OptimumBank Q2 2024 Earnings Call Transcript

Quartr
Provided by Quartr
August 8, 2024

There are 11 speakers on the call.

Operator

Hello, ladies and gentlemen, and welcome to the Autolus Therapeutics call to discuss its Q2 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.

Speaker 1

Thanks, Sean. Good morning or good afternoon, everyone, and thanks for joining us on today's call. With me today are Doctor. Christian Itin, our Chief Executive Officer and Rob Dolsky, our Chief Financial Officer. So on slide 2, 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.

Speaker 1

These may include, but are not limited to, statements regarding the state of clinical trials and development and or regulatory time lines for our product candidates and our expectations regarding our cash runway. These statements are subject to a variety of risks and uncertainties that could cause actual results to differ materially from expectations and reflect our views only as of today. We assume no obligation to update any such forward looking statements. For a discussion of the material risks and uncertainties that could affect our actual results, please refer to the risks identified in today's press release and our SEC filings, both available on the Investors section of our website. On slide 3, you'll see the agenda for today's call.

Speaker 1

Christian is 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 and A. So over to you, Christian.

Speaker 2

Thanks a lot, Olivia, and welcome everybody to our second quarter earnings call. A real pleasure to have you all on. And I'd like to start on Slide number 4 with 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 omicel, both in the U. S.

Speaker 2

As well as in Europe and most recently now also in the U. K. 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 PDUFA target date, as you may remember, is November 16 year and we're tracking well towards that timeline.

Speaker 2

We've also initiated or are currently ongoing 2 Phase 1 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 ovisel 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 relapsed typerefractory stage of systemic lupus. This is the Carlyle study.

Speaker 2

We opened this study in the beginning of the year and we dosed our 1st patient in the Q2 and we continue to evolve in that study as we have projected. More importantly, as we went through the course of the quarter, we did focus obviously very much on the update of 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 haven't actually explored to the same extent in our prior publications and presentations around the program. 1, 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 platform 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.

Speaker 2

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 at 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. 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 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. 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 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 inatumumab. Now in terms of the operational side of the business and the governance side, we did strengthen our Board.

Speaker 2

We had Mike Bonney join as the new Chair of the company and Robin Rau, who is an expert in autoimmune diseases and inflammatory diseases. So broadening of 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 robotic bodies background is obviously very strong, but also an expansion from a medical perspective into adjacent indications outside of oncology, whereas clearly where Rabi Rao's particular experience is extremely valuable. Now in addition, obviously, we've been driving through remarkable amount of growth and maturation of the organization as we're setting up our commercial manufacturing capabilities, getting through 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 the recognition of their work and their leadership have been promoted to Senior Vice Presidents within the organization. This includes Brian on the regulatory side, Riskway, Sitehead for Stevenage, Marcus Grill on quality, Claudia Mercedes, really operations of the from the manufacturing technical operations side, but also actually in a broader role than that.

Speaker 2

And then, Dylik Patel, who is 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 having made substantial contributions that we expect to see a lot of important contributions going forward to the business. Moving to Slide 6. 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.

Speaker 2

What we did focus on is actually look at the totality of the data from the Felix study. And as you remember, Felix study 3 cohorts. By far the largest cohort are the patients that have relapsed that are 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. We have also had 2 small cohorts in addition that we have included in the study a small cohort for patients that have isolated extra medullary 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 2

So disease burden below 5% but above 10 to the minus 3%. So a very relatively narrow corridor of MRD positive disease. So that's the group. We actually analyzed the totality of that data. And as you can see, this is a total of 127 infused patients.

Speaker 2

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. And that is I think really important because about 40% of the patients that are to continue in remission without any need for additional therapy. We also have this smaller subgroup that I also refer to now on the next slide that received a subsequent stem cell there's 18 patients. They've received this transplant while being in complete remission, not only in complete remission, but also being MRD negative. So no signs of measurable disease in these patients at the time of transplant.

Speaker 2

And then obviously we had also a group of patients that were moving to other therapies or have relapsed and died. So that's the status with immediate follow-up of 21 months, which was the data cut that we were using for the ASCO and EHA presentations. Moving on Slide number 7, 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 2 curves with and without sensing 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 disease. When you see the curve actually for patients that had include the stem cell transplant, that's the green curve.

Speaker 2

The blue curve are the patients where we center 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, we'd observe that patients that actually with a stem cell transplant would do better and would actually give you a better event free survival. What we're seeing here, it looks like inverse certainly not doing better, possibly doing a bit worse if they actually receive the stem cell transplant after receiving obese cell. Now when we look at the on Slide number 8, at the overall survival, we see a similar picture.

Speaker 2

Certainly, no evidence that a patient receiving a transplant provided them a survival benefit. 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 2 of the key findings that we were presenting at ASCO and EHA and which we move on to Slide number 9. What we're evaluating there on the left hand side is the impact of the CAR T persistence in the entry survival in the patients. 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 eventually survival.

Speaker 2

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 in 6 months, it's the red curve are tracking is tracking below. Indicating that indeed longer persistence of the CAR T cells appears to be associated with a better performance on the natural survival And just as other surrogate to look at sort of the impact, we're looking at B cell aplasia and you can see also there the same type of stagger, with 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 for longer term outcome. 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.

Speaker 2

And this is now with a median follow-up of 21.5 months. We clearly see evidence of a plateau forming both in eventually 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 online persistence and improved eventually survival in these patients. 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.

Speaker 2

As you remember, 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, I would say, 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. And that onboarding process is very involved, not only from a company, but also from a center perspective.

Speaker 2

That's a real effort that actually has to be put in. That goes across quite a wide range of activities that we need to sort of integrate in, whether it's related to apheresis, to the actual delivery of the product, handling product of the product at the center, as well as additional support that we're looking to provide both to the centers downstream to 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. So very substantial amount of work that's ongoing there. We're on track to have between 3036 centers ready for activation by the time of an approval and are going to move once we are getting to that point would expect to be within the 1st year of launch at a level of about 60 centers onboarded and active with the product.

Speaker 2

So we're moving here in a very significant way as well as at a significant number of centers even for the initial start up phase. 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 process used to different systems. And that's a very involved process that we're actually engaged in this Q3 and leading into the Q4 to make sure that all elements required to deliver this therapy are fully operational and 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 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.

Speaker 2

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. 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. 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.

Speaker 2

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 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 the once an 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. 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 spelled out 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 time point where the center actually can get activated until it actually would enroll the 1st patient.

Speaker 2

And we will see certainly a variability among centers in terms of the time it will take to be on board FDA enrolling patients. To look at that in a bit more detail, we will go to the next slide. 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 will take anywhere from 2 to 12 weeks with the centers that we have prepared for the through the onboarding process. But they're now from the time point where you can actually initiate the site activation will have take anywhere between 2 12 weeks.

Speaker 2

Also, patients screening LUKA free sync scheduled and having that completed anywhere from 1 to 2 weeks at that point in time and then obviously ready to delivery time of 16 days. So when you think about that and you think about it, a target date, PDUFA target date of middle of November and as well as for the 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 those timelines. So I think that sort of I think 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 first patient's dose and then obviously we'll gear up from there as we go through the course of the year. Now with that what I'd like to do is switch gears and just briefly talk about sort of the OV Cell product family on Slide 16, franchise opportunity, it's just a slide you've seen before. OV has continued to work not only on the current activity in on the adult ALL side, but also working on the pediatric side as well as the autoimmune side with OV cell.

Speaker 2

And we'll continue to actually work on AUTO1 hundred and twenty two as well as AUTO8. AUTO1 hundred and twenty two are mostly on 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. And we're also obviously with AUTO8 continue to work on the multiple myeloma type, but we're also looking to cevixent 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 when that the environment on the autoimmune side of this space that many of you have watched very carefully. We had one major conference that happened in Q2, which is the Eular Conference, interesting dataset presented during the course of the conference.

Speaker 2

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 factor variability in the patients that are being treated. But certainly very interesting development that we're seeing, but overall, I think also very nice collaboration of the initial observations that we have seen with the airline that indeed there is very profound impact that can be had in those patients using CAR T approaches. When we look at the next slide, just to remind you, obviously, that we have a program that has a remarkable set of similarity in terms of the clinical properties to the program that's used in Erlanger. We have but also not only do we have a high degree of similarity in terms of efficacy, 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 and which also is an area where we can see differentiation to the program in Airline, but as a differentiation to any of the other CAR T programs that are currently commercially available.

Speaker 2

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 OV Cell. And I think give 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. Now the study on Slide 19, the CAROLYLE study, our Phase I study in SLE, as I indicated, the study of a startup happened in the during the latter part of Q1 and into Q2. First patient dosed in Q2 and we continue to enroll in the study. We're planning 6 patients at a 50,000,000 cell dose level, which also is a level that we know to be highly active in pediatric ALL giving us molecular complete responses and also a level of dose that is also highly active in the adult patient population where as a reminder we're using as little as 10,000,000 cells to induce complete permissions first insights from a data perspective and we'll also continue to collect that 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 late in the year.

Speaker 2

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 AUTO8, I already indicated that we're looking at 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 early 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 line with all of those 6 mg, That program also is enrolling patients. The first patient actually has been treated as well in the second quarter and as part of the progress that we were making during the quarter.

Speaker 2

So overall, progressing well and was also expect additional publications to come out during the second half of the year related to our clinical programs that we've been conducting. With that, I'd like to hand over to Rob, who will hand you through the financial results.

Speaker 3

Thanks, Christian, good morning or good afternoon to everyone. It's my pleasure to review our financial results for the Q2 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 $705,900,000 that's compared to $239,600,000 at the end of last year December 31. Our total net operating expenses for the 3 months ended June 30, 2024 were $58,900,000 as compared to $44,400,000 for the same period of 2023. For research and development, these expenses increased from $33,200,000 to $36,600,000 for the 3 months ending June 30, 2024 compared to same period in 2023.

Speaker 3

This change was primarily driven by increases in operating costs related to our new manufacturing facility, employee salaries and related costs and obicel clinical trial and manufacturing costs. These were partially offset by a more favorable UK R and D tax credit reimbursement for the period as well. General and administrative expenses increased from $11,100,000 to 21,900,000 for the 3 months ending June 30, 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, net loss was $58,300,000 for the 3 months ended June 30 compared to 45 $600,000 for the same period in 2023.

Speaker 3

Autolus estimates that with current cash and cash equivalents, we are well capitalized to drive the full launch and commercialization of OV Cell in relapsedrefractoryadult ALL as well as to advance its pipeline development plans, including runway to date in the 1st pivotal study of obicel in autoimmune disease. 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.

Speaker 3

We're waiting for Christian. 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 Krish just mentioned, that's November 16, 2024. And we'll have updates certainly at the end of ASH.

Speaker 3

You've seen some of those with the ASCO data in EHA that will be further 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.

Speaker 2

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 we're going to be obviously laser focused on getting the program through the registration for the first approval and getting the launch of the brand with the product. That will be the primary focus of the company. Looking forward to the data update 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.

Speaker 2

And now we're happy to actually go into Q and A.

Operator

Thank you. At this time, we will conduct a question and answer session. And our first question comes from Gil Blum with Needham and Company.

Speaker 4

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 2

Hi, Neil. 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 about 2 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 frankly patients that are in need of therapy and that usually actually accelerates the process and the final stretch of the activation.

Speaker 2

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 the internal part of the centers. That compares very favorably to almost all launch that actually have been done in our space. And if you go from there to 60 centers within a year, it 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.

Speaker 4

Thank you for the clarification.

Speaker 2

And maybe going to the

Speaker 4

autoimmune data. So probably the top question is, what level of data disclosure should we expect at this interim topic of modeling safety? Or will there be some follow-up to suggest efficacy as well?

Speaker 2

I think that most of the update will clearly be on safety and short term impact or shorter term impact of the therapy. As I indicated, we treated the 1st patient in Q2, so that gives you the max of 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 initial data that will indicate activity, but obviously will not be a substantial amount of follow-up yet for most of the patients. Okay.

Speaker 4

And maybe a bit of in the weeds question. So we saw data updates for CAR Ts that include 41BB 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 maybe higher toxicities and four-1BB can link to really long aplasia. Maybe there are AID autoimmune indications that are more amenable to one versus the other, kind of probing your thoughts here.

Speaker 2

So what you're basically referring to is that the cost inventory domain has sort of a 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 being generically true that most programs would show a faster altered proliferation of the CAR Ts with the CD28 somewhat slower in 4 1BB. But then 4 1 1BB would give you longer persistence and the CD28 can be a typically give you very little persistence. And that also then have an impact obviously on the longer term B cell aphasia, etcetera, you'd see because you frankly in one case you have no active agent, the other case you have active agent. But I think it's worthwhile remembering certainly for OV Cell is that actually the key expansion that we're seeing with our product exceeds that of the CD28 CAR, okay?

Speaker 2

So the story certainly is a bit more complex than just for simulation. So we actually see have an excess level of in terms of maximum expansion of the CAR Ts, which are beyond what the CD28 CARs were able to do and that combines in addition with a very long persistence. So that gives you 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 T programs. 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 is the mechanism of action.

Speaker 2

And the mechanism of action obviously that we have is the removal of B cells, CD19 positive cells and also plasma blasts. In the case of autoimmune disease, what you have to get rid of typically are clones that of cells that actually drive the auto reactive antibodies. And so you need to actually have a complete depletion of those cells if you want to get to reset the disease and that I think sort of should be the expected outcome for CAR T therapy, which is obviously very involved therapy for this type of disease. So that mechanism is shared across the board. And I think what you need to ask then is, will there be properties that we need to have to achieve that goal?

Speaker 2

And in my view, what you need to have is because it's a cell based mechanism, you obviously need to have an ability to actually have proper cell to cell engagements. In other words, your CAR T cells have to find those particular cells that drive all immunity and then actually have to be able to take them out. Because it's a cell based process, you need to have to go through cell migration, distribution, etcetera to do that and you need to get all of those cells eliminated that have been accounted, they will need to drive long and new reaction. And that means there is a certain amount of time required to actually do that. What we do not know is we do not know what's the minimal amount of time to actually achieve that goal.

Speaker 2

What we do know is that the time that actually 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 in terms of presence, depth of copy to the B cell compartment and sufficient persistence to actually achieve that goal, shares that with the alarm program, but has a better safety profile. 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 knows at this point because we haven't seen enough data from other programs with different profiles from these Alarm products to get a feel when something else might also work. But what we do know is that that profile that we had seen in the lung does work.

Speaker 4

All right. That's very helpful, Christian, and thanks for taking our questions today. Thanks a lot, Phil.

Operator

One moment for our next question. And our next question comes from Asthika with Truist.

Speaker 5

Thanks. Good morning. Good afternoon, guys. Thanks for taking the question. So congrats on the progress as well, Christian.

Speaker 5

I'm going to add on to Gil's questions on the centers here. And then maybe ask you 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 give some color here, all in, how long does it take for a center to become an ATC, including the whole qualification process and

Speaker 2

site activation required?

Speaker 5

And then I got a couple of quick follow ups.

Speaker 2

So there's sort of 2 steps to that. First of all, the center has to be obviously interested to actually onboard the product. That's the first hurdle we have to take. 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 0.30 to 0.36 centers ready to be activated at time of approval.

Speaker 2

So that's a very significant involvement. Just to put that in numbers, that is those centers do cover about 65% to 70% 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. So that's the level of interest to actually even engage.

Speaker 2

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. 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's contractual pieces that you have to put in place and so on.

Speaker 2

So it's a very involved process and typically takes in that order of magnitude of 6 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 in ongoing in terms of process already at this stage.

Speaker 2

So those are kind of the key things. But then the final bit is, obviously, we can go with these 3036 centers as far as we want to go, but there are, I would say, the final steps do require the actual label in hand.

Speaker 3

And that is sort of

Speaker 2

the final step that actually gets you to that into that between 2 weeks and 12 weeks max time to actually get the centers fully activated on enrolling pensions. So that's sort of that stretch. And obviously the vast majority of the centers we're working with obviously have made the decision to actually put all the work into the onboarding process ahead of actually having the label in hand. There's some obviously that would actually want to wait until the label is there and would sort of actually engage in more higher workload of the activity later on. But those obviously will be beyond 36 centers and will be at that end.

Speaker 2

But the overall majority of the centers actually have been remarkably engaged and willing to actually proactively work on the activation.

Speaker 5

Thank you, Christy. That's really helpful. Then maybe bigger picture, with the recent deal with BioNTech and Duraise, you've got a good nice pot of cash that you can kind of dispense for clinical development here. We see a lot of obviously a lot of prioritization done for commercializing obicel as well as doing the autoimmune study. Maybe it's a good time to also revisit what comes next?

Speaker 5

What's next on your really high on the priorities list after these 2 top two priority items?

Speaker 2

Right. So look, we're very keen, I'll say, on sort of committing to the next pivotal study. So this is very much a workflow that is in full swing at the company. And obviously, at the same time, we're not on a distract from what we need to do now, which is very heavy lift for any organization going through the first time through an approval and the launch. So we want to be mindful that on the one hand that we're having the focus required to execute and execute with what we hope to be a best in class launch.

Speaker 2

At the same time, obviously, we're preparing for that significant engagement into the next pivotal study. So that's what we're working on. And we'll see if we will update that from a public perspective at the right time around 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.

Speaker 2

There is really great chemistry between the teams, a lot of good engagement, broader discussions that are going on. And I think that sort of also key activity that it also doesn't have yet that level of visibility in terms of news flow, but it's an area where you cited that, I think, will 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, get the approval, get the launch of the grant, get into the next pivotal 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 will bring.

Speaker 5

Great. Thanks so much for taking my question.

Speaker 2

Thanks a lot.

Operator

And one moment for our next question. Our next question comes from Kelly Hsieh with Jefferies.

Speaker 6

Congrats on the progress and thanks for taking my questions. As we are very close to the first launch for ATLAS, Curious, just a quick question, maybe like it's too early to comment on the price of Aubicel, but curious if the split dosing regimen would add additional cost to compare to single dose of a cell therapy?

Speaker 2

Hi, Kelly. Really good question. The 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 sort of the carb price levels that we see with Tecardus, which is around $462,000,000 in the U.

Speaker 2

S, dollars 1,000,000 and Cambria, which is around $5,82,000,000 There is an overlap, there's offset age range where we know Felix Dental was study was from 18 years onwards. When you look at the labels for the 2 commercial products, one obviously goes up to 25 years, which is Kymriah and the second one, ticardis 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 than that and just actually basically point to 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 OV Cell is we do a tumor burden adjusted dosing.

Speaker 2

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 the design, but also takes into account of tumor burden. And remember, these are very sick of the older patients, tend to be fairly frail patients. And a lot of these patients certainly cause a lot of issues with early Part D programs 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 of the study actually was about 10 years older than some of the other studies that were done in the space.

Speaker 2

So and despite we did that whole thing through the pandemic, we adjust the aggravated a lot of the safety related challenges further. So those things that we have in combination with our profile gives us a very substantially improved safety profile. The primary cost that actually you see for the delivery of the CAR T is not the delivery itself, it's not the administration because that's pretty uneventful. That's literally an infusion in that statin that tend to be very short infusion. So we're talking maybe 15 minutes or something like that.

Speaker 2

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 CRS or they experience high grade ICANN. And in fact, the ICANN is almost worse because they tend to take a substantially longer period of time to actually get on the control. And also often associated also with long term steroid use and a combination can lead to sepsis and treatment related mortality.

Speaker 2

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 Aubicell and the Pheli 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 while the onboarding also 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

Speaker 6

Super helpful and thanks very much. And also have follow-up on autoimmune, follow your comments from opening remarks. So although we saw better tolerability of CD19 CAR T cell therapy autoimmune indications when compared to HIM onc trials from Doctor. Shaz's pioneer work. We started seeing your talks from other ongoing trials in lupus.

Speaker 6

So curious if you could share your insights if the patient, the baseline difference as more like a dominating factor or CAR design or maybe other reasons regarding the impact on safety? And also another important question here is how Aubicell achieved much better neurotox control in the hem oncology indications, generally speaking, and also whether this is transferable to autoimmune trials in your opinion? Thank you very much.

Speaker 2

Yes. Very good question, Michele. 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. Also 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 toxicity.

Speaker 2

So that's one element. So it's the number of cells. Now when we look at the neurologic at the autoimmune indications, we do not expect to see significant variation in terms of the nonteral cells that have to be removed. 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 our immunity as a consequence of it.

Speaker 2

But it is not a proliferative disease as we would see in lymphoma or leukemia. So we see a pretty steady level of pretty much a normal level of B cells and plasma labs that need to be removed. So that's sort of basically becomes a constant. Well, then actually it becomes a variable and that's the second element that can drive toxicity is really the design of the CAR T product. There are 2 key components there.

Speaker 2

We already talked and I think Aspica 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 cells proliferate and how much site can release it and actually do that. So an element that is sort of in part coming from the cost inventory domain. But what we have proven with obicel 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 engages with the target cell. 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 also being a generic pathogen receptor trying to be as close to a normal T cell engagement.

Speaker 2

And what's characteristic for a normal T cell engagement is that the engagement is short lived. So T cell actually recognizes the target cell, forms the sinus, delivers the cytotoxic compound which drives the cell death or a metabolic process in the target cell and then actually disengages that we were talking minutes in terms of engagement max. And that short engagement is really characteristic of a normal physiological engagement. And it is that engagement that actually is clearly different for the 1st generation of CD19 CAR T programs in the space, but also will be through promotion of products currently being developed for all new diseases. And that is that the most of those designs use antibodies fragments to CD19 that are high affinity in nature, which means they have a cash on rate and a very slow off rate.

Speaker 2

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 actions between the cells and very, very long interactions between them. 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 CAR T cell. That over activation drives the cytokine release as well as actually drives exhaustion of the cells.

Speaker 2

And ultimately, it's 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 OvuCell is really obviously a product that has the ability to be specific, but disengaged rapidly after delivering the kill and we do that by having about 100 fold faster off rate 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. That difference is will be relevant in any setting and will give you a substantially better safety profile in any setting you would actually apply to the car consumer.

Speaker 6

Really appreciate your insights. Thanks, Christian.

Speaker 2

Thanks a lot, Cody.

Operator

One moment for our next question. And our next question comes from James Hsin with Deutsche Bank.

Speaker 7

Hi, good morning guys.

Speaker 2

I had a

Speaker 7

question on the onboarding activity. The range of 2 to 12 weeks for accreditation, 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 1 and I have a follow-up.

Speaker 2

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. I think it has a lot more to do with the workflow at the centers.

Speaker 2

They're currently probably 4 to 5 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 capacity component. And I think ultimately, it will be very much driven by needs 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.

Speaker 3

So I

Speaker 2

think there's a lot more to do with that. Most of these centers also are active CAR T centers. We're talking about the top centers in the U. S, which frankly all of them have tend to have multiple CAR T programs already on board.

Speaker 7

Appreciate that. And then on the P and L side, are we pretty much at full commercial run rate for the commercial activity on the spread side that is?

Speaker 3

Hi, James. It's Rob. Yes. So we are still going to be building towards the end of the year. We haven't fully built out the team yet in the U.

Speaker 3

S. So, I wouldn't necessarily project kind of a flat run rate from Q2.

Speaker 7

Thank you very much.

Operator

Thanks a lot, James. One moment for our next question. And our next question comes from Matthew Phipps with William Blair.

Speaker 8

Hey, Christian. Thanks for the update and taking my questions. Following on a little bit with what Kelly asked on earlier, but with Caboleta reporting a grade 4 ICANN this morning from their lupus trial, they said they're implementing some protocol modifications, including some seizure prophylaxis. 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, phirotomy, 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 OZO so far?

Speaker 2

Yes. Good to have you all, Matt. And thanks for the question. So I think probably the best surrogate here. Obviously, we're going to indicate that we're early on in our Phase I study.

Speaker 2

So not seeing something in that early stage doesn't really get you sort of give you a clear cut answer. So I think the better part of looking at the way we're looking at it is really in the ORIX extension part of the study where we have about 40 patients with the various forms of namustriptystrophin follow-up. And what we did observe in those patients is that without prophylaxis, so just normal 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 observe the VICAD in patients, which I think is giving us a lot of confidence around the overall product property.

Speaker 2

And similarly, also, patients with low disease burden in ALL also had very limited neurological activity and in fact no great disease even in those settings. So overall, I think the product profile is obviously what really is different here for OV 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 non Hodgkin's data, which is probably a good way of sort of comparing, although we do have also localized high tumor burden in these patients. There's not a lot of bone marrow burden is intended to be very low or normal and normal circulating details that in that setting, obviously, we have not seen neurological toxicity in the patients.

Speaker 2

So it gives us a lot of confidence that we are obviously in a good space. But it's early days in autoimmune and that includes a lot of development.

Speaker 8

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?

Speaker 2

I think we're also we're going to go through kind of the launch process. I think kind of the next trajectory and update we're probably going to provide in Q1 in terms of 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 on getting through the regulatory process and getting into its way to the launch before we diverting in a broader way that we're in focus.

Speaker 8

Great. Thanks, Christian.

Speaker 2

Thanks, Rob.

Operator

Rob. One moment for our next question. Our next question comes from Yanan Zhu with Wells Fargo.

Speaker 9

Great. Thanks for taking our questions. On the autoimmune side, I was wondering, you mentioned the 3 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 3 centers?

Speaker 9

The other question related to autoimmune is, I was wondering about your thoughts on the recent cell publication regarding allogeneic CAR T and demonstrating some efficacy in some autoimmune indications. As you look into that data, what is the learnings and takeaways with the regarding the prospects of AlloCAR T autoimmune? Thanks.

Speaker 2

Thanks, Yaron. First off, with regards to the centers, the answer is all three centers have been Felix centers. So there's experience in all centers and they're all enrolling. 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, deep permission to deep responses in the B cell and plasma glass compartment.

Speaker 2

Obviously, there's sort of 3 basic categories that are sort of under investigation. You have the autologous CAR T cells, which is what we talked about mostly on the call. We have LHA CAR T cells, which is what the question is. And then also there are bispecific T cell engagers, which is in the 3 categories of, as a C cell mediated approaches to reset the B cell compartment. What we do know at this point is obviously that with the autologous programs that we do get very deep responses.

Speaker 2

If you look at also the original data in airline, I think the indicative that we can get the transformational outcomes, What we know in pediatric ALL or in adult ALLs, we can get extremely deep responses being MRD negative at a level of the other pentativirus 6. It is the first stringent way in time to test it. And the other test is get patients in long term remission in those settings, which obviously is what we have seen with our product and what we've seen with Kymriah in pediatric NOL as well. So clearly, those are called the most stringent tests you can run to evaluate the activity of these products. We do know that the other NA programs can make a cup into the compartment.

Speaker 2

To date, all the data we have on the oncology side is indicative of the fact that that cup isn't as steep or as consistent. And I think that is certainly going to be true, I think also in the autoimmune setting. But you do expect that when you do make a cut in the compartment that you see an impact. And even if you do even much less of cut as we've seen in the compassionate use work with Linzago in the trials that were published earlier in the year, you could see that actually at least temporarily you could actually have a reduction of T cell counts in those patients and see an improvement, a clinical improvement in those patients. It doesn't really appear to be actually sustainable, but you would see an improvement.

Speaker 2

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, is there going to be a differentiation between T cell engagers and allogeneic programs? And do either one of those actually get you to a place where you can get sustained outcome. And I think we just don't know at this point in time, I think we have a pretty good feel that if all of these programs, if any, we'll have probably the best chance of actually giving you a transformational outcome. I think that's sort of where we are at this point.

Speaker 2

Also, it'd be interesting to see how these other programs evolve over time and we simply will be carefully watching the space.

Speaker 9

Great. On the oncology side, I was just wondering your confidence about delivering the 16 day vein to delivery time and also your sense of manufacturing failure rate and how do these compare with Tokares 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.

Speaker 2

Yes, really good question. So this is a patient population wherein where you need to deliver you need the therapy to 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 on the delivery.

Speaker 2

What we're able to show in our clinical study, if you compare to the clinical studies with each other and remind you, we did our student pandemic with a lot of limitations. We actually have a higher intensity. We actually have a higher level of intent to treat that was seen in the prior study, around 84% and that clearly was a very good outcome overall on intent to treat. So we can show we can look at it from that perspective. We can look at it from the perspective of the out of spec range, which is around 6% in the Felix study, which is very low.

Speaker 2

And we're at 21 days across the Felix study. And one of the things that we have included and sort of implemented in the course of the Felix study is a set of faster analytical methods that would actually allow us to accelerate the release of the follow-up. So a big chunk of the time you actually have the rate of delivery time is not your manufacturer. It's actually the analytical testing and to sort of achieve the release. And then the final part is related to logistics.

Speaker 2

And one of the things that we think were implemented for the commercial delivery, this is part of the collaboration, the deal that we have with Cardinal Health is that we are shipping product before the release is completed to the U. S. 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. But what that does is basically takes that element of the turnaround time out of the equation.

Speaker 2

So between the logistics element as well as the faster analytics, we're able to be able to cost about 6 days out of the event delivery time. And so what we're guiding is partly 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.

Speaker 9

Very helpful. Thanks, Christian.

Speaker 5

Thanks a lot, Dan.

Operator

One moment for our next question. Our next question comes from Sebastian Van Der Schuchat with Van Loaneshoeck Kempen.

Speaker 10

Hi, team. This is Chiara Montironi on behalf of Sebastian. Congrats on the progress. Thank you for taking my question. So I was wondering whether you could provide your thoughts or some insight in the recent approval of BLINCITO in the consolidation phase of the multiphase chemotherapy of the first line ALL.

Speaker 10

So what do you anticipate the effect will be on the number of patients in the relapsed refractory setting of this disease? Thank you.

Speaker 2

Thanks a lot for joining. Pleasure to have you on. So this is a question related to the recent approval of Flincyte and the frontline consolidation. Obviously, this is data that sort of have been, first of all, known about for quite a while and presented over the last 2 to 3 years, both in consolidation of both MRD positive as well as patients as well as patients that are gone through the initial induction and initial consolidation with chemo hydrotherapy with that irrespective of status or exposed to the placebo. 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.

Speaker 2

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 I think we're going to need some follow-up and I think better understanding, but it was clearly certain patients that did actually benefit whereas obviously did not benefit at all. And so that's, I think, interesting just when you look at that part of it, at that part of the data.

Speaker 2

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 an ECOG study. There's a large number of centers involved. There's a lot of patients that actually will be managed and in sort of using glintycin in the frontline setting. And in fact, that also is baked in.

Speaker 2

And you can see that also when you look at the trajectory of glintycin 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 for the approval. 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. And but certainly, we'd 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 to relapse given that the consolidation has actually been used for an extended period of time certainly in the U.

Speaker 2

S.

Speaker 10

Okay. Thank you. Very helpful.

Speaker 2

Thank you very much.

Operator

And this concludes the question and answer session. I would now like to turn it back to Christian for closing remarks.

Speaker 2

Well, thank you very much for joining. Really a pleasure to have you all on. Looking obviously, as we said, all focus on getting to the final stretch and hopefully get to approval later in the year and be in a position where we can get this goal occupation, which is really 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 keep you updated.

Operator

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

Powered by Quartr
Earnings Conference Call
OptimumBank Q2 2024
00:00 / 00:00