Q2 2024 Autolus Therapeutics PLC Earnings Call
Hello ladies and gentlemen and welcome to the Autolus Therapeutics call to discuss its second quarter 2024 financial results and business updates. As a reminder, this conference call is being recorded. I would now like to turn this conference over to your host, Olivia Manser. Please go ahead.
Operator: 24 Financial Results and Business Updates. As a reminder, this conference call is being recorded.
Olivia Manser: I would now like to turn this conference over to your host, Olivia Manser. Please go ahead.
Olivia Manser: Thanks, Sean.
Olivia Manser: Good morning, all. Good afternoon, everyone. And thanks for joining us on today's call. With me today are Dr. Christian Itin, our Chief Executive Officer, and Rob Dolski, our Chief Financial Officer.
Olivia Manser: Thanks Sean, good morning or good afternoon everyone and thanks for joining us on today's call. With me today are Dr. Christian Itin, our Chief Executive Officer and Rob Dolski, our Chief Financial Officer.
Christian Itin: So, on slide two, before we begin, I just want to remind you again 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 regulatory timelines for our product candidates and our expectations regarding our cash runway.
Christian Itin: So, on slide two, before we begin, I just want to remind you again that during today's call, we will make statements related to our business. This is a forward-looking under federal securities laws and the safe part of provisions of the Private Securities Litigation Reform Act of 1995. These may include, but are not limited to, statements regarding the state's clinical trials and development and or regulatory timelines for our product candidates and our expectations regarding our cash runway. These statements are subject to a variety of risks among certainties that could cause actual results with different material from the expectations and reflect our views only as of today.
Olivia Manser: On slide two, before we begin, I just want to remind you again 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 state of clinical trials and development and regulatory timelines for our product candidates and our expectations regarding our cash runway.
Olivia Manser: These statements are subject to a variety of risks and uncertainties that could cause after results with different materialism and expectations. We 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, refer to the risks identified in today's press release and our SEC filings, both available on the investor section of our website. One slide for three.
Speaker Change: So on slide two before we begin I just want to remind you again that during today's call we will make statements related to our business that are forward-looking under federal securities laws
and the Safe Harbour 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.
Christian Itin: These statements are subject to a variety of risks and uncertainties that could cause actual results that differ materially from our 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 ACTRA 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.
These statements are subject to a variety of risks and uncertainties that could cause actual results that differ materially from expectations and reflect our views only as of today. We assume no obligation to update any such forward looking statements.
Christian Itin: We see no obligation to update any such forward-looking statement.
Christian Itin: For a discussion of the material risks and uncertainties that could affect our actual results, these refer to the risks identified in today's press release and our SEC filing, both available on the investor section of our website.
Olivia Manser: 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.
Christian Itin: On slide three, you will see the agenda for today's call. Christian can provide an overview of our operational highlights. Rob will then discuss the financial results before handing back to Christian to conclude and take Q&A.
Olivia Manser: You'll see the agenda for today's call. Christian can provide an overview of our operational highlights. Rob will then discuss the financial results before handing back to Christian to conclude and take Q&A. So, over to you, Christian.
On slide three you'll see the agenda for today's call. Christian's going to provide an overview of our operational highlights. Rob will then discuss the financial results before handing back to Christian to conclude and take Q&A. So over to you Christian.
Christian Itin: So, over to you, Christian. Thanks a lot, Olivia, and welcome everybody to our second quarter earnings call. Real pleasure to have you all on, and I'd like to start on slide number four, but just a brief summary of the key highlights for the quarter. As you can imagine, we're in the process of going to the various review processes for OV cell, both in the US as well as in Europe, most recently now also in the UK. So that's been the primary focus from an operational perspective. I think we've been making good progress and are on track with all the various interactions that we have with the regulatory authorities.
Christian Itin: Thanks a lot, Olivia, and welcome, everybody, to our second quarter earnings call. It's a real pleasure to have you all on, and I'd like to start on slide number four with just a brief summary of some of the key highlights for the quarter. As you can imagine, we're in the process of going through the various review processes for OVCell, both in the US as well as in Europe, but most recently, also in the UK.
Christian Itin: thanks lot libya and welcome everybody to have second quarter earnings call and real plesure to have hold on and i'd like to start on slide down before we just a bef summary also the key highlights for the quarter
Rob Dolski: as you can imagine we re in the process of going to the various review processes for o cell both the us as well as in europe most recently now also u k so that's been the primary focus from an operational perspective i think we've making good progress and ' track with all the various interactions that we have with the regulatory authorities
Christian Itin: So that's been the primary focus from an operational perspective. I think we're making good progress and are on track with all the various interactions that we have with the regulatory authorities. The BDUFA target date, as you may remember, is November 16th this year, and we're tracking well toward that timeline.
Christian Itin: The due for target date, as you may remember, is November 16th this year, and we're tracking well towards that timeline. We've also initiated or have currently ongoing two phase one clinical trials; one is in pediatric ALL, which is a trial that is moving very nicely, and obviously we're excited about applying and having OV cell evaluated in pediatric patients. That's ongoing, and what we're for obviously in the upcoming periods on that trial. And in addition, the phase among trial with patients that have an advanced stage, a relaxed flash refractory stage of systemic lupus. This is the Carlisle Study.
Olivia Manser: The BDUFA target date, as you may remember, is November 16th this year, and we're tracking well towards that timeline.
Christian Itin: We've also initiated, or are currently ongoing, two Phase I clinical trials. One is in pediatric ALL, which is a trial that is moving very nicely, and obviously, we're excited about applying and having OBCell evaluated in pediatric patients. That's ongoing, and we'll report, obviously, in the upcoming periods on that trial. And, in addition, the Phase I trial with patients that have an advanced stage, a relapsed type, slash, refractory stage of systemic lupus. This is the Carlisle study.
Olivia Manser: We've also initiated, or are currently ongoing, two Phase I clinical trials, one is in pediatric ALL, which is a trial that is moving very nicely, and obviously we're excited about applying and having OBCell evaluated in pediatric patients, and that's ongoing, and we'll report obviously in the upcoming periods on that trial. And in addition, the Phase I trial, with patients that have an advanced stage, a relapsed type slash refractory stage of systemic lupus.
Christian Itin: We opened this study at the beginning of the year, and we dosed our first patient in the second quarter, and we continue to be involved in that study as we have projections. More importantly, as we went through the course of the quarter, we did focus, I would say, very much on updating the clinical data from our Pivotal Felix study, the Phase 2 study that's underpinning the regulatory filings that we've made with the various authorities. Importantly, we looked at a number of aspects that we hadn't actually explored to the same extent in our prior publications and presentations about the program.
Christian Itin: We opened the study in the beginning of the year, and we those are first patients, the second quarter, and we continue enrollment in that study as we have projected. We importantly, as we went through the course of the quarter, we did focus on the update of the clinical data from our pivotal Felix study, the phase two study that on the pinning the regulatory filing that we've made with the various authorities. Importantly, we looked at a number of aspects that we haven't actually explored to the same extent in our prior publications and presentations around the program.
Speaker Change: This is the Carlisle study. We opened this study in the beginning of the year and we dosed our first patient in the second quarter and we continue involvement in that study as we have projected.
Olivia Manser: more importantly as we went through the course of the quarter we did focus i was a very much on the update of the clinical data from our appeartal felix study the phase twoi studady that underpinning the regulatory filings that we've made the various authorities
Olivia Manser: Importantly, we looked at a number of aspects that we hadn't actually explored to the same extent in our prior publications and presentations about the program. One of course is to look for the longer term outcome.
Christian Itin: One of course is to look for the longer-term outcome. And what we do see is that we do start to see a stabilization of both event-free survival as well as overall survival in the page and in the study, and we're starting to see a plateau forming, which is obviously something we've been very keen to evaluate. And we start seeing that now actually stabilized with more follow-up in the study. What was quite interesting, and I'll show you the data a little later as well, is that quite typically what we have in this particular patient setting is that you actually look to consolidate the effect that you could deduce of the particular therapy to induce longer term outcome.
Christian Itin: One, of course, is to look for the longer-term outcome. And what we do see is that we do start to see a stabilization of both event-free survival as well as overall survival in the study, and we're starting to see a plateau forming, which is obviously something we've been very keen to evaluate, and we start seeing that now actually stabilize with more follow-up in the study. What was quite interesting, and I'll show you the data a little later as well, is that quite typically what we have in this particular patient setting is that you actually look to consolidate the effect that you could induce with a particular therapy to induce longer-term outcome, and typically what you do is you actually have the patients undergo a stem cell transplant when they are in complete remission and ideally MRD negative, which was the case for all our patients.
Olivia Manser: And what we do see is that we do start to see
Olivia Manser: a stabilization of both entry survival as well as overall survival the page in the study and we're start to see a platform performing which is obviously something we've been very keen to evaluate and we started seeing that now actually stabilizede with more follow-up with the study
Speaker Change: well was quite interesting and i'll showyou the data ly later as well is that quite typically what we have in this particular a patient said it except you actually look to consolidate the effect that he could do cer
Christian Itin: And typically, what you do is you actually have the patients on the go a stem cell transplant when they are in complete remission and ideal in market negative, which is the case for all our patients. What was quite surprising to see, and you'll see the data in a short while as well, is that we didn't appear that the consolidation with the stem cell transplant improves the outcomes for the patients, which is very different from the other therapeutic options that are currently available in the space. We also, I think, had a closer look at the role of persistence into longer term outcome, as well as the impact of bridging therapies and particularly also the use of in a twosomap in patients that have very high tumor burden at time of inclusion, and where we did see a very effective approach here in terms of bridging with in a twosomap.
Speaker Change: if you haven't already.
Christian Itin: What was quite surprising to see, and you'll see the data in a short while as well, is that it didn't appear that the consolidation with a stem cell transplant improved outcomes for the patients, which is very different from the other therapeutic options that are currently available in the space. We also, I think, had a closer look at the role of persistence into longer-term outcomes, as well as the impact of bridging therapies, and particularly the use of inotuzumab in patients that have very high tumor burden at time of inclusion, and where we did see a very effective approach here in terms of bridging with inotuzumab. Now, in terms of the operational side of the business and the governance side, we did strengthen our board.
Speaker Change: What was quite surprising to see, and you'll see the data in a short while as well, is that it didn't appear that the consolidation with a stem cell transplant improved the outcomes for the patients, which is very different from the other therapeutic options that are currently available in the space.
Speaker Change: we also i think closer look at the bol of persistence into longer term outcome as well as the impact of bridging therapies in particularly also the use of inittwoes and ap in patients that have very high to a burden at time of inclusion and where we did to very effective
Christian Itin: Now, in terms of the operational side of the business and the government side, we get strength in our board. We had Mike Barney join as the new chair of the company and Robin Brown, who's an expert in autoimmune diseases and inflammatory diseases. So, broadening off the skill set on the board and obviously a sort of the next step in terms of the evolution, both from a movement towards commercialization, which is obviously where I want Mike Barney's background is very strong. But also an expansion from a medical perspective into adjacent indications outside of oncology, where it's clearly where Robby Raul's piece of a particular experience is extremely valid.
Olivia Manser: approach here in terms of bridging with Innituzumab.
Christian Itin: We had Mike Bonney join as the new chair of the company and Ravi Rao, who is an expert in autoimmune diseases and inflammatory diseases. So broadening the skill set on the board and obviously a sort of the next step in terms of the evolution, both from a movement towards commercialization, which is obviously where Monique Bonny's background is very strong, but also an expansion from a medical perspective into adjacent indications outside of oncology, where it's clearly where Robbie Rowell's particular experience is extremely valuable.
Speaker Change: now in terms of the operational side of the business and the governance side we get strengthen our board we had ike bonny joy as the new chair of the company and dromgrowrow who's an expert in au immunediseases
Olivia Manser: in flabmatattwentyic diseases so broadening off ice skills head on the board and and i ll see a sort of the next step in terms of the evolution though from a movement towards commercialization which is obviously roomic body background is also
Speaker Change: very strong but also an expansion from a medical perspective into a adjon indications outside of oncology where' clearly roy ros feet at particular experience is extremely ardable
Christian Itin: Now, in addition, obviously we've been driving through a remarkable amount of growth and maturation of the organization as we're setting up our commercial manufacturing capabilities, you know, getting through first regulatory filings and keep pushing through that process and preparing for commercialization. And there is a group of very talented leaders within the companies that have really risen to the challenge and have started to tackle fantastic job and recognition of their work and their leadership have been promoted to Senior Vice Presidents within the organization. And this includes Brian on the regulatory side, Chris Gray, site head for Steven H.
Christian Itin: Now, in addition, obviously, we've been driving through a remarkable amount of growth and maturation of the organization as we set up our commercial manufacturing capabilities, you know, getting through our first regulatory filings, and now keep pushing through that process, and are preparing for commercialization. And there is a group of very talented leaders within the company that have really risen to the challenge and have done a fantastic job, and in recognition of their work and their leadership, they have been promoted to senior vice presidents within the organization.
Christian Itin: Now, in addition, obviously, we've been driving through a remarkable amount of growth and maturation of the organization as we set up our commercial manufacturing capabilities, you know, getting through our first regulatory filings, and now keep pushing through that process and are preparing for commercialization. And there is a group of very talented leaders within the company that have really risen to the challenge and have done a fantastic job, and in recognition of their work and their leadership, they have been promoted to senior vice presidents within the organization. This includes Brian on the regulatory side, Chris Gray, site head for Stevenage, Marcus Grill on quality, and Claudia Mercedes, really operations from the manufacturing technical operations side, but also in a broader role than that.
Speaker Change: Now, in addition, obviously, we've been driving through a remarkable amount of growth and maturation of the organization as we're setting up our commercial manufacturing capabilities.
Olivia Manser: You know, getting through first regulatory filings and now keep pushing through that process and are preparing for commercialization.
Olivia Manser: and there is a group of v caliate leaders within the company that have really risen to the challenge and has done a fantastic job and the recognition of their work and their leadership have been promoted to senior vice presidents within the organization
Christian Itin: This includes Brian on the regulatory side, Chris Gray, site head for Stevenage, Marcus Krill on quality, Claudio Mercedes, really operations from the manufacturing technical operations side, but also in a broader role than that. And then Dilip Patel, who's looking into market access, and obviously did a fantastic job on that side as well. So great to see this group of leaders really grow up and within the organization.
Christian Itin: Marcus Creel on quality, Claudia Mercedes to really operations of the manufacturing technical operations side that also actually in a broader role in that, and then Dylan Patel, who's looking into market access and obviously in a fantastic job on that side as well. So great to see this group of leaders really grow up and within the organization and, you know, having made substantial contributions that we expect to see a lot of important contributions going forward to the business. Moving to slide number six. I would like to just briefly remind you of some of the key data that we did update on at that store, as well as the EHA. Both meetings happened during the course of June this year.
Speaker Change: This includes Brian on the regulatory side, Chris Gray as the site head for Stevenage.
Olivia Manser: Marcus Creel and Claudia Mercedes, really operations from the manufacturing technical operation side, but also actually in a broader role than that.
Christian Itin: And then Dilip Patel, who's looking into market access and obviously did a fantastic job on that side as well. So great to see this group of leaders really grow up and within the organization and, you know, having made substantial contributions that we expect to see a lot of important contributions going forward. Moving to slide number 6.
Olivia Manser: and Dilip Patel, who's looking into market access and obviously did a fantastic job on that side as well. So great to see this group of leaders really grow up and within the organization and, you know, having made substantial contributions that we expect to see.
Christian Itin: And, you know, having made substantial contributions that we expect to see a lot of important contributions going forward. So disease burden below 5% but above 10 to the minus 3. So a very relatively narrow corridor of MRD MRD positive.
Olivia Manser: A lot of important contributions going forward to the business.
Christian Itin: I would like to just briefly remind you of some of the key data that we did update at ASCO as well as at the EHA. Both meetings happened during the course of June this year. What we did focus on was actually looking at the totality of the data from the FELIX study, which has three cohorts. By far, the largest cohort are the patients that have relapsed, that have proper relapsed refractory disease with morphological disease, so more than 5% of the burden.
Olivia Manser: moving to slightide number six
Speaker Change: I would like to just briefly remind you of some of the key data that we did update on at ASCO as well as at EHA. Both meetings happened during the course of June this year.
Christian Itin: What we did focus on is actually look at the totality of the data from the Felix study and as you remember the Felix study has three boards that might by far the largest cohort are the patients that have relaxed their proper relax for factory disease with morphological disease some more than five percent to a burden. And this is the vast majority of the patients that we have treated. We have also had two small cohorts in addition that we have included in the study: a small cohort for patients that have isolated extra money disease; that's typically a cohort that actually gets excluded from clinical trials because of the difficult nature of the disease and the challenges of managing those patients, but also a small cohort of patients that have minimal residual disease.
Speaker Change: what we did focus on is actually look at the totality of the data from the feenlix study as a remember felixcel yester reports
Speaker Change: My, by far, the largest cohort are the patients that have relapsed, that have proper relapsed refractory disease with morphological disease, so more than 5% tumor burden, and this is the vast majority of the patients that we have treated.
Christian Itin: And this is the vast majority of the patients that we have treated. We have also had two small cohorts, in addition, that we have included in the study. A small cohort of patients that have isolated extramedullary disease, that's typically a cohort that gets excluded from clinical trials because of the difficult nature of the disease and the challenges of managing those patients. But also a small cohort of patients that have minimal residual disease, so the disease burden is below 5% but above 10 to the minus 3. So this is a very relatively narrow corridor of MRD positive cases. So that's the group.
Speaker Change: We have also had two small cohorts, in addition that we had included in the study,
Speaker Change: a small co work for patients that have isolated extra auor disease that's typically a core that actually gets excluded from clinical trials because with the difficult mediure of the disease
Speaker Change: and the challenges of managing those patients but also a small cohort of patients that have minimal residual disease.
Christian Itin: So disease burden below five percent, but of off 10 to the minus three. So very relatively narrow corridor or MRD, MRD positive disease. So that's the group. We actually analyze the totality of that data, and as you can see, this is a total of 127 and huge patients. And what we're starting to see is incredibly encouraging in terms of the patients that actually are in ongoing remission without subsequent cell cancer or other therapy. And that is, I think, really important because about 40 percent of the patients that actually continue in remission without any need for additional therapy.
Olivia Manser: so disease burden below five percent but off pent to the minorthree so a very screressic in nar record or oril mrt emerd positive disease
Christian Itin: We actually analyzed the totality of that data, and as you can see, this is a total of 127 infused patients. And what we're starting to see is incredibly encouraging in terms of the patients that actually are in ongoing remission without subsequent stem cell cancer or other therapy. And that is, I think, really important.
Olivia Manser: so that's the group we had actually analyzed the totality of that data and as you can see this is a total of theone hundred and twenty-seven huge in q patients
Speaker Change: And what we're starting to see is incredibly encouraging in terms of the patients that actually are in ongoing remission without subsequent stem cell transplant or other therapy.
Christian Itin: We've got about 40% of the patients that actually continue in remission without any need for additional therapy. And we also have this smaller subgroup, which I'll also refer to now on the next slide, that received a subsequent stem cell transplant. There are 18 patients. They received this transplant while being in complete remission, not only in complete remission, but also being MRD negative. So there are no signs of measurable disease in these patients at the time of transplant.
Olivia Manser: And that is, I think, really important because about 40% of the patients that actually continue in remission without any need for additional therapy.
Christian Itin: We also have this smaller subgroup that also refer to now the next slide, then that received a subsequent stem cell transplant. There's 18 patients. They've received this transplant while being in complete remission, not only complete remission, but also being MRD negative. So no signs of measurable disease in these patients at the time of transplant. And then, obviously, we had also a group of patients that are moving to other therapies or have relapse. So that's the status with the median follow-up of 21 months, which was the data cut that we were using for the ASCO and DHA presentations.
Olivia Manser: We also have this smaller subgroup that I'll also refer to now in the next slide, then, that received a subsequent stem cell transplant. There's 18 patients.
Olivia Manser: They received this transplant while being in complete remission, not only in complete remission, but also being MRD negative.
Christian Itin: And then obviously we had, I'll say, a group of patients that were moving to other therapies or have relapsed. So that's the status with a median follow-up of 21 months, which was the data cut that we were using for the ASCO and DHA presentation. Moving on to slide number seven, we're looking, actually, at the event-free survival of the patients, and as you can see, the event-free survival, and we're looking here at the, at the two curves with and without sensoring for stem cell transplant, but both curves you can see are stabilizing and actually are starting to form a plateau, which is very indicative of a substantial portion of these patients remaining in continued remission, which is also extremely encouraging in this very difficult group of patients who have a very aggressive form of cancer.
Speaker Change: so no sign of metrical disease in these patients at the time of transpl and then alsoiously we had also group of patients that were moving to other therapies or have relapsedsent i
Olivia Manser: so that's the status with the mediian follow up of twenty one months which was the data dropped that were using for the as twent h h presentations
Christian Itin: Moving on slide number seven, we're looking actually at the event-free survival of the patients. And as you can see, the event-free survival, and we're looking here at the two curves, with and without sensing for stem cell transplant, but both curves you can't see are stabilizing. And actually are starting to form a plateau, which is very indicative of a substantial portion of these patients remaining in continued remission, which is also extremely encouraging in this very difficult group of patients who have a very aggressive form of disease. When you see the curve actually for patients that include the stem cell transplant, that's the green curve.
Olivia Manser: Moving on slide number seven, we're looking actually at the event-free survival of the patients. And as you can see, the event-free survival, and we're looking here at the.
Olivia Manser: at the two curse
Olivia Manser: with and without a sensor for stem cell transplant, but both curves you can see are stabilizing.
Olivia Manser: actually are starting to form a plateau which is very indicative of a substantial portion of these patients remaining in continued remission which is also extremely encouraging in this very difficult group of patients who have a very aggressive form of disease.
Christian Itin: When you see the curve, actually, for patients that include the stem cell transplant, that's the green curve. The blue curve is the group where we center our patients that went on to receive the stem cell transplant. What you see when you look at those two curves is actually a picture which is the opposite of what you would normally observe in these studies.
Speaker Change: when you see curve actually for patients that have includde the stemsale transplant that's the gree curve the blue curve of the patients where we cent drive patients that would all sse so trans
Christian Itin: The blue curve are the patients where we send to our patients that went on to stem cell transplant. What you see when you look at those two curves is actually a picture, which is the opposite of what you would normally observe in these studies. Normally would have served their patients that actually with the stem cell transplant would do better. I would actually give you a better event-free survival. What we're seeing here, it looks like the inverse; certainly not doing better, possibly doing a bit worse, if they actually receive the stem cell transplant after receiving OV cell.
Speaker Change: what do you see when you look at those two curves is actually a picture which is the opposite of what youwe would normally observed these studies
Christian Itin: Normally, we'd observe that patients that are actually with a stem cell transplant would do better and would actually give you a better, eventually, survival. What we're seeing here, it looks like the inverse, certainly not doing better, possibly doing a bit worse if they actually receive the stem cell transplant after receiving ovacell. Now, when we look at slide number eight, at overall survival, we see a similar picture, certainly no evidence that a patient receiving a transplant provided them with survival.
Speaker Change: Normally, we'd observe that patients that actually with stem cell transplant would do better and would actually give you a better, eventually, survival. What we're seeing here, it looks like the inverse.
Olivia Manser: certainly not doing better, possibly doing a bit worse if they actually receive the stem cell transplant after receiving ovacell.
Christian Itin: Now, when we look at the, on slide number eight, at the overall survival, we see a similar picture; certainly, no evidence that a patient receiving a transplant provided them survival remission. And so, very interesting in the sense that clearly the product on its own appears to be able to deliver a longer-term outcome and may actually be able to serve as a standalone therapy for a subset of the patients. So, these are two of the key findings that we were presenting at ASCA and EHAID, which we move on to slide number nine. But we're evaluating there on the left-hand side the impact of these of car key persistence in event-free survival and the patients.
Olivia Manser: Now when we look at the, on slide number eight, at the overall survival, we see a similar picture. Certainly no evidence that a patient receiving a transplant provided them a survival benefit.
Christian Itin: And so, very interesting in the sense that clearly the product on its own appears to be able to deliver a longer-term outcome, may actually be able to serve as a stand-alone therapy for a subset of patients. So these are two of the key findings that we were presenting at ASCA and DHA, which we move on to slide number nine. What we're evaluating on the left-hand side is the impact of CAR-T persistence on event-free survival in patients.
Speaker Change: and so very interesting in the sense that clearly the product on its own ier should be able to liver a longer term outcome may actually be able to serve as a standal onean therapy for a subset of the patients
Speaker Change: So these are two of the key findings that we were presenting at ASTHO and EHA. If we move on to slide number nine, what we're evaluating there on the left-hand side is
Christian Itin: What you can see on the blue curve on the top are patients that have actually ongoing car key persistence, and you can see that these tend to do very well again with the stabilization of event-free survival. Patients that lose car key presence at 12 months, you can see that's the median curve, the green curve, and patients that would lose car key persistence over the in six months, if the record are tracking is tracking below. Indicating that indeed longer persistence of the car key cells appears to be associated with a better performance on the entry survival.
Christian Itin: What you can see on the blue curve on the top are patients that have actually ongoing CAR-T persistence, and you can see that these tend to do very well again with the stabilization of event-free survival. Patients that lose CAR-T presence at 12 months, you can see that's the median curve, the green curve, and patients that would lose CAR-T persistence already at six months if the red curve is tracking below, indicating that indeed longer persistence of the CAR-T cells appears to be associated with better performance in event-free survival.
Speaker Change: the impact of the of carkey persistence
Speaker Change: in the entry survival the patients what you can see on the blue curve on the top or patients that have actually ongoing car y persistence and you can see that tethtend to do very well again with the stabilization of eventually survival patients that lose cart and presence at twelve months you can see that's the mediaian incurve we incur
Speaker Change: and patients that would lose CAR T persistence already at six months if the red curve is tracking below.
Speaker Change: indicating that indeed longer persistence of the CAR T-cells appears to be associated with a better performance under that pre-survival and just as this other surrogate to look at sort of the impact, we're looking at B-cell inflation and you can see also there the same type of stagger but less differentiation between the patients. So persistence seems to be a better readout than a more reliable readout.
Rob Dolski: And just as this other surrogate to look at that, so that the impact we're looking at the celebration, you can see also there the same type of stagger, but less differentiation between the patients. So, persistence seems to be a better readout than a more reliable readout if you want to understand the potential impact for longer term outcome. Now, in summary, on slide number 10, quick takeaways from this school analysis. First of all, 40% of the responders are in ongoing remission with panic, any subsequent therapy. And this is now with immediate follow-up of 21.5 months. We clearly see evidence of a plateau forming both in event-free survival as well as an overall survival.
Christian Itin: And just as a surrogate to look at the impact, we're looking at B-cell inflation, and you can also see the same type of stagger but less differentiation between the patients. So persistence seems to be a better readout and a more reliable readout if you want to understand the potential impact on longer-term outcomes. Now, in summary, on slide number 10, quick takeaways from this pooled analysis. First of all, 40% of the responders are in ongoing remission without any subsequent therapy, and this is now with a median follow-up of 21.5 months.
Speaker Change: if you want to understand the potential impact for longer-term outcome
Speaker Change: now in summary on sllight ten quick take away from these tool analysis firstarch of all forty percent of the responders are an ongoing revismission with p any subsequent therapy and this is now with a mediian full up of twenty one point five months
Christian Itin: We clearly see evidence of a plateau forming both in event-free survival as well as in overall survival, and it does not appear that stem cell transplant-based consolidation provides an advantage for the patients and does not appear to improve event-free survival or overall survival, which is certainly an important outcome consistent with the effects we're seeing but certainly unusual in the field so far. And clearly, we do see an interesting correlation between ongoing persistence and improved event-free survival in these. With that, what I'd like to do is actually move to sort of the operational side.
Speaker Change: We clearly see evidence of a plateau forming, both in ventric survival as well as in overall survival.
Rob Dolski: And it does not appear at that stem cell transplant-based consolidation provides an advantage for the patients and does not appear to improve event-free survival or overall survival, which is certainly an important outcome. Consistent with the effects for seeing, but certainly unusual in the field so far. And clearly, we do see an interesting correlation between among persistence and improved event-free survival.
Speaker Change: and
Speaker Change: It does not appear that stem cell transplant-based consolidation provides an advantage for the patients and does not appear to improve event-free survival or overall survival.
Speaker Change: which is certainly an important outcome consistent with the effects we're seeing but certainly unusual in the field so far.
Speaker Change: And clearly we do see an interesting correlation between online persistence and improved eventually survival in these patients.
Christian Itin: With that, what I'd like to do is actually move to sort of more the operational side, and so they're getting to commercial launch readiness and move to slide number 12. As you remember, you know, we sort of have been already very active in the preparatory steps to get ready for commercialization for quite an extended period of time already. And a lot of that obviously was really focused on a key area of activities. Clearly, it's creating awareness around the medical affairs activities, as you would expect, building the value stories for market access of the product. But then what's very involved is certainly the onboarding of the treatment centers.
Speaker Change: with that what i'd like to do is actually moveved to so the more of the operational side unt il they're getting to commercial launch readiness moved to slightide down twelve
Christian Itin: And so they're getting to commercial launch readiness; move to slide number 12. As you remember, we have already been very active in the preparatory steps to get ready for commercialization for quite an extended period of time already. And a lot of that, obviously, was really focused on a key area of activity.
Speaker Change: As you remember, we sort of, you know, have been already very active in the preparatory steps to get ready for commercialization for quite an extended period of time already.
Speaker Change: And a lot of that obviously was really focused on a key area of activities.
Christian Itin: Clearly, it's the, you know, creating awareness around the medical affairs activities, as you would expect, building the value stories for market access of the product. But then, what's very involved is certainly the onboarding of the treatment centers. And that onboarding process is very involved, not only from a company perspective but also from a center perspective. That's a real effort that actually has to be put in.
Speaker Change: clearlyit's creating an awareness around the medical affairs activities as you would expect building the value stories for market access
Speaker Change: of the product. But then what's very involved is certainly the onboarding of the treatment centers.
Christian Itin: And that onboarding process is very involved, not only from a company, but also from a center perspective. That's a real effort that actually has to be put in. That goes across a kind of wide range of activities that we need to sort of integrate in, whether it's related to afferesis, to the actual delivery of the product, the handling product of the product at the center, as well as additional support that we're looking to provide both to the centers. There's on the statutory to the patients as well. It's quite an involved process, including everything related to the cell journey from the collection of the cells at the center to the manufacturing process and back.
Speaker Change: And that onboarding process is very involved, not only from a company, but also from a center perspective. That's a real effort that actually has to be put in.
Christian Itin: That goes across quite a wide range of activities that we need to sort of integrate, whether it's related to aphoresis, to the actual delivery of the product, the handling of the product at the center, as well as additional support that we're looking to provide both to the centers but also downstream to the patients as well. So it's quite an involved process, including everything related to the cell journey from the collection of the cells at the center to the manufacturing process and back. And the IT systems required to really be able to track the product and to ensure that we have a very clear chain of identity throughout the entirety of the process.
Speaker Change: that goes across a kind of wide range of activities that we need to sort of integrating
Speaker Change: whether it's related to aphoresis, to the actual delivery of the product, the handling product of the product at the center, as well as additional support that we're looking to provide both through the center as well as downstream to the patients as well.
Speaker Change: So it's quite an involved process, including everything related to the cell journey from the collection of the cells at the center to the manufacturing process and back.
Christian Itin: And the IT systems required to really be able to track the product and ensure that we have a very clear chain of identity throughout the entirety of the process. So very substantial amount of work that's ongoing there. We're on track to have between 30 and 36 centers ready for acceleration by the time of approval. And are going to move once we are getting to that point, would expect to be within the first year of launch at a level of about 60 centers onboarded and access with the product. So we're moving here in a very significant way as well as, you know, at a significant number of centers even for the initial startup phase.
Speaker Change: and the IT systems required to really be able to...
Speaker Change: to track the product and to ensure that we have a very clear chain of identity throughout the entirety of the process.
Christian Itin: So a very substantial amount of work that's ongoing there. We're on track to have between 30 and 36 centers ready for activation by the time of approval. And we are going to move once we are getting to that point, would expect to be within the first year of launch at a level of about 60, 70, on-boarded and active with the product. So we're moving here in a very significant way as well as, you know, at a significant number of centers even for the initial startup phase.
Speaker Change: So a very substantial amount of work that's ongoing there. We're on track to have between 30 and 36 centers ready for activation by the time of the
Speaker Change: and approval and are going to move once we are we're getting to that point would expect to be within the first year of launch at a level of about 60 centimeters.
Speaker Change: on-boarded and active with the product. So we're moving here in a very significant way as well as you know at a significant number of centers even for the initial startup phase.
Christian Itin: Now what we're particularly focusing on at where we are at this point in time is really looking at the integration of the workings and testing, frankly, of all the systems required to deliver the product. So there's a lot of activity going on making sure that all the interfaces are working between the different processes, the different systems. And that's a very involved process that we're actually engaging in this third quarter and leading into the fourth quarter to make sure that all elements required to deliver this therapy are fully operational and tested out. And actually has achieved the level of robustness required for a commercial operation.
Christian Itin: Now, what we're particularly focusing on where we are at this point in time is really looking at the integration of the workings and testing, frankly, of all the systems required to deliver the product. So there's a lot of activity going on, making sure that all the interfaces are working between the different processes, the different systems.
Speaker Change: now what we're particularly focusing on where we are at this point in time is really looking
Speaker Change: the integration of the workings and testing and frankly of all systems required todeliver the po there's a lot of activity going on making sure that all the interfaces those will have working between the different processes the different systems
Christian Itin: And that's a very involved process that we're actually engaged in, in the third quarter and leading into the fourth quarter, to make sure that all elements required to deliver this therapy are fully operational, tested out, and actually have achieved the level of robustness required for a commercial operation. Now, on the next slide, it's just a brief view of kind of where we are and what some of those activities are that we actually need to think about at the time when we actually do get to an approval.
Speaker Change: And that's a very involved process that we're actually, you know, engaged in.
Speaker Change: in this the third quarter and leading into the fourth quarter to make sure that all elements required to thedeliverthis therapy are fully operational tested out and actually have achief the level of robustments required for a commercial operation
Christian Itin: Now, on the next slide, just a brief view on kind of where we are and what some of those activities are that we actually need to think about at the time point when we actually do get to an approval. Obviously, we talked about the path there on the prior slide. We eventually get to a point where hopefully, along the target day, we do receive an approval for the product. Once that happens, there are several activities that need to take place on our side, and driven from the company side is really kind of the activities that are defined by the label itself.
Christian Itin: Now, on the next slide, we get a brief view of kind of where we are and what some of those activities are that we actually need to think about at the time when we actually do get to an approval. Obviously, we talked about the path there on the previous slide. We eventually get to a point where, hopefully, around the target date, we do receive approval for the product. Once that happens, there are several activities that need to take place.
Speaker Change: Now, on the next slide, it's just a brief view on kind of where we are and what some of those activities are that we actually need to think about at the time point when we actually do get to an approval. Obviously, we talked about the path there on the prior slide. We eventually get to a point where hopefully around the target date, we do receive an approval for the product.
Christian Itin: Obviously, we talked about the path there on the prior slide. We eventually get to a point where, hopefully, around the target date, we do receive approval for the product. Once that happens, there are several activities that need to take place. On our side, and driven from the company side, these are really just the activities that are defined by the label itself.
Christian Itin: On our side, and driven from the company's side, are really kind of activities that are defined by the label itself. There are certain aspects of training and activity that can only be finalized and run through at the time when the label is fully set and determined. That actually has to do with a set of trainings that have to be consistent, obviously, with the approved label, as well as, obviously, implementing a REMS strategy and training that needs to actually be implemented at that point in time.
Speaker Change: Once that happens, there are several activities that need to take place. On our side, and driven from the company side, is really kind of the activities that are defined by the label itself.
Christian Itin: And there are certain aspects of training and activity that only can actually be finalized and run through at the time when the label is fully set and determined. And that actually has to do with a set of trainings that have to be consistent, obviously, with the approved label, as well as, obviously, administering a REMS strategy and training that needs to actually be implemented at that point of time. So those are elements that from a company perspective, you'll be able to complete once the approval is in. Now the centers themselves need to run through quite a range of activities at that point in time that really make sure that they're internally ready to be able to actually manage this type of a therapy, both from an administrative perspective, as well as from an actual physical operational perspective.
Christian Itin: And there are certain aspects of training and activity that can only be finalized and run through at the time when the label is fully set and determined. And that actually has to do with a set of trainings that have to be consistent, obviously, with the approved label, as well as, obviously, administering a REMS strategy and training that needs to actually be implemented at that point in time. So those are elements that, from a company perspective, you'll be able to complete once an approval is in.
Speaker Change: and there are certain aspects of training and activity that only can actually be finalized and run through at the time when the label is ll this set
Speaker Change: anddeterminine
Speaker Change: and that actually has to do with set of trainings that are have to be consistent obviously with the approved label as well as obviously administering rents a strategy and training that needs to actually be implemented at that point time
Speaker Change: so those are elements that from a company perspective you'll be able to complete once the once an approval isin
Christian Itin: Those are elements that, from a company perspective, you'll be able to complete once approval is in. Now, the centers themselves need to run through quite a range of activities at that point in time that really make sure that they're internally ready to be able to actually manage this type of therapy, both from an administrative perspective, as well as from an actual physical operational perspective. You see quite a set of those activities that will actually have to be worked through on the center and the inside of the center.
Christian Itin: Now, the centers themselves need to run through quite a range of activities at that point in time that really make sure that they're internally ready to be able to actually manage this type of therapy, both from an administrative perspective, as well as from an actual physical operational perspective. And you see quite a set of those activities that sort of will actually have to be worked through on the center and the inside of the center. And you can see that on the right-hand side spelled out in a bit more detail.
Speaker Change: Now the centres themselves need to run through quite a range of activities at that point in time that really make sure that they're internally ready to be able to actually manage this type of a therapy both from an administrative perspective as well as from an actual physical operational perspective and you see quite a set of those activities that sort of will actually have to be
Christian Itin: And you see quite a set of those activities that sort of will actually have to be worked through on the center and the inside of the center. And you can see that at the right-hand side, spell that in a bit more detail. Now, when we think about what that means from an overall timing perspective, you can see the blue curve or blue arrow up there is actually quite a range of time that we actually see where, from that high point, where the center actually can get. It actually, until it actually would enroll a first patient, and we will see certainly a variety of human centers in terms of the time it will take to be on board and be enrolling patients to look at that in a bit more detail.
Speaker Change: work through on the center and the inside of the center and you can see that at the right hand side spell that in a bit more detail.
Christian Itin: Now, when we think about what that means from an overall timing perspective, you can see the blue curve or blue arrow up there is actually quite a range of time that we actually see from that time point where the center actually can get activated until it actually enrolls the first patient. And we will certainly see variability among centers in terms of the time it will take to be on board and enroll patients.
Speaker Change: now when we think about what that means from an overall timing perspect as you can see the blue curve or blue arrow there is actually s quite a range of time that we actually see
Speaker Change: where from that time point where the center actually can get activated until it actually would enroll the first patient. And we will see certainly a variability among centers in terms of the time it will take to be on board and be enrolling patients.
Christian Itin: To look at that in a bit more detail, we will go to the next slide and just look at, in a relatively simple way, what are some of those key activities in time lapse.
Christian Itin: and just look at sort of the sort of in a relatively simple way of what are some of those key activities and timelines. So, completing the site accreditation, we expect we'll take anywhere from two to 12 weeks with the sensors that we have prepared for the Young Boarding process, but are now from the time point where you can actually initiate the site activation. We'll have to take anywhere between two and 12 weeks. Autotatients, cleaning, lubricants, schedule, then having that completed, anywhere from one to two weeks at that point in time, and then obviously he anticipated ready to delivery time of 16 days.
Speaker Change: to look at that in a bit more detail we will go to the next slide
Speaker Change: and just look at sort of the sort of in a relatively simple way of what are some of those key activities and timelines.
Christian Itin: So completing the site accreditation, we expect it will take anywhere from two to 12 weeks with the sensors that we have prepared for the onboarding process but are now from the time point where you can actually initiate the site activation. We'll have take anywhere between two and 12. Of the patient screening, glucose resync schedule, then having that completed anywhere from one to two weeks at that point in time, and then obviously the anticipated ready-to-delivery time of 16 days.
Speaker Change: so completing ide a creditation we expect will take anywhere from two to twelve weeks
Speaker Change: with the sensors that we have prepared for the onboarding process, but are now, from the time point where you can actually initiate the site activation, will take anywhere between 2 and 12 weeks.
Speaker Change: Of the patient screening, glucofree is scheduled and having that completed anywhere from one to two weeks.
Christian Itin: So when you think about that, and you think about a target date, a PDUFA target date of the middle of November, and as well as sort of year-end holidays, it is reasonable to assume that the first patient dose will be happening in the early part of 2025, if we're operating on that. So I think that sort of, hopefully, gives you a sense for what it means to start up and what are sort of reasonable assumptions around when to expect kind of the first patient's dose. And then, obviously, it would gear up from there as we go through the course of the year.
Christian Itin: So, when you think about that, and you think about a target date for the target date of middle of November, and as well as for the year and holidays, it is reasonable to assume that the first patient dose will be happening in the early part of 2025. So, I think that sort of I think hopefully gives you a sense for what it means to start up, and whatever sort of reasonable assumptions around when to expect kind of first patient status, and then obviously would get up from there as we go to the course of the year.
Speaker Change: at that point in time, and then obviously the anticipated ready-to-delivery time of 16 days. So when you think about that,
Speaker Change: and you think about it a target date u a target date the middle of november and as well as of the year and holiday it is reasonable to sue that the first patient does will be happening in the early part of two thousand and twenty five if we're operating on those time
Speaker Change: so i think that sort of i think hopefully gives you sense for what it means to start up and whatought are of the reasonable assumptions around going to expect kind of first patient st and then obviously it would give up from d as we go through the course of the year
Christian Itin: Now, with that, what I'd like to do is switch gears and just briefly talk about sort of the OVCEL product family on slide 16, such as the opportunity. If this is a slide you've seen before, also continue to work normally on the current activity in on the adult AML side, but also working on the pediatric side as well as the old immune side with OVCEL, and we'll continue to actually work on order 122 as well as all the way. So, all the 122, most of the pediatric ALL side where we do additional work with the UCLH and GOSH, our partners for that program for a long period of time.
Christian Itin: Now, with that, what I'd like to do is switch gears and just briefly talk about sort of the OVCell product family on slide 16, Franchise Opportunity, if this is a slide you've seen before. Also, we continue to work not only on the current activity on the adult ALL side but also on the pediatric side as well as the autoimmune side with OVCell. And we'll continue to work on Auto-122 as well as Auto-8.
Speaker Change: Now, with that, what I'd like to do is switch gears and just briefly talk about sort of the OBCell product family on slide 16, Franchise Opportunity, if it's a slide you've seen before.
Speaker Change: also have continued to work in no mily on the current activity in d a well side but also are working on a pediatric side as well last o inside would be so and we'll continue to actually at work on over ong twenty two as well as all the way
Christian Itin: Auto-122 mostly on the pediatric ALL side where we do additional work with UCLH and GOSH, our partners for that program for a long period of time, and we're also obviously with AutoAid continuing to work on the multiple myeloma side, but we're also looking to sort of expand the opportunity for that program going forward as well, and we'll update you as we go as we go forward and initiate next studies with that We had one major conference that happened in Q2, which was the ULAR conference. Interesting data sets were presented during the course of the conference.
Speaker Change: All the 122 are mostly on the pediatric ALL side, what we do.
Speaker Change: additional work with the UCLH and GOSH, our partners for that program for a long period of time.
Christian Itin: And we're also obviously with all the way continue to work on the multiple OVCEL, but we're also looking to expand the opportunity for that program going forward as well, and we'll update you as we go as we go forward and initiate next studies with that program when that actually happens. So, with that, just a quick word on the environment on the autoimmune side of the state that many of you have watched very carefully. We have one major conference that happened in Q2, which is the UR conference, interesting data set presented during the course of the conference.
Speaker Change: And we're also, obviously with AutoAID, continue to work on the multiple myeloma side, but we're also looking to sort of expand the opportunity for that program going forward as well. And we'll update you as we go forward and initiate next studies with that program.
Speaker Change: when that actually happens.
Speaker Change: So, with that, just a quick word on the environment on the autoimmune side of CIS space that many of you have watched very carefully. We had one major conference that happened in Q2, which is the ULAR conference. Interesting data sets presented during the course of the conference.
Christian Itin: I think what we're starting to see is some differences that appear between programs. Still early days in terms of understanding what is contributing to some of the differences that are being observed. To what extent are those product driven, to what extent are those factors variability in the patients that are being treated. But certainly very interesting development that we're seeing, but also overall, I think also very nice cooperation of the initial observations that we have seen with GARCES in airline that indeed there is a very profound impact that can be had in those patients using CARTI approaches.
Christian Itin: I think what we're starting to see is some differences that appear between programs, still early days, in terms of understanding what is contributing to some of the differences that are being observed, to what extent are those product-driven, and to what extent are those factors variability in the patients that are being treated. But certainly very interesting development that we're seeing, but also overall, I think also very nice cooperation of the initial observations that we have seen with Gare of Shetland Airlines that indeed there is a very profound impact that can be had on those patients using CAR-T approaches.
Speaker Change: i think we're be starting to see it some differences that appear between programs still early days in terms of understanding what is contributing to some of the differenceses that are being observed to what extent or there was
Speaker Change: product-driven, to what extent are those factors of variability in the patients that are being treated.
Speaker Change: But certainly very interesting development that we're seeing, but also overall I think also very nice cooperation.
Speaker Change: of the initial obxidations that we have seen with their shipped in airline in that and we that profound impact that can be
Christian Itin: When we look at the next slide, just to remind you, obviously, that we have a program that has a remarkable service similarity in terms of the clinical properties to the program that's used in Air London. We have, but also not only do we have a high degree of similarity in terms of the efficacy, the persistence on the pediatric LL side where we can compare the programs directly. But also, obviously, we do have a very substantial amount of safety data, and which also is an area where we can see differentiation to the program in airline, but also the differentiation to any of the other CARTI programs that are currently commercially available.
Christian Itin: When we look at the next slide, just to remind you, obviously, that we have a program that has a remarkable degree of similarity in terms of clinical properties to the program that's used in air lunging. We have, but also, not only do we have a high degree of similarity in terms of the efficacy and the persistence on the pediatric ALL side, where we can compare the programs directly, but also, obviously, we do have a very substantial amount of safety data, which also is an area where we can see differentiation between the program in air lung and also differentiation to any of the other CAR-T programs that are currently commercially available.
Speaker Change: had in those patients using CAR T approaches.
Speaker Change: When we look at the next slide, just to remind you, obviously, that we have a program that has a remarkable set of similarity.
Speaker Change: in terms of the clinical properties to the program that's used in Erlangen. We have, but also, not only do we have a high degree of similarity in terms of the efficacy, the persistence on the pediatric ALL side where we can compare the programs directly,
Speaker Change: But also, obviously, we do have a very substantial amount of safety data, which obviously is an area where we can see differentiation to the program in airline, but also, obviously, differentiation to any of the other CAR-T programs.
Christian Itin: And what you see is just a summary on the right of the table of the various key outcomes that we have seen across the various studies that we've conducted with OBCell, and I think it gives you a very good view of the level of activity that we're seeing and the ability to achieve those levels of activity with a very attractive safety profile. Now, the study on slide 19, the Carlisle study, our phase one study in SLE, as I indicated, the study obviously, the start-up happened during the latter part of Q1 and into Q2.
Christian Itin: And what you see is just a summary there on the live and the table on the various key outcomes that we have seen across the various studies that we've conducted with OBSEL. And I think if you have a very good view on the level of activity that we're seeing, and the ability to achieve those levels of activity with a very attractive safety process. Now, the study on slide 19, the Curlized Study Outface, one study in SLE, as they indicated, the study of a study startup happened during the latter part of Q-Ominin, Q-2, first patient, Dostin, Q-2, and the continued control control of the study.
Operator: 24 Financial Results and Business Updates. As a reminder, this conference call is being recorded.
Speaker Change: that are currently commercially available. And what you see is just a summary there on the right on the table on the various key outcomes that we have seen across the various studies that we've conducted with OBCell. And I think gives you a very good view on the level of activity that we're seeing and the ability to achieve those levels of activity with a very attractive safety profile.
Olivia Manser: I would now like to turn this conference over to your host, Olivia Manser. Please go ahead. Thanks, Sean.
Olivia Manser: Good morning, all good afternoon, everyone. And thanks for joining us on today's call. With me today are Dr. Christian Itin, our Chief Executive Officer and Rob Dolski, our Chief Financial Officer. So on slide two, before we begin, I just want to remind you again that during today's call, we will make statements related to our business. This is a forward looking under federal securities laws and the safe part of provisions of the private securities litigation reform act of 1995.
Speaker Change: Now, the study on slide 19, the Carlisle study, our Phase I study in SLE, as I indicated,
Speaker Change: The study, I would say, the start-up happened during the latter part of Q1 and into Q2.
Christian Itin: The first patient dosed in Q2, and we're continuing to enroll in the study. We're planning six patients at a 50 million cell dose level, which obviously is a level that we know to be highly active in pediatric ELL and actually be a well-given hospital response and also a level that is also highly active in the adult patient population where, as a reminder, we're using as little as 10 million cells to induce complete permissions in patients with high tumor burden.
Olivia Manser: These may include but are not limited to statements regarding the state's clinical trials and development and or regulatory timelines for our product candidates and our expectations regarding our cash runway. These statements are subject to a variety of risks among certainties that could cause actual results with different material from the expectations and reflect our views only as of today. We see no obligation to update any such forward looking statement. For a discussion of the material risks and uncertainties that could affect our actual results, these refer to the risks identified in today's press release and our SEC filing, both available on the investor section of our website.
Christian Itin: We're planning six patients at a 50 million cell dose level, which obviously is a level that we know to be highly active, and to be able to get a little bit of a small record in these responses, and also a level of those that is also highly active in the adult patient population, where, as a reminder, we're using as little as 10 million cells to induce complete permissions in patients with high tumor burden in that setting. So overall, I think we're at a very interesting stage; we're starting to sort of get first insights from a data perspective, and we'll also continue to collect that data with a plan to have an additional update on clinical data later in the year.
Speaker Change: first patient go in q two and we continue r congol in the study wewerere planning six patients at a fifty million cellgos level which obalso is lel that we know that be highly active in the attributbe elevget much morerecord
Speaker Change: forsted and and also a level of those step is also highly actiated theadult patient population where as a remind of reusing as little as ten million sales to induce complete permissions and patensiions call u revert mean that setting
Christian Itin: So overall, I think we're in a very interesting stage. We're starting to sort of get first insights from a data perspective, and we'll also continue to collect that data with a plan to have an additional update on clinical data later. Now, other pipeline programs on slide 21, as you remember, there are a number of other programs we're working on. I think, with regard to AutoAID, I already indicated that we're looking at potentially expanding the program into additional indications.
Olivia Manser: On slide three, you will see the agenda for today's call. Christian can provide an overview of our operational highlights, Rob will then discuss the financial results before handing back to Christian to conclude and take Q&A.
Speaker Change: so overall i think we're a very interesting stage we're starting to sort of get first insight from a data perspective and well to continue to collect that data with a plan to have an additional update on clinical data late in the year
Christian Itin: So over to you, Christian. Thanks a lot Olivia and welcome everybody to our second quarter earnings call, real pleasure to have you all on and I'd like to start on slide number four, but just a brief summary of the key highlights for the quarter. As you can imagine, we're in the process of going to the various review processes for OV cell, both in the US as well as in Europe, most recently now also in the UK.
Christian Itin: Now, other pipeline programs on slide 21, as you remember, there's a number of other programs we're working on. I think with regards to Auto-A, they're already indicated that we're looking at the potential expanding the program into additional indications, so that's something that's ongoing, and we'll update, certainly, by the end of the year, or the next year, so that the trajectory is going to be on. And then just as a quick highlight, because we haven't actually talked about that in a while, as all of six NG, that program also is enrolling patients and the first patient actually has been treated as well in the second quarter, as part of the progress that we were making through the quarter.
Speaker Change: now other pipeline programs on slide twenty-one as you remember there's a numberof ofother programs are working on
Speaker Change: I think with regards to...
AutoAIDA: AutoAIDA already indicated that we're looking at potentially expanding the program.
Christian Itin: So that's something that's ongoing, and we'll update you, certainly by the end of the year or the next year, on sort of the trajectory we're going to be on. And then just as a quick highlight, because we haven't actually talked about that in a while, there's Auto6MG. That program is also enrolling patients, and the first patient actually has been treated as well in the second, as part of the progress that we were making during the quarter.
Speaker Change: tradditional indications so that's something that's ongoing and we'll update sort of lilive by the end of the year urban next year on so the the trjectje we're going to beond
Christian Itin: So that's been the primary focus from an operational perspective. I think we've making good progress and are in track with all the various interactions that we have with the regulatory authorities. The due for target date, as you may remember is November 16th this year and we're tracking well towards that timeline. We've also initiated or have currently ongoing two phase one clinical trials, one is in pediatric ALL, which is a trial that is moving very nicely and obviously we're excited about applying and having OV cell evaluated in pediatric patients.
Speaker Change: And then, just as a quick highlight, because we haven't actually talked about that in a while, is Auto6MG. That program also, obviously, is enrolling patients and first patients actually has been treated as well in the second quarter.
Christian Itin: So overall, progressing well, and was also expected additional publications to come out during the second half of the year related to our clinical programs that we've been conducting.
Speaker Change: and as part of the progress that we were making during the quarter.
Speaker Change: so overall progressing well and was also expected additional publications to come out during the second half of the year related to our clinical programs
Rob Dolski: With that, I'd like to hand over to Rob, who will landly use through the financial results. Thanks, Christian, and good morning and good afternoon to everyone. It's my pleasure to review our financial results for the second quarter of 2024. So I am on slide 23, where we see at the top our cash and cash equivalence at the end of June 2024, total 705.9 million. That's compared to 239.6 million at the end of last year, December 31st. Our total net operating expenses for the three months ended June 30th, 2024, were 58.9 million as compared to 44.4 million for the same period of 2023.
Christian Itin: So, overall, progressing well, and we also expect additional publications to come out during the second half of the year related to our clinical programs that we've been. With that, I'd like to hand over to Rob, who will lead you through the financial results. Thanks, Christian, and good morning or good afternoon to everyone. It's my pleasure to review our financial results for the second quarter of 2024.
AutoAIDA: that we've been conducting.
Speaker Change: With that, I'd like to hand over to Rob, who will lead you through the financial results.
Rob: Thanks, Christian. And good morning or good afternoon to everyone.
Christian Itin: You can see that on the right-hand side. I'll spell that out in a bit more detail. Thanks, Christian, and good morning or good afternoon to everyone. It's my pleasure to review our financial results for the second quarter of 2024.
Christian Itin: That's ongoing and what we're for obviously in the upcoming periods on that trial. And in addition, the phase among trial with patients that have an advanced stage, a relaxed flash refractory stage of systemic lupus. This is the Carlisle study. We opened the study in the beginning of the year and we those are first patients, the second quarter, and we continue enrollment in that study as we have projected. We importantly, as we went through the course of the quarter, we did focus on the update of the clinical data from our pivotal Felix study, the phase two study that on the pinning the regulatory filing that we've made with the various authorities.
Rob Dolski: Thanks, Christian. And good morning or good afternoon to everyone. It's my pleasure to review our financial results for the second quarter of 2024.
Rob: It's my pleasure to review our financial results for the second quarter of 2024. So I am on slide 23, where we see at the top our cash and cash equivalents at the end of June 2024 totaled $705.9 million. That's compared to $239.6 million at the end of last year. Our total net operating expenses for the three months ended June 30, 2024, were $58.9 million as compared to $44.4 million for the same period in 2023.
Rob Dolski: so i am on slide twenty three where we see at the top our cash and cash equivalents at the end of june two thousand and twenty four total seven hundred five point nine million that's compared to two hundred and thirty nine point six million at the end of last year december thirty first
Speaker Change: Our total net operating expenses for the three months ended June 30, 2024, were $58.9 million as compared to $44.4 million for the same period of 2023.
Rob Dolski: For research and development, these expenses increased from 33.2 million to 36.6 million for the three months ending June 30th, 2024, compared to the same period in 2023. This change was primarily driven by increases in operating costs related to our new manufacturing facility, employee salaries, and related costs, and OB cell clinical trial and manufacturing costs. These were partially offset by a more favorable UK R&D tax credit reimbursement for the period as well. General administrative expenses increased from 11.1 million to 21.9 million for the three months ending June 30th, 2024, compared to the same period last year.
Rob: For research and development, these expenses increased from $33.2 million to $36.6 million for the three months ending June 30, 2024, compared to the same period in 2023. This change was primarily driven by increases in operating costs related to our new manufacturing facility, employee salaries and related costs, and OVCell clinical trial and manufacturing costs. These were partially offset by a more favorable U.K. R&D tax credit reimbursement for the period as well. However, general administrative expenses increased from $11.1 million to $21.9 million for the three months ending June 30, 2024, compared to the same period last year.
Speaker Change: For research and development, these expenses increased from $33.2 million to $36.6 million for the three months ending June 30, 2024, compared to the same period in 2023.
Christian Itin: Importantly, we looked at a number of aspects that we haven't actually explored to the same extent in our prior publications and presentations around the program. One of course is to look for the longer term outcome. And what we do see is that we do start to see a stabilization of both event free survival as well as overall survival in the page and in the study and we're starting to see a plateau forming, which is obviously something we've been very keen to evaluate.
Speaker Change: This change was primarily driven by increases in operating costs related to our new manufacturing facility, employee salaries and related costs, and OV-Cell clinical trial and manufacturing costs.
Speaker Change: these were partially offset by a more favorable u k r indtax credit reimbursement for the period as well
Speaker Change: General administrative expenses increased from $11.1 million to $21.9 million for the three months ending June 30, 2024, compared to the same period last year.
Christian Itin: And we start seeing that now actually stabilized with more follow-up in the study. What was quite interesting and I'll show you the data a little later as well is that quite typically what we have in this particular patient setting is that you actually look to consolidate the effect that you could deduce of the particular therapy to induce longer term outcome. And typically, what you do is you actually have the patients on the go a stem cell transplant when they are in complete remission and ideal in market negative, which is the case for all our patients.
Rob Dolski: This increase was primarily due to salaries and other employment-related costs driven by increased headcount supporting our overall pre-commercialization activities. And finally for the company, NetLoss was 58.3 million for the three months end of June 30th, compared to 45.6 million for the same period in 2023.
Rob: This increase was primarily due to salaries and other employment-related costs, driven by increased headcount supporting our overall pre-commercialization activity. And finally, for the company, its net loss was $58.3 million for the three months ending June 30th, compared to $45.6 million for the same period in 2023.
Speaker Change: This increase was primarily due to salaries and other employment-related costs, driven by increased headcount supporting our overall pre-commercialization activities.
Speaker Change: And finally for the company, net loss was 58.3 million for the three months ending June 30th compared to 45.6 million for the same period in 2023.
Rob Dolski: Autolus estimates that with current cash and cash equivalents, we are well-capitalized to drive the full launch and commercialization of OBSEL in relapse refractory adult ALO, as well as to advance its pipeline development plans, including runway to date in the first pivotal study of OBSEL in autoimmune disease.
Christian Itin: Autolus estimates that with its current cash and cash equivalents, it is well-capitalized to drive the full launch and commercialization of OBCell in relapsed refractory adult ALL, as well as to advance its pipeline development plans, including a runway to date for the first pivotal study of OBCell in autoimmune disease. I'll now hand things back to Christian to wrap up with a brief outlook on milestones. Christian.
Christian Itin: What was quite surprising to see and you'll see the data in a short while as well is that we didn't appear that the consolidation with the stem cell transplant improves the outcomes for the patients, which is very different from the other therapeutic options that are currently available in the space. We also, I think, had a closer look at the role of persistence into longer term outcome, as well as the impact of bridging therapies and particularly also the use of in a twosomap in patients that have very high tumor burden at time of inclusion and where we did see a very effective approach here in terms of bridging with in a twosomap.
Autolus: Autolus estimates that with its current cash and cash equivalents, we are well capitalized to drive the full launch and commercialization of OBCell in relapsed refractory adult ALL, as well as to advance its pipeline development plans, including a runway to date in the first pivotal study of OBCell in autoimmune disease.
Christian Itin: I'll now hand things back to Christian to wrap up with a brief outlook on milestones.
Christian Itin: Christian, okay, let me, I'll jump in here. We're ready for Christian.
Speaker Change: I'll now hand things back to Christian to wrap up with a brief outlook on milestones. Christian?
Christian Itin: Okay, let me, I'll jump in here. We're waiting for a question. Maybe we should move to slide 25.
Christian Itin: Now, in terms of the operational side of the business and the government side, we get strength in our board. We had Mike Barney join as the new chair of the company and Robin Brown, who's an expert in autoimmune diseases and inflammatory diseases. So, broadening off the skill set on the board and obviously a sort of the next step in terms of the evolution, both from a movement towards commercialization, which is obviously where I want Mike Barney's background is very strong.
Christian Itin: Maybe moving to slide 25. Just again to hit on some of the anticipated milestones through the year end. We've got the target action date on the FDA side with the PDUFA, as Christian mentioned, that's November 16th, 2024. And we'll have updates certainly at the end of Ash. You've seen some of those with the ASCO data in IHA that'll be further advanced in and presented towards the end of the year. And then, as Christian mentioned on the SLE phase one study, we expect initial data from that program later in the year.
Speaker Change: Okay, let me, I'll jump in here. We're waiting for Christian. Maybe moving to slide 25.
Christian Itin: Just again, to hit on some of the anticipated milestones through the year end. We've got the target action date on the FDA side with the PDUFA, as Christian mentioned, that's November 16, 2024. And we'll have updates certainly at the end of ASH. You've seen some of them with the ASCO data and EHA. That'll be further advanced and presented towards the end of the year. And then, as Christian mentioned in the SLE phase one study, we expect initial data from that program later in the year.
Speaker Change: Just again to hit on some of the anticipated milestones through the year end.
Speaker Change: We've got the target action date on the FDA side with the PDUFA, as Christian mentioned, that's November 16, 2024.
Speaker Change: And we'll have updates certainly at the end of ASH. You've seen some of those with the ASCO data and EHA. That'll be further discussed.
Christian Itin: But also an expansion from a medical perspective into adjacent indications outside of oncology, where it's clearly where Robby Raul's piece of a particular experience is extremely valid. Now, in addition, obviously we've been driving through a remarkable amount of growth and maturation of the organization as we're setting up our commercial manufacturing capabilities, you know, getting through first regulatory filings and keep pushing through that process and preparing for commercialization. And there is a group of very talented leaders within the companies that have really risen to the challenge and have started to tackle fantastic job and recognition of their work and their leadership have been promoted to senior vice presidents within the organization.
Speaker Change: advanced in and presented towards the end of the year. And then as Christian mentioned on the SLE Phase 1 study, we expect initial data from that program later in the year.
Christian Itin: So Rob, thanks a lot for jumping in. My headset was basically given up, so what I actually wanted to say in addition to the news flow is that we're going to be obviously laser-focused on getting the program through registration, through first approval, and getting the launch off the ground with the product. That will be the primary focus of the company. Looking forward to the data updates, absolutely, but operationally, that is what we're really going to be keeping our eye on, and we're looking forward to keeping you updated on the progress there. And now we're happy to actually go into the Q&A.
Christian Itin: So Rob Faxilov for jumping in, I had my headset was basically given up. So what I actually wanted to say, in addition to the news flow, is really that we're going to be able to stay lazy, focused on getting the program through the registration for first approval and getting the launch of the grant with the product. That will be the primary focus of the company. Looking forward to the data updates absolutely, but operationally that is what we're really going to be having our eye on, and we're looking forward to keeping the update in on the progress there.
Speaker Change: So Rob, thanks a lot for jumping in. My headset was basically given up. So what I actually wanted to say, in addition to the news flow, is really that
Rob Dolski: We're going to be obviously later focused on getting the program through the registration to first approval.
Speaker Change: and getting the launch off the ground with the product. That will be the primary focus of the company. Looking forward to the data updates, absolutely, but operationally that is what we're really going to be having our eye on and we're looking forward to keeping you updated on the progress there.
Operator: And now we're happy to actually go into TNA.
Christian Itin: And this includes Brian on the regulatory side, Chris Gray, site head for Steven H. Marcus Creel on quality, Claudia Mercedes to really operations of the manufacturing technical operations side that also actually in a broader role in that and then Dylan Patel, who's looking into market access and obviously in a fantastic job on that side as well.
Operator: Thank you.
Operator: Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you'll need to press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A transcript. And our first question comes from Gil Blum with Needham & Company.
Operator: At this time, we will conduct the question-and-answer session. As a reminder, to ask a question, you'll need to press star 11 on your telephone and wait for all your questions. Please press star 11 again. Please stand by while we compile the Q&A roster.
Speaker Change: And now we're happy to actually go into Q&A.
Speaker Change: Thank you. At this time, we will conduct the question and answer session.
Speaker Change: As a reminder, to ask a question, you'll need to press star 11 on your telephone and wait for your name to be announced.
Speaker Change: To withdraw your question, please press star 1 1 again.
Speaker Change: Please stand by while we compile the Q&A roster.
Christian Itin: So great to see this group of leaders really grow up and within the organization and, you know, having made substantial contributions that we expect to see a lot of important contributions going forward to the business moving to slide number six. I would like to just briefly remind you of some of the key data that we did update on at that store, as well as the EHA, both meetings happened during the course of June this year.
Gil Bloom: And our first question comes from Gil Bloom with Needham and Company. Hi, good morning everyone, and thanks for taking our question. So first one, as it relates to the launch, I'm sensing here maybe something about rolling launch. Would we see sites coming on, you know, over time basically?
Speaker Change: right
Gil Blum: Hi, good morning, everyone, and thanks for taking our questions. So, first one, as it relates to the launch, I'm sensing here maybe something of a rolling launch. Would we see sites coming on? over time, basically.
Speaker Change: And our first question comes from Gil Blum with Needham and Company.
Gil Blum: Hi, good morning, everyone, and thanks for taking our questions.
Gil Blum: so first one as it relates to the launch that i'm sensing here maybe something of a rolling launch would we see s coming on you know
Christian Itin: Over time, basically.
Christian Itin: Hi Gil, that's actually not what it is. What we're trying to do is just explain that the actual activation at the centers is ultimately a decision or, frankly, a process that's governed by the centers. And the timeline that we're seeing, you know, anywhere from about two weeks to twelve weeks is pretty much what we see across the space with centers that are ready to actually get activated and then the actual time of activation.
Christian Itin: Hi, Gil. That's actually not what it is. What we're trying to do is just explain that the actual activation at the centers is ultimately a decision, or frankly, a process that's governed by the centers. And the timeline that we're seeing anywhere from two weeks to 12 weeks is pretty much what we see across the space with centers that are ready to actually get activated and then the actual time of activation. A lot of time it is actually also driven in the centers by fragmentation theory and neotherapy, and that usually actually accelerates the process and the final stretch of the activation.
Speaker Change: you know over time basically.
Christian Itin: What we did focus on is actually look at the totality of the data from the Felix study and as you remember the Felix study has three boards that might by far the largest cohort are the patients that have relaxed their proper relax for factory disease with morphological disease some more than five percent to a burden. And this is the vast majority of the patients that we have treated. We have also had two small cohorts in addition that we have included in the study a small cohort for patients that have isolated extra money disease that's typically a cohort that actually gets excluded from clinical trials because of the difficult nature of the disease and the challenges of managing those patients, but also a small cohort of patients that have minimal residual disease.
Speaker Change: Hi Gil, that's actually not what it is. What we're trying to do is just explain that the actual activation at the centers is ultimately a decision or frankly a process that's governed by the centers.
Speaker Change: And the timeline that we're seeing, you know, anywhere from about 2 weeks to 12 weeks is pretty much what we've seen.
Speaker Change: across the space with senders that are ready to actually get activated and then the actual time of activation a lot of time it is actually also driven is centers by frankic patients therevery other therapy
Christian Itin: A lot of time, it is actually driven in the centers by, frankly, patients that are in need of therapy, and that usually actually accelerates the process and the final stretch of the activation. This is not a rolling launch by any stretch of the imagination. Being able to be out of the gate, you have 30 to 36 centers ready to activate at that point, which has been all, you know, the internal part of the centers. That compares very favorably to almost all launches that have actually been done in our space. And could you go from there to 60 centers within a year? That would give us more than 90% access, patient access, in this indication, which is obviously very,
Christian Itin: This is not a role in launch by any stretch of the imagination. Being able to be out of the gate, you have 30 to 36 centers ready to activate at that point, which has been all, you know, the internal part of the centers that compares very favorably to almost all launches that actually have been done in our space. Could you go from there to 60 centers within a year, or give us more than 90% access, patient access in this indication, which is obviously a very, very happy field, a much more happy thing to see across the competitive programs. Thank you for the clarification.
Speaker Change: and that's usually actually accelerates the process and the filed search of the activation
Speaker Change: This is not a rolling launch by any stretch of the imagination.
Speaker Change: Being able to be out of the gate, to have 30 to 36 centers ready to activate at that point, which has been all, you know, the internal part of the centers, that compares very favorably to almost all launches that actually have been done in our space.
Christian Itin: So disease burden below five percent, but of off 10 to the minus three. So very relatively narrow corridor or MRD, MRD positive disease. So that's the group. We actually analyze the totality of that data and as you can see, this is a total of 127 and huge patients. And what we're starting to see is incredible encouraging in terms of the patients that actually are in ongoing remission without subsequent cell cancer or other therapy.
Speaker Change: Could you go from there to 60 centers within a year will give us more than 90% access, patient access, in this indication, which is obviously a very, very rapid build, much more rapid than I think we've seen across the competitive programs.
Christian Itin: Thank you for the clarification. And maybe moving to the autoimmune data, so... Probably then. The top question is, what level of data disclosure should we expect at the center? Are we talking mostly safety, or will there be some follow-up to suggest efficacy as well?
Christian Itin: And maybe going to the autoimmune data, so for...
Christian Itin: And maybe going to be on immune data.
Speaker Change: Thank you for the clarification.
Christian Itin: So probably the top question is, what level of data disclosure should we expect to the center in talking about the safety, or will there be some follow-up to suggest efficacy as well? I think the motion of the update will clearly be on take and short term impact, or shorter term impact of the therapy as indicated between the first patient Q2. So that gives you the maximum observation time that you will have. And obviously the rest of the patients will be at a shorter time period than obviously a Q2 to the end of the year timeline.
Speaker Change: Let me go over to the autoimmune data.
Christian Itin: And that is I think really important because about 40 percent of the patients that actually continue in remission without any need for additional therapy. We also have this smaller subgroup that also refer to now the next slide then that received a subsequent stem cell transplant, there's 18 patients. They've received this transplant while being in complete remission, not only complete remission, but also being MRD negative. So no signs of measurable disease in these patients at the time of transplant.
Speaker Change: Probably the top question is, what level of data disclosure should we expect at the center? Are we talking mostly safety or will there be some follow-up to suggest efficacy as well?
Christian Itin: I think that most of the update will clearly be on safety and the short-term impact or shorter-term impact of the therapy. As I indicated, we treated the first patient in Q2, so that gives you the maximum observation time that you will have, and obviously, the rest of the patients will be at a shorter time period than obviously a Q2 to end-of-the-year timeline. So there's going to be, you know, initial data that will indicate activity, but obviously, there will not be a substantial amount of follow-up yet.
Speaker Change: I think most of the update will clearly be on safety and short-term impact.
Speaker Change: or shorter-term impact of the therapy. As I indicated, we treated the first patient in Q2, so that gives you the maximum observation time that you will have. And obviously, the rest of the patients will be at a shorter time period than obviously a Q2 to end-of-the-year timeline.
Christian Itin: So there's going to be, you know, initial data that will indicate the activity that also will not be a substantial amount of follow-up yet or no participation.
Christian Itin: And then obviously we had also group of patients that are moving to other therapies or have relapse. So that's the status with the median follow-up of the 21 months, which was the data cut that we were using for the ASCO and DHA presentations. Moving on slide number seven, we're looking actually at the event-free survival of the patients. And as you can see, the event-free survival, and we're looking here at the two curves, with and without sensing for stem cell transplant, but both curves you can't see are stabilizing.
Speaker Change: So there's going to be, you know, initial data that will indicate activity, but obviously will not be a substantial amount of follow-up yet for most of the patients.
Christian Itin: Maybe a bit of a end of week's question. So we saw data updates for parties that include 4-1-B-B coast them versus CT-28 coast them. And, you know, historical people have talked about how CT-28 tends to, you know, have very high ramp up in cells but also leads to maybe higher toxicities. And 4-1-B-B can link to, you know, really long-up playshoes.
Christian Itin: Maybe a bit of an in-the-weeds question. So we saw data updates for CAR T's that include 4-1BB co-stem versus CD28 co-stem. And, you know, historically, people have talked about how CD28 tends to, you know, have very high ramp-up in cells but also leads to maybe higher toxicities, and 4-1BB can link to, you know, really long aplasias. Maybe there are AID, you know, autoimmune indications that are more amenable to one versus the other. I'm hoping your thoughts will help me.
Speaker Change: and maybe a bit of an in-the-weeds question. So, we saw data updates for CAR-2s that include 4,1BB co-stem versus CD28 co-stem. And historically, people have talked about how CD28 tends to have very high ramp up in cells, but also leads to...
Christian Itin: and you know, historically, people have talked about how CD28 tends to have a very high ramp-up in cells but also leads to
Christian Itin: And actually are starting to form a plateau, which is very indicative of a substantial portion of these patients remaining in continued remission, which is also extremely encouraging in this very difficult group of patients who have a very aggressive form of disease. When you see the curve actually for patients that include the stem cell transplant, that's the green curve. The blue curve are the patients where we send to our patients that went on to stem cell transplant.
Speaker Change: Maybe it's higher toxicities, and 4-1BB can link to really long aplasias.
Christian Itin: Maybe there are AID, you know, autoimmune indications that are more amenable to one versus the other of kind of probing your thoughts here. So what you mentioned is referring to is that the costumatory domain has sort of an impact on the initial activity that we see of the cells, particularly the cell expansion of the CAR-T cells that we're seeing. And that is circulated generically through that. We, you know, most programs we show a faster ulceric flowagration of the CAR-Ts with the CT-28 is somewhat slower 4-1-B-B. But then 4-1-B-B would give you longer persistence, and the CT-28 typically gives you very little persistence.
Speaker Change: Maybe there are AID, you know, auto-immune indications that are more amenable to one versus the other. I'm kind of probing your thoughts here.
Christian Itin: So what we're basically referring to is that the co-stimulatory domain has sort of an impact on the initial activity that we see of the cells and particularly the cell expansion of the CAR-T cells that we're seeing. And that is certainly, it's been generically true that most programs would show a faster offset proliferation of the CAR-Ts with the CD28, somewhat slower in 411BB, but then 411BB would give you longer persistence, and the CD28 typically gives you very little persistence, and that also then has an impact, obviously, on the longer-term B-cell aphasia, especially because, frankly, in one case you have no active What I think is worthwhile remembering, certainly for OBCell, is that the peak expansion that we're seeing with our product actually exceeds that of the CD28.
Speaker Change: So, what we're basically referring to is that the co-stimulatory domain has sort of an impact on the initial activity that we see of the cells, and particularly the cell expansion of the CAR T cells that we're seeing.
Christian Itin: What you see when you look at those two curves is actually a picture, which is the opposite of what you would normally observe in these studies. Normally would have served their patients that actually with the stem cell transplant would do better. I would actually give you a better event-free survival. What we're seeing here, it looks like the inverse, certainly not doing better, possibly doing a bit worse, if they actually receive the stem cell transplant after receiving OV cell.
Speaker Change: and that is circ ists they generically true that we most programs we show
Speaker Change: A faster offset proliferation of the CAR T's with the CD28 is somewhat slower in 4.1BB, but then 4.1BB would give you longer precisions, and the CD28 typically gives you very little precisions.
Christian Itin: And that also then has an impact obviously on the longer-term, you know, piece of a pleasure, especially because you're Franklin, Monk case, you have no activation; the other case, you have active agent. Well, I think it's worth all remembering circulated aerobic cell waste that actually the peak expansion that we're seeing with our product exceeds that of the CT-28. Car, okay? So the story certainly is a bit more complex than just post-simulation, so we actually see have an excess level of in terms of maximum expansion of the parties, which are beyond what the CD-28 cons were able to do and that combines in addition with a very long persistence.
Speaker Change: and that also then has an impact obviously on the longer-term you know B-cell aphasia, especially because you frankly in one case you have no active agent, in the other case you have active agent.
Christian Itin: Now, when we look at the, on slide number eight, at the overall survival, we see a similar picture, certainly no evidence that a patient receiving a transplant provided them survival remission. And so, very interesting in the sense that clearly the product on its own appears to be able to deliver a longer term outcome and may actually be able to serve as a standalone therapy for a subset of the patients. So, these are two of the key findings that we were presenting at ASCA and EHAID, which we move on to slide number nine, but we're evaluating there on the left hand side is the impact of these of car key persistence in event-free survival and the patients.
Speaker Change: i i think is worth all rememberred certainircit for osalies that actually a peak exexpansion we're seeing with out of our exceeds out of the cd twenty eight k
Christian Itin: Okay, so the story certainly is a bit more complex than just co-stimulation, so we actually see an excess level of in terms of maximal expansion of the CAR-Ts, which is beyond what the CD28 CARs were able to do, and that combines, in addition, with very long persistence. So that gives you a very, I think, unique set of properties that we do have with OV-Cell that is quite different from the rest of the commercially available CAR-Ts.
Speaker Change: Okay
Speaker Change: So the story certainly is a bit more complex than just co-stimulation. So we actually see, have an excess level of, in terms of maximal expansion of the CAR Ts, which are beyond of what the CD28 CARs were able to do. And that combines, in addition, with a very long persistence.
Christian Itin: So that means you very, I think you need set of properties that we do without we sell that is quite different from the rest of the commercially available party programs. That in terms of the type of activity you may need depending on the indication, that's an interesting question and I think I will probably answer it from the position of what is the mechanism of action. And the mechanism of action obviously that we have is the removal of the cells, the CD-19 positive cells and also plasma blasts. In the case of autoimmune disease where you have to get rid of typically our clones, that of cells that actually drive the auto reactive active bodies.
Speaker Change: so that means you very i think you needque set properties that we do have we sell that is quite different from the rest so that commercially v able carke program
Christian Itin: Now, in terms of the type of activity you may need, depending on the indication, that's an interesting question, and I think I would probably answer it from the position of what the mechanism of action is. And the mechanism of action, obviously, that we have is the removal of B cells, C19-positive cells, and also plasma. In the case of autoimmune disease, what you typically have to get rid of are clones that are cells that actually drive the autoreactive activity.
Speaker Change: now in terms of the the type of activity you may need depending on the indication that's an interesting question and i think i will probably answerate from the position of what is the mechanism of action and the meagchanis of actioni'll say that we have it the removal of of we cells see how been partbab the cells and also class last
Christian Itin: What you can see on the blue curve on the top are patients that have actually ongoing car key persistence, and you can see that these tend to do very well again with the stabilization of event-free survival. Patients that lose car key presence at 12 months, you can see that's the median curve, the green curve and patients that would lose car key persistence over the in six months, if the record are tracking is tracking below.
Speaker Change: in the case of our mnew itiesase where you have to get id out typically our clones that of cells that actually drive the auto acxis at thevies
Christian Itin: And so you need to actually have a complete depletion of those cells if you want to get to a reset of the disease, and that, I think, sort of should be the expected outcome for a CAR-T therapy, which is also a very promising therapy for this type of disease. So that mechanism is shared across the board. And I think what we need to ask then is, what are the properties that we need to have to achieve that goal?
Christian Itin: And so you need to actually have a complete depletion of those cells if you want to get to a reset of the disease, and that I think sort of should be the expected outcome for an allergy therapy, which is obviously very more of a therapy for this type of disease. So that mechanism is shared across the board. And I think what we need to ask is whether the properties that you need to have to achieve that goal. And in my view, what you need to have is because this is a cell-based mechanism, you also need to have an ability to actually have proper cell salvagements.
Christian Itin: Indicating that indeed longer persistence of the car key cells appears to be associated with a better performance on the entry survival. And just as this other surrogate to look at that, so that the impact we're looking at the celebration, you can see also there the same type of stagger, but less differentiation between the patients. So, persistence seems to be a better readout than a more reliable readout if you want to understand the potential impact for longer term outcome.
Speaker Change: and so you need to actually have a complete depletion of those cells if you want to get to a reset of disease and that I think sort of should be the expected outcome for a CAR T therapy which is also a very normal therapy for this type of a disease.
Speaker Change: So, that mechanism is shared across the board, and I think what we need to ask then is, what are the properties that we need to have to achieve that goal?
Christian Itin: And in my view, what you need to have is, because it's a cell-based mechanism, you also need to have the ability to actually have proper cell-cell engagements. In other words, your CAR T cells have to find those particular cells that drive autoimmunity, and then they actually have to be able to take them out. Because it's a cell-based process, you need to go through cell migration, distribution, et cetera, to do that. And you need to get all of those cells eliminated to have that ability to drive the autoimmune reaction.
Speaker Change: and in my vie what we need to have these because it's a hell-basase mechanation ys in need to have an ability to actually have proper he sealligenggagements in other words your cares sells have to find that to particular themselves that triesve on immunity and men actually has to be able to take them out
Christian Itin: In other words, your carpeas cells have to find that the particular cells that drive autoimmunity and then actually have to be able to take them out. Because it's a cell-based process, you need to go through cell migration, distribution, etc. to do that. And you need to get all of those cells eliminated to have that ability to drive well in the reaction. And that means there's a certain amount of time required to actually do that. What we do not know is we do not know what's the minimum amount of time to actually achieve that goal. What we do know is that the time that actually the program had in the airline study was sufficient to do that.
Christian Itin: Now, in summary, on slide number 10, quick takeaways from this school analysis. First of all, 40% of the responders are in ongoing remission with panic any subsequent therapy. And this is now with immediate follow-up of 21.5 months. We clearly see evidence of a plateau forming both in event-free survival as well as an overall survival. And it does not appear at that stem cell transplant based consolidation provides an advantage for the patients and does not appear to improve event-free survival or overall survival, which is certainly an important outcome. Consistent with the effects for seeing, but certainly unusual in the field so far. And clearly, we do see an interesting correlation between among persistence and improved event-free survival.
Speaker Change: Because it's a cell-based process, you need to go through cell migration, distribution, et cetera, to do that. And you need to get all of those cells eliminated. To have that, they would need to drive the autoimmune reaction. And that means there's a certain amount of time required to actually do that.
Christian Itin: And that means there's a certain amount of time required to actually do that. But what we do not know is we do not know what the minimal amount of time is to actually achieve that. What we do know is that the time that the program had in the airline study was sufficient to do that. So the importance of the message that I was looking to give before in the prepared remarks was that our product actually shares all of those properties, of Presence, Beth of Coffee to the Vita compartment, and sufficient persistence to actually achieve that goal. It shares that with the LRM program, but has a better.
Speaker Change: What we do not know is, we do not know what's the minimal amount of time to actually achieve that goal.
Christian Itin: What we do know is that the time that the program had in the airline study was sufficient to do that.
Speaker Change: What we do know is that the time that actually the program had in the airline study was sufficient to do that.
Christian Itin: So the importance of the message that I was looking to give before in the prepare the box was that our product actually shares all of those properties in terms of presence, best of coffee to the visa compartment, and sufficient persistence to actually achieve that goal, shares that with the airline program, but has a better safety profile. So that's the way I would answer the question.
Speaker Change: So the importance of the message that I was looking to give before in the prepared remarks was that our product actually shares all of those properties.
Speaker Change: in terms of presence, depth of cup into the B-cell compartment, and sufficient persistence to actually achieve that goal, shares that with the LRM program, but has a better safety profile.
Christian Itin: With that, what I'd like to do is actually move to sort of more the operational side, and so they're getting to commercial launch readiness and move to slide number 12. As you remember, we sort of, you know, have been already very active in the preparatory steps to get ready for commercialization for quite an extended period of time already. And a lot of that obviously was really focused on a key area of activities.
Christian Itin: So that's, I think, the way I would answer the question. How short you can go, that's frankly a thing that none of us know at this point because we haven't seen enough data from other programs with different profiles from the HLAM product to get a feel for whether something else might also work. But what we do know is that the profile that we had seen in HLAM does work.
Christian Itin: How short you can go? That's frankly, I think that none of us knows at this point. Because we haven't seen enough data from other programs with different profiles from these airline products to get a feel where something else might also work. But what we do know is that that pro probably gets even among does work. All right, that's very helpful.
Speaker Change: so that's nothing think the way iable to answer the question
Speaker Change: how short you can go that's frankly i think that none of us know at this point
Speaker Change: because we haven't seen enough data from other programs with different profiles from the HLAAM product to get a feel whether something else might also work. But what we do know is that that profile that we had seen in HLAAM does work.
Christian Itin: Clearly it's creating awareness around the medical affairs activities as you would expect, building the value stories for market access of the product. But then what's very involved is certainly the onboarding of the treatment centers. And that onboarding process is very involved not only from a company, but also from a center perspective, that's a real effort that actually has to be put in. That goes across a kind of wide range of activities that we need to sort of integrate in, whether it's related to afferesis, to the actual delivery of the product, the handling product of the product at the center, as well as additional support that we're looking to provide both to the centers.
Christian Itin: All right. That's very helpful, Christian. And thanks for taking our questions today.
Operator: Christian, and thanks for taking our questions today. Thank you. One moment for our next question.
Speaker Change: All right. That's very helpful, Christian, and thanks for taking our questions today.
Operator: One moment for our next question, and our next question comes from Asthika with Truist.
Speaker Change: backloio
Asthika Goonewardene: And our next question comes from us to go with Trueist. Thank you. Good afternoon, guys. Thanks for taking the question. So congrats on the progress as well, Christian. I'm going to add on to the dual questions on the centers here and maybe ask something related here. Among the 60 centers targeted, how many centers require an approval in hand to even begin the qualification process? And just to get some color here, all in, how long does it take per cent to become an ATC, including the whole qualification process and, and, and, and a site activation record.
Speaker Change: One moment for our next question.
Operator: Hi, good morning and good afternoon, guys. Thanks for taking the question. So congratulations on the progress as well, Christian.
Asthika Goonewardene: Hi, good morning and good afternoon, guys. Thank you for taking the question. So congratulations on the progress as well, Christian.
Speaker Change: And our next question comes from Asthika with Truist.
Asthika: i on to gu sci ific a question
Christian Itin: I'm going to add to Gil's questions on the centers here, and I'll maybe ask something related. Among the 60 centers targeted, how many centers require approval in hand to even begin the qualification process? And just to give some color here, all in, how long does it take for a center to become an ATC, including the whole qualification process and site activation required? And then I've got a couple of quick follow-ups.
Asthika: So congrats on the progress as well, Christian. I'm going to add on to Gil's questions on the centers here. And I'm maybe asking something related here. Among the 60 centers targeted,
Asthika Goonewardene: I'm going to add to Gil's questions on the centers here, and I'm maybe asking something related. Among the 60 centers targeted, how many centers require approval in hand to even begin the qualification process? And just to give some color here, all in, how long does it take for a center to become an ATC, including the whole qualification process and site activation required? And then I've got a couple of quick follow-ups. Thank you.
Speaker Change: How many centers require an approval in hand to even begin the qualification process?
Asthika: And just to give some color here, all in, how long does it take for a center to become an ATC, including the whole qualification process and site activation required? And then I've got a couple of quick follow-ups.
Christian Itin: There's on the statutory to the patients as well. It's quite an involved process, including everything related to the cell journey from the collection of the cells at the center to the manufacturing process and back. And the IT systems required to really be able to track the product and ensure that we have a very clear chain of identity throughout the entirety of the process. So very substantial amount of work that's ongoing there.
Christian Itin: And then I got a couple of quick polls. So there are sort of two steps to that. First of all, the essentially has to be, you know, it's interesting to actually all of them work the product. That's the first part that we have to take. We had remarkable success in, you know, having a center's interest in actually taking the product on board. It's the, you know, very foolish guidance that will give it not 30 to 36 centers ready to be activated at time, at time of approval. So that's a very significant involvement; just to put that in numbers, that is those, you know, the centers do cover about 65 to 70% of the ALL population of the US.
Christian Itin: So there's sort of, you know, two steps to that. First of all, the center has to be, you know, interesting to actually onboard the product. That's the first hurdle we have to meet. They can pay anywhere from $6,000 to $12,000.
Christian Itin: So there's sort of, you know, two steps to that. First of all, the center has to be, you know, interesting to actually onboard the product.
Speaker Change: So there's sort of, you know, two steps to that. First of all, the center has to be, you know, interesting to actually onboard the product. That's the first hurdle we have to take.
Christian Itin: That's the first hurdle we have to meet. We had remarkable success in, you know, having the centers interested in actually taking the follow-up on board. It's the, you know, very bullish guidance that we're giving of 30 to 36 centers ready to be activated at the time of approval. So that's a very significant involvement. Just to put that in numbers, that is, those centers do cover about 65 to 70 percent of the ALL population in the U.S. So that's the magnitude we're talking about, and that's right out of the gate.
Speaker Change: We had remarkable success in having the centers interested in actually taking the product on board. It's the very bullish guidance that we're giving of 30 to 36 centers ready to be activated at a time.
Christian Itin: We're on track to have between 30 and 36 centers ready for acceleration by the time of approval. And are going to move once we are getting to that point, would expect to be within the first year of launch at a level of about 60 centers onboarded and access with the product. So we're moving here in a very significant way as well as, you know, at a significant number of centers even for the initial startup phase.
Speaker Change: at time of approval.
Speaker Change: So, that's a very significant involvement, just to put that in numbers, that is, those centres do cover about 65-70% of the ALL population.
Christian Itin: So that's the magnitude we're talking about, and that's where I died of the gig. So that's, you know, the level of interest to actually even engage; if that's a first thing you need to do. In the second, you need to actually go through all the preparatory steps so that you can get, when you get to the level, you can actually activate the center. That can take anywhere from 60 to 12 months. So that is a very involved process that, you know, has a lot to do on the IT side. There's contractual pieces that you have to put in place and so on.
Christian Itin: So that's, you know, the level of interest to actually even engage. That's the first key thing. The second is that you need to actually go through all the preparatory steps so that when you get to the level, you can actually activate. That can take anywhere from 6 to 12 months. So that is a very involved process that has a lot to do on the IT side; there are contractual pieces that you have to put in place, and so on.
Speaker Change: So that's the magnitude we're talking about.
Speaker Change: And that's right out of the gate. So that's, you know, the level of interest to actually even engage. That's the first key thing you need to do. The second is, you need to actually go through all the preparatory steps so that you can get, when you get to the level, you can actually activate the center.
Christian Itin: So that is a very involved process that, you know, has a lot to do on the IT side. There are contractual pieces that you have to put in place, and so on. So it's a very involved process and typically takes of the order of magnitude of six to 12 months. This is why we've been working on this for an extended period of time. Many of the centers that we expect to get ready for activation after an approval is in are already in the onboarding process, just to be clear.
Christian Itin: Now what we're particularly focusing on at where we are at this point in time is really looking at the integration of the workings and testing, frankly, of all the systems required to deliver the product. So there's a lot of activity going on making sure that all the interfaces are working between the different processes, the different systems. And that's a very involved process that we're actually engaging in this third quarter and leading into the fourth quarter to make sure that all elements required to deliver this therapy are fully operational and tested out. And actually has achieved the level of robustness required for a commercial operation.
Speaker Change: That can take anywhere from 6 to 12 months.
Speaker Change: So that is a very involved process that, you know, has a lot to do on the IT side. There's contractual pieces that you have to put in place and so on. So it's a very involved process and typically takes in that order of magnitude of 6 to 12 months.
Christian Itin: So it's a very involved process and typically takes of the order of magnitude of six to 12 months. This is why we've been working on this for an extended period of time. Many of the centers that we expect to get ready for activation after an approval is in are already in the onboarding process, just to be clear. So that's a continuous process. And most of these centers are actually ongoing in terms of process already at this stage.
Christian Itin: So it's a very involved process and typically takes in that order of magnitude of 60 to 12 months. This is why we've been working on this for an extended period of time. Many of the centers that we expect to get ready for activation after an approval is in are already now in the onboarding process, just to be clear. So that's a continuous process, and most of these centers actually are ongoing in terms of process already at this stage. So those are kind of the key things, but then the final base is, obviously, you know, we can go with these 30, 36 centers as far as we want to go, but there are, obviously, the final steps do require the actual label in hand.
Speaker Change: This is why we've been working on this for an extended period of time, as many of the centers that we expect to get ready for activation after an approval is in, are already now in the onboarding process.
Christian Itin: So that's a continuous process, and most of these centers are already ongoing in terms of process at this stage, ahead of actually having the label in hand. There are some, obviously, that would actually want to wait until the label is there and would sort of actually engage in the higher workload of the activity later on. But those, obviously, will be the only 36 centers that will be at that end. But the overall majority of the centers actually have been remarkably engaged and willing to actually proactively work on the app.
Speaker Change: Just to be clear, so that's a continuous process and most of these centres actually are ongoing in terms of process already at this stage.
Christian Itin: So those are kind of the key things. But then the final bit is, obviously, you know, we can go with these 30-36 measures as far as we want to go, but there are, obviously, the final steps do require the actual labeling. And that is sort of the final step, that's kind of the step that actually gets you to that, into that, you know, but between two weeks as well as weeks is the max time to actually get the centers fully activated and enrolling.
Speaker Change: So those are kind of the key things, but then the final bit is obviously, you know, we can go with these 30-36 standards as far as we want to go, but there are obviously, the final steps do require the actual label in hand.
Christian Itin: Now on the next slide, just a brief view on kind of where we are and what some of those activities are that we actually need to think about at the time point when we actually do get to an approval. Obviously, we talked about the path there on the prior slide. We eventually get to a point where hopefully, along the target day, we do receive an approval for the product. Once that happens, there are several activities that need to take place on our side and driven from from the company side is really kind of the activities that are defined by the label itself.
Christian Itin: And that is sort of the final step that actually gets you to that, you know, between two weeks and 12 weeks max time to actually get the centers fully activated on enrollment pensions. So that's sort of that that stretch, and obviously, the vast majority of the centers are working with, obviously, have made the decision to actually put all the work into the onboarding process. A hand of actually having the label into hand. There's some, obviously, that would actually want it one way until the label is there and would actually engage the more higher workload of the activity later on.
Speaker Change: And that is sort of the final, that's then the step that actually gets you to that, into that, you know, between two weeks and 12 weeks max time to actually get the centers fully activated and enroll in pensions.
Christian Itin: So that's sort of a stretch. And obviously, the vast majority of the scientists we're working with have made the decision to actually put all their work into the onboarding process ahead of actually having the label in hand. There are some, obviously, that would actually want to wait until the label is there and would sort of actually engage in the higher workload of the activity later on. But those, obviously, will be the only 36 centers that will be at that end. But the overall majority of the centers actually have been remarkably engaged and willing to actually proactively work on the app.
Speaker Change: So that's sort of that stretch, and obviously the vast majority of the scientists we're working with obviously have made the decision to actually put all their work into the onboarding process.
Christian Itin: And there are certain aspects of training and activity that only can actually be finalized and run through at the time when the label is fully set and determined. And that actually has to do with a set of trainings that have to be consistent, obviously, with the approved label, as well as obviously administering a REMS strategy and training that needs to actually be implemented at that point of time. So those are elements that from a company perspective, you'll be able to complete once the once an approval is in.
Speaker Change: ahead of actually having the label in the hand. There's some, obviously, that would actually want to wait until the label is there, and would sort of actually engage the higher workload of the activity later on. But those, obviously, will be the only 36 enthys that will be at that end.
Christian Itin: But those, obviously, will be the only 36 centers and will be at that end. But the overall majority of the centers actually have been, you know, remarkably engaged and willing to actually productively work on the, obviously, on the operation. Thank you, Chris.
Speaker Change: But the overall majority of the centres actually have been, you know, remarkably engaged and willing to actually proactively work on the activation.
Christian Itin: Thank you, Christy. That's really helpful.
Christian Itin: That's really helpful. Then maybe bigger picture with the, with the recent deal with the Ontic and the raise, you know, it's not a good, nice pot of cash that you can kind of dispense for the clinical development here. We see a lot of, obviously, a lot of prioritization done for commercializing OBSL, as well as doing the auto unit at the study. Maybe you can also revisit what comes next. What's next on your really high on the priorities of these two top priority items? Right, so look, we're very keen on sort of, you know, committed to the next good little study.
Asthika Goonewardene: Then maybe bigger picture. With the recent deal with BioNTech and the Rays, you've got a good pot of cash that you can dispense for clinical development here. We see a lot of prioritization done for commercializing OBCell as well as doing the autoimmune study. Maybe it's a good time to also revisit what comes next. What's next on your really high-level priority list after these two top two priority items?
Christian Itin: Now the centers themselves need to run through quite a range of activities at that point in time that really make sure that they're internally ready to be able to actually manage this type of a therapy, both from an administrative perspective, as well as from an actual physical operational perspective. And you see quite a set of those activities that sort of will actually have to be work through on the center and the inside of the center.
Speaker Change: Thank you, Christy. That's really helpful. Then maybe bigger picture, with the recent deal with Biontech and DeRays, you know, you've got a good, nice pot of cash that you can kind of
Speaker Change: Dispense for Clinical Development here. We see a lot of, obviously, a lot of prioritization done for commercializing OBCell as well as doing the autoimmune study.
Christian Itin: And you can see that at the right hand side, spell that in a bit more detail. Now when we think about what that means from an overall timing perspective, you can see the blue curve or blue arrow up there is actually quite a range of time that we actually see where from that high point where the center actually can get. It actually, until it actually would enroll a first patient, and we will see certainly a variety of human centers in terms of the time it will take to be on board and be enrolling patients to look at that in a bit more detail, and just look at sort of the sort of in a relatively simple way of what are some of those key activities and timelines.
Speaker Change: Maybe we can, this is a good time to also revisit, what comes next? What's next on your really high-level priority list after these two top two priority items?
Christian Itin: Right, so look, we're very keen, obviously, on sort of, you know, committing to the next virtual study. So this is, you know, very much a process that is in full swing at the company.
Speaker Change: Right, so, look, we're very keen, I'll say, on sort of, you know,
Christian Itin: So this is, you know, very much a workflow that is in full swing at the company. So what we need to do now, which is a very heavy lift for any organization going through the first time through an approval on the launch. So we want to be mindful that, you know, the long hand that we're having to focus required to execute and execute with what we hope to be an extra class of, at the same time, obviously we're preparing for that, for that significant engagement since into an extra little study. So that's what we're working on, and we're also, you know, from public perspectives, you know, at the right time or at that, but that's also really a lot of activity.
Speaker Change: Committed to the next digital study. So this is, you know, very much a workflow that is in full swing at the company.
Christian Itin: Obviously, at the same time, we would not want to distract from what we need to do now, which is a very heavy lift for any organization going through the first time through an approval and a launch. So we want to be mindful that, on the one hand, we're having the focus required to execute and execute on what we hope to be a best-in-class launch. At the same time, obviously, we're preparing for that significant engagement in the next virtual study.
Speaker Change: All of that at the same time, we don't want to distract from what we need to do now, which is a very heavy lift for any organization going through the first time through an approval and a launch. So, we want to be mindful that, you know, on the one hand, that we're having a focus required to execute.
Speaker Change: execute what we hope to be a best-in-class launch.
Christian Itin: So, completing the site accreditation, we expect we'll take anywhere from two to 12 weeks with the sensors that we have prepared for the Young Boarding process, but are now from the time point where you can actually initiate the site activation, we'll have to take anywhere between two and 12 weeks. Autotatients, cleaning, lubricants, schedule, then having that completed, anywhere from one to two weeks at that point in time, and then obviously he anticipated ready to delivery time of 16 days.
Speaker Change: At the same time, obviously, we're preparing for that significant engagement into the next typical study. So that's what we're working on. And we'll update, you know, the...
Christian Itin: So that's what we're working on, and obviously, we'll update, you know, from a public perspective, you know, at the right time or at that, but that's obviously where there's a lot of activity in. We're also very excited about the interaction we're having with BioNTech. There's, you know, really, you know, great chemistry between the teams, a lot of good engagement, broader discussions that are going on, and I think that's sort of, obviously, you know, also a key activity that obviously doesn't have yet that level of visibility in terms of news flow, but it's an area we're very excited about, and I think will create additional opportunities as well that are not necessarily visible at this point from an overall company perspective.
Speaker Change: for a publicly perspective you know at the right time er right that but that's polbablyy le a lot vacdated and we're also very excited about the interaction we're having with biope
Christian Itin: We're also very excited about the interaction we're having with biotech. It's really, you know, a great chemistry between teams; a lot of good engagement, a lot of discussions that are going on. And I think that sort of also, you know, sort of key activity that is also doesn't have yet that level of visibility in terms of the slow, but it's an area very excited and I think we'll create additional opportunities as well that are not necessarily visible at this point from an overall company perspective. So I'm excited about those next steps, but first things first, you know, get the approval, get the launch of the grant, get into the next little study, and then we're going to move from there. But very excited about kind of what the end of the year and then also the next year.
Speaker Change: It's really great chemistry between the teams, a lot of good engagement, broader discussions that are going on.
Christian Itin: So, when you think about that, and you think about a target date, for the target date of middle of November, and as well as for the year and holidays, it is reasonable to assume that the first patient dose will be happening in the early part of 2025. So, I think that sort of I think hopefully gives you a sense for what it means to start up, and whatever sort of reasonable assumptions around when to expect kind of first patient status, and then obviously would get up from there as we go to the course of the year.
Speaker Change: And I think that's sort of also a key activity that obviously doesn't have yet that level of visibility in terms of news flow, but it's an area where we decided that I think we'll create additional opportunities as well that are not necessarily visible at this point.
Christian Itin: So I'm excited about those next steps, but first things first, you know, get the approval, get the launch off the ground, get into the next pivotal study, and then we're very excited about kind of what the end of the year and then also the next year will bring.
Speaker Change: and a global company perspective.
Speaker Change: So I'm excited about those next steps, but first things first, you know, get the approval, get the launch off the ground, get into the next pivotal study, and then we're kind of we're going to
Speaker Change: and move from there. But very excited about kind of what the end of the year and then also the next year will bring.
Operator: Thanks so much for taking my question. Thanks a lot.
Asthika Goonewardene: Great, thanks so much for taking my questions.
Christian Itin: Now, with that, what I'd like to do is switch gears and just briefly talk about sort of the OVCEL product family on slide 16, such as the opportunity, if this is slide you've seen before, also continue to work normally on the current activity in on the adult AML side, but also working on the pediatric side as well as the old immune side with OVCEL, and we'll continue to actually work on order 122 as well as all the way. So, all the 122, most of the pediatric ALL side where we do additional work with the UCLH and gosh, our partners for that program for a long period of time.
Kelly: And one moment for our next question. Our next question comes from Kelly; she with Jeffries. I'm going to press on the progress, and then thanks for taking my questions. I was very close to the first launch for Autos.
Operator: In one moment for our next question. Our next question comes from Kelly Shee with Jeffreys.
Speaker Change: thanks thank you much for ingking my question
Speaker Change: Thanks a lot.
Speaker Change: in one moment for our next question
Kelly Shee: Congratulations on the progress, and thanks for taking my questions. As we are very close to the first launch for Autolus, I'm curious, just a quick question. Maybe it's too early to comment on the price of Avicell, but I'm curious if the split dosing regimen would add additional cost compared to a single dose of cell therapy.
Speaker Change: Our next question comes from Kelly Shee with Jeffreys
Kelly Shee: Congrats on the progress and thanks for taking my questions.
Christian Itin: Kelly, just a quick question. Maybe like it's too early to comment on the price of the sell, but the currency if the split dosing regimen would add additional cost compared to single dose of the sell therapy. Hi Kelly, really good question. So first of all, I'll say on price you're right; that would be too early to actually give any specific guidance. I think we can only remind sort of the the car price that we see with the cars, which is around 462 in the U.S. 2000 and via which is around 82. There's an overlap; there's also an age range where we know finished that, although study was from 18 years onwards.
Speaker Change: And we are very close to the first launch for Atlas.
Kelly Shee: I'm curious, just a quick question, maybe like, it's too early to comment on the price of Avicell, but I'm curious if the split dosing regimen would add additional cost compared to a single dose of cell therapy.
Christian Itin: Hi Kelly, really good question. So first of all, obviously, on price, you're right, that would be too early to actually give any specific guidance. I think we can only remind ourselves sort of the current price levels that we see with Descartes, which is around $4.62 in the U.S., Thousand, and Kumbaya, which are around $5.82.
Speaker Change: Hi Kelly, really good question.
Christian Itin: And we're also obviously with all the way continue to work on the multiple OVCEL, but we're also looking to expand the opportunity for that program going forward as well, and we'll update you as we go as we go forward and initiate next studies with that program when that actually happens.
Speaker Change: So, first of all, obviously, on price, you're right. That would be too early to actually give any specific guidance. I think we can only...
Speaker Change: Reminds of the car price levels that we see with Takartas, which is around $4.62 in the U.S.
Christian Itin: There's an overlap, but there's also an age range. We have finished all those studies from 18 years onwards. When you look at the labels for the two commercial products, one obviously goes up to 25 years, which is Kumbaya, and the second one, Descartes, goes above 25 and older.
Speaker Change: and Kibay, which is the last one.
Christian Itin: So, with that, just a quick word on the environment on the autoimmune side of the state that many of you have watched very carefully. We have a one major conference that happened in Q2, which is the UR conference, interesting data set presented during the course of the conference. I think what we're starting to see is some differences that appear between programs still early days in terms of understanding what is contributing to some of the differences that are being observed.
Carly: and Carly baby too.
Speaker Change: There's an overlap, there's also an age range, where we know Felix Stadelbosch studied us from 18 years onwards. When you look at the labels...
Christian Itin: When you look at the labels for the two commercial products, one obviously goes up to 25 years, which is Come Right Up, and the second Monte Carlos goes about 25 and older. So that's the range that's currently the market. I think we can get more guidance from that. and just that with, you know, basically, point to the reference that the reference sizes that we have here in the space. In terms of the cost or the added cost related to dosing, what we do, obviously, with Ovisail, is we do a two-rovert and adjusted dosing. And that actually has proven to give us an enormous amount of robustness in terms of the safety data, which is driven on the long-half of the design, but also takes into account.
Speaker Change: For the two commercial products, one obviously goes up to 25 years, which is Kymriah, and the second, Bronte Carters, goes above 25 and older. So, that's sort of the range that's currently in the market, and I think we can give more guidance on that.
Christian Itin: So that's sort of the range that's currently in the market. I think we can give more guidance on that, point to the references, the reference places that we have here in the book. In terms of the added costs related to dosing, what we do obviously with OBCEL is we do tumor burden-adjusted dosing, and that actually has proven to give us an enormous amount of robustness in terms of the safety data, which is driven on the one hand by the design, but also takes into account tumor burden.
Christian Itin: To what extent are those product driven, to what extent are those factors variability in the patients that are being treated. But certainly very interesting development that we're seeing, but also overall, I think also very nice cooperation of the initial observations that we have seen with GARCES in airline that indeed there is very profound impact that can be had in those patients using CARTI approaches. When we look at the next slide, just to remind you, obviously, that we have a program that has a remarkable service similarity in terms of the clinical properties to the program that's used in Air London.
Carly: basically point to the references that we have here in this space.
Speaker Change: In terms of the added costs related to dosing,
Speaker Change: What we do obviously with OB cell is we do a tumor burden adjusted dosing. And that actually has proven to give us an enormous amount of robustness in terms of the safety data, which is driven on the long half of the design, but also takes into account the safety.
Christian Itin: of Cystic Tumor Burden. And remember, these are very, particularly older patients, tend to be fairly frail patients. And a lot of these patients certainly cause a lot of issues with early CAR T programs and lead to treatment-related mortality. We've seen that in some of the real-world data as well, that being a real issue. And as you may remember, our median age in the study actually was about 10 years older than some of the other studies that were done in the study.
Christian Itin: And remember, these are very, particularly older patients tend to be fairly frail patients, and a lot of these patients certainly cause a lot of issues with early CAR T programs that lead to treatment-related mortality. We've seen that in some of the real-world data as well, that being a real issue. And as you may remember, our median age in the study actually was about 10 years older than some of the other studies that were done in the study.
Christian Itin: Also, two-rovert, and remember, these are very thick of the old patients, tend to be very old patients. And a lot of these patients certainly cause a lot of issues with early-party programs, need to actually driven related mortality. We see that in some of the real world data as well, that being a real issue. And as you may remember, our median agent of study actually was about 10 years older than some of the other studies that were done in the past in the industry. So, at this point, we did that whole thing through the pandemic, which also aggravated a lot of the safety-related challenges for us.
Carly: Also tumor burden, and remember these are very sick, the older patients tend to be fairly frail patients.
Carly: And a lot of these patients certainly caused a lot of issues with early CAR T programs.
Christian Itin: We have, but also not only do we have a high degree of similarity in terms of the efficacy, the persistence on the pediatric LL side where we can compare the programs directly. But also, obviously, we do have a very substantial amount of safety data, and which also is an area where we can see differentiation to the program in airline, but also the differentiation to any of the other CARTI programs that are currently commercially available.
Speaker Change: lead to actually treatment-related mortality. We've seen that in some of the real-world data as well, that being a real issue. And as you may remember, our median age in the study actually was about 10 years older.
Christian Itin: So, and despite that, we did that whole thing through the pandemic, which also aggravated a lot of the safety-related challenges further. So, the dosing that we have, in combination with our profile, gives us a very substantially improved safety profile. The primary cost that you see for the delivery of the currency is not the delivery itself, it's not the administration, because that's pretty uneventful. That's literally an infusion, and that's it, and those tend to be very short infusions. We're talking maybe 15 minutes or something like that.
Christian Itin: And despite doing that whole thing through the pandemic, which also aggravated a lot of the safety-related challenges further. So the dosing that we have, in combination with also the CAR T profile, uses a very substantially improved safety profile. The primary cost that you actually see for the delivery of the currency is not the delivery itself, it's not the administration, because that's pretty uneventful. That's literally an infusion in that statement that tends to be very short infusions.
Christian Itin: that some of the other studies that were done in this way. So and despite we did that whole thing through the pandemic which also aggravated a lot of the safety related challenges further. So
Christian Itin: So, the other thing that we have, in combination with also the health profile, uses a very substantial improvement, say, the profile. The primary cost that actually you see for the delivery of the quality is not the delivery itself, it's not the administration, just that's pretty out of handful, that's literally an infusion, and that's happened to tend to be very short. Infusions with talking, maybe 50 minutes or something like that. So, it's a very short infusion that doesn't actually add a significant amount of burden, but actually expert and what really drives cost is related to the management of the patients, where they actually do experience hybrid CLS, or the experience hybrid ICANN, and in fact, the ICANN are almost worse because they tend to take a substantially longer period of time to actually get out of control.
Christian Itin: And what you see is just a summary there on the live and the table on the various key outcomes that we have seen across the various studies that we've conducted with OBSEL. And I think if you have very good view on the level of activity that we're seeing, and the ability to achieve those levels of activity with a very attractive safety process.
Speaker Change: The dosing that we have, in combination with our profile, gives us a very substantially improved safety profile.
Christian Itin: The primary cost that actually you see for the delivery of the currency is not the delivery itself, it's not the administration, because that's pretty uneventful, that's literally an infusion in that statement that tend to be very short infusions, we're talking maybe 15 minutes or something like that.
Christian Itin: We're talking maybe 15 minutes or something like that, so it's a very short infusion. That doesn't actually add a significant amount of burden. What actually adds burden and what really drives cost is related to the management of the patients where they actually do experience high-grade TLS, or they experience high-grade eye cancer. And in fact, the eye cancer almost works because they tend to take a substantially longer period if you actually get them under control, and obviously, they're often associated also with long-term steroid use, and this combination can lead to sepsis and treatment-related mortality.
Christian Itin: Now, the study on slide 19, the Curlized Study Outface, one study in SLE, as they indicated, the study of a study startup happened during the latter part of Q-Ominin, Q-2, first patient, Dostin, Q-2, and the continued control control of the study. We're planning six patients at a 50 million cell dose level, which obviously is a level that we know to be highly active, and to be able to get a little bit of a small record in these responses, and also a level of those that is also highly active in the adult patient population, where as a reminder, we're using as little as 10 million cells to induce complete permissions in patients with high tumor burden in that setting.
Christian Itin: So it's a very short infusion that doesn't actually add a significant amount of burden. What actually adds burden and what really drives cost
Christian Itin: is related to the management of patients where they actually do experience hybrid TLS or do experience hybrid ICAMs. And in fact, the ICAMs are almost worse because they tend to take a substantially longer period of time.
Christian Itin: And obviously, often associated also with long-term serenade use and accommodation can lead to sepsis and treatment-related mortality. So, that's where the real cost actually comes in. To be able to reduce the number of events massively, but also shorten the recovery time, which is both elements we've seen with OBSL in the field study, actually reduces massively the cost. And it's actually one of the key attractors elements for onboarding the product, which is that the product actually will be less intense to manage, because it's less intense to manage actually the profitability goes up for the centers, and that actually is one of the key drivers that from the financial perspective is attractive for the centers, why the onboarding also is going as well as it does.
Christian Itin: to actually get under control and also often are associated also with long-term steroid use and a combination can lead to sepsis and treatment-related mortality.
Christian Itin: So that's where the real cost actually comes in. To be able to reduce the number of events massively, but also shorten the recovery time, which is both elements we've seen with Obucel and the Felix study, actually reduces massively the cost, and is actually one of the key attractive elements for onboarding the product, which is that the product actually will be less intense to manage, because it's less intense to manage, actually the profitability goes up for the centers, and that actually is one of the key drivers that from a financial perspective is attractive for the centers, why the onboarding also is going as well as it does, and what is also recognized not just as a clinical improvement as well as the longer-term outcome, but also an immediate financial improvement that I think is visible and quite well understood within the centers that we're engaging with.
Speaker Change: So that's where the real cost actually comes in. To be able to reduce the number of events massively, but also shorten
Speaker Change: The recovery time, which is both elements we have seen with Obstetile Endothelial Study,
Christian Itin: So overall, I think we're a very interesting stage, we're starting to sort of get first insights from a data perspective, and we'll also continue to collect that data with a plan to have an additional update on clinical data later in the year.
Carly: Actually, reduce is massively the cost, and it's actually one of the key attractive elements.
Christian Itin: for me.
Christian Itin: Now, other pipeline programs on slide 21, as you remember, there's a number of other programs we're working on. I think with regards to Auto-A, they're already indicated that we're looking at the potential expanding the program into additional indications, so that's something that's ongoing, and we'll update, certainly, by the end of the year, or the next year, so that the trajectory is going to be on. And then just as a quick highlight, because we haven't actually talked about that in a while, as all of six NG, that program also is enrolling patients and first patient actually has been treated as well in the second quarter, as part of the progress that we were making through the quarter. So overall, progressing well, and was also expected additional publications to come out during the second half of the year related to our clinical programs that we've been conducting.
Christian Itin: And what is also recognized, not just as a clinical improvement, as well as a longer-term outcome, but also an immediate financial improvement that I think is visible and quite well on shoots within the centers that we're engaged in. You could help for and thanks very much and also have follow up on until you know, follow the follow your comments from opening remarks. So, although we saw better tolerability of city 19 car key South therapy, auto new indications when compared to him on cutriots from Dr. Sheth pioneer works. We start seeing neurotox from other ongoing trials in your Lopus.
Carly: is attractive for the centers, why the onboarding also is going as well as it does, and what is also recognized not just as a clinical improvement as well as the longer-term outcome, but also an immediate financial improvement that I think is visible and quite well understood.
Christian Itin: Super helpful and thanks very much, and also have follow-up on autoimmune, follow the, follow your comments from your opening remarks so Although we saw better tolerability of CD19 CAR-T cell therapy in autoimmune indications when compared to heme-oncotrials from Dr. Sheth's pioneer work, we started seeing neurotoxins from other ongoing trials in lupus, so curious if you could share your insights on if the patient And also another important question here is how Obacel achieved much better neurotoxin control in hemo-oncology indications, generally speaking, and also whether this is transferable to autoimmune trials, in your opinion.
Speaker Change: within the centers that we're engaging with.
Speaker Change: super helpful and thanks very much and also have follow-up on autoimmune follow the follow your comments from opening remark so
Speaker Change: although we saw a better tolerability of city nineteen car key south therapy new indications when compared to him on trialals from do shaf's pioneer work
Robert Dolski: With that, I'd like to hand over to Rob, who will landly use through the financial results. Thanks, Christian, and good morning and good afternoon to everyone. It's my pleasure to review our financial results for the second quarter of 2024. So I am on slide 23, where we see at the top our cash and cash equivalence at the end of June 2024, total 705.9 million. That's compared to 239.6 million at the end of last year, December 31st.
Christian Itin: So curious if you could share your insights on if the patient's baseline difference is more like a dominating factor, all card design, all maybe other reasons regarding the impact on safety. And also another important question here is, how obviously achieved much better neurotox control in the hem oncology indications, generally speaking, and also whether this is a transferable to auto email trials in your opinion. Thank you very much. Yeah, very good question, Kelly. So the, what we're also seeing is, in general, what we're seeing is that there's several parameters that apply immunological toxicity, and this is both actually CRS and neurotox.
Speaker Change: We start seeing your talks from other ongoing trials in your loopers.
Speaker Change: So I'm curious if you could share your insights on...
Speaker Change: if the patient baseline difference as more like a dominating factor.
Speaker Change: All Card Bizarre or maybe other reasons.
Speaker Change: regarding the impact on safety. And also, another important question here is, how Orbital Cell achieved much better neurotoxin control in the hemo-oncology indications?
Generally speaking, and also whether this is transferable to autoimmune trials, in your opinion. Thank you very much.
Robert Dolski: Our total net operating expenses for the three months ended June 30th, 2024 were 58.9 million as compared to 44.4 million for the same period of 2023. For research and development, these expenses increased from 33.2 million to 36.6 million for the three months ending June 30th, 2024, compared to the same period in 2023. This change was primarily driven by increases in operating costs related to our new manufacturing facility, employee salaries, and related costs, and OB cell clinical trial and manufacturing costs.
Christian Itin: Yeah, very good question, Kelly. So, what we're also seeing is, in general, what we're seeing is that there are several parameters that drive immunological toxicity, and this is both CRS and neurotoxin. And the parameters, on the one hand, are the number of target cells that, you know, have to be taken out, have to be removed. Obviously, that means that defines the number of CAR T cells that get activated. And with that, depending on the design of the CAR T cells, gives you a base level of activity, potential cytokine release, and also the risk of neurological.
Christian Itin: Thank you very much. Yeah, a very good question, Kelly.
Speaker Change: Yeah, very good question, Kelly. So, what we're also seeing is, in general, what we're seeing is that there's several parameters that drive immunological toxicity, and this is both actually CRS and NeuroTox.
Christian Itin: And the parameters on the one hand are the number of target cells that have to be taken and have to be removed. Obviously, that defines the number of CAR T cells that could activate it, and with that, depending on the design of the CAR T cells, gives you a base level of activity, potential cytokine release, and also the risk of neurological toxicity. So that's one element. So it's the number of cells. When we look at the neurologic at the own immune indication, we do not expect to see significant variation in terms of the number of cells that have to be removed.
Carly: And the parameters, on the one hand, are the number of target cells that, you know, have to be taken out, have to be removed.
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Robert Dolski: These were partially offset by a more favorable UK R&D tax credit reimbursement for the period as well. General administrative expenses increased from 11.1 million to 21.9 for the three months ending June 30th, 2024, compared to the same period last year. This increase was primarily due to salaries and other employment related costs driven by increased headcount supporting our overall pre-commercialization activities. And finally for the company, NetLoss was 58.3 million for the three months end of June 30th compared to 45.6 million for the same period in 2023.
Christian Itin: So that's one element, so it's the number of cells. Now, when we look at the neurologic and autoimmune indications, we do not expect to see significant variation in terms of the number of cells that have to be removed. These are patients that have an overall normal immune system. They are lucky in the sense that they have individual clones that recognize structures in the body and drive autoimmunity as a consequence of it, but it is not a proliferative disease, as we would see in lymphoma or acute.
Christian Itin: So that's one element; it's the number of cells. Now, when we look at the neurological and autoimmune indications, we do not expect to see significant variation in terms of the number of cells that have to be removed. These are patients that have an overall normal immune system. They are lucky in the sense that they have individual clones that recognize structures in the body and drive autoimmunity as a consequence of it, but it is not a proliferative disease, as we would see in lymphomarker Q.
Carly: so that's one element to the number of sales that when we look at laun at the all the indication
Christian Itin: These are patients that have overall normal immune system. They have are lucky in the sense that they have individual clones that recognize structures in the body and drive all immunity as a consequence of it, but it is not a proliferative disease, as you would see in the form of a key. So we see a pretty steady level of pretty much a normal level of B cell and plasma as last that needs to be removed. So that's sort of basic, what becomes a constant, but then actually it becomes a variable, and that's the second element that can drive the disease, where the design of the CAR T program.
Christian Itin: We do not expect to see significant variation in terms of the nombro cells that have to be removed.
Speaker Change: These are patients that have overall normal immune system. They are lucky in the sense that they have individual clones that recognize structures.
Christian Itin: in the body and drive autoimmunity as a consequence of it, but it is not a proliferative disease as we would see in lymphoma or leukemia. So we see a pretty steady level, pretty much a normal level, of B-cells and plasma blasts that need to be removed.
Christian Itin: So we see a pretty steady level, pretty much a normal level, of B-cells and plasma at last. So that sort of basically becomes a constant. But then actually, it becomes a variable, and that's the second element that can drive. So this is really the design of the CAR-T product. There are two key components there. We have already talked, and I think Asthika was mentioning that before, which are the co-similatory elements and the impact that the co-similatory elements can have.
Robert Dolski: Autolus estimates that with current cash and cash equivalents, we are well-capitalized to drive the full launch and commercialization of OBSEL in relapse refractory adult ALO as well as to advance its pipeline development plans, including runway to date in the first pivotal study of OBSEL in autoimmune disease.
Speaker Change: So that's sort of basically what becomes a constant, but then actually it becomes a variable, and that's the second element that can drive. So this is really the design of the CAR-T product.
Christian Itin: There are two key components there. We already talked, and I think Oscar was mentioning that before, which is the cost inventory elements and the impact that the cost inventory elements can have. They do have an impact in terms of how quickly the cell proliferate and how much nitric and release they have to do with that. That's an element that is sort of in part coming from the cost inventory domain, but what we have proven with OB cell is really that the primary diagram from the most important parameters that we're dealing with is actually the way that the CAR T cells physically engages with the target cells.
Christian Itin: There are two key components there. We already talked, and I think Asthika was mentioning that before, which is the co-similatory elements and the impact that the co-similatory elements can have.
Christian Itin: I'll now hand things back to Christian to wrap up with a brief outlook on milestones. Christian Okay, let me, I'll jump in here. We're ready for Christian.
Christian Itin: They do have an impact in terms of how quickly the cells proliferate and how much time they can release. That's sort of an element that is sort of coming from the co-similatory domain.
Speaker Change: They do have an impact in terms of how quickly the cells proliferate and how much time it can release and how to do that sort of element that is sort of in part
Christian Itin: But what we have proven with OBCell is really that the primary driver and probably the most important parameter that we're dealing with is actually the way that the CAR-T cells physically engage with the target. And what you should remember about the design of OBCell is that what we're looking to do with OBCell is create a product that behaves as physiologically as possible while obviously being a canary-gathagin receptor but trying to be as close to a normal T-cell engagement.
Speaker Change: coming from the co-stimulatory domain. But what we have proven with OB cell is really that the primary diagram, probably the most important parameter that we're dealing with is actually the way that the CAR T cells physically engages with the target cell.
Christian Itin: And what you do remember about the design of OB cell is what we're looking to do with OB cell is create a product that behaves as physiological as possible, while obviously being a generic attitude receptive to trying to be as close to a normal piece of engagement. And what's characteristic for a normal piece of engagement is that the engagement is short-lived. So a key cell actually recognizes the target cell or the sign acts delivers the sign of proxy contact which drives the cell after an apoptotic process in the target cell. And then actually, these engages rapidly.
Christian Itin: Maybe moving to slide 25. Just again to hit on some of the anticipated milestones through the year end. We've got the target action date on the FDA side with the Padufa, as Christian mentioned, that's November 16th, 2024. And we'll have updates certainly at the end of ash. You've seen some of those with the ASCO data in IHA that'll be further advanced in and presented towards the end of the year. And then as Christian mentioned on the SLE phase one study, we expect initial data from that program later in the year.
Speaker Change: And what you do remember about the design of OV-Cell is what we're looking to do with OV-Cell is create a product that behaves as physiological as possible, while obviously being a canary-gathagin receptor, but trying to be as close to a normal T-cell engagement.
Christian Itin: And what's characteristic of a normal T-cell engagement is that the engagement is short-lived. So a T-cell actually recognizes a target cell, forms a synapse, delivers the cytotoxic content, which drives the cell death or the metabolic process in the target cell, and then actually disengages rapidly. We're talking minutes in terms of engagement. And that short engagement is really characteristic of a normal physiological engagement.
Christian Itin: And what's characteristic for a normal T-cell engagement is that the engagement is short-lived.
Christian Itin: So a T-cell actually recognizes a target cell, forms a synapse, delivers the cytopoxy compound, which drives the cell death or apoptotic process in the target cell, and then actually disengages rapidly. We're talking minutes.
Christian Itin: We're talking minutes in terms of engagement. and that short engagement is really characteristic of a normal physiological engagement, and it is that engagement that actually is clearly different for the first generation of CD-19 CART programs in the space, but also will be true for most of the products currently being developed for all the diseases. And that is that most of those designs use antibodies, transums to CD-19, that are high affinity and nature, which means they have a cast on rate at a very slow off rate. And net, if you then think about thousands of cars on the side of the car, T-cell, thousands of CD-19 molecules on the target cell, you do basically an enormous amount of high affinity interactions between the cells and very, very long interactions between them.
Speaker Change: in terms of engagement maps.
Christian Itin: And it is that engagement that actually is clearly different for the first generation of CD90 CAR-T programs in the space but also will be true for most of the products currently being developed for our users. And that is that most of those designs use antibodies present on CD19 that are high affinity in nature, which means they have a fast start rate and a very slow off rate. And next, if you then think about thousands of CARs on the side of the CAR T-cell, thousands of CD19 molecules on the side of the target cell, gives you basically an enormous amount of high affinity interactions between the cells and very, very long interactions between them.
Speaker Change: And that short engagement is really characteristic of a normal physiological engagement.
Christian Itin: So Rob Faxilov for jumping in, I had my headset was basically given up. So what I actually wanted to say in addition to the news flow is really that we're going to be able to stay lazy focused on getting the program through the registration for first approval and getting the launch of the grant with the product. That will be the primary focus of the company, looking forward to the data updates absolutely, but operationally that is what we're really going to be having our eye on and we're looking forward to keeping the update in on the progress there.
Christian Itin: And it is that engagement that actually is clearly different for the first generation of CD19 CAR-T programs in the space, but also will be true for most of the products currently being developed for all immune diseases.
Christian Itin: And that is that most of those designs use antibodies present to CD19.
Christian Itin: that are high affinity in nature, which means they have a fast on-rate and a very slow off-rate. And NET-NET, if you then think about thousands of CARs on the side of the CAR T-cell, thousands of CD19 molecules on the target cell, gives you basically an enormous amount of high affinity interactions.
Operator: And now we're happy to actually go into TNA. Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you'll need to press star 11 on your telephone and wait for all your question, please press star 11 again. Please stand by while we compile the Q&A roster.
Christian Itin: Now, those long interactions do not actually help the kill; that already happens within a minute or so, but what they do is they drive an over-activation of the CART T-cell. That over-activation drives the side of kind of release as well as actually drives exhaustion of the cells. And ultimately, it is really contributing in a very significant way to toxicity, and that toxicity is unrelated and unnecessary to get the activity. And so, what we designed with OV cell is really also a product that has the ability to be specific, but this engages rapidly after delivering the kill, and we do that by having about a hundredfold faster and operate from the target than any of the other products out there.
Christian Itin: And those long interactions do not actually help the kill; that already happens within a minute or so. But what they do is they drive an over-activation of the CAR T-cell, that over-activation drives the cytokine release, as well as actually drives exhaustion of the cells, and ultimately is really contributing in a very significant way to toxicity, which is unrelated and unnecessary to get the activation. And so what we designed with OviCell is really a product that has the ability to be specific but disengage rapidly after delivering the kill, and we do that by having about a hundred-fold faster off-rate from the target than any of the other products out there.
Speaker Change: between the ce and very very long interactions between them and those low long interactions do not actually help the kill that already happens within a minuteor so but what they do is they drive an overaccination of the
Gil Blum: And our first question comes from Gil Bloom with Needham and Company. Hi, good morning everyone and thanks for taking our question.
Christian Itin: RT cell. That over-activation drives the cytokine release as well as actually drives exhaustion of the cells and ultimately is really contributing in a very significant way to toxicity and that toxicity is unrelated and unnecessary to get the activity.
Christian Itin: So first one, as it relates to the launch, I'm sensing here maybe something about rolling launch. Would we see sites coming on, you know, over time basically? Hi, Gil. That's actually not what it is. What we're trying to do is just explain that the actual activation at the centers is ultimately a decision, or frankly a process that's governed by the centers. And the timeline that we're seeing anywhere from two weeks to 12 weeks is pretty much what we see across the space with centers that are ready to actually get activated and then the actual time of activation. A lot of time it is actually also driven in the centers by fragmentation theory and neotherapy, and that usually actually accelerates the process and the final stretch of the activation.
Christian Itin: And so what we designed with OviCell is really, obviously, a product that has the ability to be specific.
Speaker Change: But disengage rapidly after delivering the kill, and we do that by having about a hundred-fold faster off-rate.
Christian Itin: And that gives us a very different behavior of the CAR-T cell and fundamentally changes the toxicity profile. That difference will be relevant in any setting and will give you a substantially better safety profile in any setting you would actually apply it to.
Christian Itin: And that is a very different behavior of the CART T-cell and fundamentally changes the toxicity profile.
Speaker Change: from the target than any of the other products out there. And that gives us a very different behavior of the CAR-T cell and fundamentally changes the toxicity profile.
Christian Itin: That difference will be relevant in any city and will give you a substantially better safety profile in any city you will actually apply the CART T-cell.
Christian Itin: That difference will be relevant in any setting, and will give you a substantially better safety profile in any setting you would actually apply the CAR-Q serum.
Operator: Really appreciate all your insights.
Christian Itin: I really appreciate your insights. Thanks, Kirchen. Thanks a lot, Cody.
Operator: Thanks, Christian.
Operator: Thanks a lot, guys. One moment for our next question.
Christian Itin: Really appreciate your insights. Thanks, Christian.
Operator: One moment for our next question.
James Shin: And our next question comes from James Shin with Deutsche Bank. All right. Good morning, guys.
Christian Itin: One moment for our next question.
Christian Itin: This is not a role in launch by any stretch of the imagination. Being able to be out of the gate, you have 30 to 36 centers ready to activate at that point, which has been all, you know, the internal part of the centers that compares very favorably to almost all launches that actually have been done in our space. Could you go from there to 60 centers within a year, or give us more than 90% access, patient access in this indication, which is obviously a very, very happy field, a much more happy thing to see across the competitive programs. Thank you for the clarification.
Speaker Change: our next question comes from team's shin with tororutia bank
James Shin: How to question on the onboarding activity. The range of two to 12 weeks for accreditation. Are the sites that would fall into the two week range centers that have existing CART programs, and those that fall into 12 week range are centers that are CART naive.
Speaker Change: All right, good morning guys. I had a question on the onboarding activity.
Speaker Change: The range of 2-12 weeks for predation
Speaker Change: Are the sites that would fall into the 2-week range centers that have existing CAR-T programs and those that fall in the 12-week range are centers that are CAR-T naive? That's question number one, and I have a follow-up.
James Shin: That's question number one, and I have a follow-up.
Rob Dolski: Okay.
James Shin: Okay. Hi James.
Christian Itin: Hi James. Good, good, good way to think about it. It suggests that that could be the case, but I don't think actually that's true. I think it has a lot more to do with the workflow at the centers. The CART have probably four to five programs for many of the centers that they're onboarding. So there's a very involved process for many of the centers, so there's a fantastic component. And I think ultimately will be very much driven by practicalization needs as well. I think that's going to be a big driver of actually how quickly that final stretch on the activation will occur.
Christian Itin: Okay, hi James, good way of thinking about it. It's suggested that that could be the case, but I don't think actually that's true.
Christian Itin: Good way of thinking about it. It's suggested that that could be the case, but I don't think that's actually true. I think it has a lot more to do with the workflow at the centers. There are currently probably four to five programs for many of the centers that they're onboarding. So there's a very involved process for many of them, and I think ultimately we'll be very much driven by, frankly, patient need as well.
Speaker Change: I think it has a lot more to do with the workflow at the centers. There are currently probably four to five programs for many of the centers that they're onboarding. So there's a very involved process for many of the centers.
Christian Itin: And maybe going to be on immune data. So probably the top question is, what level of data disclosure should we expect to the center in talking about the safety, or will there be some follow-up to suggest efficacy as well? I think the motion of the update will clearly be on take and short term impact, or shorter term impact of the therapy as indicated between the first patient Q2. So that gives you the maximum observation time that you will have.
Christian Itin: staff and the components.
Christian Itin: So I think that's going to be a big driver of actually how quickly that final stretch on the activation will occur. So I think there's a lot more to do with that. Most of these centers, obviously, are active CAR T centers. We're talking about the top centers in the U.S., which, frankly, all of them tend to have multiple CAR T programs already on-demand. Thank you.
Speaker Change: There's a capacity component.
Speaker Change: And I think ultimately we'll be very much driven by practice-patient need as well. So I think that's going to be a big driver of actually how quickly that final stretch on the activation will occur.
Christian Itin: So I think there's a lot more to do with that. Most of these centers, those are actually CART centers. We're talking about the top centers in the US, which frankly all of them have tended to have multiple CART programs over the home. Lord.
Christian Itin: So I think there's a lot more to do with that. Most of these centers, obviously, are active CAR-T centers. You know, we're talking about the top centers in the U.S., which, you know, frankly, all of them have, tend to have multiple CAR-T programs already on board.
Christian Itin: And obviously the rest of the patients will be at a shorter time period than obviously a Q2 to the end of the year timeline. So there's going to be, you know, initial data that will indicate the activity that also will not be a substantial amount of follow-up yet or no participation. Maybe a bit of a end of week's question. So we saw data updates for parties that include 4-1-B-B coast them versus CT-28 coast them.
Rob Dolski: Appreciate that. And then on the PNL side, are we pretty much at full commercial run rate for the commercial activity? On this road?
Speaker Change: I appreciate that. And then on the P&L side, are we pretty much at full commercial run rate for the commercial activities?
Rob Dolski: That is.
Rob Dolski: Hi, James. It's Rob. Yeah. So we have a stripping to be building towards the end of the year. We haven't fully built out the team yet.
Rob: Hi James. It's Rob.
Speaker Change: On the flip side, that is.
Rob: Hi James, it's Rob.
Speaker Change: Yeah, so we are still going to be building towards the end of the year. We haven't fully built out the team.
Rob Dolski: In the US, so I wouldn't necessarily project kind of, you know, a flat run rate from Q2. Thank you very much.
Christian Itin: And, you know, historical people have talked about how CT-28 tends to, you know, have very high ramp up in cells but also leads to maybe higher toxicities. And 4-1-B-B can link to, you know, really long-up playshoes. Maybe there are AID, you know, autoimmune indications that are more amenable to one versus the other of kind of probing your thoughts here. So what you mentioned is referring to is that the costumatory domain has sort of a impact on the initial activity that we see of the cells, particularly the cell expansion of the CAR-T cells that we're seeing.
Speaker Change: yet in the U.S., so I wouldn't necessarily project kind of, you know, a flat run rate from Q2.
Operator: Thanks a lot, James. One moment for our next question.
Operator: One moment for our next question.
Operator: Thank you very much.
James: Thanks a lot James.
Matthew Phipps: Your next question comes from Matthew Phipps with William Blair. Hey, Christian. Thanks for the update and taking my questions. Following on a little bit with Kelly asked on earlier, but with Cavalette reporting a grade four, I can't this morning from their loop is trial. They said they're implementing some protocol modifications, including some seizure profile access. I wonder if that's something that you guys have used or thought about using.
Operator: One moment for our next question.
Rob: Yeah, so I, we are still going to be building towards the end of the year; we haven't fully built out the team yet in the US. So I wouldn't necessarily project kind of, you know, a flat run rate from Q2.
Operator: And our next question comes from Matthew Phipps with William Blair.
Operator: One moment for our next question, and our next question comes from Matthew Phipps with William Blair.
Speaker Change: Hey Christian, thanks for the update and taking my questions. Following on a little bit with what Kelly asked on earlier, but with Cabaleta reporting a grade 4 ICANN this morning from their lupus trial, they said they're implementing some protocol modifications, including some seizure prophylaxis.
Christian Itin: And that is circulated generically through that. We, you know, most programs we show a faster ulceric flowagration of the CAR-Ts with the CT-28 is somewhat slower 4-1-B-B. But then 4-1-B-B would give you longer persistence and the CT-28 typically gives you very little persistence. And that also then has an impact obviously on the longer-term, you know, piece of a pleasure, especially because you're Franklin, Monk case, you have no activation, the other case, you have active agent.
Matthew Phipps: Hey Christian, thanks for the update and taking my questions. Following on a little bit with what Kelly asked earlier, but with Cabaleta reporting a grade 4 ICANN this morning from their lupus trial, they said they're implementing some protocol modifications, including some seizure prophylaxis. I was wondering if that's something that you guys have used or thought about using? And then, I realize you are very early in your trial, Ferodimy, but maybe you can just give any kind of comment on how the safety profile is reflecting the, you know, kind of Felix and other experience with those also.
Christian Itin: And then I realize you are very early in your trial for out of me, but maybe you can just give any kind of comment on how the safety profile is reflecting the kind of Felix and other experience with themselves so far. Yeah. Good to have you all met. That's actually the question. So I think from the best, so we're good here. Also, we're going to be indicated where we're early on in our phase-long study. So, you know, not seeing something in that early stage just really, you know, gets you to give you a clear answer.
Speaker Change: Wondering if that's something that you guys have used or thought about using, and then I realize you are very early in your trial ferotomy, but maybe you can just give any kind of comment on how the safety profile is reflecting the, you know, kind of Felix and other experience with Obstetrics and Gynecology so far.
Christian Itin: Yeah, good to have you all here, Matt, and thanks for the question. So, I think probably the best surrogate here, obviously, as indicated, we're early on in our phase one study, so, you know, not seeing something in that early stage doesn't really, you know, give you, sort of give you a clear-cut answer. So, I think the better part of looking at it, the better way of looking at it, is really in the old CAR-19 extension part of the study, where we had about 40 patients with various forms of neuroplasticity.
Speaker Change: Yeah, good to have you all, Matt, and thanks for the question.
Speaker Change: So, I think probably the best surrogate here, obviously we're going to be indicating we're early on in our phase one study, so, you know, not seeing something in that early stage doesn't really, you know, get you
Christian Itin: Well, I think it's worth all remembering circulated aerobic cell waste that actually the peak expansion that we're seeing with our product exceeds that of the CT-28. Car, okay? So the story certainly is a bit more complex than just post-simulation, so we actually see have an excess level of in terms of maximum expansion of the parties, which are beyond what the CD-28 cons were able to do and that combines in addition with a very long persistence.
Christian Itin: So I think the better part of looking at the way we're looking at it is really in the old car. And I think it's actually part of the study where we had about 40 patients with various forms of nausea. And what we did observe in those patients is that without prophylaxis, prophylaxis, such as normal conditioning and dosing, prophylaxis also knows there are prophylaxis and no seizure prophylaxis in these patients. We actually did not observe neurological practices in these patients. So we did not observe the right hand in these patients, which I think is giving us a lot of confidence around the overall car property.
Operator: So to give you a clear-cut answer. So I think the better part of looking at it, the better way of looking at it, is really in the old CAR-19 extension, part of the study where we had about 40 patients with the various forms of Nohushkin's lymphoma.
Christian Itin: And what we did observe in those patients is that without prophylaxis, prophylaxis, so just normal, you know, conditioning and dosing, and prophylaxis, also no steroid prophylaxis and no seizure prophylaxis in these patients, we actually did not observe neurological toxicities in these patients. So we did have sort of the right hands in these patients, which I think is giving us a And similarly, our patient with a low disease burden in ALL also had very limited neurological activity, and, in fact, no great trees even in those settings.
Operator: And what we did observe in those patients is that without prophylaxis, so just normal, you know, conditioning and dosing, and prophylaxis, also no steroid prophylaxis and no seizure prophylaxis in these patients,
Christian Itin: So that means you very, I think you need set of properties that we do without we sell that is quite different from the rest of the commercially available party programs. That in terms of the type of activity you may need depending on the indication, that's an interesting question and I think I will probably answer it from the position of what is the mechanism of action. And the mechanism of action obviously that we have is the removal of the cells, the CD-19 positive cells and also plasma blasts.
Speaker Change: We actually did not observe neurological toxicities in these patients.
Speaker Change: untso the binnerx of their i hand
Christian Itin: And similarly, the patient with low disease burden in ALL also had very limited neurological activity. And in fact, no great treatise, even in those settings. So overall, I think the prophylaxis also knows what really is different here for aerobic cell. And what we know from our product is that clearly, we do have a different behavior in the proceeding. And we're based on the knowledge of this data, which is probably a good way to sort of comparing, although we do have localized high tumor burdening these patients. There's not a lot of this, you know, bone marrow. Bone marrow burden is attempted to be very low or normal, and normal circulating these symptoms. Getting that setting up so we have not seen a lot of toxicity in the patients.
Speaker Change: in the world.
Christian Itin: So overall, I think the product profile is obviously what really is different here for OBCell, and what we know from our products is that clearly, we do have a different behavior.
Christian Itin: So, overall, I think the product profile is what really is different here for OBCell, and what we know from our products is that clearly, we do have a different behavior in the And, you know, we're based on non-hospitalized data, which is probably, you know, a good way of sort of comparing, although we do have, obviously, localized high tumor burden in these patients. There's not a lot of, you know; the bone marrow burden is attempted to be very low or normal, and normal circulating T-cells.
Christian Itin: In the case of autoimmune disease where you have to get rid of typically our clones, that of cells that actually drive the auto reactive active bodies. And so you need to actually have a complete depletion of those cells if you want to get to a reset of the disease and that I think sort of should be the expected outcome for a allergy therapy, which is obviously very more of a therapy for this type of disease.
Christian Itin: So overall, I think the product profile is obviously what really is different here for OBCell and what we know from our product is that clearly that we do have a different behavior in the proceedings.
Speaker Change: And, you know, we're based on the non-hospitalized data, which is probably, you know,
Christian Itin: So that mechanism is shared across the board. And I think what we need to ask and is whether the properties that you need to have to achieve that goal. And in my view what you need to have is because this is cell-based mechanism, you also need to have an ability to actually have proper cell salvagements. In other words, your carpeas cells have to find that the particular cells that drive autoimmunity and then actually have to be able to take them out.
Speaker Change: A good way of sort of comparing, although we do have...
Speaker Change: was a localized high tumor burden in these patients. There's not a lot of, you know, bone marrow, bone marrow burden is attempted to be very low or normal and normal circulating B-cells.
Christian Itin: But in that setting, obviously, we have not seen neurological toxicity in the patients. So it gives us a lot of confidence that we are, obviously, in a good space. But, you know, it's early days in autoimmune, and I think there's a lot to be learned.
Christian Itin: So it gives us a lot of confidence that we are posted in a good space. But, you know, it's early days in other noon and that there's a lot of fever.
Christian Itin: that in that setting obviously we have not seen neurological toxicity in the patient. So it gives us a lot of confidence that we are obviously in a good space, but you know, it's early days in autoimmune and I think there's a lot to be learned.
Christian Itin: Great, one quick follow-up. I don't think you discussed this, but when do we get an announcement on, I guess, the next autoimmune disease beyond lupus that you guys might explore? I think we're, you know, also we're going to go through kind of the launch process. I think, you know, kind of the next trajectory and update we're probably going to provide in Cuba in terms of the next steps, and that's sort of what we're working towards. But at this point, we're keeping the focus where we think it needs to be, which is really not getting through the regulatory process and getting into its way into the launch, before we got working in a thorough way that we're going to focus.
Matthew Phipps: Great. One quick follow-up. I don't think you discussed this, but when do we get an announcement on, I guess, the next autoimmune disease beyond lupus that you guys might explore? I love you.
Christian Itin: Because it's a cell-based process, you need to go through cell migration, distribution, etc, to do that. And you need to get all of those cells eliminated to have that ability to drive well in the reaction. And that means there's a certain amount of time required to actually do that. What we do not know is we do not know what's the minimum amount of time to actually achieve that goal. What we do know is that the time that actually the program had in the airline study was sufficient to do that.
Speaker Change: Great. One quick follow-up. I don't think you discussed this, but when do we get an announcement on, I guess, the next autoimmune disease beyond lupus that you guys might explore?
Christian Itin: I think we're, you know, obviously going to go through kind of the launch process. I think, you know, the next trajectory and update we're probably going to provide in Q1, in terms of next steps. And, you know, that's sort of what we're working on. But at this point, we're keeping the focus where we think we need to be, which is really on getting through the regulatory process and getting, you know, into, way into the launch before diverting, in a broader way, our focus.
Speaker Change: I think we're, you know, obviously we're going to go through kind of the launch process. I think, you know, kind of the next trajectory and update we're probably going to provide in Q1 in terms of next steps. And, you know, that's sort of what we're working towards.
Christian Itin: So the importance of the message that I was looking to give before in the prepare the box was that our product actually shares all of those properties in terms of presence, best of coffee to the visa compartment, and sufficient persistence to actually achieve that goal, shares that with the airline program, but has a better safety profile. So that's the way I would answer the question. How short you can go? That's frankly, I think that none of us knows at this point.
Speaker Change: But at this point, we're keeping the focus where we think we need to be, which is really on getting through the regulatory process and getting way into the launch before we divert in a broader way, diverting focus.
Operator: Great, thanks, Christian. Thank you.
Operator: One moment for our next question. Our next question comes from Yanan Zhu with Wells Fargo. Great, thanks for taking out questions on the autoimmune side. I was wondering, you mentioned the three centers are enrolling in the UK and Spain. I'm just wondering, are all these centers also Felix centers and have you enrolled patients SLE patients at all of the three centers? The other question related to autoimmune is wondering about your thoughts on the recent Cell publication regarding allogeneic CAR-T and demonstrating some efficacy in some autoimmune indications. Like, as you look into that data, what are the learnings and takeaways with regard to the prospects of auto CAR-T in autoimmune?
Operator: One moment for our next question.
Operator: One moment for our next question. Our next question comes from Yanan Zhu with Wells Fargo.
Speaker Change: Good. Thanks, Christian.
Operator: That's all.
Operator: One moment for our next question.
Yanan Zhu: Great. Thanks for taking our questions. On the autoimmune side, I was wondering which three centers are enrolling in the UK and Spain. I'm just wondering, are all these centers also FELIX centers?
Speaker Change: Our next question comes from Yanan Zhu with Wells Fargo.
Speaker Change: Great. Thanks for taking our questions.
Christian Itin: Because we haven't seen enough data from other programs with different profiles from these airline products to get a feel where something else might also work. But what we do know is that that pro probably gets even among does work. All right, that's very helpful. Christian and thanks for taking our questions today. Thank you. One moment for our next question.
Speaker Change: On the autoimmune side, I was wondering, you mentioned the three centers are enrolling in UK and Spain. I'm just wondering, are all these centers also FELIX centers?
Operator: And have you enrolled patients, SLE patients, at all of the three centers?
Christian Itin: And have you enrolled patients, SLE patients, at all of the three centers? The other question related to autoimmune diseases is wondering about your thoughts on the recent Cell publication regarding allogeneic CAR-T and demonstrating some efficacy in some autoimmune indications. Like, as you look into that data, what are the learnings and takeaways regarding the prospects of alloCAR-T in autoimmune diseases? Thanks. Thank you, Yanan. First off, with regard to the sensors...
Operator: The other question related to autoimmune is wondering about your thoughts on the recent Cell publication.
Asthika Goonewardene: And our next question comes from us to go with trueist. Thank you. Good afternoon, guys. Thanks for taking the question. So congrats on the progress as well, Christian. I'm going to add on to the dual questions on the centers here and maybe ask something related here. Among the 60 centers targeted, how many centers require an approval in hand to even begin the qualification process? And just to get some color here, all in, how long does it take per cent to become an ATC, including the whole qualification process and, and, and, and a site activation record.
Speaker Change: regarding allogeneic CAR-T and demonstrating some efficacy in some autoimmune indications. As you look into that data, what is the learnings and takeaways?
Yanan Zhu: Thanks.
Speaker Change: regarding the prospects of allocar T in autoimmune. Thanks.
Christian Itin: Thank you, Adam. First off, with regards to the centers, the entire three centers have been Felix centers, so there's experience in all centers and they're all involved. So that's, I think, the first part of the question. The second part of the question is related to just different modalities. That could be giving you a deep, deep remission, the deep responses in the V-cell and POSA blast compartment. Also, there are three basic categories to this under investigation. You have the autologous CAR-T cells, which is what we talked about. We have autologous CAR-T cells, which is what answers the question is, and then also the advice to see if these seven cultures, which are the three categories of LACW-EA approaches to be some compartment.
Christian Itin: Thanks, Yanan. First off, with regard to the centers, the answer is that all three centers have been FELIX centers. So there's experience in all centers, and they're all enrolling patients. So that's, I think, the first part of the question. The second part of the question is related to just different modalities that could be giving you deep, sort of deep remission, deep responses in the B-cell and plasma blast compartment. Obviously, there are sort of three basic categories to this sort of under-investigation.
Yolan: Thanks Yolan. First off, with regards to the centers, the answer is all three centers have been FELIX centers.
Speaker Change: So there's experience in all senses at the roller bowling.
Asthika Goonewardene: And then I got a couple of quick polls. So there are sort of two steps to that. First of all, the essentially has to be, you know, it's interesting to actually all of them work the product. That's the first part that we have to take. We had remarkable success in, you know, having a center's interest in actually taking the product on board, it's the, you know, very foolish guidance that will give it not 30 to 36 centers ready to be activated at time, at time of approval.
Asthika Goonewardene: So that's a very significant involvement, just to put that in numbers, that is those, you know, the centers do cover about 65 to 70% of the ALL population of the US. So that's the magnitude we're talking about, and that's where I died of the gig. So that's, you know, the level of interest to actually even engage, if that's a first thing you need to do in the second is, you need to actually go through all the preparatory steps so that you can get, when you get to the level you can actually activate the center.
Operator: So that's, I think, the first part of the question. The second part of the question is related to just different modalities. That could be giving you deep...
Speaker Change: Professor in Biomedical Science, Utah State University, Chapel Hill, NJ
Christian Itin: You have the autologous CAR T-cells, which is what we talked about mostly in the call. We have allergen A CAR T-cells, which is what the question is about. And then also there are biospecific B-cell engagers, which are sort of the three categories of at least B-cell mediated approaches to B-cell compartments.
Operator: We have Allergen A CAR T-cells, which is what the question is, and then also their bispecific T-cell engagers.
Operator: which are sort of the three categories of at least EWDA approaches to reset the B-cell compartment.
Christian Itin: What we do know at this point is obviously that with the autologous programs, we do get very deep responses. So, you know, if you look at the original data in heirloom, and I think it is indicative that we can get to transformational outcomes. What we know in pediatric ALL or in adult ALLs, we can get extremely deep responses being, you know, MRD negative at a level of beyond 10 to the minus 6.
Christian Itin: What we do know at this point is that, with the autologous program, we do get very deep responses. If we look at the original data in the air longer, I think the indicative that we can get to transformational outcomes. What we know, pediatric LL, or if that autologous, we can get extremely deep responses, being, you know, MRD negative at the level of the autotent to the bottom of six. This is the first strange way it has been tested, and the altitude of the test is get patient with long term emission in those settings, which is what we have seen with our product and what we've seen with DRIA in pediatric LL as well.
Operator: What we do know at this point is obviously that with the Autologous programs that we do get very deep responses, you know, if you look at also the original data in
Speaker Change: in their long and I think indicative that we can get to transformational outcomes.
Operator: What we know in pediatric ALL or adult ALL is we can get extremely deep responses being, you know, MRD negative at a level of beyond 10 to the minus 6. It's the most stringent way how you can test it and the ultimate test is to get patients with long-term remission in those settings.
Asthika Goonewardene: That can take anywhere from 60 to 12 months. So that is a very involved process that, you know, has a lot to do on the IT side, there's contractual pieces that you have to put in place and so on. So it's a very involved process and typically takes in that order of magnitude of 60 to 12 months. This is why we've been working on this for an extended period of time. Many of the centers that we expect to get ready for activation after an approval is in are already now in the onboarding process, just to be clear.
Christian Itin: It's the most stringent way you can test it, and the ultimate test is getting patients with long-term remission in those settings, which obviously is what we have seen with our product and what we've seen with pariah in pediatric ALL as well. So clearly, those are the most stringent tests you can run to evaluate the activity of these products. We do know that the other main programs can, you know, make a cut into the compartment.
Operator: which obviously is what we have seen with our product and what we have seen with Kymriah in pediatric ELL as well. So clearly those are probably the most stringent tests you can run to evaluate the activity of these products.
Christian Itin: So, clearly, those are called an earthquake test; you can run to evaluate the activity of these products. We do know that the autotent programs can, you know, take a cup into the compartment to date. All the data we have on the ecology side is indicative of the fact that that cup isn't as deep or as consistent. And I think that is certainly going to be true; I think, also in the audio setting. But you do expect that when you do make a college, to compartmentally see it. And even if you do even much less of a public house, as we've seen in the contestant use work, with Blake Dykel in the trial of the Republic of Syria in the year, you could see that actually, at least temporarily, you could actually have a reduction of diesel cans in those stations and see it improved from a clinical improvement in those stations.
Christian Itin: You know, to date, all the data we have on the oncology side is indicative of the fact that that cut isn't as deep or as consistent, and I think that is certainly going to be true, I think, also in the all-new setting. But you do expect that when you do make a cut in the compartment that you see it in. And even if you do even much less of a cut, as we've seen in the contagious use work with Linzaito in the Trials of Republic Charity trials this year, you could see that actually, at least temporarily, you could actually have a reduction in B-cell counts in those patients and see an improvement, a clinical improvement in those patients.
Operator: We do know that the other MED-AID programs can, you know, make a cut into the compartment. You know, to date, all the data we have on the oncology side is indicative of the fact that that cut is in their sleep.
Asthika Goonewardene: So that's a continuous process and most of these centers actually are ongoing in terms of process already at this stage. So those are kind of the key things, but then the final base is, obviously, you know, we can go with these 30, 36 centers as far as we want to go, but there are, obviously, the final steps do require the actual label in hand. And that is sort of the final step that actually gets you to that into that, you know, between two weeks and 12 weeks max time to actually get the centers fully activated on enrollment pensions.
Speaker Change: or as consistent and I think that is certainly going to be true I think also in the all-new setting but you do expect that when you do make a cut in the compartment that you see an impact.
Operator: And even if you do even much less of a cut, as we've seen in the contagious use work with Linzaito in the trials that were published earlier in the UK.
Christian Itin: Trials of the Republican Chariot
Asthika Goonewardene: So that's sort of that that stretch and obviously the vast majority of the centers are working with, obviously, have made the decision to actually put all the work into the onboarding process. A hand of actually having the label into hand. There's some, obviously, that would actually want it one way until the label is there and would actually engage the more higher workload of the activity later on. But those, obviously, will be the only 36 centers and will be at that end. But the overall majority of the centers actually have been, you know, remarkably engaged and willing to actually productively work on the, obviously, on the operation. Thank you, Chris.
Christian Itin: In the year, you could see that actually, at least temporarily, you can actually have a reduction of B-cell cancer in those patients and see an improvement, a clinical improvement in those patients.
Christian Itin: It doesn't seem to appear to be actually sustainable, but you would see an improvement. So I think what we've seen so far is consistent, I think, with what we know about what these products can do. The fundamental question is: will there be a differentiation between T-Cell Engagers and other genetic programs? And do either one of those actually get you to a place where you can get a sustained outcome?
Christian Itin: There's a bit of fear to be actually sustainable, but you would see an improvement. So I think what we've seen so far is consistent, but I think with what we know what these products can do, the fundamental question is going to be, is there going to be a differentiation between these indicators in other genetic programs, and do either one of them is actually getting to a place where it can get a sustained outcome. And I think we just don't know what this point is in time. I think we have a pretty good feel that it follows this program, so if any, we'll have further the best chance of not to be giving you a transformation ladder.
Christian Itin: doesn't appear to be actually sustainable but you would see an improvement. So I think what we've seen so far is consistent I think with what we know what these products can do the fundamental question is going to be
Christian Itin: These are going to be a differentiation between T-cell engages and other genetic programs.
Yanan Zhu: And I think we just don't know at this point in time. I think we have a pretty good feel that the Autolus programs, if any, will probably have the best chance of actually giving you a transformational outcome. I think that's sort of where we are at this point. Also, it would be interesting to see how these other programs evolve over time. And we'll certainly be carefully watching.
Christian Itin: and do either one of those actually get you to a place where you can get a sustained outcome. And I think we just don't know at this point in time. I think we have a pretty good feel that the Autolus programs, if any, will have probably the best success.
Christian Itin: I think that's sort of where we are at this point.
Christian Itin: That's really helpful. Then maybe bigger picture with the, with the recent deal with the ontic and the raise, you know, it's not a good, nice pot of cash that you can kind of dispense for the clinical development here. We see a lot of, obviously, a lot of prioritization done for commercializing OBSL, as well as doing the, the auto unit at the study. Maybe you can also revisit what comes next. What's next on your really high on the priorities of these two top priority items?
Christian Itin: Also, it'd be interesting to see how these other programs evolve over time, and then we're certainly going to be here, carefully watching the space. Great.
Christian Itin: I think that's sort of where we are at this point. Obviously it will be interesting to see how these other programs evolve over time. And we will be carefully watching the space.
Christian Itin: Great. On the oncology side, I was just wondering... your confidence about delivering the 16-day Lane 2 delivery time and also your sense of manufacturing failure rate and how these compare with Tocara's? Because that's something when we talk to some experts, these aspects of reliable delivery seem to be one of the factors that could drive the shift from one product to the other. Thanks. Yeah, really.
Christian Itin: On the oncology side, I was just wondering your confidence about delivering the 16-day range to delivery time, and also your sense of manufacturing failure rate, and how do these compare with Toccars? Because that's something, when we talk to some experts, these aspects of reliable delivery seem to be one of the factors that could drive the shift from one product to the other. Thanks. Yeah, really good question. So, you know, this is a patient population ring where you need the delivery; you need the therapy to actually be delivered. These patients don't have extra time. There's no other redo typically possible, so you have to have very high levels of reliability, open delivery.
Speaker Change: Great. On the oncology side, I was just wondering,
Christian Itin: your confidence about delivering the 16-day lane 2 delivery time and also your sense of manufacturing failure rate, and how do these compare with Tocara's?
Christian Itin: your confidence about delivering the 16-day vein 2 delivery time and also your sense of manufacturing failure rate and how do these compare with Toccara's?
Christian Itin: Right, so look, we're very keen on sort of, you know, committed to the next good little study. So this is, you know, very much a workflow that is in full swing at the company. So what we need to do now, which is a very heavy lift for any organization going through the first time through an approval on the launch. So we want to be mindful that, you know, the long hand that we're having to focus required to execute and execute with what we hope to be an extra class of, at the same time, obviously we're preparing for that, for that significant engagement since into an extra little study.
Speaker Change: Because that's something, when we talk to some experts, these aspects of reliable delivery seems to be one of the factors that could drive the shift from one product to the other. Thanks.
Christian Itin: Yeah, really good question. So, you know, this is a patient population we're in where you need delivery; you need the therapy to actually be delivered. These patients don't have extra time, there's not a redo typically possible, so you have to have very high levels of reliability in the delivery. What we're able to show in our clinical study, if you compare the clinical studies with each other, and, you know, remind yourself we did ours during the pandemic with a lot of limitations, we actually have a higher intensity, a higher level, that we'll see in Which is a very good outcome overall.
Christian Itin: Yeah, really good question. So, you know, this is a patient population where
Speaker Change: You need the therapy to actually deliver. These patients don't have extra time.
Christian Itin: There is not a redo typically possible, so you have to have very high levels of reliability on the delivery. What we're able to show in our clinical studies, if you compare to the clinical studies with each other, and, you know, remind you we did ours during the pandemic with a lot of limitations.
Christian Itin: Well, we're able to show, without clinical study, if you compare to clinical studies with each other, and you know, reminding, we get out of this through the pandemic with a lot of limitations. We actually have a higher appendity tree, higher level of appendity tree. That will see in the prior study, about 84%, and that clearly was a very good outcome overall on the appendity tree. So, we can show, we can look at it from that perspective; we can look at it from the perspective of the, you know, that is that range, which is around 6% of the Felix study, which is very low.
Christian Itin: So that's what we're working on and we're also, you know, from public perspectives, you know, at the right time or at that, but that's also really a lot of activity. We're also very excited about the interaction we're having with biotech. It's really, you know, a great chemistry between teams, a lot of good engagement, a lot of discussions that are going on. And I think that sort of also, you know, sort of key activity that is also doesn't have yet that level of visibility in terms of the slow, but it's an area very excited and I think we'll create additional opportunities as well that are not necessarily visible at this point from an overall company perspective.
Speaker Change: We actually have a higher level of intensity treatment.
Christian Itin: That was seen in the prior study, around 84%, and that clearly was a very good outcome overall on attempted treatment.
Christian Itin: So, we can show, we can look at it from that perspective, we can look at it from the perspective of the, you know, out-of-spec range, which is around 6%, and the FELIX study, which is very low, and we're at 21 days across the FELIX study, and one of the things that we have included and sort of implemented through the course of the FELIX study is a set of faster analytical methods that would allow, actually allow us to accelerate the release of the product, so a big chunk of the time you actually have in your rate of delivery time is not your manufacturer, but it's actually the analytical testing to sort of achieve the release. And then the final part...
Christian Itin: So, we can show, we can look at it from that perspective, we can look at it from the perspective of the, you know, out-of-spec range, which is around 6%, and the FELIX study, which is very low, and we're at 21 days across the FELIX study, and one of the things that we have included and sort of implemented through the course of the FELIX study is a set of faster analytical methods that would So, a big chunk of the time you actually have in your rates of delivery time is not your manufacturing, but it's actually the analytical testing to sort of achieve the release.
Christian Itin: So we can show, we can look at it from that perspective, we can look at it from the perspective of the
Christian Itin: And we're at 21 days across the Felix study, and one of the things that we have included and implemented in the course of the Felix study is a set of faster analytical methods that would allow to actually allow us to accelerate the release of the product. So, the big chunk of the time you actually have at your end of the delivery time is not going that fast, but it's actually the analytical testing and tools to sort of achieve the release. And then the final part is related to the logistics. And one of the things that we're implemented for the commercial delivery, this is part of the collaboration, the deal that we have with Cardinal Health, is that we are shipping a product before the release is completed, so that the product is already close to the site, it's on our custody, and will then actually be released once the product release is through.
Christian Itin: at a spec range which is around 6% in the Felix study, which is very low.
Christian Itin: numberwere twenty-one that days across the felix study and a lot of things that we have included to the implemented to the course of a feliic study
Christian Itin: is a set of faster analytical methods that would actually allow us to accelerate the release of the product. So a big chunk of the time you actually have in your rates of delivery time is not your manufacturing. It's actually the analytical testing to sort of achieve the release.
Christian Itin: So I'm excited about those next steps, but first things first, you know, get the approval, get the launch of the grant, get into the next little study and then we're going to move from there, but very excited about kind of what the end of the year and then also the next year. Thanks so much for taking my question. Thanks a lot.
Christian Itin: And then the final part... is related to logistics. And one of the things that we implemented for commercial delivery, this is part of the collaboration, the deal that we have with Cardinal Health, is that we are shipping a product before the release is completed in the US so that the product is already closed at the site in our custody and will then actually be released once the product release is through.
Christian Itin: And then the final part...
Christian Itin: is related to logistics.
Christian Itin: And a lot of the things that were implemented for the commercial delivery, this is part of the collaboration, the deal that we have with Cardinal Health.
Kelly Shi: And one moment for our next question. Our next question comes from Kelly, she with Jeffries. I'm going to press on the progress and then thanks for taking my questions. I was very close to the first launch for Autos. Kelly, just a quick question. Maybe like it's too early to comment on the price of the sell, but the currency if the split dosing regimen would add additional cost compared to single dose of the sell therapy.
Christian Itin: is that we are shipping products before the release is completed.
Christian Itin: to the U.S. so that the product is already close to the site.
Christian Itin: But what that does is basically takes that element of the turnaround type out of the equation. So, between the logistics element as well as the faster analytics, where we're able to be able to cut about six days out of the available delivery time. And so, what we're guiding is currently 16 days of time of launch, with an opportunity to reduce, and that time's pretty much in line with what the best competitor today looks like.
Christian Itin: But what that does is it basically takes that element of the turnaround time out of the equation. So between the logistics element as well as the master analytics, we've been able to cut six days out of the event delivery time. And so what we're guiding is partly 16 days at the time of launch with an opportunity to reduce that time, and that time is pretty much in line with what the best competitive data looks like.
Christian Itin: It's on our custody and will then actually be released once the product release is through. But what that does is it basically takes that element of the turnaround time out of the equation.
Christian Itin: So between the logistics element as well as the master analytics, we've been able to compromise six days out of the event delivery time. And so what we're guiding is partly 16 days at the time of launch with an opportunity to reduce that time, and that time is pretty much in line with what the best competitive data looks like.
Christian Itin: So between the logistics element as well as the master analytics.
Kelly Shi: Hi Kelly, really good question. So first of all, I'll say on price you're right, that would be too early to actually give any specific guidance. I think we can only remind sort of the the car price that we see with the cars, which is around 462 in the U.S. 2000 and via which is around 82. There's an overlap, there's also an age range where we know finished that although study was from 18 years onwards.
Christian Itin: where we're able to be able to talk about six days out of the event delivery time. And so what we're guiding is currently 16 days at time of launch with an opportunity to reduce and that time is pretty much in line with what the best competitive data looks like today.
Christian Itin: Thank you very much today. Very helpful. Thanks.
Christian Itin: Very helpful. Thanks. Thanks, Christian.
Christian Itin: Thanks, Christian. Thanks a lot for that.
Sebastiaan van der Schoot: One moment for our next question. Our next question comes from Sebastiaan van der Schoot with Van Longshort Kempen. Hi, Tim. This is Kiaramun Tironi. I'm on behalf of Sebastiaan. Congrats on the progress. Thank you for taking my question.
Operator: One moment for our next question.
Operator: One moment for our next question. The next question comes from Sebastiaan van der Schoot with Van Loonschoot Kempeit.
Speaker Change: Very helpful. Thanks, Christian.
Speaker Change: Thanks a lot for now.
Operator: One moment for our next question.
Speaker Change: Our next question comes from Sebastiaan van der Schoot with Van Loonschoot Kempen.
Kelly Shi: When you look at the labels for the two commercial products, one obviously goes up to 25 years, which is come right up and the second Monte Carlos goes about 25 and older. So that's the range that's currently the market. I think we can get more guidance from that, and just that with, you know, basically, point to the reference that the reference sizes that we have here in the space. In terms of the cost or the added cost related to dosing, what we do, obviously, with ovisail, is we do a two-rovert and adjusted dosing.
Operator: Hi team, this is Chiara Muntironi, I'm on behalf of Sebastiaan, congrats on the progress, thank you for taking my question. So I was wondering whether you could provide your thoughts for
Christian Itin: So I was wondering whether you could provide your thoughts or some insight into the rest of the approval of Blincito in the consolidation phase of the multi-phase chemotherapy of the first line ALL. So what do you anticipate the effect will be on the number of patients in the relapse, refractory settings of this disease? Thank you. Thanks a lot for joining. Pleasure to have you along.
Speaker Change: on the inside and the residence approval of Blincito.
Speaker Change: in the consolidation phase of the multi-phase chemotherapy of the first line ALL.
Speaker Change: What do you anticipate the effect will be on the number of patients in the relapsed refractory setting of this disease? Thank you.
Sebastiaan van der Schoot: Thanks a lot for joining us. It's a pleasure to have you along.
Kelly Shi: And that actually has proven to give us an enormous amount of robustness in terms of the safety data, which is driven on the long-half of the design, but also takes into account. Also, two-rovert, and remember, these are very thick of the old patients, tend to be very old patients. And a lot of these patients certainly cause a lot of issues with early-party programs, need to actually driven related mortality. We see that in some of the real world data as well, that being a real issue.
Christian Itin: So this is a question related to the recent approval of Blincito in the front line consolidation. Also, this is data that sort of has been, you know, first of all, known about quite a while and presented as the last two to three years, both in consolidation of both the MRD positive as well as patients, as well as patients who are gone through the initial relapse. So this is the final introduction and the initial consolidation with team of high-dose chemotherapy, but then here's a section of the status of exposed treatment title. What's been very interesting about that part of the data is that when you look at the data, be more carefully realized, there's a subset of patients that appear to benefit.
Christian Itin: So this is a question related to the recent approval of Flinside and frontline consolidation. Obviously, this is data that sort of has been, you know, first of all, known about for quite a while and presented over the last two to three years, both in consolidation of both MRD positive as well as patients as well as patients that have gone through the initial induction and the initial consolidation with chemotherapy, but then irrespective of the status going exposed.
Speaker Change: Thanks a lot for joining. Pleasure to have you along. So this is a question related to the recent approval of FlintSite and the frontline consolidation. Obviously, this is data that sort of has been, you know, first of all, known about for quite a while and presented as the last.
Speaker Change: for two to three years, both in consolidation of both MRD-positive, as well as patients that are gone through the initial induction and initial consolidation with chemo-hydrostimulant therapy, but then, irrespective of status, got exposed.
Kelly Shi: And as you may remember, our median agent of study actually was about 10 years older, that some of the other studies that were done in the past, in the industry. So, at this point, we did that whole thing through the pandemic, which also aggravated a lot of the safety-related challenges for us. So, the other thing that we have, in combination with also the health profile, uses a very substantial improvement, say, the profile.
Christian Itin: What's been very interesting about that part of the data is that when you look at the data more carefully, you realize there's a subset of patients that appear to benefit, and there's another subset that does not appear to benefit from that consolidation, and the group that did not appear to benefit actually were patients that were a bit older. And that's a very interesting kind of observation, and I think it's certainly something that we're going And so that's, I think, interesting just when you look at that part of it, at that part of the data.
Speaker Change: Thank you for your time. Thank you.
Speaker Change: What's been very interesting about that part of the data is that when you look at the data more carefully, you realize there's a subset of patients that appear to benefit.
Christian Itin: There's another subset that does; there's not, if you benefit from that consolidation. And the group that did not appear to benefit actual patients that were bit older. And that's a very interesting kind of observation. And I think this is something that I think we're going to need to follow up and I think better understanding, but it was clearly, you know, certain patients that they actually benefit, whereas always actually these not benefit goals. And so, so that's I think interesting. Just when you look at that part of the data overall, we think that most of the impact actually of the study has already been pretty much in the space.
Speaker Change: There's another subset that does not appear to benefit from that consolidation.
Speaker Change: and the group that did not appear to benefit actually were patients that were a bit older.
Kelly Shi: The primary cost that actually you see for the delivery of the quality is not the delivery itself, it's not the administration, just that's pretty out of handful, that's literally an infusion, and that's happened to tend to be very short. Infusions with talking, maybe 50 minutes or something like that. So, it's a very short infusion, that doesn't actually add a significant amount of burden, but actually expert and what really drives cost is related to the management of the patients, where they actually do experience hybrid CLS, or the experience hybrid ICANN, and in fact, the ICANN are almost worse because they tend to take a substantially longer period of time to actually get out of control.
Speaker Change: And that's a very interesting kind of observation, and I think it's certainly something that I think we're going to need to follow up and I think better understanding, but it was clearly
Christian Itin: And so that's, I think, interesting just when you look at that part of it, at that part of the data. Overall, we think that most of the impact, actually, of the study has already been pretty much in the space, given that the data actually has been well-known. It was an e-cough study, so there was a large number of centers involved. There were a lot of patients that actually were being managed in, sort of, using flint-type in the frontline setting.
Christian Itin: You know, certain patients, that they'd actually benefit, whereas others actually do not benefit.
Christian Itin: oh
Christian Itin: And so that's, I think, interesting just when you look at that part of it, at that part of the data. Overall, we think that most of the impact, actually, of this study has already been pretty much in the space.
Christian Itin: Overall, we think that most of the impact of the study has already been pretty much in the space, given that the data actually did well, and it was an ECOG study, so there were a large number of centers involved, and a lot of patients that actually were being managed in sort of using plants in the front-line setting. And in that sense, also staked in, and you can see that also when you look at the trajectory of Blunt-Cypher sales, is that clearly the sales upswing actually went ahead of the approvals, although it was driven off exactly that data that was driving, and actually ultimately was the basis.
Christian Itin: Given that the data actually is well known, it was a recall study. There's a lot of numbers that are involved; there's a lot of patients that actually would be managed in sort of using the site in the front line study. And in fact, then it's also spaked in, and you can see that also when you look at the trajectory of the site, the sales, is that clearly the sales upswing actually went ahead of the approvals, although it was driven off exactly that data that was thriving. And actually, ultimately, will see the basis for the approval.
Christian Itin: Given that the data actually is well known, it was an ECOG study, so there's a large number of centers involved. There's a lot of patients that actually will be managed in sort of using pleptitis in the front line setting.
Christian Itin: And, in that sense, also staked in, and you can see that also when you look at the trajectory of flint-type sales, is that clearly the sale upswing actually went ahead of the approvals, although it was driven off exactly that data that was driving and actually ultimately was the basis.
Kelly Shi: And obviously, often associated also with long-term serenade use and accommodation can lead to sepsis and treatment related mortality. So, that's where the real cost actually comes in. To be able to reduce the number of events massively, but also shorten the recovery time, which is both elements we've seen with OBSL in the field study, actually reduces massively the cost. And it's actually one of the key attractors elements for onboarding the product, which is that the product actually will be less intense to manage, because it's less intense to manage actually the profitability goes up for the centers, and that actually is one of the key drivers that from the financial perspective is attractive for the centers, why the onboarding also is going as well as it does.
Christian Itin: And in that sense also staked in, and you can see that also when you look at the trajectory of Blunt Cycle Sales, is that clearly the sale upswing actually went ahead of the approvals, although it was driven off exactly that data that was driving and actually ultimately was the basis for the approval.
Christian Itin: So we think most of that is actually baked in, and we do not expect to actually have a major impact on the relapsed refractory setting, but certainly would expect that there is some delay of some of the patients actually becoming refractory, so buying some time, but we also believe that a lot of that actually already starts to be realized, that many of these patients actually start to get back to the point of relapse, given that deconsolidation has actually been used for an extended period of time, certainly.
Christian Itin: So I think most of that is actually based in, and we do not expect to actually have a major impact of the last factory setting. And but certainly, you know, what is expected there is some delay of some of the patients actually coming with that. So buying some time, but we also believe that a lot of that actually starts to be realized that many of these patients actually start to get back to the point to relax. Given that the consolidation has actually been used for an extended period of time, certainly.
Christian Itin: revol
Christian Itin: So we think most of that is actually baked in, and we do not expect to actually have a major impact on the relapsed refractory setting, but certainly would expect that there is some delay of some of the patients actually becoming refractory, so buying some time, but we also believe that a lot of that actually already starts to be realized, that many of these patients actually start to...
Christian Itin: Get back to the point of relapse, given that deconsolidation has actually been used for an extended period of time, certainly in the US.
Kelly Shi: And what is also recognized, not just as a clinical improvement, as well as a longer-term outcome, but also an immediate financial improvement that I think is visible and quite well on shoots within the centers that we're engaged in.
Operator: And this concludes the question-and-answer session.
Christian Itin: Okay, thank you. Very helpful.
Operator: And that concludes the question and answer session. I would now like to turn it back to Christian for closing remarks.
Christian Itin: And that concludes the question and answer session. I would now like to turn it back to Christian for closing remarks.
Christian Itin: I would now like to turn it back to Christian for closing remarks. Well, thank you very much for joining. Really pleasure to have you all on. Looking forward to keeping you updated and obviously, as we said, you know, the old focus on getting through the final stretch and hopefully get to approval later in the year. And then be in a position where we can get this call out to patients, which is way to something that we've been working towards for many years now. And I think we'll be fantastic to be able to transition as we get to the end of the year to that stage.
Christian Itin: Thank you very much.
Christian Itin: Well, thank you very much for joining us. It is really a pleasure to have you all along. I'm looking forward to keeping you updated. And obviously, as we said, all focus on getting to the final stretch and hopefully getting approval later in the year and being in a position where we can get this call out to patients, which is really something that we've been working towards for many years now and I think it would be fantastic to be able to transition as we get to the end of the year to that stage. Thank you very much, and I'm looking forward to keeping you updated. Thank you for your...
Christian Itin: Well, thank you very much for joining us. It is really a pleasure to have you all here. I'm looking forward to keeping you updated. And obviously, as we said, you know, all focus on getting to the final stretch and hopefully getting approval later in the year and being in a position where we can get this full occupation, which is really something that we've been working towards for many years now and I think would be fantastic to be able to transition as we get to the end of the year to that stage. Thank you very much, and I am looking forward to keeping you updated.
Christian Itin: And this concludes the question and answer session. I would now like to turn it back to Christian for closing remarks.
Christian Itin: Well, thank you very much for joining. Really a pleasure to have you all on. I'm looking forward to keeping you updated and obviously, as we said, you know, all focus.
Christian Itin: You could help for and thanks very much and also have follow up on until you know, follow the follow your comments from opening remarks. So, although we saw better tolerability of city 19 car key South therapy, auto new indications when compared to him on cutriots from Dr. Sheth pioneer works. We start seeing neurotox from other ongoing trials in your lopus. So curious if you could share your insights on if the patient's baseline difference as more like a dominating factor, all card design, all maybe other reasons regarding the impact on safety.
Christian Itin: on getting to the final stretch and hopefully get to approval later in the year and then be in a position where we can get this call out to patients which is really something that we've been working towards for many years now and I think would be fantastic to be able to transition as we get to the end of the year to that stage. Thank you very much and looking forward to keeping you updated.
Christian Itin: Thank you very much, and looking forward to keeping you updated.
Operator: Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.
Operator: Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.
Speaker Change: Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.
Operator: What happened, Christian, when you dropped off?
Operator: What happened, Christian, when you dropped off?
Operator: What happened, Christian, when you dropped off?
Christian Itin: What happened Christian when you dropped off?
Operator: Thank you for watching!
Christian Itin: And also another important question here is, how obviously achieved much better neurotox control in the hem oncology indications, generally speaking, and also whether this is a transferable to auto email trials in your opinion. Thank you very much. Yeah, very good question, Kelly. So the, what we're also seeing is in general what we're seeing is that there's several parameters that apply immunological toxicity, and this is both actually CRS and neurotox. And the parameters on the one hand are the number of target cells that have to be taken and have to be removed.
Christian Itin: Obviously that defines the number of CAR T cells that could activate it, and with that, depending on the design of the CAR T cells gives you a base level of activity, potential cytokinerolase, and also the risk of neurological toxicity. So that's one element. So it's the number of cells. When we look at the neurologic at the own immune indication, we do not expect to see significant variation in terms of the number of cells that have to be removed.
Christian Itin: These are patients that have overall normal immune system. They have are lucky in the sense that they have individual clones that recognize structures in the body and drive all immunity as a consequence of it, but it is not a proliferative disease, as you would see in the form of a key. So we see a pretty steady level of pretty much a normal level of B cell and plasma as last that needs to be removed.
Christian Itin: So that's sort of basic, what becomes a constant, but then actually it becomes a variable, and that's the second element that can drive the disease, where the design of the CAR T program. There are two key components there. We already talked and I think Oscar was mentioning that before, which is the cost inventory elements and the impact that the cost inventory elements can have. They do have an impact in terms of how quickly the cell proliferate and how much nitric and release they have to do with that.
Christian Itin: That's an element that is sort of in part coming from the cost inventory domain, but what we have proven with OB cell is really that the primary diagram from the most important parameters that we're dealing with is actually the way that the CAR T cells physically engages with the target cells. And what you do remember about the design of OB cell is what we're looking to do with OB cell is create a product that behaves as physiological as possible, while obviously being a generic attitude receptive to trying to be as close to a normal piece of engagement.
Christian Itin: And what's characteristic for a normal piece of engagement is that the engagement is short-lived. So a key cell actually recognizes the target cell or the sign acts delivers the sign of proxy contact which drives the cell after an apoptotic process in the target cell. And then actually these engages rapidly. We're talking minutes in terms of engagement, and that short engagement is really characteristic of a normal physiological engagement and it is that engagement that actually is clearly different for the first generation of CD-19 CART programs in the space, but also will be true for most of the products currently being developed for all the diseases.
Christian Itin: And that is that most of those designs use antibodies, transums to CD-19, that are high affinity and nature, which means they have a cast on rate at a very slow off rate. And net, if you then think about thousands of cars on the side of the car, T-cell, thousands of CD-19 molecules on the target cell, you do basically an enormous amount of high affinity interactions between the cells and very, very long interactions between them.
Christian Itin: Now, those long interactions do not actually help the kill, that already happens within a minute or so, but what they do is they drive an over-actingation of the CART T-cell, that over-activation drives the side of kind of release as well as actually drives exhaustion of the cells. And ultimately, it is really contributing in a very significant way to toxicity and that toxicity is unrelated and unnecessary to get the activity. And so, what we designed with OV cell is really also a product that has the ability to be specific, but this engage rapidly after delivering the kill, and we do that by having about a hundredfold faster and operate from the target than any of the other products out there.
Christian Itin: And that is a very different behavior of the CART T-cell and fundamentally changes the toxicity profile. That difference will be relevant in any city and will give you a substantially better safety profile in any city you will actually apply the CART T-cell. Really appreciate all your insights. Thanks, Christian. Thanks a lot, guys.
Operator: One moment for our next question.
James Shin: And our next question comes from James Shin with Deutsche Bank. All right. Good morning, guys.
James Shin: How to question on the onboarding activity. The range of two to 12 weeks for accreditation. Are the sites that would fall into the two week range centers that have existing CART programs, and those that fall into 12 week range are centers that are CART naive. That's question number one, and I have a follow-up. Okay. Hi James. Good, good, good way to think about it. It suggests that that could be the case, but I don't think actually that's true.
James Shin: I think it has a lot more to do with the workflow at the centers. The CART have probably four to five programs for many of the centers that they're onboarding. So there's a very involved process for many of the centers, so there's a fantastic component. And I think ultimately will be very much driven by practicalization needs as well. I think that's going to be a big driver of actually how quickly that final stretch on the activation will occur.
James Shin: So I think there's a lot more to do with that. Most of these centers, those are actually CART centers. We're talking about the top centers in the US, which frankly all of them have tend to have multiple CART programs over the home. Lord. Appreciate that.
Robert Dolski: And then on the PNL side, are we pretty much at full commercial run rate for the commercial activity? On this road? That is. Hi, James. It's Rob. Yeah. So we have a stripping to be building towards the end of the year. We haven't fully built out the team yet. In the US, so I wouldn't necessarily project kind of, you know, a flat run rate from Q2. Thank you very much. Thanks a lot, James.
Matthew Phipps: One moment for our next question.
Matthew Phipps: Your next question comes from Matthew Phipps with William Blair. Hey, Christian. Thanks for the update and taking my questions. Following on a little bit with Kelly asked on earlier, but with Cavalette reporting a grade four, I can't this morning from their loop is trial. They said they're implementing some protocol modifications, including some seizure profile access. I wonder if that's something that you guys have used or thought about using. And then I realize you are very early in your trial for out of me, but maybe you can just give any kind of comment on how the safety profile is reflecting the kind of Felix and other experience with themselves so far. Yeah. Good to have you all met.
Christian Itin: That's actually the question. So I think from the best so we're good here. Also, we're going to be indicated where we're early on in our phase long study. So, you know, not seeing something in that early stage just really, you know, get you to give you a clear answer. So I think the better part of looking at the way we're looking at it is really in the old car. And I think it's actually part of the study where we had about 40 patients with various forms of nausea.
Christian Itin: And what we did observe in those patients is that without prophylaxis, prophylaxis, such as normal conditioning and dosing, prophylaxis also knows there are prophylaxis and no seizure prophylaxis in these patients. We actually did not observe neurological practices in these patients. So we did not observe the right hand in these patients, which I think is giving us a lot of confidence around the overall car property. And similarly, the patient with low disease burden in ALL also had very limited neurological activity.
Christian Itin: And in fact, no great treatise even in those settings. So overall, I think the prophylaxis also knows what really is different here for aerobic cell. And what we know from our product is that clearly that we do have a different behavior in the proceeding. And we're based on the knowledge of this data, which is probably a good way to sort of comparing, although we do have localized high tumor burdening these patients.
Christian Itin: There's not a lot of this, you know, bone marrow, bone marrow burden is attempted to be very low or normal and normal circulating these symptoms. Getting that setting up so we have not seen a lot of toxicity in the patients. So it gives us a lot of confidence that we are posted in a good space. But, you know, it's early days in other noon and that there's a lot of fever.
Matthew Phipps: Great, one quick follow-up. I don't think you discussed this, but when do we get an announcement on, I guess, the next autoimmune disease beyond lupus that you guys might explore? I think we're, you know, also we're going to go through kind of the launch process. I think, you know, kind of the next trajectory and update we're probably going to provide in Cuba in terms of the next steps and that's sort of what we're working towards.
Matthew Phipps: But at this point, we're keeping the focus where we think it needs to be, which is really not getting through the regulatory process and getting into its way into the launch, before we got working in a thorough way that we're going to focus. Great, thanks, Christian. Thank you. One moment for our next question.
Yanan Zhu: Our next question comes from Yanan Zhu with Wells Fargo. Great, thanks for taking out questions on the autoimmune side. I was wondering, you mentioned the three centers are enrolling in UK and Spain. I'm just wondering, are all these centers also Felix centers and have you enrolled patients SLE patients at all of the three centers? The other question related to autoimmune is wondering about your thoughts on the recent cell publication, regarding allogeneic CAR-T and demonstrating some efficacy in some autoimmune indications.
Yanan Zhu: Like, as you look into that data, what is the learnings and takeaways with the regarding the prospects of auto CAR-T in autoimmune? Thanks. Thank you, Adam. First off, with regards to the centers, the entire three centers have been Felix centers, so there's experience in all centers and they're all involved. So that's, I think, the first part of the question. The second part of the question is related to just different modalities. That could be giving you a deep, deep remission, the deep responses in the V-cell and POSA blast compartment.
Yanan Zhu: Also, there's a three basic categories to this under investigation. You have the autologous CAR-T cells, which is what we talked about. We have autologous CAR-T cells, which is what answers the question is, and then also the advice to see if these seven cultures, which are the three categories of LACW-EA approaches to be some compartment. What we do know at this point is that, with the autologous program, we do get very deep responses.
Yanan Zhu: If we look at the original data in the air longer, I think the indicative that we can get to transformational outcomes. What we know, pediatric LL, or if that autologous, we can get extremely deep responses, being, you know, MRD, negative at the level of the autotent to the bottom of six. This is the first strange way it has been tested, and the altitude of the test is get patient with long term emission in those settings, which is what we have seen with our product and what we've seen with DRIA in pediatric LL as well.
Yanan Zhu: So, clearly, those are called an earthquake test, you can run, to evaluate the activity of these products. We do know that the autotent programs can, you know, take a cup into the compartment to date, all the data we have on the ecology side is indicative of the fact that that cup isn't as deep or as consistent. And I think that is certainly going to be true, I think, also in the audio setting.
Yanan Zhu: But you do expect that when you do make a college, to compartmentally see it. And even if you do even much less of a public house, as we've seen in the contestant use work, with Blake Dykel in the trial of the Republic of Syria in the year, you could see that actually, at least temporarily, you could actually have a reduction of diesel cans in those stations and see it improved from a clinical improvement in those stations.
Yanan Zhu: There's a bit of fear to be actually sustainable, but you would see an improvement. So I think what we've seen so far is consistent, but I think with what we know what these products can do, the fundamental question is going to be, is there going to be a differentiation between these indicators in other genetic programs, and do either one of them is actually getting to a place where it can get a sustained outcome.
Yanan Zhu: And I think we just don't know what this point is in time. I think we have a pretty good feel that it follows this program, so if any, we'll have further the best chance of not to be giving you a transformation ladder. I think that's sort of where we are at this point. Also, it'd be interesting to see how these other programs evolve over time, and then we're certainly going to be here, carefully watching the space.
Yanan Zhu: Great.
Christian Itin: On the oncology side, I was just wondering your confidence about delivering the 16-day range to delivery time, and also your sense of manufacturing failure rate, and how do these compare with Toccars? Because that's something when we talk to some experts, these aspects of reliable delivery seems to be one of the factors that could drive the shift from one product to the other. Thanks. Yeah, really good question. So, you know, this is a patient population ring where you need the delivery, you need the therapy to actually be delivered.
Christian Itin: These patients don't have extra time. There's no other redo typically possible, so you have to have very high levels of reliability, open delivery. Well, we're able to show, without clinical study, if you compare to clinical studies with each other, and you know, reminding, we get out of this through the pandemic with a lot of limitations. We actually have a higher appendity tree, higher level of appendity tree. That will see in the prior study, about 84%, and that clearly was a very good outcome overall on the appendity tree.
Christian Itin: So, we can show, we can look at it from that perspective, we can look at it from the perspective of the, you know, that is that range, which is around 6% of the Felix study, which is very low. And we're at 21 days across the Felix study, and one of the things that we have included and implemented in the course of the Felix study is a set of faster analytical methods that would allow to actually allow us to accelerate the release of the product.
Christian Itin: So, the big chunk of the time you actually have at your end of the delivery time, is not going that fast, but it's actually the analytical testing and tools to sort of achieve the release. And then the final part is related to the logistics. And one of the things that we're implemented for the commercial delivery, this is part of the collaboration, the deal that we have with Cardinal Health, is that we are shipping a product before the release is completed, so that the product is already close to the site, it's on our custody, and will then actually be released once the product release is through.
Christian Itin: But what that does is basically takes that element of the turnaround type out of the equation. So, between the logistics element as well as the faster analytics, where we're able to be able to cut about six days out of the available delivery time. And so, what we're guiding is currently 16 days of time of launch, with an opportunity to reduce, and that times pretty much in line, with what the best competitor today looks like. Thank you very much today. Very helpful. Thanks. Thanks, Christian. Thanks a lot for that.
Sebastiaan Schoot: One moment for our next question. Our next question comes from Sebastiaan van der Schoot with Van Longshort Kempen. Hi, Tim. This is Kiaramun Tironi. I'm on behalf of Sebastiaan. Congrats on the progress. Thank you for taking my question.
Christian Itin: So I was wondering whether you could provide your thoughts or some insight into the rest of the approval of Blincito in the consolidation phase of the multi-phase chemotherapy of the first line ALL. So what do you anticipate the effect will be on the number of patients in the relapse, refractory settings of this disease? Thank you. Thanks a lot for joining. Pleasure to have you along.
Christian Itin: So this is a question related to the recent approval of Blincito in the front line consolidation. Also, this is data that sort of has been, you know, first of all, known about quite a while and presented as the last two to three years, both in consolidation of both the MRD positive as well as patients as well as patients who are gone through the initial relapse. So this is the final introduction and the initial consolidation with team of high-dose chemotherapy, but then here's a section of the status of exposed treatment title.
Christian Itin: What's been very interesting about that part of the data is that when you look at the data, be more carefully realized, there's a subset of patients that appear to benefit. There's another subset that does, there's not, if you benefit from that consolidation. And the group that did not appear to benefit actual patients that were bit older. And that's a very interesting kind of observation. And I think this is something that I think we're going to need to follow up and I think better understanding, but it was clearly, you know, certain patients that they actually benefit, whereas always actually these not benefit goals.
Christian Itin: And so, so that's I think interesting, just when you look at that part of the data overall, we think that most of the impact actually of the study has already been pretty much in the space. Given that the data actually is well known, it was a recall study, there's a lot of numbers that are involved, there's a lot of patients that actually would be managed in sort of using the site in the front line study.
Christian Itin: And in fact, then it's also spaked in and you can see that also when you look at the trajectory of the site, the sales, is that clearly the sales upswing actually went ahead of the approvals, although it was driven off exactly that data that was thriving. And actually ultimately will see the basis for the approval. So I think most of that is actually based in and we do not expect to actually have a major impact of the last factory setting.
Christian Itin: And but certainly, you know, what expected there is some delay of some of the patients actually coming with that. So buying some time, but we also believe that a lot of that actually already starts to be realized that many of these patients actually start to get back to the point to relax. Given that the consolidation has actually been used for an extended period of time, certainly.
Christian Itin: And this concludes the question and answer session. I would now like to turn it back to Christian for closing remarks. Well, thank you very much for joining. Really pleasure to have you all on. Looking forward to keeping you updated and obviously, as we said, you know, the old focus on getting through the final stretch and hopefully get to approval later in the year. And then be in a position where we can get this call out to patients, which is way to something that we've been working towards for many years now. And I think we'll be fantastic to be able to transition as we get to the end of the year to that stage. Thank you very much and looking forward to keeping you updated.
Operator: Thank you for your participation in today's conference. This does conclude the program. You may now disconnect. What happened Christian when you dropped off?