially deliver the product and is a necessary license that we actually need to hold.
Christian: We started the year.
Christian: The acceptance of our BLA filing.
Christian: It was an important event that also sets the target date for the Medusa, which is expected for November 16.
Christian: We also managed by the end towards the end of the quarter to get the <unk>.
Christian: European filing acceptance.
Christian: So we have had both major jurisdictions to filings under review.
Christian: It was very important because it led to also the overall preparedness of the company towards our commercialization was the inspection that we had of the nuclear facility by the MH array that was very successful and resulted in a license for both clinical and commercial supply from the facility.
Christian: <unk>.
Christian: From the duplex facility.
Christian: What's important to understand is that this is actually a prerequisite for us to actually be able to commercially deliver product.
Christian: And that is a necessary license that we actually need to hold so getting through that first full inspection and successfully completing that obviously was a huge accomplishment and sets us up very well for the ongoing interactions in the review process, both with the FDA as well as with the European Agency.
Christian Martin Itin: 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 agencies. We also started the phase one dose confirmation study in SLE during the quarter and involved our first patient. Now, when you think about data updates, the important next updates are going to be at ASCO and at EHA, which are at the end of May and the beginning or middle of June.
Christian: We also obviously started.
Christian: Phase one dose confirmation study.
Speaker Change: Hey, Savi.
Savi: During the quarter and also involved there our first patients.
Savi: The when you think about data updates the important next updates.
Savi: Going to be at ESCO, and EAA, which are at the end of May at the beginning or middle of June.
Christian Martin Itin: 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 the stem cell transplant that patients may have received, as well as the impact of persistence on outcomes. Now, in addition, at EHA, we have two further analyses that will be presented in the form of posters. One looks at the impact of inotuzumab-based bridging regimens in the trial, and the second is on sensitive methodologies to determine the presence of CAR T cells to measure persistence, and also linking that then to outcomes in the study.
Savi: At both meetings, we have no confirmation that we have an oral presentation of updated Felix results with a particular focus on longer follow up for the study.
Speaker Change: The impact of stem cell transplant patients may have received as well as.
Speaker Change: The impact of persistence on head count.
Speaker Change: Now in additional Neha, we have two further analysis that will be presented in the form of posters, one looks at the impact of.
Speaker Change: In a Tuesday math based bridging regiments.
In the trial.
Speaker Change: The second is decorative methodology used to determine the presence of car T cells to measure persistence and obviously also linking that then to outcome.
Christian Martin Itin: So, a very significant amount of updates, a lot of accomplishments through the course of this year, which sets us up very well for the further review of the program, both by the FDA and the European Agency and also sets us on a very good trajectory for the Target-BDUFA 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 two announcements in the early February timeframe.
Speaker Change: Study.
Speaker Change: Very.
Speaker Change: Significant amount of update a lot of accomplishments through the course of this year, which sets us up very well.
Speaker Change: For further review of the program both by the FDA and European Agency at all Chris.
Speaker Change: Uh huh.
Speaker Change: On the very good trajectory for the targets that you referred to it as well in the middle of November.
Speaker Change: On the operational corporate side, obviously, there was a lot of activity leading into this year, which resulted in the early February timeframe in two announcements.
Christian Martin Itin: 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 that are part of this collaboration. For example, 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.
Speaker Change: The first one I'll C&I spent of the strategic collaboration with biotech, which obviously is an important cornerstone in terms of our relationships that we're building.
Speaker Change: A significant set of options are part of this collaboration there are options related to access.
Speaker Change: <unk> Tec will have for the lead program.
Speaker Change: To the nucleus manufacturing facility to support the launch of Air lease Khaki program Thats one area that we're looking at very closely including support on the commercial loss side. We then have.
Christian Martin Itin: That's one area that we were looking at very closely, including support on the commercial launch side. We then have, obviously, an area of activities around access to two of our pipeline programs. That's Auto 1.22 and Auto 6.NG.
Speaker Change: Obviously, an area of activities around.
Speaker Change: Access to two of our pipeline programs that order $122 six Mg.
Christian Martin Itin: 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, also on the technology side, providing access to technology we've developed, particularly for the use with in vivo cell therapy approaches, but also for certain applications, also in the context of other treatment modalities as well. So it's a very comprehensive relationship that we're building, and we're very excited about the relationship and the interactions that we're having with BioNTech. Now, in parallel to the transaction with Beltec, or just following the transaction, we also did a capital markets transaction and added additional capital.
Both of those have option option exercised high comps that are before the start of the pivotal study and each one of these programs.
Speaker Change: We then look.
Speaker Change: Yes.
Speaker Change: In addition to those key areas and also on the technology side, providing access to technology, we've developed particularly for the use with.
Speaker Change: Vivo cell therapy approaches, but also for certain applications also the context of other treatment modalities as well so it's a very comprehensive relationship that we're building.
Speaker Change: Very excited about the relationship that the interactions that we're having with Val Tex.
Speaker Change: In parallel to the transaction with Val Tex.
Speaker Change: Following the transaction. We also did a capital markets transaction that added additional capital between the two transactions, we added $600 million to our balance sheet, which obviously sets us up well to deliver on the launch of Ob cell, but also gives us the ability to expand the <unk>.
Christian Martin Itin: Between the two transactions, we added $600 million to our balance sheet, which obviously sets us up well to deliver on the launch of OBCell, but also gives us the ability to expand the footprint of education, particularly for OBCell, and that also gives us a very significant opportunity for future growth and expansion for the business. Now, we also have, as we're transitioning the company from a development stage to a commercial stage, have also actually had transitions at the level of the board that sort of actually go alongside that transformation of the company. We had, at the end of last year, Liz Leiderman and Bob Apleby join, obviously both with very strong capital markets experience and operating experience, as well as very strong commercial experience.
Footprint of applications, particularly for Ob cell.
Speaker Change: That also it gives us a very significant opportunity for future growth and.
Speaker Change: <unk> expansion for the business.
Speaker Change: We also have as we're transitioning the company from a development stage to a commercial stage at both actually.
Speaker Change: Traditions at the level of the board that sort of actually go alongside that transformation of the company.
Speaker Change: We had at the end of last year leaves Leiterman 12 April be joined obviously, both with very strong capital markets experience and operating experience as well as a very strong commercial experience.
Christian Martin Itin: And then we had, in addition, this quarter, 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 rounds out 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 become a commercial stage company and also a company that starts expanding into a broader set of indications. Now with that, moving to slide number six.
Speaker Change: And then we had an addition, this quarter join Mike Bondi Who's taken over as the chair of the company from John Johnson, and Ravi will also join who is an expert on particularly.
Speaker Change: Immunology.
Speaker Change: Autoimmune diseases and kind of at that level and that aspect in terms of the experience base overboard.
Speaker Change: Very important part of the transition that we're making sure we're sort of getting the company very well setup and forward looking to becoming a commercial stage company and also a company that starts expanding into a broader set of indications.
With that moving to the.
Christian Martin Itin: I'd like to start out with OBCell and actually answer one of the questions we're getting quite a bit which is, well, you guys have built up this manufacturing facility, a nucleus in the UK, but how do you actually ensure that it can actually deliver product, and is that even possible to do that? within the US as well as outside of the UK, And what I thought might be actually helpful is just to look back at our FELIX study and actually kind of just remember in what kind of environment we actually did the FELIX study in.
Slide number six.
Speaker Change: Well I'd like to start out with Ob salaries actually.
Speaker Change: As you wanted to or illustrates one of the questions, we're getting quite a bit which is well you guys are built out space manufacturing facility, a new place in the UK, but how do you actually ensure that we can actually deliver product and be staffed we said in the past.
Speaker Change: We hope to do that within the U S as well as outside of the U S.
Speaker Change: What I thought might be actually helpful is just to look at actually back at our Felix study actually Codexis remember on what kind of environment, we actually get the CLEC stuff yet.
Christian Martin Itin: 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 involvement of the study. Obviously, that sort of coincides with, you know, the majority of the entire 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 have been reported across the globe.
Speaker Change: And so what you see is basically a timeline that goes for 2019 to 2023 of the actual study was conducted from the middle of 2020 towards the end of 2022 2022 in terms of the enrollment of the study.
Speaker Change: I would say that so that coincides with the majority of that.
Speaker Change: Entire a key period for the COVID-19 pandemic it you could see.
Speaker Change: Blue shaded area you see all the various types of infection peaks that we've seen over time that were reported across the globe.
Christian Martin Itin: 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, you know, being based in the U.K. for manufacturing makes us obviously highly reliant on international flights actually taking place and the ability to really reach every site in the U.S. as well as elsewhere from our manufacturing site.
Speaker Change: What you also see the Green line.
Speaker Change: Actually the number of international flights.
That basically have gone in.
Speaker Change: Out of the U S. During that entire period. This is data from the U S government.
Speaker Change: And as you can see this was a very challenging period from a logistics perspective, because clearly you have huge variability and the number of available fly internationally and clearly.
Speaker Change: Being based in the UK for manufacturing. It makes is obviously highly reliant on international flights actually taking place and the ability to really reach every size of the U S as well as elsewhere from our manufacturing site.
Christian Martin Itin: Now, what was quite remarkable is when you then actually look at the small fever curve in the middle, this is actually the actual range of delivery time over that entire period for the phase 2 trial, 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 plotted on that particular jagged line. But what it means is that despite all the variability, the challenges with infection, 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, actually had virtually no impact on our range of delivery times, and we were able to deliver on time for every single product.
Speaker Change: But what's quite remarkable is when you actually look on the <unk>.
Speaker Change: Small fever curve in the middle of this is actually the actual base a deliberate time over that entire period for the phase III.
Speaker Change: Phase II conduct and Youll see that through the ranges at the low end. It's 15 days 30 days on the upper end of DC literally every one of these products actually.
Speaker Change: I applauded on that particular, jakafi, but what it means is that despite all the variability the challenges with infections. The shutdowns of clinical factors to shutdown of flights and so forth. All the limitations. We have is that in terms of access moving people at all had actually virtually no impact from a range of deliberate and in fact, we were able to do.
Speaker Change: Labor all time for every single product.
Christian Martin Itin: And one of the things that we've 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.
Speaker Change: And one of the things that we obviously learned that many of you do know.
Speaker Change: That many of you are traveling internationally quite a bit as one of the things that we obviously have in our favor.
Speaker Change: International flights have priority, that's where the airlines make most of their money.
Speaker Change: Those slides go on time and that actually has been a huge asset to the pandemic and actually gave us.
Christian Martin Itin: 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 going into the pandemic, but that's the reality that we have been able to see. But it also obviously gives us a lot of confidence that the systems that we have put in place have been pressure tested in an extreme way and have actually delivered throughout this challenging period. Now, if we go to the next slide, slide seven.
Speaker Change: Not only a good ability to serve but natural advantage in terms of the robustness and stability of our logistics.
Speaker Change: This is not what you would've expected base going into the pandemic.
Speaker Change: 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.
Speaker Change: Now if we go to the next slide slide seven.
Christian Martin Itin: Just as a brief reminder of the FELIX study and what we're actually looking to do with the study. And I think the first thing I want to point out is that this is a study that actually included all risk categories of patients that have relapsed refractory disease, acute lymphoblastic leukemia. And what we have here is obviously the largest group, which is cohort A, which are patients that have disease burdens that range somewhere between 5% of cells in the marrow all the way up to close to 100%.
Speaker Change: Just as a brief reminder of the Felix study on what we are actually we are looking to do with the study and I think the first thing I want to point out is that.
Speaker Change: This is a study that actually included all risk categories of patients that have relapsed refractory disease acute lymphoblastic.
Christian Martin Itin: And what we have in there is obviously the largest group, which is the cohort K, which are patients that have disease burden that range somewhere between eight 5%.
Christian Martin Itin: Sales in the marrow all the way up to close to 100%. So we have this entire bucket of very high levels.
Christian Martin Itin: So we have this entire bucket of very high levels of... We also have in the middle with the core patients that have very low levels of disease, so-called minimal residual disease, disease levels you can pick up by flow analysis by TCR or by NGS. 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 core 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 relapse.
Speaker Change: Also of disease with <unk>.
Also have in the middle with the cohort the patients that have very low levels.
Speaker Change: The so called minimal residual disease.
Speaker Change: These levels you can pick up by flow analysis by TCR or Brian Gx sequencing.
Speaker Change: But it's important because it's basically just actually catching the relax a little bit earlier before the standard methodology starts to pick it up.
Speaker Change: And then the last.
Speaker Change: Group of patients in cohort C, where patients did actually didn't have a relapse in the marrow, which is normally the place where you find the disease, where you typically also have the relapses, but these are patients that have isolated extra medullary disease, which is basically the disease. It almost had a gain of function could actually escaped the matter settlement and other tissue.
Christian Martin Itin: But these are patients that have isolated extramedullary disease, which is basically the disease that almost gained function and 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 morph to a certain extent and actually gain this ability to survive and succeed in a very different environment.
Speaker Change: <unk>.
Speaker Change: These are particularly difficult to treat patients.
Speaker Change: Because obviously the disease has managed to actually morph to certain extent actually gained its ability to survive and succeed in a very different environment.
Christian Martin Itin: So, having all of these different groups is actually important when you think about it from a treating physician's perspective because what it basically gives you is the ability to see the patients that will actually walk into your practice, the patients you care for; you'll see them represented in the study. And that doesn't often happen in clinical studies. Often, clinical studies are quite selective. They're quite protected to make sure the outcome is as maximal as possible. And often, with that, you actually do not have a representation of the real world.
Speaker Change: 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 work in your practice to your practice to patients you care for Youll see them represented in the stock.
Speaker Change: That doesn't often happen eight clinical studies clinical studies are quite selective there are quite protected to make sure that the outcome is as maximo as possible.
Speaker Change: And with that you actually do not have a representation of the real world. What we have with this study as a remarkable representation of the real world setting up the experience that the physicians are actually having this is also why the study resonates as well as it does now.
Christian Martin Itin: What we have with this study is a remarkable representation of the real world setting and the experience that 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 previous 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.
Speaker Change: A few things just to point that tie to the prior part of the conversation on supply and logistics at deliberate we actually managed to get 83% of all of the patients across the entirety of the study.
Christian Martin Itin: 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 patient, the selection of the patient, and every aspect. So it just tells you something about robustness and delivery alongside. So with that, moving to slide number eight, what we're looking at here is event-free survival across the entirety of the experience.
Speaker Change: Treated with the product.
Speaker Change: 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 have every level of control of the patients the selection of the patients at every aspect on logistics.
Speaker Change: It tells you something about robustness and delivery.
Speaker Change: Alongside this study.
Christian Martin Itin: And as you can see, we see a stabilization of that curve. It looks like the curve starts to go horizontal after a certain period of time, indicative that indeed we may have a group of patients that actually have a chance for long-term outcomes. Now, this is the snapshot, the data snapshot that underpins the ASH presentation. This is where this slide is.
So with that moving to slide number eight what we're looking at here is C.
Speaker Change: Event free survival across the entirety of the experience and as you can see it.
Speaker Change: Is that we see a stabilization of that curve it looks like the curve starts to go horizontal.
Speaker Change: 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.
Speaker Change: This is the snapshot of the data snapshot that underpins the ash presentation. This is where this slide it's slow.
Christian Martin Itin: I would say the next update that we're going to have at ASCO EHA will be somewhere between five and six months of 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 are actually starting to see stabilization. And so we believe the update in the 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 at later time points as well.
Speaker Change: The next update that we're going to have at Astro DHA will be somewhere between five to six 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 the stabilization and so we believe the updates middle of this year will be important because it will give us a very good understanding.
Speaker Change: We're very happy we have this robustness of the data also either later time points as well.
Christian Martin Itin: 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 had prior to lymphodepletion actually was giving you a pretty good predictor of what to expect these patients would 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, And as you can see on the blue line, these are patients that have less than 5% tumor burden.
Speaker Change: Now as you May remember one of the things we looked at and we have pointed out.
Speaker Change: Several types of conversations that presentation is that we did find that the level of disease burden to patients have prior to lift for the patient.
Speaker Change: Actually what's giving you a pretty good predictor of what to expect.
Speaker Change: These patients will experience on the one hand from an efficacy perspective, but also from a safety perspective.
Speaker Change: Start with the efficacy side and again, we're now looking at these events free survival curves, but we look at it by the leukemic burden prior to lift to the patient before we actually do the intervention and as you can see on the Blue line. These are patients that have less than 5% to book as you can see that these patients do exceptionally well so.
Christian Martin Itin: And you can see that these patients do exceptionally well. So, low tumor burden not only gives us a very high overall response rate, but it also gives us, obviously, a very attractive long-term outcome in that patient. Below that, in the green curve, we see 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.
Speaker Change: Low tumor burden not only does give us a very high overall.
Speaker Change: Pulse rate, but it also gives us obviously a very attractive.
Speaker Change: Long term outcome in that patient group.
Speaker Change: Below that in the green curve receipt of patients that are in the range.
Speaker Change: Ill go back five to up to 75% to avert such a wide range of two of our make these patients but it is not going to the very extreme off.
Christian Martin Itin: But as you can see, these patients still do remarkably well, and you see a stabilization also in the green curve, which is very encouraging. Where you see that patients struggle more is in that group in the orange curve, where you have patients that have more than 75% disease burden of lymphococcus lesions, which are clearly the ones that could not be controlled by bridging therapy. They're, you know, have almost a, by definition, refractory nature to disease.
Speaker Change: After the FERC made tomorrow, but as you can see these patients still do remarkably well, let you see a stabilization US also in the green curve, which is very encouraging.
Speaker Change: Where do you see that the patient struggled more is in that group and the Orange curve, where you have patients that have more than 75% disease ferret that liquid depletion, which are clearly the ones that could not be controlled by bridging therapy.
Speaker Change: Almost.
By definition, the refractory nature of the disease.
Christian Martin Itin: And you do see that these patients all 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 BlinkSideDoor. So it gives you a very good sense of the actual power of therapy even in the worst cases 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 outcomes.
Speaker Change: And you do see that these patients all of these stock a little more than the.
Speaker Change: The other groups of patients now the outcome here is still substantially different to what you would have seen.
Speaker Change: In overall picture for ethane Tycho. So it gives you that gives you a very good sense of terms of the actual power of therapy, even in <unk> patients.
Speaker Change: We have been treating but it also tells you that obviously finding ways to actually reduce disease burden on these patients before you treat them actually has a very significant impact on that outcome.
Christian Martin Itin: Now, it's not only on the side of efficacy, but also, when you look at the next slide, slide 10, there's also a difference that we see in safety. 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 or the high- 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.
Speaker Change: 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.
Speaker Change: The safety signals.
Speaker Change: <unk> received the totality of the data across all patients that you see that but standing out is at the dark blue areas, which are obviously very small and these are the high grade cytokine release syndrome patients or the high grade <unk> patients. So the levels are low or 2%.
Speaker Change: <unk>, 7%, which is substantially below any of the other T cell engaging or car T therapies in this space. So again, a very attractive overall profile, but when we then look at the impact of disease burden, we can see that the patients that have actually less than 5% disease burden that lift for depletion both.
Christian Martin Itin: So again, a very attractive overall profile. But when we then look at the impact of disease burden, we can see that the patients that have actually less than 5% disease burden have lymphodepletion, both for CRS in the middle or for ICANNs on the right-hand side. None of these patients have high-grade events, such as immunological toxicity events.
Speaker Change: For Crs at the middle or pro <unk> on the right hand side, none of these patients had a high grade.
Speaker Change: I think the immunological toxicity event no high grade ICANN no high grade.
Christian Martin Itin: No high-grade ICANNs; no high-grade CRSs. If you then look at the middle group, the middle group still does remarkably well. It has actually, now you see some of the patients that actually do experience higher-grade cytokine relief syndrome and ICANN, but it's still at a relatively low level. But what you do see is you do see somewhat of an increase, actually to a level which is, you know, similar maybe to what it would look like overall inside the population would look like in terms of CLS and ICANN if you're above 75% tumor burden after bridging therapy at the time.
Speaker Change: Crs.
Speaker Change: If you then look at the Middle group the Middle group, that's still remarkably well. It has actually now you see some of the patients that actually do experience high grade cytokine release syndrome.
Speaker Change: And I can't but it's still at a relatively low level, but what you do see as you do see somewhat of an increase actually to a level, which is similar maybe to what an overall fleet size of the population would look like.
Speaker Change: In terms of Crs and I can't if youre above 75% tumor burden after bridging therapy at the at the time of limitation.
Christian Martin Itin: 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. 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 managed 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 patient.
Speaker Change: So also there not only do you see differences in the.
Speaker Change: Outcome from advanced free survival perspective, but we also see differences in.
Speaker Change: The risks.
Speaker Change: Risk of safety signals.
Speaker Change: 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 in feature that we'll see actually worked on.
Speaker Change: 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.
Christian Martin Itin: Now, in terms of commercial launch readiness, moving to slide number 12, obviously, we have been, I talked 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 is quite a wide range of activities. You see on the left-hand side basically the four key areas that we're working with in terms of preparation, and how we manage the regions within the U.S. It's basically a regional view.
Speaker Change: Now in terms of commercial launch readiness move into slide number 12, obviously, we have been.
Speaker Change: I talked about briefly about the trajectory here from a regulatory milestone perspective.
Speaker Change: Honestly, we are a full suite of.
Speaker Change: Making sure we're adequately prepare for launch there.
Speaker Change: There are quite a wide range of activities you would see the left hand side basically the four key.
Speaker Change: Areas that were sort of working with.
Speaker Change: It was a preparation how we manage the regions within the U S. It's basically a regional view.
Christian Martin Itin: That's kind of the way we sort of 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. It's a very focused amount of activity that's going on. A lot of effort, a lot of direct engagement, and also, of course, a lot of work and support in the context of the onboarding of the center.
Speaker Change: It's kind of the way it was sort of also are overlaying our organization across dose when we look in terms of the areas that we're particularly focused on first of all obviously in terms of communication creating awareness.
Speaker Change: And at supporting frankly every activity, whether it's with engagement with centers with payers et cetera is through the medical affairs team so very.
Speaker Change: Focus denied if activity thats going on a lot of airports a lot of direct engagements.
Speaker Change: And also of course, a lot of work in supporting the context of the Onboarding of centers. So that's very significant amount of.
Christian Martin Itin: So that's a very significant amount of activities. A lot of that will be quite visible because it will result in presence at conferences, et cetera, and presentations and publications. There's obviously a very significant work stream around demonstrating the value of the therapy, so there's a lot of activity going on on that side.
Speaker Change: Activities, a lot of that will be quite visible because it will result in presence at conferences et cetera, and presentations and publications.
Speaker Change: There is obviously, a very significant work stream around demonstrating the value of the therapy. So there is a lot of activity going on on that side and we're looking at a number of parameters importance here. When you think about value there is the obvious.
Christian Martin Itin: And we're looking at, obviously, a number of parameters. Important here when you think about value are the obvious ones: how much long-term benefit can you induce? You know, what is sort of the overall safety profile, et cetera.
Speaker Change: How much long term benefit and you induce.
Speaker Change: What is sort of the overall safety profile et cetera, but there is also much more nuanced elements there.
Christian Martin Itin: But there are also much more nuanced elements there. The fact that we have such a reduction in high-grade CRS and in high-grade ICANNs and substantially shorter events when we have high-grade events, that has a huge impact on resource utilization at hospitals. It has a huge impact on cost and 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 that lives in the patient, there is also more predictability. There's more plannable.
Speaker Change: The fact that we have.
Speaker Change: Such a reduction in high grade Crs and high grade ICANN and substantially shorter events. When we have higher grade events that has a huge impact on the resource utilization hospitals as a huge impact on cost of patient management.
Speaker Change: And when you think also about the ability to sort of actually have an understanding of what to expect based on the disease.
Speaker Change: And that led to the patient also more predictability there is more plentiful.
Christian Martin Itin: These treatments are more plannable, and there's a way to anticipate what's going to happen to the patient and what type of support you need to actually prepare for that. That is very important, because all of those are important cost drivers. That's value.
Speaker Change: Treatments are more plentiful and there is a way to anticipate what's going to happen to the patients at what type of support do you need to actually prepare for that is very important because all of those are important cost drivers thats value.
Christian Martin Itin: But those are really important aspects that we have to not only display from a clinical perspective but 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, with the relevance of those conversations and also a key element in terms of preparing the market that we're looking to enter. The onboarding of the centers is probably the single biggest work stream that we have, which requires us also to make sure that the product can be appropriately handled, whether it is from a cell collection, handling perspective, delivery perspective, safety management, and long-term outcome management. There's a lot of training involved.
Speaker Change: Those are really important aspects that we have to not only the slide 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 wrong in that segment I think we're relevant ads on those conversations and also a key element in term.
Speaker Change: Preparing the market that.
Speaker Change: That we're looking to get into.
Speaker Change: The onboarding of our centers is probably the single biggest.
Speaker Change: Work stream that we have.
Speaker Change: Which requires us also to make sure that the product can be appropriately handle.
Speaker Change: Whether it's from a b cell collection.
Speaker Change: Handling perspective delivery perspective safety management long term outcome management.
Christian Martin Itin: There is a lot of interaction and support involved, and all of that actually has a corollary in terms of systems that we are holding on our side in support of the centers and are managed through a center coordinator that really is the triaging point to support the centers in whatever the need is and the support required. So, getting the centers onboarded, and accredited, is absolutely crucial. This is a very involved activity, also involved from the center.
Speaker Change: There's a lot of training involved there is a lot of.
Speaker Change: Actually that support involved.
Speaker Change: And all of that actually has a corollary in terms of systems that we are holding on our site in support of the centers.
Speaker Change: At our managed to a center coordinated that really these are triaging the triage a point to support percentages in whatever the new dates at the support required.
Speaker Change: So getting that.
Speaker Change: <unk> on boarded a credit it's absolutely crucial this is a very involved activity also in both trauma center. It takes a commitment from the center. It takes time and we're very pleased to see the residents that the product has the interest and willingness of the centers to onboard product.
Christian Martin Itin: It takes commitment from the center, it takes time, and we're very pleased to see the resonance that the product has and the interest and willingness of the centers to onboard products. So that preparation is all ongoing and very well on track. And then we have already talked about supply chain logistics.
Speaker Change: So that's.
Speaker Change: That preparation is all ongoing and very well on track and that we already talked about supply chain logistics. There's obviously a lot of implementation of testing as well that with you.
Christian Martin Itin: There's obviously a lot of implementation of testing as well that we do. What you also have seen is that we have, or as I mentioned before, closed the transaction with Cardinal Health. That's an important transaction for us because it actually complements some of the backbone infrastructure pieces that we want to have in place and need to have in place. It also gives us an element of logistics which allows us to actually ship products during the release process.
Speaker Change: You also have seen is that we have.
Speaker Change: I mentioned before.
Speaker Change: Close the transaction with Carnival health, that's an important transaction for us because it actually complements some of the backbone.
Speaker Change: Infrastructure pieces that we want to have in place that need to have in place. It also gives us an element of our logistics, which allows us to actually.
Speaker Change: Ship products during the release process and with that also take some.
Christian Martin Itin: And with that, also take some of the time out of the vein 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.
Speaker Change: Some of the time out of the bank to delivery time.
Speaker Change: Which is important.
Speaker Change: From a patient perspective, and physician perspective as well.
Speaker Change: So this is kind of the preparation work that we're doing obviously very engaged very involved fantastic team on the graph.
Christian Martin Itin: And we're seeing a very nice resonance and good dynamic. Moving to the next slide and just briefly talking about the commercial manufacturing facility, the Nucleus. So the image in the middle was actually taken a week ago. It was one of the few sunny days we had in the last few weeks in the UK.
Speaker Change: <unk> very experienced team.
Speaker Change: And we're seeing a very nice residents that good dynamics there.
Speaker Change: Moving to the next slide just briefly talk about the commercial manufacturing facility to nuclear.
You mentioned that in the middle actually I took a.
Speaker Change: A week ago. It was one of the few solid days, we had the last few weeks in the U K so what's the opportunity.
Christian Martin Itin: 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 grant-breaking to MHRA approval within about 20,000 square feet. 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.
Speaker Change: So this is a.
Speaker Change: True industrial setup.
Speaker Change: For the production of cell therapy products to 70000 square foot facility.
Speaker Change: And facilities that we really ramped from groundbreaking to NHRA approval.
Speaker Change: Within about 27 months. So this is a remarkable.
Speaker Change: Delivery actually office facility with very different approaches that we took in terms of the design.
Speaker Change: Set up a facility, but also taking into operation and validation of the facility.
Christian Martin Itin: We did it in a very different way than, I think, 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 starting point with a good level of capacity to support a future launch.
Speaker Change: And a very different mode than I think.
Speaker Change: Mostly most of our colleagues in the industry would do but it allowed us to actually massively reduce the time.
Speaker Change: To get a fully functioning fully validated inspected facility.
Speaker Change: And with that obviously put us in a very strong position to be in.
Speaker Change: Very good.
Speaker Change: Very good starting point with good level of capacity.
Speaker Change: Support a future launch.
Christian Martin Itin: 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 ovacell family of products, there's ovacell itself with opportunities both in human oncology as well as in autoimmune disease. And then there are obviously the two daughters of ovacell, Auto-122 and Auto-8, that allow us to actually give us sort of a next layer into the respective disease areas with a dual targeting approach.
With that.
Speaker Change: Just moving to slide 15, this slide you've seen before really looking at sort of the opportunities in terms of the <unk> family of products with <unk> cel itself with opportunities both in immuno oncology as well as an autoimmune disease and then there are obviously the two daughters of all B cell Ottawa 22 at <unk> eight.
Speaker Change: <unk>.
Speaker Change: That allows us to actually give us sort of a next layer into the respective disease areas.
Speaker Change: With a dual targeting approach.
Speaker Change: If we move to.
Christian Martin Itin: 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. It's obviously a hugely active space, there's a lot of communication happening, and every time there is a paper coming out, I tend to get, and we tend to get, obviously, things from some of you about how to interpret the data and how to think about it.
Speaker Change: Slide 16, maybe just a few words.
Speaker Change: Kind of the dynamics that we're seeing.
Speaker Change: And in the space, particularly when it comes to autoimmune disease.
Speaker Change: Usually active space a lot of communication is happening.
Speaker Change: Every time, there was a paper coming out.
Speaker Change: I tend to get as we tend to get paid.
Speaker Change: <unk> from some of you in.
Speaker Change: Two how to interpret the data and how do you think about it.
Christian Martin Itin: 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, and certainly no long-term outcomes in these... So very impressive outcomes, but obviously still very low patient numbers and very limited observation.
Speaker Change: In general I think what's important to keep in mind is that.
Speaker Change: Most all data points that we look at it today.
Speaker Change: Our base of compassionate use not clinical trials.
Speaker Change: While the data is very impressive and quite compelling given that we've seen long term outcomes in patients.
Speaker Change: Frankly, it was not possible to actually get reversals disease, and certainly no long term. Many of these patients so very impressive outcomes, but obviously still very low patient numbers and very limited observation.
Christian Martin Itin: Most of what we know is from a Kymriah-like product, so this has a receptor that's identical to the Kymriah CAR with a modified manufacturing process which is somewhat closer to the way we manufacture it, but that product is really what all, almost all the information is based on, particularly when we look at longer-term observations. Of all the patients that have been treated, be it in SLE, in myositis, in scleroderma, et cetera, there's one patient so far that's been reported to actually have relapsed. That relapse happened after 18 months.
Speaker Change: Most of what we know is from a <unk> like product. So this is a it has a receptor.
Speaker Change: Identical to that can buy a car.
Speaker Change: With a modified manufacturing process, which is somewhat closer to the way we manufactured.
Speaker Change: But that product is really what all almost all of the information is based on particular loans when we looked at longer term observation.
Speaker Change: Okay.
Speaker Change: Although all the patients that were treated.
Speaker Change: Necessarily.
Speaker Change: In.
Scientists in scleroderma et cetera. This one patient so far that's been reported to actually have relapsed relapse happened. After 18 months patients is still a lot better than obviously what are the patient boss, but there's clearly recurrence of antibodies that was visible in that patient.
Christian Martin Itin: The patient is still a lot better than where the patient was, but there's clearly recurrence of antibodies that were visible in that patient. And what we're starting to see is that we're starting to learn where maybe the limitations are of some of these approaches, where the opportunities are, but we're still in a phase where there's a lot of learning going on. I think with that, I think it's important to, you know, keep, basically look at the data with certainly a grain of salt and remind ourselves that it is still a very limited amount of data, very exciting, but limited amount of data.
Speaker Change: And what we're starting to see is obviously that we're starting to learn where maybe the limitations or some of these approaches where the opportunities are but we're still in a phase where there is a lot of learning going on.
Speaker Change: With that I think it's important to.
Speaker Change: Keith.
Speaker Change: Basically look at the data with certainly a grain of salt.
Speaker Change: And remind ourselves, but it is still very limited United State are very exciting with limited amount of data. We also have seen now in addition to these initial work that was done at the University of Arizona.
Christian Martin Itin: We've also seen, in addition to this initial work that was done at the University of Erlangen, first work with Linatumumab, also part in Erlangen, part in Munich, to explore the use in RA 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 Sheth gave a recent interview, which was actually published by one of your colleagues, Seb Cantor, and was actually asked about the data, which were obviously taken also at the University of Erlangen with the rheumatoid arthritis patient.
Speaker Change: We've seen that first work with two of the map also partnered early part in Munich to explore the use in <unk> patients have been single.
Speaker Change: Sclerosis patients.
Speaker Change: Indicating that there was an ability to induce a an.
Speaker Change: <unk> in these patients.
Speaker Change: Without actually selling a reset of the b cell compartment.
Speaker Change: A lack of clarity whether these activities would actually be sustainable.
Speaker Change: What was interesting is that Jeff gave.
Speaker Change: Gave a recent interview.
Speaker Change: And which was actually published by one of your colleagues at Cantor.
Speaker Change: And was actually asked about the data, which obviously was taken also at university of airline with rheumatoid arthritis.
Christian Martin Itin: And he indicated clearly that he would see, and was obviously seeing good deep responses, which seemed to be meaningful, giving meaningful clinical outcomes. But at the same time, obviously, there is a lot to be learned, and it's unclear whether there would be an ability to see longer-term outcomes in this approach. So there's a lot of movement.
George: George a private patients.
Speaker Change: He indicated clearly that we would see platelets, obviously seeing good good deep responses, which seemed to be meaningful get a meaningful clinical outcomes, but at the same time. Obviously there is a lot to be learned and it's unclear whether there would be an ability to see longer term outcomes. In these in this approach. So it's a.
Christian Martin Itin: And one of the things that certainly will be interesting to see as we're sort of thinking going forward is how many shots do we actually have in an autoimmune patient with a very active immune system to actually re-dose 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 more variability introduced in outcomes.
Speaker Change: Lot of movement and one of the things that certainly will be interesting to see as we're sort of thinking going forward is.
Speaker Change: How many shops do we actually have an autoimmune patient with a very active immune system to actually re dose a patient.
Speaker Change: And that's certainly an area, where I think we start to learn I think that's more mechanism.
Speaker Change: It is highly likely going to be one of the areas, where it is going to be probably more variability introduced and outcomes.
Christian Martin Itin: Now, on the next slide, what I'd like to do is just briefly sort of show the relationship between OBCell and the product that was used at the University of Air London for their work. I think it's important, as I pointed out, that the product is very similar to Kumraya, 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 to form that product in PEATS.
Speaker Change: On the next slide where I would like to do is just briefly.
Speaker Change: So the show kind of the relationship between <unk> and the product that was used at the University of Arizona for their work and I think it's important as I pointed out is that the.
Speaker Change: The product is very similar to <unk>.
And it was designed it actually used initially for the treatment of pediatric AML patients. So there's actually quite a good set of data available.
Christian Martin Itin: And not surprisingly, the data was very similar to the data we knew from Kymriah's original trials. So, high levels of activity, long persistence, two to three years of persistence in these patients, and you know, giving you the 85%, give or take rate of molecular complete remission as was seen with Kymriah. You see the reference on the right hand side, the Iliana study, which is the summary of the data from the original study with Kymriah.
Speaker Change: A form that product e&ps.
Speaker Change: And not surprisingly.
Speaker Change: The data.
Speaker Change: Was very similar to the data we knew from <unk> original trials. So the high level of activity long persistence two to three years persistence in these patients and giving you in the 85% give or take rate of molecular complete remissions as foreseen with Ryan if you see the reference on the right hand, lower side to be honest study, which.
Speaker Change: The summary of the data from the original study with <unk>. The initial data from the pediatric experience with the airline car actually was published at presented at the Ash meeting in 2021, and it's likely going to be a publication at some point with the full dataset.
Christian Martin Itin: The initial data from the pediatric experience with the airline car actually was published at or presented at the ASH meeting in 2021, and it's likely going to be a publication at some point with the fuller data. 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.
Now I would like to 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 CD 19.
Speaker Change: Rather than having the high affinity character, which is the fast on rate with a very slow off rate as you can see.
In the Blue box called FMC, 63, which is the binder used in that particular product.
Christian Martin Itin: The Cat19 binder in green, that's actually the property that we see for our product, for OBCella, which you can see is that we have the same on rate, which gives you the same specificity, but about 100-fold faster off rate.
Speaker Change: 19, Binder and Green that's actually the property that we see for our product for <unk>.
Speaker Change: You can see is that we have the same on rate, which gives you the same specificity, but about a 100 fold faster off rate with that obviously, having that differentiation that you've heard us talk about it quite a bit which gives us the difference in it.
Christian Martin Itin: 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 a 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 can also delineate from the comparison between our experience with OBCella in the light blue columns and the dark blue columns experience with Kymriah and Yeliana. Now...
Speaker Change: In terms of toxicity and much.
Speaker Change: A significant reduction.
Speaker Change: In Hematological toxicity, but also overall and increased level of activity.
Speaker Change: Our task.
Speaker Change: Overall, we see very similar properties of the product.
Speaker Change: From an activity perspective, we see differences in toxicity is you could also to alleviate from the comparison between our experience with Ob cell in the light blue.
Speaker Change: Columns and the dark blue column, the experience with <unk> at the Eliana study now.
Christian Martin Itin: The remarkable thing is that, obviously, we have this similarity, we have a better safety profile, and with that, we believe we're in a very attractive position to 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 autoimmune patients. In fact, it went from two to three years in pediatric ALL to about three months, maximally six months, in autoimmune patients.
Speaker Change: No.
Speaker Change: The remarkable thing is obviously, we have the similarity and 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.
Speaker Change: One of the things that I would like to highlight is.
Speaker Change: This long persisting products in pediatric AML had a much shorter.
Speaker Change: <unk>.
Speaker Change: The autoimmune patients in fact, it went from two to three years in pediatric ALLL to about three months maximally six months in autoimmune patients. This is not a difference based on amount of target available are target cells available, which some folks were thinking about it that's not what the difference is because of that long persistence is all.
Christian Martin Itin: This is not a difference based on the 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, so patients with extremely low levels of target cells. You still get two to three years of persistence.
Speaker Change: So true if you have <unk> positive patients or patients with extreme low levels of target sales you still get two to three years of persistence.
Christian Martin Itin: Now, the difference between those two settings is predominantly the ability of the immune system to mount a response. And we actually assume that the key driver for the difference in persistence is, in fact, the ability of the patients with autoimmune disease, of their immune system, to recognize the cells eventually and clear them. And that also was corroborated by the myositis patients I mentioned before. That was actually an attempt to actually retreat with CD19 CAR, and in fact, the cells were cleared very rapidly, consistent with the fact that, indeed, the patients actually had built up over time an immunological reaction and rejection.
Speaker Change: Leukemia.
Speaker Change: The difference between those two settings is predominantly.
Speaker Change: The ability of immune system to match our response.
Speaker Change: And we actually assume that the key driver for the difference in persistence is in fact, the different the ability of the.
Speaker Change: Patients with autoimmune disease of their immune system to recognize itself eventually at clear them.
Speaker Change: That also was corroborated by the MA side.
Speaker Change: Myositis patients that makes it before.
Speaker Change: That was actually I was an attempt to actually retreat with CD 19 car and in fact, the sales were clear very rapidly.
Speaker Change: With the fact that indeed, the patient actually has built up over time of immunological reaction.
Christian Martin Itin: Now, quite similarly, if you think about the delivery of products and antibodies, there's also a pretty significant risk there that you might actually induce some immunogenicity, and that certainly has been seen with a number of products, also T cell engagement. 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 re-dose, which certainly for some approaches. All right, so with that, I'm going to slide 18.
Speaker Change: The rejection.
Speaker Change: Now quite similarly, if you think about to deliver product. Some antibodies is also pretty significant risk there that you might actually induce as well some immunogenicity and that certainly has been seen with a number of product closer to sell engages 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 overtime.
Speaker Change: Or the ability to re dose, which certainly for some approach it seems more important than others.
Christian Martin Itin: The phase one study is obviously open for involvement. We had our first center open during the course of Q1. We have now two 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 translating the pediatric ALL dose into 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.
Speaker Change: Alright, so with that going to slide 18.
Speaker Change: Phase one study obviously is opened for enrollment we had our first centers center opened.
Speaker Change: In the.
Speaker Change: During the course of Q1, we are now.
Speaker Change: Two patients enrolled and we're well on track for the initial data that we have guided you to towards the end of the year.
Speaker Change: Just to remind you. This is a dose confirmation study were basically translate the pediatric ALLL dose in a fixed dose for adults, which is a 50 million cell dose.
Speaker Change: We don't need to do a DLT period, so any of those types of restrictions within vehicle that we can actually enroll.
Speaker Change: Old patients as they come without limitations of that nature.
Christian Martin Itin: All right, so with that, just 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 in the AutoAid program, the Auto6NG program, and obviously both of those. We're looking forward to additional data, and we're also enrolling additional patients with Auto122 as well. All right, so with that, I'd actually like to transition to the financial results, and I'll hand over to Rob.
Speaker Change: Alright, so with that just a.
Speaker Change: Fast Alaska sort of view in terms of the pipeline a bit broader view.
Speaker Change: Obviously, we're in active.
Speaker Change: Digital programs certainly there is more activity on the auto program.
Speaker Change: The <unk> program.
Speaker Change: And I would say both of those we are looking forward for additional data and we're also enrolling additional patients with <unk> 22 as well.
Speaker Change: Alright, so with that I'd like to actually transition we go through financial results.
Robert F. Dolski: Hand over to Rob.
Robert F. Dolski: Thanks, Christian. And good morning or good afternoon to everyone.
Robert F. Dolski: Thanks, Christian and good morning, or good afternoon to everyone.
Robert F. Dolski: 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 12B25 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 on that. As Christian highlighted in February, we completed a license and option agreement with BioNTech, as well as the underwritten registered direct equity finance, that in part enables the company to accelerate its expansion of OBCell into autoimmune diseases.
Robert F. Dolski: Pleasure to review our financial results for the first quarter 2024.
Robert F. Dolski: And I will be on slide 22 of the presentation.
Robert F. Dolski: As you saw from our press release and form <unk> 25 that we filed with the SEC earlier. This week, we delayed this call by a few days and I would like to provide some additional color around that decision.
Robert F. Dolski: 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 evaluation, 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 2012-B-25 gave us a five-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.
As Christian highlighted in February we completed a license and option agreement with biotech.
As well as the underwritten registered direct equity financing that in part enables the company to accelerate our expansion of Ob sounds autoimmune diseases.
Robert F. Dolski: The biotech deal was a complex transaction.
Robert F. Dolski: As noted a number of different components to it.
Robert F. Dolski: We required additional time to evaluate certain technical accounting matters related to the biotech deal as well as the projected impact of the autoimmune opportunity on our existing Blackstone liability valuation.
Robert F. Dolski: Each of which impacted our financial statements for the quarter.
Robert F. Dolski: 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.
Robert F. Dolski: The 420, <unk> 25 gave us a five day extension on the 10-Q filing which would otherwise have been due this past Wednesday.
Robert F. Dolski: We plan to file the Form 10-Q later today.
Robert F. Dolski: So now, we summarize our results for the quarter. Cash and Cash Equivalents at March 31st. 2024 totaled $758.5 million, as compared to $239.6 million at December 31st, 2023. Our total operating loss for the three months ended March 31st, 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 three quarters ended March 31, 2024, compared to that same period in 2016.
Robert F. Dolski: So to summarize our results for the quarter cash and cash equivalents at March 31.
2024 totaled $758 million 50.
Robert F. Dolski: $58 5 million.
Robert F. Dolski: As compared to $239 6 million at December 31.
Robert F. Dolski: This change was primarily due to increases in operating costs related to our new commercial manufacturing facility, employee salaries and related costs, Obstetrics and Gynecology clinical trial costs, and a decrease in our UK reimbursable R&D tax credit. These were partly offset by decreases in professional services and consulting fees.
Robert F. Dolski: 2023.
Robert F. Dolski: Our total operating loss for the three months ended March 31 2024.
Robert F. Dolski: Was $38 8 million as compared to $39 1 million for the same period in 2023.
Robert F. Dolski: On the operating expense side, our research and development expenses increased from $27 4 million to $30 7 million for the three quarters ended March 31, 2024 compared to that same period and 23.
Robert F. Dolski: This change was primarily due to increases in operating costs related to our new commercial manufacturing facility employee salaries and related costs will be some clinical trial costs and a decrease in our UK reimbursable R&D tax credits.
Robert F. Dolski: These were partly offset by decreases in professional services and consulting fees.
Robert F. Dolski: OBCell 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 three months ending March 31st, 2024, compared to that same period in 2020. This increase was primarily due to salaries and other employment-related costs, driven by an increase in general and administrative headcount, supporting the overall growth of the business and primarily related to commercialization activities.
Obi: Obi felt clinical material supply costs, and some other general admin fees and expenses.
Obi: Our general and admin expense increased from $9 3 million to $18 2 million for the three months ended March 31, 2024 compared to that same period in 2023.
Obi: 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.
Robert F. Dolski: Our net loss was $52.7 million for the three months ending March 31, 2024, compared to $39.8 million for the same period again in 2020. Autolus estimates that with its current cash and cash equivalents, and the proceeds received from the Strategic Alliance with BioNTech and our Equity Finance, we are well-capitalized to drive the full launch and commercialization of OBCell in relapsed refractory adult ALL, as well as advance our pipeline development plans, which include providing runway for data in our first pivotal study of OBCell 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. Thanks a lot.
Our net loss was $52 7 million for the three months ending March 31 2024.
Obi: Compared to $39 8 million for the same period again in 2023.
Analyst estimates it was this current cash and cash equivalents.
Obi: And the proceeds received from the strategic alliance with biotech and our equity financing that we are.
Obi: Well capitalized to drive the full launch and commercialization of <unk> in relapsed refractory adult AML as well as advance our pipeline development plans, which includes providing runway to data in our first pivotal study of Ob sell in autoimmune disease.
Speaker Change: I'll now hand things back to Christian to wrap up with a brief outlook on expected milestones for the rest of the rest of the year Kristian back to you.
Christian Martin Itin: Thanks a lot. Obviously, the next key event that we're looking forward to is really the mid-year conferences with ASCO and EHA, the oral presentations, and the update on 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 obviously gearing up, particularly during the second half of the year for the full reviews on the regulatory side, getting towards November 16th to do for date on the FDA review, but also expect to have quite an involved process with the European agency, a process a bit different than the way it's operated under the FDA.
Kristian: Thanks, Rob.
Kristian: Obviously, the next peak event that we're looking forward to is right at the mid year competencies with <unk> DHA the oral presentations at the update in the posters at ehi inhibition.
Kristian: Obviously looking forward to seeing you hopefully there and connecting at that point as well hopefully in person.
Speaker Change: We're also gearing up particularly for during the second half of the year for the full reviews on the regulatory side getting.
Speaker Change: Towards the November <unk> date.
Speaker Change: CA review, but also expect to have.
Speaker Change: <unk> involved process with the European agency process, a bit different than the way. It's operated under the FDA and we're also planning to obviously initiate and drive the process is the UK as well as we go through the second half of the year.
Christian Martin Itin: And we're also planning to obviously initiate and drive the process in the UK as well as in the second half of the year. In parallel, we'll keep you posted on our start-up activities toward our next pivotal study, and we are also excited to keep you posted on that and looking forward to your questions.
Speaker Change: We will keep you posted on that.
Speaker Change: Sure.
Speaker Change: Startup activities towards our next pivotal study.
Speaker Change: And obviously, we're excited to keep you posted on that.
Speaker Change: Now looking forward to your questions.
Operator: As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again, and please stand by while we compile our Q&A roster. And our first question will be coming from. Excuse me, Kelly Shye of Jeffries, your line is
Speaker Change: As a reminder to ask a question. Please press star one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one again and please standby, while we compile the Q&A roster.
Speaker Change: And our first question will be coming from.
Kelly Shy: Excuse me Kelly shy of Jefferies. Your line is open.
Kelly Shye: Congratulations on the great progress made, and thank you for taking my questions. The first question for Delta ALL, Christian, do you expect ad hoc meetings based on prior communications with both regulatory agencies in the U.S. and Europe? And also have follow-up. Thank you.
Kelly Shy: Congrats on the great progress made and thank you for taking my question. The first question.
Kelly Shy: Delta.
Speaker Change: Question do you expect an call meetings based on the prior communication.
Speaker Change: What is your andas in the U S and Europe.
Speaker Change: And also helps a lot. Thank you.
Christian Martin Itin: Well, thanks a lot for joining us, Kelly. The agency did not expect to hold an adcom meeting. They did communicate as much at the acceptance of the filing, and there's been no other communication to the contrary of that. So we don't expect an adcom meeting for this product.
Speaker Change: Well, thanks, a lot for joining Kelly.
Speaker Change: The agency did not expect to our holding outcome meeting.
Speaker Change: Communicate as much.
Speaker Change: At the acceptance of the filing.
Speaker Change: And Theres been no.
Speaker Change: No other communication to the country of that so we don't expect an outcome for the stock.
Kelly Shye: Terrific. And also for the SLE program, and you mentioned that two patients have been enrolled. Could you also add more color in terms of patient baseline characteristics? Do we expect similar results from the trials from Dr. Sheth's team? And also for the year-end data disclosure, what do we expect from all six patients? And on top of that, you also mentioned T cell engagers as a comparison to CAR-T for tackling autoimmune disorders, and you talked about the efficacy prediction.
Speaker Change: Terrific and also forward.
Speaker Change: E program and.
Speaker Change: You mentioned that two patients.
Speaker Change: Could you also add in the.
Speaker Change: In terms of patient baseline characteristics.
Speaker Change: Pat.
Speaker Change: Similar to the trials from Dr <unk> team and.
Speaker Change: Also for the year and the data disclosure.
Where do we expect.
Speaker Change: From all six patients and on top of that you also mentioned.
Speaker Change: T cell engaging.
Speaker Change: Comparison to like Keith will tactfully auto Neil and you talk about.
Speaker Change: Africa pre.
Kelly Shye: But I'm curious, given your rich experience with BlinCyto, how do you think about its safety profile in autoimmune indications, given the prior clinical profile showing hema oncology indications? Thank you very much. I know there are a lot of questions in one. Yeah, I'll try.
Speaker Change: Predictions I'm curious given that to you all which visteon has dealt with.
Speaker Change: Blaine cycle hold.
Speaker Change: Do you think of about 15 profile.
Speaker Change: The new indications given the prior.
Speaker Change: Clinical profile shortly.
Speaker Change: In oncology.
Speaker Change: You very much I know theres a lot of question anyone.
Christian Martin Itin: Yeah, I'll try to sort of go through that. So first of all, in terms of the types of patients that we're enrolling in this trial, they're very close in terms of the characteristics that you've seen in the airline study. These tend to be younger patients initially, certainly, that have very severe forms of disease, a very significant impact on their outlook on life. Obviously, organ involvement is one of the parameters that all of these patients do share, typically at least one to two organs that are impacted. So it's a very advanced, very involved state of the disease. And in that sense, very similar to the patients that have been treated as described in the initial airline evaluation. So that's the first thing.
Yes.
Speaker Change: 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 are very close in terms of the.
Christian Martin Itin: The second thing was around 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 patients and get them treated. We'll probably have variable results, 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 based on what we're seeing at the trial in the process.
The characteristics as you've seen.
Speaker Change: In the airline.
Speaker Change: Tend to be younger patients initially certainly.
Speaker Change: Very severe forms of disease very significant impact on their life.
Speaker Change: Obviously organ involvement is what are the parameters that all of these patients do share typically.
Speaker Change: We sponsored two organs that are impacted.
Speaker Change: So it's a very advanced very involve state.
Speaker Change: Orphan disease.
Speaker Change: That said, it's very similar to the patients that have been treated as described in the aviation airline with evaluation.
Speaker Change: So that's the first thing the second thing.
Speaker Change: <unk> was ranked <unk>.
Speaker Change: Enrollment that what we expect to see this.
Speaker Change: For the end of the year. So our expectation is that we should be able to enroll patients that get treated we will probably have variable all patients treated but we expect to have obviously variable will follow up with these patients.
Speaker Change: And so that's sort of what the current expectation is that some.
Speaker Change: What we're seeing at the trials in progress receive in the trial.
Christian Martin Itin: 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 decent engagers. I think what you see in the publications that were made on sclerosis patients and BRNA patients is that clearly both teams were taking a very cautious approach to dosing, both the duration of the dosing as well as the level of dose that was used, and also very careful in terms of managing the patients. And a lot of that certainly has to do with concerns around safety signals, and we'll need to see kind of how that obviously evolves going forward.
Speaker Change: So that's our current expectation in that regard in terms of what to expect which is initial data understanding initial activity and safety.
Speaker Change: You then asked about.
Speaker Change: Additional modalities treatment modalities to answer.
Speaker Change: <unk>.
Speaker Change: <unk>.
Speaker Change: What do you see it.
Speaker Change: Publications that were made on sclerosis patients at the R&D patients.
Speaker Change: Clearly both teams, we're taking a very cautious approach to dosing.
Speaker Change: Both the duration of the dosing as well as the level of dose that was used.
And obviously, we're very careful in terms of managing the patients have a lot of that certainly has to do with concerns of that.
Speaker Change: Safety Cyclicals, and we'll need to see kind of how that obviously rolls forward.
Christian Martin Itin: But also, what we did see was obviously that the level of B-cell depletion was limited, but at the same time, it also induced some clinical benefits 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 glycytor perspective with contiguous hyaluronic fusion in these patients. Not an easy way to go, and for sub-Q, the challenge would be that we would have to be very frequent.
Also what we did see is obviously that the the level of B cell depletion with limited.
These patients.
Speaker Change: Same time also inducing some clinical benefit.
Speaker Change: In all the patients that are treated so I think it's early days.
Speaker Change: But certainly.
Speaker Change: Not an easy profile, if you look at it.
Speaker Change: Good signs of perspective with continuous IV infusion in these patients.
Speaker Change: Not an easy way to go and for soft to the challenge would be what would have to be very frequent and in that setting certainly on the oncology side. The toxicity has gone up quite substantially. So those are certainly some of the considerations there, but all early days and I think premature.
Christian Martin Itin: And in that setting, certainly on the oncology side, the toxicity has gone up quite substantially. So those are certainly some of the considerations there, but these are early days, and I think it is premature to have a firm view on how that might develop.
Premature too I think.
Speaker Change: So our view on how that might develop.
Kelly Shye: Thank you very much.
Speaker Change: Thank you very much.
Speaker Change: Andrew.
Operator: One moment for our next question, and our next question will come from James Shin of Dochi Bank. Your line is open.
Speaker Change: One moment for our next question.
Speaker Change: Yeah.
Speaker Change: And our next question will come from James <unk> of Deutsche Bank. Your line is open.
James John Shin: Again, our session is a little poor, so I apologize. Hi, can you hear me? Yes, we can. I apologize, Christian.
Speaker Change: There's a lot of core so I apologize alright can you hear me.
Operator: 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 BALL launch. Can you help us understand or quantify Cardinal's benefit to Obezal's delivery logistics and Bain's delivery times? And then I'll have a follow-up. Yeah, really good.
Speaker Change: Yes, we can.
I apologize Christian my reception is a little more.
Speaker Change: Thank you for conceptualizing, the manufacturing and logistics hurdles that you went through during Felix.
Speaker Change: Our carnal support.
Speaker Change: For the <unk> launch can you help us understand or quantify cardinal benefit to oversell delivery logistics and data delivery times, and then I'll have a follow up.
Christian Martin Itin: Yeah, really good question James. So the opportunity we have with Cardinal's presence across the U.S. and the presence of centers that we can basically hold product in gives us the 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 three days out of the return time of the product because it allows us to get the product close to the centers, to the respective center, already before we're fully signed off.
James: Yes, really good question James So the opportunity we have with.
James: Carnival's presence across the U S.
James: <unk>.
James: Temperatures that we can basically hold product.
This is an ability to ship product while in parallel we are completing the.
James: The final steps of the quality control release process.
In practical terms, what this allows us to do is take approximately three days out of it.
James: In the return type of product because it allows us to get the product close to the centers to the respective center.
Christian Martin Itin: And then as soon as the product is signed off, the product obviously can then be shipped. And we basically save almost all of the logistics part around it. And it's literally typically a truck drive from the particular holding spot to the center. So it's about three days that we expect, all in between the... 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 in the length of delivery time from about 21 days to 60 days at time of launch. So it has a very significant impact between the two measures that we took and the improvements that we introduced in the process and puts us in a very competitive market.
James: Already before we are fully signed off and then let soon as the product has signed all the product obviously can that be shifts and we basically saved over almost all of those basics part around it and it's literally typically it is.
James: As the chart drive.
James: From a particular holding spot to be.
James: To the sector so.
James: Our three days that we expect all in between.
James: Sure.
James: The elements here on there from.
James: From.
James: The holdings there.
James: Together with the cash analytics that we introduced in the second half the pivotal study.
James: Give us actually a reduction.
Speaker Change: Quaker delivered volume towards our 21 days to 60 days.
Speaker Change: At time of launch so it has a very significant impact between the two measures that we took in improvements that we introduced.
Speaker Change: In the process and puts us in a very competitive market.
Speaker Change: Bucket.
James John Shin: And then for autoimmune, Christian, you nicely walked through the rapidly moving field, you have five specific CAR T's, and there's probably gonna be more B cell approaches. I mean, BTKs are also being looked at. Do you see this autoimmune field becoming a zero-sum clinical or commercial environment? Medical Evolution Where Patients Possibly Cycle Through These Regimens.
Speaker Change: Fantastic.
Christian: Then for autoimmune Christian nicely walked through the rapidly moving field Bispecific car T and there's probably going to be more b cell approaches Ptk's are also being looked at.
Speaker Change: My question is do you see this autoimmune field, becoming a neuro some clinical or commercial environment.
Speaker Change: Or is it just going to be more of like.
Speaker Change: Medical evolution, where patients possibly cycle through these regiments.
Christian Martin Itin: Well, it's a really interesting question, and it's one we're speculating in the absence of, it's almost a void of data we're speculating. Okay, 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 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 we offer.
Speaker Change: Well, it's a really interesting question.
Speaker Change: We're speculating in the accents.
Speaker Change: Almost avoided respectively.
Speaker Change: Ultimately the excitement comes from the observation that with a car T approach.
Speaker Change: Do you have the possibility to get to a very deep.
Speaker Change: For most patients lasting remission.
Speaker Change: That's a quality of outcome that no other therapy actually today testing that should be able to get anywhere close.
Speaker Change: So, it's a new quality and I think thats, where the excitement we have it is and that's what the opportunity is massive.
Christian Martin Itin: 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 became valuable for the first time with the availability of myotoxins. So that story is all that we've been looking at.
Speaker Change: Using or impacting the sales that's obviously not entirely a new story that goes back to delay the <unk> into the <unk> and the.
The first time that on April with with the availability of an approximate.
Christian Martin Itin: The field has been looking for better ways to sort of actually drive into the B-cell compartment itself. Most of ACE and CD20 are, Well, the interesting aspect here, in terms of the biology, and the thing that, or the element, really, that Dirk and Andreas' data was opening up, is the revelation that, indeed, the majority, or maybe most, of the autoantibodies appear to be produced by early forms of plasma cells, so-called plasma proteins, and not by a mature plan.
Speaker Change: So that story is hold that we've been looking at deals and looking for better ways to sort of actually.
Speaker Change: Five into the B cell compartment itself, most debate and CD tiny approaches.
Saturday aspect here in terms of the biology of the thing that really ever created.
Speaker Change: Okay, Eric Andreas as data grows.
Speaker Change: Generation diabetes the.
Speaker Change: Majority are maybe most of the auto antibodies.
Speaker Change: Peer to be produced.
Speaker Change: By early forms of tobacco sales, so called plasma glass.
Speaker Change: Not by mature plasma cells and plasma blasts different from plasma sales still carries CD 19, Arbor surface, which makes the targeted with the CD 19 car on with that.
Christian Martin Itin: And the plasma blasts, different from plasma cells, still carry CD19 on the surface, which makes them targetable with the CD19 car. And with that, you not only have an ability to remove the memory of the auto-reactive antibody, but you also have an ability to remove the factory of the auto-reactive antibody. And that actually gave you two things. It gave you something very fast, with a very deep and lasting effect. That's the memory removal process.
Speaker Change: The ability to remove the memory of the auto reactivity.
Speaker Change: But you also have the ability to remove the factory after the auto reactive antibodies.
Christian Martin Itin: But it also has a fast effect, and that is the removal of the plasma. And I think that's really where the remarkable part of biology is. Now, the question is, what mechanisms can you actually deploy that give you that level of depth in an outcome? BTKI is not very likely to be able to do that.
Speaker Change: And that actually gave you two things that gave you a stat.
Yes.
Speaker Change: With a very deep and lasting effect, that's the memory removal, but it goes also have passed effects announced the removal of the plasma glass.
Speaker Change: And I think Thats really where the remarkable part of the biology is now. The question is what are what mechanisms do you plan to actually deploy that gives you that level of depth of an outcome <unk>.
Speaker Change: Yes.
Christian Martin Itin: It will impact B-cells, but it will not impact the plasma blasts in that way. With that, it may have an effect similar to a toxin antibody, which has some activity and some indications, and then some others it doesn't have. So that may not be getting you where you need to go.
Speaker Change: Not very likely to be able to do that will impact visa allstate will not either.
Speaker Change: The impact.
The plasma glass in that in that way with that May have an effect similar to a customer and body, which has some activity in some of the indications that some obviously it doesn't have much of an impact.
Speaker Change: So that may not be actually get any ready to go.
Christian Martin Itin: If you have a monoclonal antibody to CD19, you may also not have enough, frankly, power in your therapeutic approach to be able to really make that deep cut 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 this played out; we see it also with T cell engagement. And with all of those modalities, we see quite a difference when you look at sort of the completeness of the removal of B cells.
Speaker Change: If you have a monoclonal to CD 19.
Speaker Change: You may also not have enough frankly.
Speaker Change: Power.
Speaker Change: <unk> approach to be able to really make that these costs are really ftes compartments.
Speaker Change: Where those particular sales reside we seen that oncology perspective very clearly.
Speaker Change: If you then go to the ADC as we see at play that we see and also with T cell engagement 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 client dramatically in terms of our long term outcomes et cetera, what he can do very related to that.
Christian Martin Itin: We see the difference 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. So there are differences in performance, and depending on that difference in performance, you may be able to actually get a lasting effect, or you may get a temporary effect. And I think what we'll be seeing is that, what I think I would expect is that agents that give you sort of a temporary effect probably are agents that you would use in a broader range if they're very safe, if they're very benign in their safety profile.
Speaker Change: <unk>.
Speaker Change: So there are different phases performance and depending on that difference on performance you may be able to actually get elastic effect you get a temporary effect.
Speaker Change: What will we see it is that.
Speaker Change: I think I would expect based at agents that gives you a sort of a temporary effect.
Speaker Change: Probably our agents, they're able to use into more broader range, if theyre very safe very.
Speaker Change: A very benign safety profile you could use it more broadly in an urban setting since you've considered.
Christian Martin Itin: You could use them more broadly and in those settings, and you could sort of, you know, add them on to the current standard of care, which is most hysterical, 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 where you don't have time to mess around, or you have a condition you really don't can't afford to. 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, hopefully, to a footing in a state where they are not dealing with these very horrific conditions that they're frankly dealing with that they're having
Speaker Change: Had it all to the current standard of care, which is mostly in aerospace.
Speaker Change: Well as a few other.
Speaker Change: Pages on pulp.
Speaker Change: But if you really want to get a reset if youre going to be a compromise will change, particularly in those patients develop very severe forms of the disease, where you don't have to mess around where you have the condition to you really.
Speaker Change: Not a forecast.
Speaker Change: What's going with a therapy that has the ability to here to get a proper reset and get these patients back to.
Speaker Change: Hopefully FERC footing.
Speaker Change: State, where they are not dealing with these very terrific.
Speaker Change: Additionally, refractory dealing with S&P capital.
Speaker Change: Thank you.
Speaker Change: Yes.
Speaker Change: Thanks James.
Speaker Change: Our next question.
Speaker Change: Yes.
Asthika Sarith Goonewardene: Our next question will be coming from Asthika Goonewardene of Truist. Your line is open.
Speaker Change: Our next question will be coming from Africa.
<unk> of Truest your line is open.
Christian Martin Itin: Hey, good afternoon, guys, and thanks for taking our questions. Christian, I want to ask about the updates coming down to the FELIX study at ASCO and EHOP. 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 Change: Hey, good afternoon, guys and thanks for taking our question.
So.
Christian: Christian I wanted to ask about.
Speaker Change: The update is coming down to the Felix study at <unk>.
Speaker Change: Obviously, a 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 range of transplant free survival.
Asthika Sarith Goonewardene: It's a really good question, Asthika, thanks for joining us. One of the questions that you have when you look at cell-based therapy is that whenever you have a cell-based therapy and you follow it after that with a stem cell transplant, you have to go through a step where you literally kill the cell-based therapy and then replace it with a stem 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 normal cells, and try to reset the bone marrow. But it's a very tricky trade-off.
Speaker Change #100: It's a really good question Oscar and thanks for joining.
Speaker Change: Yeah, a lot of the questions that.
Speaker Change #101: You have when you look at the cell based therapy.
Speaker Change #102: But let me have a cell based therapy and you follow after that.
Speaker Change #102: Stem cell transplant, you have to go through a separate track will kill the cell based therapy, and then replace it with the same cell transplant.
Speaker Change #103: Problem with that.
If your therapy, Brazil actually about that point yourself there people still actually if you also would take that out and replace it.
Speaker Change #103: With it with another with basically normal cells and tried to reset the bone marrow compartment, but it's a very tricky tradeoffs now.
Christian Martin Itin: Now, in some instances, we've seen that actually happen, particularly for colic with a short persistence, so where the cells basically, the CAR T cells disappear quickly. If you then, after that, come in with a transplant, you would expect to actually see, at least have a chance for improvement if they don't have that. In the case of ovacells, obviously, one of the questions is, well, you know, does that actually hold for ovacells, which we know to have long-term effects?
Speaker Change #103: In some instances, we've seen that actually happen, particularly I can't recall off with a short persistence over to sales basically the car T cells in the tier quickly if you'd add to that come in with a transplant.
Speaker Change #103: Assay.
Speaker Change #103: We would expect to actually see at least have a chance for improvement.
Speaker Change #103: Some of the patients.
Speaker Change #103: In the case of RV sales, obviously, one of the questions as well that's not actually holds for Ob cell, which we know to have long persistence.
Christian Martin Itin: And we also see, you know, that clearly the patients that have space in our long-term IT study, the patients that have long-term outcomes also tend to have long-term outcomes. So, in that setting, if you were to actually intervene with a stem cell transplant, you kill the CAR T cells off, and then you actually put a new marrow in, basically. And also, at that point, you know, it's a real question: is that going to be beneficial or not? And so, one of the things that we're looking to do is at least give a first impression of the answer, based on the experience that we had in the study. So Christian, can you maybe...
Speaker Change #103: And we also see that clearly for patients to have based on our oil from 19 study. The patients have long term outcome also take Jeff has low persisting car T cell.
Speaker Change #103: That said, if you were to actually to being with a stem cell transplant you kill the car T cells off and then you actually put a numero basically.
Speaker Change #103: And also at that point.
Speaker Change #103: The real question is going to be beneficial or not and so one of the things that we're looking to do is at least gave a first view.
Based on the experience that we had in the study.
Speaker Change #103: Certainly.
Speaker Change #103: Area that study took about beaches worthy for the treating physicians.
Speaker Change #103: Another one of the key focus of the presentation.
Christian Martin Itin: Christian, can you maybe give us a little bit of color on what you think is the threshold by which the physician community will feel this is differentiated from TACARAS? I know Zoom at 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.
Speaker Change #104: 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 fuel. This is differentiated from to Carlos I know.
Zuma three doesn't give you the right kind of data to make that kind of comparison, but perhaps you can comment on kind of real world data.
Speaker Change #105: That's all set the bar to beat.
Asthika Sarith Goonewardene: So first of all, you know, the data is going to be limited because, in our trial, we had a very limited number of patients that received a transplant after receiving OBCell. So there is the limitation of a small number. But it certainly will give you a view on whether there is a likely improvement in outcome or not. That certainly will answer that question for sure.
Speaker Change #106: So first of all.
Speaker Change #107: Data is going to be limited because it's certainly in our trial, we had a very limited number of patients that were receiving a samsung.
Speaker Change #107: After receiving all of the cell.
Speaker Change #107: So so there is the limitation.
Speaker Change #108: Of a small number.
Speaker Change #108: But in terms of your view on whether the whether there is a likely improvement of outcome. We're not that certainly will answer we will answer that question for sure.
Christian Martin Itin: And I think it's sort of indicative 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 outcomes, which is sort of the other side of that story. And we're going to be walking through both of those, and we'll present analysis for both of those. So it really depends, I think, on the experience of the physician in the field, you know, what they have in their hands, frankly, in terms of products.
Speaker Change #109: And I think you sort of if they did it.
Speaker Change #109: Kind of what we expect the other flip side of that is is obviously the analysis of persistence and whether longer term persistence correlate with longer term outcome, which is the other side of that story.
Speaker Change #109: We are quite a few actually.
Speaker Change #109: Really walking through both of those and we.
Speaker Change #109: We will present analyses to both of those.
Speaker Change #109: So it really depends I think all of the experience for the physician.
Speaker Change #109: <unk>.
Speaker Change #109: What happened what they have in their hands in terms of products.
Christian Martin Itin: What is interesting, when you look at some of the real-world experiences, there was a clear conclusion, basically: the competitive program should be consolidated with another therapeutic program, which typically would be a stem cell transplant. So that was an interesting conclusion in its own right, and I think it'll be interesting to see our data at ASCO DHA, and actually, I think we get a pretty good view on the difference between the programs in that regard.
Speaker Change #109: Well, it's interesting when you look at the some of the real growth experiences because it wasn't clear.
Speaker Change #109: The conclusion basically.
Speaker Change #109: Yes.
Cash.
Speaker Change #109: We will certainly put a competitive program just after competitive products should be consolidated with another therapy.
Speaker Change #109: Which typically would be a stem cell transplant. So that was an interesting conclusion, it's otherwise it'll be I think it'll be interesting to see.
Our data.
Speaker Change #109: At Astro DHA and actually I think youll get a good view on.
Speaker Change #109: On.
Speaker Change #109: The difference between the programs in that regard.
Asthika Sarith Goonewardene: Got it. And then I've got two quick questions that are autoimmune, of course, Christian. The two patients that were recruited, were those from a single site, or was that kind of one piece from the UK and the Spanish side?
Speaker Change #110: Got it and then I got two quick questions on autoimmune of course Christian.
Speaker Change #111: The two patients have recruited was that from a single site or is that kind of one piece from the UK.
Christian Martin Itin: And both of those, sorry, the answer to that first question is that both were recruited in the UK at this...
Manish: Manish site.
Speaker Change #113: Both of those so the attitude that the first question is it was.
Speaker Change #113: Both were recruited in the UK.
Speaker Change #113: At the same sites.
Christian Martin Itin: Got it. Okay.
Speaker Change #114: Got it Okay and then also to meet your target recruitment of about six patients with data by year end.
Speaker Change #113: <unk>.
Speaker Change #113: Expected to see.
Speaker Change #115: See the recruitment rates step up maybe around a patient a month. So what do you what needs to happen to get that kind of recruitment rate and then do you see is there any potential for it.
Speaker Change #115: Exceed that.
Christian Martin Itin: And also, to meet the target recruitment of about six patients with data by year-end, it is expected that 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? Well, first of all, you know...
Christian Martin Itin: Well, first of all, every time that physicians use a modality for the first time, um, you know, you want to make sure you really pick the perfect patient for that first, uh, for that first dose. So that's true for every, I think, every agent you test and every site that is a first site with that type of agent and an indication.
Speaker Change #116: Well first of all every time.
Speaker Change #116: Physicians use a modality for the first time.
Speaker Change #116: You want to make sure you're really to take the appropriate patients for that versus sort of that first dose. So that's true for every every I think every agency.
Speaker Change #116: Every site is at first sight.
Speaker Change #116: With that type of an agent and an indication. So the first patients are always the most challenging months because.
Asthika Sarith Goonewardene: So the first patients are always the most challenging ones because, you know, that's where you have no experience. Once you see the therapy work, you see the impact, that's where you see confidence build nicely. And then you see actually things kind of start moving at that point. We've seen it, frankly, even with, you know, across the various Hopkins indications, where the first patient was always the biggest hurdle, where you wanted to make sure you got everything right, and then actually after that, confidence starts to build, and then recruitment starts to pick up at that. That's very normal, and I think you see it pretty much across all studies with bariatric substances and patients with asthma.
Speaker Change #116: Thats, where no experience once you see the therapy work do we see the impact that's where you see.
Speaker Change #116: Here with confidence the Chrysler debt, you see actually things kind of start moving it therefore, we seen it faster even with.
Speaker Change #116: Across the various non hodgkin's indications with.
Speaker Change #116: When the first patient was always the biggest hurdle, where we wanted to make sure you get everything right.
Speaker Change #116: And that actually after that helping starts to build and then the recruitment is starting to pick up that debt.
Speaker Change #116: At that point in time.
Speaker Change #116: That's very normal and I think you'll see a pretty much across all studies.
Speaker Change #116: With very active substances and patients have severe disease.
Christian Martin Itin: Great. Thanks for taking my questions, guys, and congratulations on the progress. All right. Thanks, Asthika. One moment for our next question. And our next question will come from Matthew Phipps of Blair. Your line is open.
Speaker Change #117: Great. Thanks for taking my questions guys and congrats on the progress.
Speaker Change #118: Alright, Thanks Jessica.
Speaker Change #119: One moment for our next question.
Speaker Change #118: Yeah.
Speaker Change #120: And our next question will come from Matthew Phipps of Blair. Your line is open.
Matthew Christopher Phipps: Alright Christian, thanks for taking my questions.
Matthew Christopher Phipps: Alright, guys. Thanks for taking my question sorry for some more noise.
Matthew Christopher Phipps: I'm curious if you've had discussions.
Matthew Christopher Phipps: With the FDA on how they will treat patients that are in morphological disease versus those that are in RMB.
Speaker Change #122: In the label.
Christian Martin Itin: So, 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 goal, of the analyses. And that's actually in terms of analogies, both at the time point, of inclusion as well as the time point as well. In Europe, the difference will be that it will be the patient actually at the time of inclusion with measurable disease, and then basically a factor-intent-to-treat approach in terms of the analysis, which is sort of the difference in the view where the Europeans take the view of the treating physician and make a decision, and then you want to know what the outcome is, what outcome to expect, and with the FDA, which is more kind of looking at from a scientific perspective and actually looking at the individual patients in terms of response assessment to that, maybe to find time for them.
Speaker Change #123: So thanks for joining.
The analysis the primary analysis. The FDA will do is based on patients to have morphological repeat except the primary drivers.
Speaker Change #123: One of the of the analysis.
Speaker Change #123: And.
Speaker Change #123: That's actually in terms of.
Speaker Change #123: Analysis, both at the time points.
Speaker Change #123: Our conclusion as well as the time point is linked to the patient.
Speaker Change #123: In Europe, the difference will be set.
Speaker Change #123: The patient is actually at the time, the inclusion with measurable disease.
Speaker Change #123: And then basically.
Speaker Change #123: Frankly, they tend to treat approach.
Speaker Change #123: <unk>, which is sort of the differences if you where the Europeans take a view of the treating physician.
Speaker Change #123: And then you want to know what the outcome is.
Speaker Change #123: Will that come to expect.
Speaker Change #123: The FCA, which is more.
Speaker Change #123: We're kind of looking at from a scientific perspective, but actually looking at the <unk>.
Individual patients.
Speaker Change #123: In terms of response assessment.
Speaker Change #123: Five times or so so there's some differences there in terms of your analysis.
Christian Martin Itin: So there are 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. Thanks, Christian.
Speaker Change #123: We're looking at patients.
Speaker Change #123: Its morphological diseases the primary group.
Speaker Change #123: For the for the analysis, but the experience specific has to be reflected more broadly.
Speaker Change #123: So we will see where we are talking about.
Matthew Christopher Phipps: And then one quick one on multiple myeloma, actually, you know, obviously, now we have copacil approved in the second line. And I'm just curious how you're thinking about where the auto development path can be. At this point, would you ever consider treating a patient who had prior BCM-A CAR-T and failed?
Thanks, Christian and then one quick one on that.
Multiple myeloma.
Speaker Change #123: Obviously that we have.
Speaker Change #124: <unk> proven second line. Thank you.
Speaker Change #125: Or just how youre thinking about where ottaway development path can be deploying would you ever consider treating patients had prior be CMA car T and sale.
Christian Martin Itin: Yeah, so that's a really good question. Obviously, the multiple myeloma field is sort of, you know, filling up with a number of agents at various lines of therapy. And so we're looking at that kind very carefully. And we're looking both at multiple myeloma-related diseases. So we're taking a pretty broad look at that and at the plasma cell disease areas and are evaluating kind of the various... But it's too early to actually give you a very clear view of that.
Speaker Change #126: Yes, so that's a.
Speaker Change #127: Really good question, obviously, there are lots of myeloma field is sort of filling up with a number of ways.
Speaker Change #126: <unk>.
Speaker Change #126: Various lines of therapy.
Speaker Change #126: And so we're looking at that very carefully.
Speaker Change #126: We are looking both at both myeloma and related diseases. So we're taking a critical look at that.
Speaker Change #126: After the possible sale.
Speaker Change #128: These areas are.
Speaker Change #128: Evaluating the various path there, but too early to actually give you that.
Christian Martin Itin: But I agree with you, there is a level of competition that's building up that you want to pick your battles very carefully. OK, thanks. Okay, thank you. And our last question: who will be coming from Gil Blum?
Speaker Change #129: Kudos to you on that but I agree with you the recent level.
Speaker Change #129: Competition, that's building up that you want to pick your battle read it carefully.
Speaker Change #130: Okay. Thanks for taking questions.
Speaker Change #131: Thank you.
Gil Joseph Blum: And our last question, which will be coming from Gil Blum of Needham & Company. Gil, your line is open.
Speaker Change #132: And our last question will.
Speaker Change #133: It will be coming from Gil Blum.
Gil Joseph Blum: Of Needham <unk> company.
Speaker Change #135: Your line is open.
Gil Joseph Blum: Hi, everyone and good morning, and good afternoon, just a couple of questions from us.
Gil Joseph Blum: So first one on the commercial launch potential commercial launch for <unk>. So do.
Gil Blum: Do you expect that.
Gil Blum: <unk> treatment to be initially provided mostly in centers that already provide other car T.
Christian Martin Itin: I think what you find is that the centers that actually treat adult ALL patients tend to be highly specialized academic centers. There's certainly a high focus and aggregation of the patients in those cellular centers given the high intensity of support that these patients tend to require. So a lot of these centers already have multiple CAR-Ts available that they're actually delivering in various disease settings, and in that sense, they 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... That makes sense, and maybe an open-ended one.
Speaker Change #137: I think what you find is that the census that actually treat.
Speaker Change #137: Adult AML patients tend to be the highly specialized academic centers certainly at a high focus and aggregation on for patients with ourselves or is that just given the high.
Speaker Change #137: High intensity <unk>.
Speaker Change #137: These patients tend to equity required so a lot of these centers do actually have.
Speaker Change #137: Already multiple car Ts available that we're actually delivering in various disease settings.
Speaker Change #137: And as assets are some of the most experienced centers across the.
Speaker Change #137: The U S with car T delivery and that's certainly true.
Speaker Change #137: And also obviously.
Speaker Change #137: Actually see the.
Speaker Change #137: But at a very high degree of overlap.
Speaker Change #137: The clinical centers that participated in Phoenix.
Gil Joseph Blum: So given it took about 18 months to see a relapse in one of the SHED patients, what, in your view, would be a good leading indicator for sustained efficacy? And is there even something like that? Thanks. A really good question, Gil.
Speaker Change #138: Okay that makes sense.
Speaker Change #138: And maybe an open ended one so given it took about 18 months to see a relapsed from one of the <unk> patients.
Speaker Change #139: What in your view would be a good leading indicator for sustained efficacy and is there even something like that thanks.
Christian Martin Itin: One of the things that's interesting about that myositis patient is that, to my knowledge, probably the only patient in Georg's data set that actually had a low amount of autoreactive antibodies left that were not removed in the therapy. So in other words, there were actually autoantibodies visible in that patient even early on, although the clinical symptoms were all clear, but there was sort of a remnant of autoantibodies that remained detectable in the patient.
Speaker Change #140: Really good question one of the things Thats interesting about that myositis patients is that smaller.
Speaker Change #141: To my knowledge.
Speaker Change #141: The only patient.
Speaker Change #141: <unk> dataset that actually had a.
Speaker Change #141: A lower amount of auto reactive antibodies less that were not removed in the therapy. So in other words that were actually auto antibodies visible.
Speaker Change #141: In that patient even early on although the clinical sections, we're all clear.
Speaker Change #141: A remnant of auto antibodies that prevent the taxable into patients.
Christian Martin Itin: And that also, you know, if you think about early indicators, certainly in this case, you would consider it to be an early indicator because it would also be very directly linked to the outcome of the online survey. And so that's probably a very good one to follow. Other than that, I think it's very difficult to actually develop one. First of all, we don't have another event that we can look at, but certainly the event we can look at, we certainly have evidence.
Speaker Change #141: And that also obviously.
Speaker Change #141: If you think about early indicators certainly in this case, you would consider to be the year over year CAGR.
Speaker Change #141: Because it would be obviously very directly linked to the to the <unk> comments the underlying disease.
Speaker Change #141: So that's probably a very good path to follow other than that I think it's very difficult to actually.
Speaker Change #141: Develop on first of all we don't have another event that we could look at.
Speaker Change #141: But in the event, we can look at we have certainly evidence of sustained low level of presence on auto antibody that just wasn't cleared it tool.
Speaker Change #141: Alright.
Speaker Change #142: Thank you very much and congrats on all the progress.
Gail: Thanks, a lot Gail.
Christian Martin Itin: And I would now like to turn the call back to Christian for closing remarks. All right, well, first of all, thanks a lot, guys, for joining us today. Obviously, a very successful quarter for us. We're looking forward to, obviously, the data updates in a few weeks. I hope to see most of you at one of the meetings or conferences that are taking place. And we'll keep you updated. It will certainly be an exciting year as we get into the second leg here towards the, hopefully, approval of OBCell 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. And this concludes today's conference call. Thank you for participating. You may now disconnect.
Speaker Change #144: And I would now like to turn the call back to Christian for closing remarks.
Speaker Change #145: Alright, well first of all thanks, a lot guys for joining today.
Speaker Change #145: Obviously very.
Speaker Change #145: A successful quarter for us we're looking forward to obviously the data updates.
Speaker Change #145: A few weeks time hope to see most of you.
Speaker Change #146: The meetings or conferences that Ursula alongside and we will keep you updated and certainly an exciting year as we are getting it to the second last year towards the hopefully.
<unk> in the U S and then our next steps in Europe, the UK alright.
Speaker Change #147: Alright with that thank you very much and have a fantastic day. Thank you and this concludes today's conference call. Thank you for participating you may now disconnect.
Speaker Change #147: Okay.
Speaker Change #147: [music].