Q3 2023 Autolus Therapeutics PLC Earnings Call
Speaker 1: through the regulatory review, we're actively preparing OB cell for potential U.S. launch with critical activities underway in medical affairs, completion of Badi dossiers, and or boarding of CAR-T centers.
Adobe sell for a potential U S launch with critical activities underway in medical affairs completion of value Dossiers, and Onboarding of car T centers move.
Moving to slide five.
Speaker 1: Here's a quick overview of the pipeline progress during the third quarter. First, we continue to expand the OB cell opportunity and we are progressing the development of OB cell and autoimmune diseases, starting with a phase one, dose confirmation study and SLE patients, which we expect to start early in 2025.
Here's a quick overview of the pipeline progress during the third quarter first we continued to expand the <unk> opportunity and we are progressing the development of Ob sell in autoimmune diseases, starting with the phase one dose confirmation study in SLE patients, which we expect to start early in 2024.
Speaker 1: We held an analyst and investor event last week where we discussed this in more detail and a replay of this presentation can be found on the event section of the Audelars.
We held an analyst and Investor event last week, where we discussed this in more detail and a replay of this.
Presentation can be found on the events section of the <unk> website and.
Speaker 1: In summary, we believe that the excellent clinical profile we've seen for OB-cell will translate well into BSTL-mediated autoimmune diseases. The differentiated mechanism of action, regulatory package, clinical validation in ALL, substantial safety database, and commercial manufacturing and delivery base will provide a differentiated opportunity for OB-cell in autoimmune disease.
In summary, we believe that the excellent clinical profile, we have seen for Ob sell will translate well into b cell mediated autoimmune diseases. The differentiated mechanism of action regulatory package clinical validation in ALLL substantial safety database and commercial manufacturing and delivery base will provide a differentiated opportunity for <unk>.
B cell in autoimmune disease.
Speaker 1: Data presented at Ash last year demonstrated the potential investment class profile of OVCEL supported by the data observed from the old car extension study in B-cell on Hodgkin's lymphoma. With continued high levels of clinical activity paired with an encouraging colorability profile across the FU-ZL-M-Foma, mantle cell lymphoma, follicle lymphoma, and chronic lymphocytic leukemia.
Data presented at Ash last year demonstrated the potentially best in class profile of Ob sell supported by the data observed from the old car extension study in B cell non Hodgkin's lymphoma with continued high levels of clinical activity paired with an encouraging tolerability profile across diffuse large b cell lymphoma mantle cell lymphoma, Follicular lymphoma and.
Chronic lymphocytic leukemia, we.
Speaker 1: We expect to complete enrollment in the old car extension study by the end of the year and to publish the data in a peer reviewed journal, as well as update data at the upcoming ash conference this year.
We expect to complete enrollment of the old car extension study by the end of the year anti published to date and a peer reviewed journal as well as update data at the upcoming Ash conference this year as well.
Speaker 1: Together with Dr. Sara Gorashian from Great Ormond Street Hospital, we published the phase one experience with auto 122 in pediatric ALL patients in blood. The study showed that patients who were not eligible for commercial CAR T therapy
Whether with Dr. Cedric aggression from Great Ormond Street Hospital, we published the phase one experience with <unk> 22 in pediatric <unk> patients in blood.
The study showed that patients who were not eligible for commercial car T therapy showed.
Speaker 1: showed a high level of clinical activity and good tolerability with over 80% of patients achieving a molecular complete remission with no antigen negative relapses seen with a median follow-up of up to 8.7 months.
Showed a high level of clinical activity and good tolerability with over 80% of patients achieving a molecular complete remission with no antigen negative relapse is seen with a median follow up of up to $8. Seven months included Ulster were patients who had relapsed after <unk> therapy with CD 19 negative disease.
Speaker 1: included ulcerative patients who had relapsed after chemriia therapy with CD19 negative.
Speaker 1: Our final pipeline updates continue during the quarter include Auto8 and Auto6-NG, both in collaboration with UCL. Auto8 is progressing well in the phase one study in multiple myeloma patients called the McCarty study. And I'll give you more information shortly on the anticipated study data at ASH. With Auto6-NG, we expect the first patient to be dosed in the neuroblastoma phase one study by the end of the year. Moot.
Our final pipeline updates continued during the quarter include <unk> eight and <unk> both in collaboration with UCL auto It is progressing well in the phase <unk> study in multiple myeloma patients called the Mccarty study and I will give you more information shortly on the anticipated study data at ash with all the <unk>.
<unk>, we expect the first patient to be dosed in the neuroblastoma phase one study by the end of the year.
Moving to slide number six.
Speaker 1: as well as from there going straight to slight number seven focusing on obi
And as well as from there going straight to slide number several focusing on <unk>.
Speaker 1: As you remember, Obisil has a unique mechanism of action. What's fundamentally different about our product candidate is that it has an ability to engage physiologically with the target.
As you remember <unk> has a unique mechanism of action, what's fundamentally different about our product candidate is that it has an ability to engage physiologically with the target cell.
Speaker 1: What this allows us is to actually have a product that can rapidly bind the target cell, which delivers specificity, paired with a fast off-rate for rapid disengagement from the target cell, once the kill has been delivered. This unique engagement drives maximal activity, while minimizing toxicity, and is at the heart of the differentiated clinical profile we are observing for OBCell and ALL, and we believe provides a great platform for future indication expansions in oncology and autoimmune diseases.
But this allows us is Jack and I have a product that can rapidly bind the target cell, which deliver specificity paired with a fast off rate for rapid disengagement from the target cell wants to kill has been deliberate this unique engagement drives maximal activity, while minimizing toxicity and is at the heart of the differentiated clinical profile, we are observing for.
<unk> and we believe provides a great platform for future indication expansions in oncology and autoimmune diseases.
Moving to slide number eight.
Speaker 1: On this slide, you can see a summary of the Felix data we presented at ASCO and EHA earlier this year.
On this slide you can see a summary of the Felix data we've presented the Bascom ehi earlier this year, while we've correct size to date and what we continue to hear from Kols as we share. The Felix data is that we enroll the study and studied patient population. Our Felix trial that is highly representative of a real world clinical setting remember we did this study.
Speaker 1: What we've characterized today and what we continue to hear from KOLs as we share the Felix data is that we enrolled a study and studied a patient population in our Felix trial that is highly representative of a real world clinical setting. Remember, we did this study during the pandemic, obviously where patient flow was very challenging, particularly given the challenges with access to centers and a lot of patients only being moved to centers.
During the pandemic, obviously, where patient flow was.
Very challenging, particularly.
Given the challenges with access to two centers and a lot of patients only being moved to centers.
Speaker 1: when there was an absolute need for them to actually move to the next therapy.
When there was an absolute need for them to actually move to the next therapy.
Speaker 1: Felix patients were refractory to multiple lines of therapy, including stem cell transplants presented with high disease burden with medium bone marrow blast of 50% of screening and extramedolary diseases present in 19% of the patients.
Felix patients were refractory to multiple lines of therapy, including stem cell transplants presented with high disease burden with medium bone marrow blast off 50% of screening and extra $1 diseases, president and 19% of the patients.
Speaker 1: Despite this challenging population with high disease burden, lots of risk features, overall older than was studied in prior programs, ob-zell delivered complete responses in 76% of patients. And of those responders, 97% actually had deep MRD negative responses.
Despite this challenging population with high disease burden lots of risk features overhaul older than most studied in prior and prior.
Programs.
We sell delivered complete responses in 76% of patients and off those responders, 97% actually had deep <unk> negative responses.
Speaker 1: The tolerability is remarkable. OVISEL had 3% high-grade CRS as well as patients with ICAGR8-3 ICANs in the range of 7.
Tolerability is remarkable <unk> had 3% high grade Crs.
As well as patients.
With <unk> III icons in the range of 7% so with both of these numbers are very low compared to any other trial conducted.
Speaker 1: So both of these numbers are very low compared to any other child conducted in this type of indication, and also obviously allows for a very good level of control of these patients. Most of these events, particularly the high grade ICANNs occurred in patients that had more than 75% tumor burden at a limb for the patient.
In this type of indication and also obviously it allows for a very good level of control. These patients most of these events, particularly the higher grade ICANN has occurred in patients can have more than 75% tumor burden outlook for depletion.
And as de Novo will providing longer term follow up from this study as well as further subgroup analysis at the Ash meeting.
Speaker 1: And as you know, we're providing longer-term follow-up from this study, as well as further subgroup analysis at the Ash Media.
Speaker 1: Regarding the manufacturing process, irrespective of disease burden and adverse prognostic factors, the manufacturing was robust and reliable. The majority of patients for whom Luca Freises was received, achieved and released product with immediate vein to delivery time of 21 days. 84% of the enrolled patients were also
Regarding the manufacturing process irrespective of disease burden and adverse prognostic factors to manufacturing with robust and reliable.
The majority of patients for whom Leukapheresis, both received achieved and released product with a median bank to delivery time of 21 days, 84% of the enrolled patients were also dosed.
Speaker 1: Cartesian and grassman and persistent look consistent with our prior observations in the old car 9-state study, where we showed that all patients with long-term outcome had also long-term persistent cartesian.
Car T cell and grasp and persistent look consistent with our prior observations in the old car 1918 study, where we showed that all patients with long term outcome and also long term persistent car T cells.
Speaker 1: Moving to slide number nine, as I've mentioned, the ash abstracts were released this morning and are available online by the conference platform, and we just would like to briefly highlight the presentations at the conference.
Moving to slide number nine as I've mentioned the Ash Abstracts were released this morning and are available online by the Ash conference platform and which.
Just would like to briefly highlight the presentations at the conference.
Speaker 1: We have had four abstract acceptates, two oral presentations, and two post-acceptance.
We have had four abstracts abstracts accepted two oral presentations and two poster presentations.
Speaker 1: In an oral presentation on Saturday afternoon December 9th, Professor Claire Rody will present the pool safety and efficacy as well as longer follow-up data from the Felix study, including self-group analysis in addition.
In an oral presentation on Saturday afternoon December nine professor Clare eroded will present, the pooled safety and efficacy as well as longer follow up.
Data from the Felix study, including subgroup analysis.
In addition.
Data from all patients treated in the Felix study continued to demonstrate high rates of overall responses Crs and Cri and a very favorable safety profile. Additionally, data suggests better outcomes in the subgroup of patients with low leukemia burden at screening.
Speaker 1: Data from all patients treated in the FELIX study continue to demonstrate high rates of overall responses, CRs and CRIs, and a very favorable phase.
Speaker 1: Additionally, data suggests better outcomes in the subgroup of patients with low leukemia burden at screening and lifted.
Sure.
Speaker 1: Data presentation will be based on a median follow-up of approximately 15 months versus nine months at ASCO earlier this year. And we look forward to sharing more details, obviously, at the actual presentation.
Data presentation will be based on the median follow up of approximately 15 months versus nine months at <unk> earlier this year and we look forward to sharing more details obviously at the actual presentation.
Second in a poster presentation will look.
Speaker 1: Second, in a person presentation, we'll look in addition at data from a pooled analysis of relapsed refractory adult ALL patients that were treated in the OLCAR-19 study as well as the FELIX Phase 1b study. So this was the precursor, the running part of the study before we conducted the pivotal study.
In addition, as data from a pooled analysis of relapsed refractory adult ALLL patients that were treated in the old car 19 study as well as the Felix Phase one B study. So this was the precursor running part of the study before we conducted the pivotal study.
Speaker 1: After a medium follow-up of more than three years, between those two studies, we approximately have 30% of patients that remain in remission without subsequent transplants or other antelithemia therapy, indicating that we have a proportion of patients that are likely to experience a long-term benefit.
After a median follow up of more than three years between those two studies, we approximately 30% of patients that remain in remission without subsequent transplant or other anti leukemia therapy, indicating that we have a proportion of patients that are likely.
To experience a long term benefit.
When we then look into the CLO and NHL cohorts of the old car 19 extreme extension study.
Speaker 1: When we then look into the CLL and NHL cohorts of the old COVID-19 extension study, we have there more than two years of follow-up at this point in time. And the study also shows durable responses and the low incidence of serious infections as well as a very good overall safety profile, which gives us, I think, a very strong, I think, rationale for moving over time into these additional disease.
We have there.
More than two years of follow up at this point in time and the study also shows durable responses and the low incidence of serious infections as well as a very good overall safety profile, which gives us I think a very strong.
Zinc rationale for moving overtime into these additional disease settings.
Speaker 1: Continuing on with the OBCell abstracts, we'll also be presenting data on our manufacturing capabilities in the post-presentation. Data gathered in the FELIX study successfully demonstrated the robust operability of OBCell manufacturing. All aphoresis starting materials were successfully processed, despite the multitude of constraints posed by the COVID-19 pandemic, and many patients that had very high levels of leukocytes and cancer cells, frankly, collected in the leukophores.
<unk> on with the <unk> abstracts, we will also be presenting data on our manufacturing capabilities in the poster presentation data gathered in the Felix study successfully demonstrated the robust operability of Ob cell manufacturing.
All apheresis, starting materials were successfully process. Despite the multitude of constraints posed by the COVID-19 pandemic and many patients that had very high levels of Luca leukocytes.
Cancer cells frankly in collected in the Leukapheresis sites.
Speaker 1: Further optimization improvements were made during the startup of the study and increased reliability, consistency, and precision of the manufacturing process, as well as improved analytics helped to minimize turnaround time and supported development of the nucleus, as well as our new OB cell manufacturing.
Other optimization improvements were made during the.
Start off with the study and increased reliability consistency and precision of the manufacturing process as well as improved analytics helps to minimize turnaround time and support the development.
Obviously, the nucleus as well as our new Ob cell manufacturing facility.
Shifting gears to our dual <unk> CD 19 targeting car T program or <unk> for multiple myeloma and an oral presentation will be sharing preliminary data from the ongoing phase one mccarty study at ash all patients treated achieved a response and doses were well tolerated with no icons or crs larger than grade III.
Speaker 1: Shifting gears to our dual BCM8 CB19 targeting CAR-T program, AutoAID for multiple myeloma. In the oral presentation, we'll be sharing preliminary data from the ongoing phase one McCarty study at ASH. All patients treated achieved a response and doses were well tolerated with no ICANs or CRS larger than grade three with a median follow-up of 4.5 months.
With a median follow up of four five months at the time of the abstract.
Speaker 1: With that, we're transitioning to slide number 11, and we're looking at the preparation for commercial launch of OBCell.
With that we're transitioning to slide number 11, and we're looking at the preparation for commercial launch of <unk>.
As you can see on slide number 11.
Speaker 1: As you can see on slide number 11, we are well on track with the activities as we have laid out.
We're well on track with the activities that we have laid out.
Speaker 1: Key obviously is getting the manufacturing supply all set up and that's obviously has progressed really well. I'll spend a little bit
The key obviously is getting the manufacturing supply all set up and Thats, obviously has progressed really well I'll spend a little bit.
Speaker 1: on the next slide on that as well. Remember what we're designing, this, what we designed, the facility for is for a capacity that will allow us to actually address and support two-thirds of the total market in the US and Europe in for a relaxed, relaxed refractory ALL patients. We have a initial capacity set for 2000 batches a year. The full capacity of the facility actually exceeds that level.
On the next slide on that as well.
Remember what we were designing this what we designed the facility for is for a capacity that will allow us to actually address and supports two thirds of the total market in the U S and Europe in our go forward, we're not relapsed refractory AML patients. So we have a initial capacity set for 2000 patches of year.
The full capacity of the facility actually exceed that level.
Speaker 1: Secondly, obviously we're working towards the filing of the BLA. The target is to get the filing in before the year end. And we're on track of delivering that important milestone for the program at the company.
Secondly, obviously, we're working towards filing of the BLA. The target is to get the filing in before year end and we're on track of delivering.
That important milestone for the program at the company.
Speaker 1: We then also will as we go through the early part of next year, obviously we'll go through a set of inspections.
We then also will as we go through the early part of next year, Obviously, we'll go through a set of inspections.
Speaker 1: of the facility, we will certainly have one from the MHRA, which we expect in the early part of next year, as well as in the context of a DLA review, obviously additional inspections that are expected during that process.
Of the facility, we will certainly have.
One from the <unk>, which we expect indeed early part of next year as well as in the context of a BLA review, obviously additional inspections that are expected during that process.
Speaker 1: The filing for a EU registration is expected in the first half of next year, and is also conducted under a prime designation similar to the R-MAT designation that we have with the F.
The filing for a EU.
Registration is expected in the first half of next year.
<unk> is also conducted.
A prime designation.
<unk> two.
Our magnification that we have with the FDA.
Speaker 1: From a commercial perspective, there's been a significant amount of activities this year, particularly in the medical affairs side, where we obviously are very active, sharing the data, running medical education, etc.
From a commercial perspective, theres been a significant amount of activity this year, particularly in the medical affair side, where.
<unk> LLC.
Very active sharing the data.
Running medical education et cetera.
Speaker 1: The second key area that we're working on is really working through the value proposition for the program and the value dossiers. So that's a key set of activity that we're well-entraquized and exactly where we expect it to be at this point in time.
A second key area that we're working on is really working through the value proposition for the program and the value to ourselves. So that's a key set of activity.
We're well on track with and they are exactly where we expect it to be at this point in time.
Speaker 1: And third, obviously we have started the onboarding of clinical centers.
Obviously, we have started the onboarding of clinical centers.
Speaker 1: for OV cell, which is a process that we had indicated in the past, it typically takes somewhere between about, between probably nine and probably 15 months, depending on the center to actually get fully onboarded and and and and
For Ob cell, which is a process as we had indicated in the past it typically takes somewhere between about.
Just between probably nine and probably 15 months, depending on the center to actually get.
Fully on boarded.
Yeah.
And registered.
Speaker 1: When we look into next year, obviously, we'll start to build up towards US launch preparation. And that obviously will be one of the key activities that we're really going to get seriously focused on in terms of build up as we're after we have filed the BLA and we're in the review process of the app.
When we look into next year, obviously, we will start to build up towards U S launch preparation.
And that obviously will be one of the key activities that we're really we're going to get.
Seriously focused on in terms of buildup.
We're after we have filed the BLA and we're in the review process of the application.
Speaker 1: So, with that, we're going to slide number 12. And this is a brief overview of the nucleus facility.
So with that we're going to slide number 12, and this is a brief overview of the nuclear facility.
Speaker 1: As you remember, this is a very compact facility, quite unusual in its design. As a total square footage of 70,000 square feet, it's a four-storey building industrial height. And in order to actually get it...
As you remember this is a.
In a very compact facility quite unusual and it's designed as a total square footage of 70000 square feet. It's a four story building.
Industrial height and in order to actually get it.
Speaker 1: get this building off the ground and operationally ready in a very very short period of time. We have taken an approach that was built on or was based on a high degree of offsite building of the facility. In fact, we had about 70% of the facility built offsite.
This building off the ground and operationally ready in a very very short period of time, we have taken all of that approach.
Built on.
It was based on.
A high degree of upside to building up the facility in fact, we had about 70% of the facility built off site.
Speaker 1: Move to the to the actual construction site and they're actually assembled by doing taking this approach and then also taking an unusual startup approach in order to get the facility up and running and qualified.
Move to the actual construct construction site and they are actually assembled.
By doing taken this approach and then also taking an unusual startup approach.
In order to get the facility up and running and qualified we're actually able to go from November eight 2020 demand with the groundbreaking.
Speaker 1: We're actually able to go from November 8th to 2021 with the grant breaking in less than two years or actually to the full qualification of the facility which is complete at this point in time. And obviously if you look at the timing for the BLA filing with just around a little bit above probably two years of time, to go from grant breaking to a full package that is admittable in its complete form.
In less than two years or actually to the full qualification of the facility, which is complete at this point in time and obviously, if we look at the timing for the BLA filing would be just around a little bit above probably two years of time.
To go from groundbreaking to full packaged in a submit <unk> in its complete for them. So thats an exceptionally fast.
Speaker 1: So that's an exceptionally fast process that we're able to run through, had a lot to do with the innovation that we're applying to both the design as well as the build up. And the design has was not just chosen for the reason of actually being fast and being able to actually set up this facility in probably less than half the time than anyone actually had done it in space so far.
<unk> process that we're able to run through a lot to do with the innovation that we're applying to both the design as well as to buildup.
The design has.
Not just chosen four.
The reason of actually being fast and be able to to actually set up this facility and probably less than half the time than anyone actually have done it in the space. So far but also because it is it gives us an ability to replicate the facility with increased demand elsewhere and also be able to do that with relatively short timelines from decision making too.
Speaker 1: But also because it is, it gives us an ability to replicate the facility with increased demand elsewhere and also be able to do that with relatively short timelines from decision making to operational action.
Operational activity that is going to be important because it has a big impact on the risk profile of investments and the timing of investments.
Speaker 1: That is going to be important because it has a big impact on the risk profile of investments and the timing of investments.
Speaker 1: What you don't see on the right hand side is the actual inside of the initial operating suite. This is a suite that's designed to deliver about 700 products a year. And what you see here is the facility, this suite actually in full.
You don't see on the right hand side is the actual inside of.
The initial.
Initial operating suite. This is a sweet that's designed to deliver about 700 products a year and what you see here is the facility this suite actually in full.
Speaker 1: at full activity level during the capacity challenge. The manufacturing processes your member is highly automated and that gives us an ability to really run a relatively large number of products in parallel within the same environment.
Full activity level during the capacity challenge.
The manufacturing process as you remember is highly highly automated and that gives us an ability to really run a relatively large number of products in parallel within the same environment.
Speaker 1: And in fact, what you see here is, in fact, a picture that comes from the actual capacity challenge where we pushed the output of that particular clean room to its limits and obviously with the key objective to be able to demonstrate sustained control throughout that level of pressure and be able to deliver high quality products during this period.
And in fact, what you see here is in fact, a picture that comes from the actual capacity challenge, where we've pushed the.
The output of that particular clean room to its limits.
And obviously with the key objective to be able to demonstrate.
Sustained control throughout that level of pressure.
And be able to deliver high quality products. During this period. So a key aspect actually also of data that goes into a BLA filing as well.
Speaker 1: So, the key aspect actually also of data that goes into a BLA filing as well.
When we look beyond.
Speaker 1: When we look beyond the ALL opportunity and moving to slide 14, what you see summarized on slide 14 is basically the evolution of the OV cell program as we see it currently. First of all, as you've seen, OCL with its anchor indication in ALL gives us a very unique product with an exceptional level of activity combined with a remarkable level of safety.
The ALLL opportunity of moving to slide 14, where do you see summarized on slide 14 is basically the evolution of the <unk> program as we see it currently first of all as you seen obviously <unk> with its anchor indication in <unk>.
It gives us a very unique product with an exceptional level of activity combined with a remarkable level of safety.
Speaker 1: And that creates a unique opportunity, not only for the development of the product in patients with acute lymphotlastic leukemia, but also, obviously, for indication sets in non-harmic lymphoma as well as in auto-immune disease.
And that gives creates.
Unique opportunity not only for the development of the product in patients with acute lymphoblastic leukemia, but also obviously for indications in non Hodgkin's lymphoma, as well as an autoimmune disease. So that's the core opportunity, we see with Ob sell in I would say were active on all those fronts with the program when we think about that.
Speaker 1: So that's the core opportunity we see with OVCL and I would say we're active on all those fronts with the program. When we think about it, so that the next steps of the program and building on the unique features of the CD19 car that's utilized in OVCL, we developed those for two next stage products. One is all the one, 22 that I mentioned before, where we published the data in blood from our phase one initial clinical trial, which is a dual targeting approach.
The next steps with the program and building on the unique.
Features of the CD 19 car that's utilized an Ob cell. We developed obviously to next stage products. One is <unk> 22 that I mentioned before what we published that data and gloves from our phase one initial clinical trial, which is a dual targeting approach.
With the aim to minimize the risk of patients relapsing with CD 19 negative disease, which is one of the major drivers for relapse in acute lymphoblastic leukemia, both in children as well as in adult patients.
Speaker 1: with the aim to minimize the risk of patients relapsing with CD19 negative disease, which is one of the major drivers for relapse in acute lymphoblastic leukemia, both in children as well as in adults.
Speaker 1: This product obviously gives us sort of a next leg up. It builds on the unique properties on the CD19 targeting, utilizing the same CD19 car as OV cell vows, but actually adds a highly potent CD22 car that was designed to recognize cells that express very low levels of CD22 on their surface.
This product obviously it gives us sort of a next leg up it builds on the a unique properties on the CD 19 targeting utilizing the same the CD 19 car as obi sell to us, but actually as a highly potent.
CD 22 car that was designed to recognize sales.
Cells that express very low levels of CD 22 on their surface, which is one of the known escape mechanisms for CD 22.
Speaker 1: which is one of the known escape mechanisms for C.E. 22.
Speaker 1: So this is the next generation program for OVCEL, which is really designed for oncology indications as to the primary area of opportunity.
So this is the next generation.
Program for Ob cell, which is really designed for.
Oncology indications.
So that the primary area of opportunity.
Speaker 1: The, the second program auto eight dimension before we're going to be presenting an oral presentation on the phase initial phase one data that we generated together with our colleagues at UCL.
The second program auto as I mentioned before we're going to be presenting an oral presentation on the phase initial phase one data that we generated together with our colleagues at UCL. This program again built on the CD 19 car from Oki cell and it adds a highly potent CMA car in this case as well.
Speaker 1: This program again builds on the CD19 car from Opicel and it adds a highly potent BCMA car. In this case, as well, optimized for recognizing very low levels of BCMA on the surface of target cells. This is a known challenge with BCMA targeting is that you do have that the target is selective, but the target is often expressed at copy numbers that are maybe as low as 10 or 20 molecules on the cell surface.
Optimized for recognizing very low levels of <unk> on the surface of target cells. This is a known challenge with Dcla targeting is that you do have that the targeted selective but the targeted often expressed at copy numbers that it may be as low as 10 or 20 molecules on the cell surface for multiple myeloma cell.
Speaker 1: for L-multiple myeloma cells. And as you can imagine, that creates somewhat of a challenge to actually efficiently recognizing these cells and making sure you can really get at all the cells and not just the higher level expressing multiple myeloma or plasma.
And as you can imagine that creates somewhat of a challenge to actually efficiently recognizing these cells and making sure you can really get at older.
And all the sales and not just a higher level of expressing.
Multi myeloma or plasma cells.
Speaker 1: So this program obviously is again, as with all the on 22, a dual targeting program. And so the starts opening up opportunities that could go both on the oncology as well as the auto-immune side. And depending on the development of the data, we'll make decisions in which direction we think we're going to be taking this.
So this program I would say is again as with auto on 'twenty to a dual targeting program.
So it starts opening up opportunities that could go both on the oncology as well as the autoimmune side and depending on the development of the data we will make decisions in which direction. We think we're going to be taking this program.
Speaker 1: Moving to slide 15, this is just a slide that we have shown last week and explained and sort of walked through in more detail. Fundamentally, we believe we're in a very good position with our program.
Moving to slide 15. This is just a.
We have showed last week and explained and sort of walk through in more detail.
<unk>, we believe we're in a very good position with our program.
Speaker 1: Given that we do obviously have a substantial amount of clinical validation, we have a large data set and an incredibly difficult to treat patient population where we show sort of a best-in-class benefit-risk ratio for sure across this indication, but also a highly attractive profile in the non-large insulin FOMO settings as well.
Given that we do obviously have substantial amount of clinical validation, we have a large data set in an incredibly difficult to treat patient population, where we show.
Sort of a best in class.
Benefit risk ratio for sure across.
Across this indication, but also a highly attractive profile.
In the non Hodgkin's lymphoma settings as well this gives us a lot of confidence around the product what do you need to do is you need to obviously in these autoimmune diseases make a very deep cup into the B cell compartment. This is what we have demonstrated obviously in all of these patients driving them, where we can demonstrate and show that indeed.
Speaker 1: This gives us a lot of confidence to ride the product, what you need to do is you need to obviously in these autoimmune diseases, make a very deep cut into the B cell compartment. This is what we've demonstrated, obviously, and in all of these patients, driving or where we can demonstrate and show that indeed these patients.
These patients.
Speaker 1: and do experience B-cell aplasia. But I think much more stringently, we can demonstrate that we also get the patients that have leukemia into a MRD-negative state, which gives us a much higher level of resolution and a much more stringent measure of removal of all CV19 positive cells.
Do experience piece of <unk>, but I think much more stringently, we can demonstrate that we also get the patients did have leukemia into a <unk> <unk> negative state, which is gives us a much higher level of resolution at a much more stringent measure of removal of old CD 19 positive cells.
In these patients so it gives us a strong amount of information about the quality of the clinical.
Speaker 1: So it gives us a strong amount of information about the quality of the clinical.
Activity that we can see in these patients and obviously combined with an exceptional safety profile safety matters a lot in autoimmune disease.
Speaker 1: activity that we can see in these patients and obviously combined with an exceptional safety profile. Safety matters a lot in autoimmune disease. It's more important actually than in oncology.
More important is actually that then in oncology.
Speaker 1: And one of the advantages that we have with OBSL is that we always have a substantial safety database now that we have to generate it in the development leading up to the, you know, imminent filing in patients with ALL. Now,
And one of the advantages that we have with Ob salaries that we always have a substantial safety database now that we have to generate it.
The development, leading up to the imminent filing.
For patients with ALS.
The.
This safety data becomes important, particularly when you think about the opportunity that we have seen.
Speaker 1: this safety data becomes important, particularly when you think about the opportunity that we have seen from the work that was done by Georg Schett and Andreas Mackensen.
From the work that was done back Eric chat and address makinson.
Speaker 1: in inducing deep responses in SLE patients and in fact by now actually have shown that indeed those responses are sustainable at least for a year to two years which is the observation time that's currently in available for those initial patients treated with their own CD19 CAR-T therapy which they manufactured on the academic side.
Inducing.
Deep responses in.
SLE patients and in fact by now actually have shown that indeed, those responses are sustainable at least for a year to two years, which is the observation time. That's currently available for those initial patients treated with their own.
CD 19 car T therapy, which they manufactured on the academic side.
Speaker 1: Now, this level of activity creates also an interesting opportunity with a large to the development path you can take.
The.
This level of activity creates.
And interesting opportunity with regards to the development path you can take in in SLE, which is a much more aggressive much more compact development path as you would normally have seen with the standard.
Speaker 1: in SLE, which is a much more aggressive, much more compact development path, as you would normally have seen with the standard add-on trial designs that have been used for the various monoclonal antibodies that have developed for the space, which tend to do sort of a limited, or can show a limited improvement over the standard of care, and obviously require very large patient numbers to demonstrate the effect as a consequence of it.
Add on trial designs that have been used for the various monoclonal antibodies that have developed for the space, which tend to do sort of <unk>.
<unk> can show a limited improvement.
Over the standard of care and <unk>.
Obviously require very large patient numbers to demonstrate the effect as a consequence of it here. We believe that if those if that level of activity can actually be confirmed that was originally seen in the airlines study that he would be able to actually run the relatively compact studies that you would then actually have to supplement with safety information from.
Speaker 1: Here we believe that if that level of activity can actually be confirmed, there was originally seen in the airline study that he would be able to actually run the relatively compact studies that he would then actually have to supplement with safety information from other studies to actually discharge the safety risks for the product.
Other studies.
Actually discharge the safety risks.
For the product we believe this puts us in a very strong position because obviously, we do have a substantial amount of data from our current development.
Speaker 1: We will leave this puts us in a very strong position because obviously we do have a substantial amount of data from our current developed.
Speaker 1: We also obviously will do have a very significant level of derasking from a manufacturing perspective, from a regulatory perspective.
We also obviously do have a very significant level of derisking from a manufacturing perspective from a regulatory perspective as well as from a commercial perspective, and I think one point I want to just highlight is that we believe it's going to be important in this indication to also have an ability.
Speaker 1: as well as from a commercial perspective, and I think one point that one teaches highlight is that we believe it's going to be important in this indication to also have an ability to deliver product with a good cost of goods.
To deliver product with a good cost of goods.
Speaker 1: as we think that the range of prices that ultimately will be realized will be similar but may not exceed what we're seeing on the oncology side. And clearly, that requires you to actually have attractive cost of goods to actually maintain profitability across these indications. And that's going to be very difficult to actually generate if you had to, for an example, utilize a CDMO on the way there.
As we think that the range of prices that ultimately will be realized will be similar but may not exceed what we're seeing on the oncology side.
And clearly that requires you to actually have attractive cost of goods to actually maintain profitability.
Across these indications.
That's going to be very difficult to actually generate if you had to for an example utilize the CMO underway there.
Speaker 1: So this is a few considerations here for why we think we're exceptionally well positioned. Obviously we're gonna be starting with the Doze Confirmation Study early next year. And with data from that study, we'll then discuss the pivotal study designs and take it from there. But we believe that this is obviously with all the work that we've done, enabling work and infrastructure pieces we have in place, puts Obishella in very, very strong position.
So this is a few considerations here for why we think we're exceptionally well positioned.
They were in.
B.
<unk> with the dose confirmation study early next year.
With data from that study will then discuss the pivotal study designs.
And take it from there, but we believe that this is obviously with all the work that we've done enabling work and infrastructure pieces, we have in place puts ob cell and very very strong position.
Speaker 1: Moving to slide number 16, this is just a quick overview in terms of the competitive environment where we have either companies to have.
Moving to slide number 16. This is just a quick overview in terms of.
So the competitive environment.
We have either companies did have.
Speaker 1: significant presence in the CAR T field, but there have changed the manufacturing process to a point where the product as far as we can tell will not be comparable to what they have used in the past in the oncology setting. At that point, you do lose the ability to actually utilize the safe information that you generate it on the oncology side and you need to actually generate more clinical data to discharge the safety risk.
Our significant presence in the car T field.
Change the manufacturing process to a point where the.
The products as far as we can tell it will not be comparable to what they have used in the past in the oncology setting at that point.
You lose the ability to actually utilize the safety information that you generated on the oncology side and you need to actually generate more clinical data to discharge safety risks.
Speaker 1: There's also the investment required to adjust manufacturing, etc. to the new manufacturing process, which we do not have to do.
There is also obviously investment required to sort of adjust manufacturing et cetera to the new manufacturing process, which we do not have to do and then obviously, we have additional new programs coming in which lack clinical data as well as infrastructure.
Speaker 1: And then obviously we have additional new programs coming in, which lack clinical data, as well as infrastructure, which obviously will require very substantial investments to be in a competitive place going forward. And it'll be interesting to see over time what potentially allogeneic approaches might do. At this point, obviously, there's still a lack of data. And obviously needs to be built, frankly, across the board in terms of capabilities.
Which obviously will require a very substantial investments to be in a competitive place going forward and it will be interesting to see over time, but potentially allogeneic approaches might do at this point obviously.
Still a lack of data.
And obviously needs to be built frankly across the board in terms of capability.
Speaker 1: So with that, I'll move on to just a quick update on the pipeline that we've touched on most of the programs and what I briefly want to just highlight is that we're in the process of writing up.
So with that I'll move on to just.
Quick update on the pipeline.
Touched on most of the programs what I briefly want to just highlight is that we are in the process of writing up.
Speaker 1: The clinical experience with all of four, which we are expect to publish in a peer review journal, as well as with regards to all the six NG, our neuroblastoma program, where we expect to dose our first patient during the fourth quarter now, as well. A program we're excited about, as we're sort of included in that program, quite a range of self-programming technology we've developed in the last few years, and they're now basically bringing together in this indication, solid tumor indication.
The clinical experience with <unk> for which we are expected to publish in the peer reviewed journal as well as.
With regards to auto <unk> Blastoma program, where we expect to dose our first patient during the quarter the fourth quarter now as well.
And we're excited about Asbury.
Included in that program quite a range of cell programming technology, we develop for the last few years, and then that basically bringing together.
In this indication solid tumor indications.
Speaker 1: So with that, I'd like to actually hand over to Rob and removing to slide number nine.
So with that I'd like to actually hand over to Rob and removing two slide number 19.
Thanks, Christian and good morning or afternoon to everyone.
Speaker 2: Thanks Christian and good morning or afternoon to everyone.
Speaker 2: It's my pleasure to review our financial results for the third quarter ended September 30th, 2023.
It's my pleasure to review our financial results for the third quarter ended September 32023.
Our cash and cash equivalents at September 30th.
Speaker 2: Our cash and cash equivalents at September 30 total 256.4 million as compared to 382.4 million in December 31st.
Total $256 4 million as compared to $382 4 million.
In December 31 2022.
Speaker 2: Total operating expenses net for the three months ended September 30 were $47.8 million as compared to $43.5 million for the same period in 2022.
Total operating expenses net for the three months ended September 30th.
$47 8 million as compared to $43 5 million for the same period in 2022.
Our research and development expenses decreased by 0.4 million to $37 2 million for.
Speaker 2: Our research and development expenses decreased by 0.4 million to 37.2 million.
Speaker 2: For the three months ended September 30th, compared to the same period in 2022.
For the three months ended September 30th compared to the same period in 2022.
This was primarily due to decreases in clinical trial and supply costs related to our <unk> clinical program.
Speaker 2: This was primarily due to decreases in clinical trial and supply costs related to our OBSEL clinical program.
Speaker 2: And these were partially offset by increases in operating costs related to our new manufacturing facility, as well as salaries and employee-related costs driven by increased headcount.
These were partially offset by increases in operating costs related to our new manufacturing facility as well as salaries and employee related costs driven by increased head count.
On the G&A side general and administrative expenses increased by $2 4 million to $10 6 million for the three months ended September 30, compared to the same period in 2022.
Speaker 2: On the G&A side, general and administrative expenses increased by 2.4 million to 10.6 million for the three months and in September 30th compared to the same period in 2022.
Speaker 2: This increase was primarily due to salaries and other employee related costs driven by an increase in general administrative head count supporting the overall business growth primarily related to pre commercialization activities.
This increase was primarily due to salaries.
And other employee related costs, driven by an increase in general administrative head count supporting the overall business growth primarily related to pre commercialization activities.
Our net loss attributable to ordinary shareholders was $45 8 million for the three months ended September 32023.
Speaker 2: Our net loss attributable to ordinary shareholders was 45.8 million for the three months ended September 30th, 2023, compared to 42.8 million for the same period in 2022.
Compared to $42 8 million for the same period in 2022.
Although this estimates that our current cash and cash equivalents on hand, and anticipated future milestone payment from Blackstone will extend the companys cash runway into 2025.
Speaker 2: Autolous estimates that our current cash and cash equivalents on hand in anticipated future milestone payment from Blackstone will extend the company's cash runway into 2025.
And just as a reminder, in our projections, we do anticipate an R&D tax refund from the U K H MRC in Q4 of this year and we would anticipate being eligible for a tax refund.
Speaker 2: And just as a reminder in our projections, we do anticipate an R&D tax refund from the UK HMRC in Q4 of this year and would anticipate being eligible for a tax refund in a similar fashion next year as well.
Fashion next year as well.
Speaker 2: I'll now hand back to Christian to wrap up with a brief outlook on expected milestones. Christian?
I'll now hand back to Christian to wrap up with a brief outlook unexpected milestones Christian.
Speaker 1: Thank you, Rob. And so we're moving to slide 21. This is a quick summary of kind of the plant news flow. And as you can see, there's a lot of activity coming up towards the end of the year and into the early part of next year.
Thank you, Rob and so we're moving to slide 21.
This is a quick summary of kind of the plant news flow and as you can see there's a lot of activity.
Coming up towards the end of the year and into the early part of next year.
Speaker 1: As mentioned before, a big item of focus and clearly where most of the organization is working towards is get the BLA filing in before the end of the year.
As mentioned before.
Big.
Item of focus clearly where most of the organization is working towards is get the BLA filing.
In before the end of the year and we obviously talked about the.
Speaker 1: We obviously talked about the OB cell phelix state update as well as the updates around all car 19 and the phelix-1b study which gives us longer term information and I think a very nice proxy for in terms of what to expect in terms of longer term outcome from the larger pivotal phelix study.
Obi self Felix data update as well as as well as the updates around old car 19.
Felix one B study, which gives us longer term information and I think a very nice proxy for in terms of what to expect in terms of longer term outcome.
The larger pivotal field study.
Speaker 1: where then obviously we'll have the update on Auto 8, which is a program that is shaping up very nicely. And I think we'll give us a first interesting look at the profile of that program.
Well, then obviously, we'll have the update on auto eight which is a program that is shaping up very nicely and I think what gives us sort of a first interesting look at at the profile of that program.
Speaker 1: And then as mentioned just before the start of the autosix NG, phase-month trial in children's neuroblastoma, which we expect to actually get the first child in before the year ends.
And then as mentioned just before the start of the auto six Mg.
Phase one trial in children with neuroblastoma.
We expect to.
Actually get the first child and before the year end.
Speaker 1: Importantly, as we go into early next year, we expect to get phase one up and running and the first patient in and the early part of next year, treating patients with autoimmune disease, particularly focus, obviously here, is SLE in this initial study. And the study is designed to confirm the dose with that and be able to have a basis for the regulatory discussion, the land of Pivillus.
Importantly, as we go into early next year, we expect to get there.
Phase one up and running.
The first patient in in the early part of next year.
Treating patients with autoimmune disease, particularly focus obviously here is actually in this initial study.
The study is designed to confirm the dose and with that and be able to have a basis for the regulatory discussions around that pivotal study design.
Speaker 1: And then as indicated also in the earlier part of next year, we're expecting to get the filing in Europe , the MAA application with the European Agency as well.
And then as indicated also in the earlier part of next year.
We're expecting to get the filing in Europe.
MAA application with the European agency as well so a lot of activity in the upcoming months I think a lot of very significant value steps for the company.
Speaker 1: So a lot of activity in the upcoming month I think a lot of very significant value steps for the company. I think we're very well set up. And we have a fantastic team also on the building up on the commercial side. And I think we'll put us in a very strong position to get to the next steps, once we've through the actual interactions on the regulatory side.
I think we're very well set up.
We have a fantastic team also now building up on the commercial side and I think will put us in a very strong position.
To get to the next steps once we are through the.
Actual interactions on the regulatory side.
Speaker 1: So a lot of good stuff ahead of us, really looking forward to seeing many of you probably at ash and
So a lot of good stuff ahead of US railroad going forward to seeing many of you are probably at ash and happy to take questions now.
Thank you at this time, we will conduct a question and answer session. As a reminder to ask a question.
Speaker 3: Thank you. At this time, we will conduct the question and answer session. As a reminder to ask a question, you will 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 rough.
Star one on your telephone and wait for your name to be announced.
Your question. Please press star one again, please standby, while we compile the Q&A roster.
Our first question comes from the line of Matthew Phipps of William Blair. Your line is now open.
Speaker 3: Our first question comes from the line of Matthew Phipps of William Blair. Your line is now open.
Alright, thanks for taking my questions and all the updates I.
Speaker 4: Thanks for taking my questions and all the updates. I guess first on Ash, will the OVSL Felix update do you think of sufficient follow-up to really show EFS curves at Ash?
I guess first on ash will be.
<unk> Felix update if you think of sufficient follow up to really show S curves at ash.
Speaker 4: And then for auto eight and other six of IO patients, were those just from the BCMA alone car, in cohort one, or were there some of those with cohort two that had the senior 19 as well? And I guess maybe how many patients do you expect from cohort two at that?
And then for auto eight.
Six evaluable patients were those just from the DCA CMA alone Caraco and core one or were there some of those with cohort two that senior team as well and I guess, maybe how many patients do you expect from cohort two at ash.
Yes, very good questions. Thanks for joining Matt. So first question is are we expecting to update our present the event free survival data and the answer is yes.
Speaker 1: Yeah, very good questions. Thanks for joining. Matt. The first question is, are we expecting to update or present eventually survival data? And the answer is yes.
Speaker 1: on the Felix study and then with regards to the auto-A program what Matt was referring to is that
On the Felix study.
And then with regards to the auto program.
Matt was referring to is that.
Speaker 1: We are started to face one clinical study, dosing patients with the BCMA car alone to establish the base profile for the BCMA car. And then actually after that was initially established, added also the CD19 car component to the product.
We are starting to.
Phase one clinical study dosing patients with SMA allowance established a base profile is in a car and then actually after that was initially established at the <unk>.
Also the CD 19 car component to the product and we're actually going to have data from both patients with <unk> only as well as with both cars present.
Speaker 1: And we're actually going to have data from both patients with BCMA only as well as with both CARs present.
Speaker 1: and that rata points where we're probably going to be in the range of about 10 patients, maybe slightly rough.
Rata points, where we're probably going to be in the range of about 10 patients maybe slightly above that.
And if I could ask just one other one on the autoimmune side again can you remind me I can't remember if this was discussed last week, but is there a safety kind of DLT period like in between patients for the initial like you have to wait a month or two.
Speaker 4: And in fact, I just one other one on the autoimmune side again. Can you remind me I can't remember if this was discussed last week, but in their safety kind of DLT period, like in between patients for the initial, like you have to wait a month or four, you can see the subsequent patient or anything like that.
Subsequent patient or anything like that.
Speaker 1: We would expect that there is a gap between probably the initial patients and then as soon as you actually have initial data, you can then actually enroll at that level. Obviously, we do have quite a number, quite a good level of data at this level of dose across the particular day of population. So there's a lot of safety data already in place. So we should be able to enroll very differently.
We would.
Spect that there is.
Sure.
GAAP between probably the initial patients and then as soon as you actually have initial data that you can then actually enroll at that level.
Obviously, we do have quite a number quite a good level of data at this level of dose.
Across particularly the AML population. So there is a lot of safety data already in place. So we should be able to enroll relatively quickly.
Great. Thanks for taking my questions.
Thanks, Matt.
One moment our next question.
Our next question comes from the line of <unk> Prasad of Jefferies. Your line is now open.
Speaker 3: Our next question comes from the line of Dev Prasad of Jeffries. Your line is now open.
Hi, Thank you for taking a question this is Dave Kelly.
Speaker 5: Hi, thank you for taking our caution. This is Dave on for Kelly's at Jeffries. So I have a quick question on SLE. How do you think about the cell persistence that can have an impact on efficacy and safety in contrast to the oncology indications that we have seen so far?
Yes.
Jefferies.
Quick question on SLE, how do you think about the cell persistence.
Can have an impact on efficacy and safety in contrast.
So the oncology indications that we have seen so far.
Hi, Dave a very good question.
Speaker 1: Hi Dave, very good question. And so as we mentioned before, what you look to achieve is a very deep cognitive compartment to remove both as is the other reactive precursor cells and memory cells as well as the other reactive plus
And so as we as.
<unk> mentioned before when you look to sort of achieve its a very big comp into the compartment to remove.
Most of the auto reactive precursor cells and memory cells as well as the.
Autoreactive plasma cells, so deep companies, what do you need given that this is a cell based therapy that will take that will take some time to be effective and complete. So you will need a certain level of assistance to be able to do that.
Speaker 1: So deep cop is what you need, given that this is a cell-based therapy that will take some time to be effective and complete. So you will need a certain level of persistence to be able to do this.
Speaker 1: What we've seen and what I think is very encouraging is that the program in the AirLong and showed very nicely that they did get
We've seen I think is very encouraging is that the program.
Are long and showed very nicely that they did get.
Speaker 1: Very deep response, the Delta obviously, a good transition in terms of translation from a clinical efficacy perspective. And when you look at the processions of the CAR T cells, you see that the CAR T cells are pretty much around for about six months.
Very deep response, the adult obviously, a good transition in terms of our translation from a.
A clinical efficacy perspective, and when you look at the persistence of the car T cells, you see that the car T cells are pretty much around for about six months.
Speaker 1: And after that, you do start to see the visa compartment.
And after that you do start to see.
The T cell compartment.
Speaker 1: You see the maturation of B cells, have from various subtypes, antibody, subtypes perspective. But what you do know, C is actually recurrence of all the reactivity. So there is a certain amount of positions that clearly will be important. What we do see is that our product, in fact, the product that was used in AirLAM in pediatric LL patients has quite very similar behavior in terms of precision.
Generate.
You see the maturation of T cells from the various subtypes antibody subtypes perspective.
But what you do not see its actually recurrence of OLED activity. So there is a certain amount of assistance that clearly will be important what we do see is that our product.
The product that was used.
In airline.
In pediatric AML patients has quite very similar behavior in terms of persistence also in their hands to do see that they have children with.
Speaker 1: I will turn their hands to bits you do see that they have children with.
Speaker 1: long-term position, we're talking two years, that leads to current experience.
Long term persistent we're talking two years.
<unk> reached the current experience.
And Thats quite that is similar to what we have seen with <unk> and so we think actually that the <unk>.
Speaker 1: And that's quite that is similar to what we have seen with OBSEL and so we think actually that the profile should match very nicely
Profile should match very nicely.
Thank you for taking our question.
Thank you.
One moment for our next question.
Speaker 3: Our next question comes from the line of Gil Blum of Needham and Company. Your line is now open.
Our next question comes from the line of Gil Blum of Needham <unk> Company. Your line is now open.
Speaker 6: Good morning and good afternoon. It makes for taking our questions. So a couple of items from us.
Good morning, and good afternoon, and thanks for taking our questions. So a couple of items from us.
Speaker 6: First of all, for AutoAid, it looks like the data is really interesting, but, you know, it's a super crowded market and there's a lot of assets going into it. What do you think is going to be a key differentiator, maybe on the angle of safety?
First of all for auto it looks like the data is really interesting but.
A crowded market and Theres a lot of assets going into it what do you think is going to be a key differentiator maybe on the angle of safety.
So first of all thanks Gil for joining a very interesting question.
Speaker 1: So, first of all, thanks for joining a very interesting question and I think one that that was sort of see actually quite a bit of an evolution in the field as well. So, in order for what we're designed the product for is to be able to get on the one hand, deep responses.
And I think one that we sort of see actually quite a bit of an evolution of the field as well. So in order for what were designed that product for us to be able to get on the one hand deep responses.
Speaker 1: So we want to actually see that, indeed, we can get to very low levels of disease burden in these patients. And obviously, you can measure in multiple myeloma similar to ALL, you can measure minimal residual disease levels. And that gives you one parameter, I think, that we're clearly very interested in looking at and pursuing. The second aspect was a bit of a conundrum, I think, in the field, in the sense that
So we want to actually see that indeed, we can get to very low levels.
Of disease burden these patients and obviously you can measure in multi myeloma similar to ALLL you can measure a minimal residual disease levels and that gives you a call and Bob parameter and I think that we are clearly very interested in looking at pursuing the second aspect.
One was a bit of a conundrum.
Think from AR in the field in the sense that.
Speaker 1: What we're seeing with regards to cell dynamics, CAR T cell dynamics in multiple myeloma patients is that the CAR T cells tend to actually not persist.
What we're seeing with regards to sell dynamics car T cell dynamics in multiple myeloma patients is that.
The car T cells tend to actually not persist as well.
Speaker 1: So one of the things we wanted to achieve is see that indeed we can actually get a longer term persistence through the CD19 car component with the basic rationale that you do have, obviously new CD19 positive cells being formed that can actually help drive a certain level of baseline acceleration and maintain that for the car key.
And so one of the things we wanted to achieve that we can actually get.
Longer term persistence.
Through the CD 19 car component with the basic rationale that you do have obviously, new CD 19 positive cells being formed that could actually help drive.
Certain level of baseline activation and maintain that for the car T cells.
The other aspect of third aspect I think goes actually links quite nicely with the car.
Speaker 1: The other aspect, the third aspect, I think, goes actually links quite nicely with the conversation we just had on.
Conversation, we just had on auto.
The good side.
Speaker 1: which is that there is at an early stage of the polyphonic cell compartment of C-G-19 positive. I've certainly been sort of postulated for probably more than 25 years than that the driver cells from Ultimalo might in fact have a C-G-19 expression.
Is that.
There is.
Early stage of the partner cell compartment as CD 19 positive.
Certainly it's been sort of postulate that therefore, probably more than 25 years then that.
The driver sales from both in myeloma might in fact have a CD 19.
<unk> expression, so but it also will allow us to do the combination is to obviously get into that.
Speaker 1: So what it also will allow us to do, the combination, is to obviously get into that.