Autolus Therapeutics plc (AUTL) Q1 2022 Earnings Report, Transcript and Summary

Ladies and gentlemen, thank you for standing by and welcome to the Autolus Therapeutics First Quarter 2022 Financial Results Conference Call. [Operator Instructions] I would now like to hand the conference over to your speaker today, Olivia Manser, Director of Investor Relations. Please go ahead, ma’am.

Thank you and good morning or good afternoon everyone and thank you for joining us to take part in today’s call on the operational highlights and financial results for the first quarter of 2022. I am Olivia Manser, Director of Investor Relations. And with me today are Dr. Christian Itin, our Chief Executive Officer, and Dr. Lucinda Crabtree, our Chief Financial Officer. Before we begin, I would like to remind you that during today’s call our discussion will contain forward-looking statements. Please make sure you are familiar with our disclaimer, which is on Slide 2 of the presentation. On Slide 3, you will see the agenda for today, which is as follows. Christian will provide an overview of our operational highlights for the first quarter of 2022. Lucinda will then discuss the company’s financial results, before Christian will conclude with upcoming milestones and any other concluding comments. Finally, of course, we will welcome your questions.

Thank you, Olivia and good morning to you all. Thank you for joining us. It’s my pleasure to review our progress for the first quarter of 2022. Please move to Slide 4. For those of you who are new to Autolus, and as a fresher for those who know us well, we are building a fully integrated CAR T company. Building on our broad platform of cell programming technologies, we are generating CAR T products that are tailored to the specific tumor setting. Illustrating this approach are obe-cel, with its focus on physiological engagement of leukemic cells, maximizing potency while improving safety and persistence. AUTO4/5 with a unique targeting approach for T-cell lymphomas and AUTO6NG, a CAR T product candidate building on a clinically validated CAR through GD2 and adding programming modules to render the CAR T-cells insensitive to checkpoint and TGF data inhibition, while increasing CAR T-cell persistence. For manufacturing, we are using common platform and process design principles to generate products that are highly active and persisting in patients. Our current operations for clinical trial supplies, working in 4 shifts, 7 days a week, in what we are anticipating to be very close to our commercial manufacturing model. The commercial manufacturing facility designed for 2,000 products per year is under construction in the UK, about a mile away from our clinical trial manufacturing site and expected to be ready for GMP supply by middle of 2023. Moving to Slide 5, we had a successful quarter with obe-cel clearing the pre-planned futility analysis in the FELIX trial and enrollment continuing to plan. In addition to the primary morphological cohort in the FELIX trial, we are expanding the MRD or minimal residual disease cohort to up to 50 patients. In clinical practice, patients that get evaluated on a regular basis for recurrence of disease typically using flow analysis of their bone marrow. Indication of MRD levels or minimal residual disease levels of leukemia triggers treatment of the patients rather than waiting for full blown relapse before starting treatment. This additional cohort does not impact our planned filing guidelines as the primary data will be based on the data from the morphological cohort. With obtaining RMAT from the FDA, we have received preferred regulatory access for obe-cel in all our key territories, the U.S., EU and UK. In addition, the EU granted also orphan drug designation for obe-cel, adding to the same designation we had received previously from the FDA. In the second quarter, we are looking forward to updates at EHA from our evaluation of obe-cel in non-Hodgkin’s lymphoma and primary CNS lymphoma and two oral presentations covering our initial evaluation of the dual targeting AUTO122 in children, with ALL who are eligible for [indiscernible] therapy and our dose escalation experience for AUTO4 in T-cell lymphoma. In addition, the clinical Phase 1 evaluation for AUTO8 in relapsed refractory multiple myeloma started and we are on track for AUTO6NG to start the Phase 1 in the second half of the year. Turning to Slide 6, here is a snapshot of our operational progress. As indicated, our new manufacturing facility in Stevenage is progressing well. During the quarter, Dr. Lucinda Crabtree was appointed as Chief Financial Officer on the retirement of Andrew Oakley, and as we prepare for the potential launch of obe-cel, Brent Rice was promoted to Senior Vice President and Chief Commercial Officer. As well as clinical progress, we continue to iterate with our SL programming platform. And earlier this week, Autolus announced the online publication of three abstracts, submitted to the American Society of Gene and Cell Therapy, ASGCT, to be held May 16 to 19 in Washington DC. The three abstracts focus on Autolus modular approach to CAR T-cell programming. The abstracts involve first enhancing CAR T-cell persistence using a constitutively active cytokine receptor, second engineering of CAR T-cells to express a fast CD-40 protein to increase its persistence and anti-tumor activity, and three, developing a minocycline mediated protein displacement platform to make cell therapies untunable with a commercially available and safe small molecule in a dose-dependent and reversible manner. Slide 7, we are jumping over and go directly to Slide #8. The focus is here on obe-cel. And just to remind you, obe-cel has a unique mechanism of action built on highly specific engagement of CD-19, coupled with a fast release from CD-19, once the kill of the leukemic cell has been initiated. This fastest engagement is based on the fast off-rate of the CAT binder and drives three key properties of obe-cel, very high clinical activity paired with minimal toxicity and excellent persistence. Moving to Slide 9, there still remains a very high unmet medical need for adult ALL patients, with approximately 3,000 patients reaching the relapsed refractory stage of the disease that are residing in the U.S. and in the EU. Whilst frontline high dose combination chemotherapy enables about 90% of the adult patients to achieve complete remissions, only about 30% to 40% will achieve long-term remissions. Once patients are relapsed, they have a median overall survival of less than a year. [indiscernible] has become the standard of care for relapsed and refractory patients. However, most patients progress rapidly. More recently, the [indiscernible] has been approved showing a higher level of clinical activity, but also a significant increase in toxicity. When we look at Slide #10, this slide summarizes the key data we have shown to-date for obe-cel in ALL, which suggests that obe-cell could be potentially a transformational therapy for adult patients with ALL. In the initial Felix Phase 1b data presented at ASH at the end of last year, obe-cel showed a favorable safety and efficacy profile, consistent with the data we have collected prior in the ALLCAR19 study in the same patient population. We saw high overall response rate and the duration of response from the ALLCAR19 study that remains highly encouraging with morphological event-free survival for obe-cel of 46% at 24 months with a median follow-up of 29.3 months and patients approaching up to 42 months of durability. We continue to see sustained obe-cel persistence in those patients as well. And to remind you, obe-cel has been granted orphan drug designation by the FDA for ALL prime designation by EMA, ILAP designation by MHRA, and most recently, RMAT designation by the FDA, and as well as orphan drug designation by EMA as well. Moving to Slide 11, we are conducting the FELIX study with 100 patients in a morphological cohort, treating those patients at sites in the U.S., UK, and in Spain. We expect to be fully enrolled as we go through the course of this year, and as mentioned, expect to have initial data starting in the second half of this year, with full data in the first half of next year. Switching gears and moving to Slide #13. Obe-cel’s unique profile means it could be applicable to a broad range of B-cell malignancies. We are evaluating the product outside of ALL in non-Hodgkin’s and B-cell lymphomas, including the typical follicular DLBCL mantel cell and CLL indications, and expect multiple clinical readouts during the course of 2022. The first clinical updates will be in June at EHA, where we have readouts from Phase 1 study, an extension of the ALLCAR study in the non-Hodgkin’s indications as well as from a separate study, the so-called CAROUSEL study in patients with primary CNS lymphoma. On Slide 14, on the right hand table, we provide a quick summary of the basic experience that we have to-date with obe-cel and pediatric ALL patients in the so-called CARPEL study. The fundamental finding was that we have excellent activity without high-grade cytokine release syndrome, but we did see about half of the patients relapse due to antigen loss of CD-19. That is why we went back and built on this favorable profile of obe-cel that we have seen in kids, adding a highly potent CD22 CAR to create a product called AUTO1/22. We will have an oral presentation at EHA of the Phase 1 data for AUTO1/22 in pediatric ALL patients that were ineligible for Kymriah therapy. Moving to Slide 16 to talk more broadly about our technology base. Although this is a wide range of technology covering mostly cell programming modules and product candidates. With over 100 patent families on the prosecution, we have a very significant technology treasure chest that we are building on. Three new cell programming approaches will be presented at ASGCT, the annual meeting in May, which showcase our industry leading T-cell programming technologies. Key areas covered by our cell program motives cover selective targeting of cancers, controlling CAR T-cell activity, shielding CAR T-cells from the cancer microenvironment as well as the patients’ immune system, and enhancing CAR T-cell persistence as well as attracting the support of the patient’s own immune system in the fight against the cancer. Moving to Slide 17, here we have tabulated next generation programs alongside the progress in the clinic. Most advanced is AUTO4, our program to address T-cell lymphomas. AUTO5 is the sister program to AUTO4 and following AUTO4 into clinical development. Both programs are run internally. In collaboration with our academic partner, UCL, we have moved AUTO8 into the clinic, in a Phase 1 clinical study in multiple myeloma patients. And I am working at AUTO6NG to get into the clinic second half of this year, targeting neuroblastoma solid tumor in children. Turning to Slide 18, I will give you further information about AUTO4. We are actively exploring T-cell lymphoma, which is an aggressive disease, with very poor prognosis for patients. The primary challenge has been defined a structure or target on the surface of T-cells that would allow you to target the T-cell lymphoma, without at the same time targeting all T-cells together. And of course, what that means is that you need to have a target that allows you to get the lymphoma, leaving the T-cells behind and with that, preserving immunity in these patients. AUTO4 is targeting a structure called TRBC1 and its sister program, AUTO4, a structure, TRBC2. Both structures are related but are part of the constant domain of the T-cell receptor value chain and are coming basically available in T-cells, in either one or the other isoform. Both targets are novel and we obviously are planning to show first data in an oral presentation at EHA for AUTO4 from our dose escalation experience in Phase 1. With that, I’d like to actually hand over into the financial section and hand over to Lucy who is moving to Slide #20.

Thanks, Christian and good morning or good afternoon to everyone. So moving to Slide 20, it’s my pleasure to review our financial results for the first quarter to March 31, 2022. On the journey to transitioning Autolus into a fully integrated CAR T company, we continued in the first quarter of 2022 to focus our research and development efforts on our lead product obe-cel and our pipeline assets addressing cancers with limited treatment options. So, starting with R&D expense for the 3 months ended March 31, 2022, research and development expenses increased to $34 million from $30.7 million for the 3 months ended March 31, 2021. Cash costs being the biggest component of our R&D expense were relatively flat at $30.6 million this quarter from $30.7 million for the quarter ended March 31, 2021. The small decrease in research and development cash cost to the tune of $0.1 million consisted primarily of a $2.8 million decrease in compensation and employment related costs, which was due to a combination of lower retention, severance payments and the timing of salary mix of new employee hires. A $0.9 million decrease in facilities costs related to the termination and excess of our U.S. manufacturing facility in the prior year and shift in our manufacturing strategy and a $0.2 million decrease in research and development costs related to cell logistics. These decreases in R&D cash costs were offset by an increase of $2.9 million in clinical costs and manufacturing costs, primarily related to our obe-cel clinical product, $0.8 million increase in legal fees and professional consulting fees, in relation to our research and development activities, and a $0.1 million increase, related to information technology, infrastructure, and support for information systems, relating to the conduct of clinical trials and manufacturing operations. Non-cash costs increased to $3.4 million for the 3 months ended March 31, 2022, from $36,000 for the 3 months ended March 31st, 2021. The increase is primarily attributable to an increase of $3.1 million in share based compensation expense, included in R&D expenses, as a result of the retention employees, post the reduction of workforce, that was implemented during the 3 months ended March 31, 2021. In addition, depreciation and amortization expense increased by $0.3 million. Just touching on the G&A side, expenses decreased by $0.7 million to $8 million, for the 3 months ended March 31st, 2022, from $8.7 million for the 3 months in the first quarter of the prior year, of which G&A cash costs, which exclude depreciation and an amortization, as well as share based compensation, decreased by no $0.6 million to $7 million. All in all, including income and net total other expense, with the largest component being the interest expense of $1.8 million, which corresponds to the liability related to future royalties and sales milestones, which arose upon entering into the Blackstone Strategic collaboration, we ended the first quarter 2022 with a net loss on a pre-tax basis, at $42.7 million, versus $39 million, in Q1, 2021. Our low income tax benefits related to qualifying research and development expenditures continue to play a role as a source of additional cash, and the tax credit for the 3 months ended March 31, 2022 amounted to $5.6 million versus $5.7 million in the prior year quarter. All in all, this resulted in net loss attributable to ordinary shareholders of $37.1 million for the 3 months ended March 31, 2022, versus $33.3 million, in the prior year quarter. This in turn gave a basic and diluted net loss, per ordinary share, for the 3 months ended March 31st, 2022, totaling $0.41, compared to a basic and diluted net loss per ordinary share of $0.53 for the 3 months ended March 31, 2021. Finally, we ended the quarter with a cash position at $268.6 million and consistent with prior guidance point to across from the cash runway into 2024, assuming procedure of Blackstone milestones. And now, let me turn back to Christian to give you an overview of the pipeline and a brief on expected milestones. Christian?

Thanks, Lucy. Moving to the final Slide #22. Finally, next steps; we believe we have an exciting year ahead of us, with obe-cel running through the pivotal study in adult ALL, delivering initial clinical data from this pivotal study later this year, and full data expected in the first half of 2023. We plan to provide clinical updates from four of our programs at EHA this June, and this is in addition to progress across the pipeline that we alluded to as well, as we went through the presentation. In particular, with obviously also looking at AUTO6NG expecting to enter the clinic in the second half of this year. Finally, as a result of our collaboration with Blackstone, we’re in a strong financial position with cash runway, including project financing payments from Blackstone into 2024. With that, we’re happy to take questions.

[Operator Instructions] Your first question comes from the line of Matt Phipps from William Blair. Your line is open.

Good morning, Christian and Lucinda. Thanks for the call. I was wondering, Christian, if you could maybe help us set the stage a little bit for the AUTO4 results? We have seen other CAR targets, we can see some malignancies for the CD-5, CD-7, do see some responses, a lot of patients maybe go to transplant, but I guess are you expecting a lot of patients in the AUTO4 trial, to go on to transplant, if they do achieve a complete response? And then I actually am also looking at things like viral infections will be another key data point for this program and the first update?

Good morning, Matt, thanks for joining. Very good question. So, as you pointed out, obviously T-cell lymphoma is a very cough disease to go after; there are a number of approaches that have been tried. What you refer to is programs like CD-5 or CD-7 have sort of a limited application. CD-7 is mostly present on acute leukemia – T-cell acute leukemia, rather than T-cell lymphoma. It’s only a very small subset of T-cell lymphomas that carry CD-7. When you look at CD-5, that’s a general activation marker for T-cells, so any T-cell that gets activated, including our CAR T-cells, would actually become CD-5 positives, which obviously creates a number of challenges. And if you go after more general CAR groups, like CD-4, as an example, you run the risk that you’re actually eliminating the compartment, as you’re trying to attack and trying to tackle the disease itself, with consequences for the patient’s ability to actually maintain a healthy T-cell median immune response. So what we’re looking to do with AUTO4, and then also with the sister program, AUTO5, is really targeting a subset, on the one hand, the disease itself, but then also only a subset of healthy T-cells, so that at least half of the remaining T-cells, in theory, would not be targetable with a CAR-T, with that sustained T-cell mediated response over time. What we’re looking to do, and what we’ve been doing in the trial that we’re going to be updating on, is obviously dose escalation; it’s a wide range of doses starting at very low levels to elevated levels. And, what we’re looking to see are several points; number one, one to understand the safety profile, number two, obviously, do we have an ability to induce complete remissions in these patients? Number three, do we see any evidence that we’re impacting the broader T-cell compartment in these patients, which obviously would be a concern from an overall safety perspective? As we’re in a dose escalation, we have varying degrees of follow-up, and we will need to see and gain more experience, to see whether indeed some of these patients may need to receive transplant in the future, or whether just the therapy on its own will be sufficient to sustain long-term remissions. That is too early to tell, but I think we’re going to get a very good understanding; it’s a novel target, it’s a novel approach. It’s first in my own experience, and I think it will give us a very good initial experience and understanding, of the potential of this approach.

Thanks, Christian. And, if I could ask one additional question; recent data from Stanford Group at ACR, with the GD2 CAR showed some encouraging results in a tough glioma setting, but also did use ICV infusions. I’m wondering if that’s something you would look at, any kind of intracranial infusions with the AUTO6 program?

Right? So, the specific indication that the Stanford group went after, is a form of glioma, which is obviously a cancer that is localized in the brain. And, there are various ways in how we can think about accessing that, whether you access the brain through an infusion of CAR T-cells into the bloodstream, and then have the CAR T-cells migrate across the blood brain barrier into the brain, and then have an ability to target the glioma. That’s one approach you can take, and what the Stanford team has done, is take the ultimate approach as literally going directly into the brain, and frankly, delivering product directly onto the lesion, in those patients. Obviously, that’s an approach that’s workable, as we’re seeing obviously, we will hopefully have data for obe-cel and primary CNS lymphoma, where we also do approach the dosing from the systemic side, so from the blood side. And, I think we can start to see and think that both sides are possible and are usable. For our own CD2 CAR program, we would envisage a normal systemic approach, because the disease they are treating, neuroblastoma, is a kidney associated tumor that it can actually very well access, just through standard administration into the bloodstream.

Alright. Thank you.

Thanks, Matt.

Your next question comes from the line of Nick Abbott from Wells Fargo. Your line is open.

Hello, good morning, thanks for taking my question. And yes, lots of things going on here team, and I apologize today, I had to join the call late. But the first question is on what we might expect as a benchmark for primary CNS lymphoma; the MGH Group just published in blood, some experience with [indiscernible]. I think what was quite surprising to me, at least, was low grade ICANS, Grade 1, Grade 2, Grade 1 CRS, and they reported a 60% response rate, 50% CR, with three of those complete responses showing significant durability of greater than 6 months, at least. So, I’m wondering what we should be expecting for primary CNS lymphoma and whether you think this is a good benchmark.

So first of all, thanks for joining Nick. On primary CNS lymphoma, what we’re planning to do is provide obviously initial information on the early patients that we have in the trial. Obviously, that gives us an initial view. I don’t think we’re at the point where we’re going to be - I think where we can easily benchmark, given the number of patients that we’re able to report on at this point. I think in general, seeing a, give or take 50% CR rate in these patients, I think is very encouraging. And, I think it certainly would be a good outcome for patients with this disease, considering also frankly, the lack of any suitable other options.

Okay. Thanks, Christian. And then I noticed that you mentioned that AUTO8 has been initiated now. When do you think you’ll be able to present some initial data from that trial?

I would assume this is a Phase 1 clinical trial, and I would assume that we will have to look at the second half of next year for early clinical data.

Okay. Great, thanks a lot, Christian.

Thanks a lot, Nick. Appreciate it.

Your next question comes from the line of Mara Goldstein from Mizuho. Your line is open.

Great. Thanks so much for taking the question. I wanted to ask just on the AUTO4 program, I think the upper dose limit has been raised there to 900 million cells. Can you talk a little bit about that, and that dynamic? And then lastly, just on obe-cel and the new MRD cohort, maybe you can talk a little bit about, what are the challenges in that cohort, and why obe-cel may be appropriate there?

Yes, happy to do that, Mara. Thanks for joining. So first, with regards to AUTO4, as I indicated AUTO4 that we ran through, a dose escalation started at relatively low levels, the initial dose that we had in I think highlighting clinical trial, our cutoff was 225 million cells. And we created an opportunity to go further than that. We will obviously provide an update on kind of the upper dose range that we went to; we didn’t go all the way to 900. And you’ll see obviously overall kind of the efficacy and safety profile that we’re starting to achieve at the higher dose levels. With regards to the MRD cohort for obe-cel, I think the importance of the MRD cohort is several fold; first off, we do have a bit of a discrepancy between the regulatory data package that we need to get to an approval, versus the data and the treatment that we actually – treatment algorithm that we do see, taking hold at clinical centers. Most clinical centers also based on the experience with Blincyto in patients with minimal residual disease are preferring to start treating patients where they have a first inkling of the disease coming back. And, what normally happens with these patients is, at periodic intervals, you take bone marrow biopsies, you run those bone marrow biopsies, typically on flow, and you look for the presence of leukemic cells. The sensitivity of that methodology gives you somewhere in the range of 10 to the minus 4, 10 to the minus 3 resolution, and very reliably. And that compares to a 5% level that you would have to cross the boundary to become a morphological patient. So, you do discover, as you actually look at that, in the clinic for these patients, and you look for these low levels of disease in these patients. Now, when you find that the patient actually does have low level disease, typically you would not want to wait for that patient to progress to full blown disease before you start treating, because there are two things that happen. On the one hand, you have obviously a lot more tumor burden, which means you have, typically when you intervene with any kind of therapy, a higher amount of toxicity, but you also have a lower probability of actually inducing a longer-term benefit in these patients. So, it’s both from a safety and efficacy side, not desirable from a patient or a physician’s perspective, to wait. And so, what we’re doing with the MRD cohort is, alongside the dataset that we need to have in place to support the regulatory approval of the product, we are also looking to generate data that actually support and basically characterize the profile of the product, against patient, in patients with lower disease burden, which is closer to what actually we are seeing in many clinical practices, both in the U.S. and in Europe, the physicians moving to. So, that’s in the backdrop to what we are doing in the work with the MRD cohort.

Alright. Thanks so much.

Thank you.

Your next question comes from the Gil Blum from Needham. Your line is open.

Good morning everyone and thanks for taking our questions. So, maybe here, clarification on the MRD population? So, are current approved CAR-Ts used in patients that are MRD positive?

Good morning Gil. Thanks for joining. What we do see is that certainly in the pediatric patients that the physicians have been moving to treating the kids very early on, typically when we have mineral residual disease. So, that’s an observation that we certainly see across, I think many of the centers, within this disease setting, and where you would start using a particular chemo [ph] very early on. I think in general, there is a view that you would like to actually treat early. And I think the best visibility at this point we have from the pediatric population, because it’s also where obviously the CAR-T therapy is probably most established.

Okay. Thank you. And maybe another question on…

Sorry. Gil, the second part obviously, of the answer is, that the experience that physicians have gained with Blincyto, also with adult patients, also moves quite significantly towards patients with mineral residual disease, rather than waiting for the patients to develop full blown morphological disease. The difference in response rate is quite significant, you have about 43% to 44% CR rate in a morphological disease of Blincyto, but you do have about 78% CRS, in molecular CRS, if you go into the MRD population for Blincyto.

Alright. So, it makes sense to have earlier treatment. Maybe a question on AUTO1/22, you said Kymriah eligible, can you remind us if any of these patients that are being enrolled, have experienced CAR-Ts in the past?

Right, so AUTO1/22, obviously, which is a dual targeting CAR. We treated in the Phase 1 experience now, kids that are ineligible for Kymriah, and you can be ineligible for Kymriah for a set of reasons. One is that you already have Kymriah and you cannot get a second dose. And that is obviously part of the population that we have enrolled. Secondly, it can be that the disease is localized in an area where you actually have to exclude patients from the treatment of Kymriah, and in particular, a localization, obviously, would be CNS localized disease. So, it’s typically related to either prior therapy with Kymriah, and not being eligible anymore for a second go, or having disease that is basically extra medullary disease, disease outside of the marrow that actually would disqualify you from being offered Kymriah as a therapeutic option.

Right. So maybe a follow up there, will the presented data be stratified based on patients who have experienced previous CAR-T therapy, or more of like a mixed bag?

We will have both categories of patients. Obviously, it’s a Phase 1 experience, so it’s a limited number of patients, but we have both patients who either have relapsed post Kymriah, or patients that have disease outside of the normal localization.

Alright. And maybe a last one, I know you guys are showing a bunch of the really interesting new technologies, modular technologies coming up with ASGCT considering the current laser focused on obe-cel, are you guys considering out licensing some of these technologies to other firms?

I think there is with – I mentioned the fact that we have a very broad portfolio with about a hundred patent families covering the various inventions. There clearly is opportunity for that, and opportunity for out-licensing. Part of that is what you saw us do last year, with the collaboration we put in place with Moderna, and there is additional opportunity with some smaller licenses we have granted as well, over the years, to aspects of technology. So, there is clearly opportunity for that, outside of another portfolio that we are pushing ourselves.

Alright. Thank you for taking all our questions.

Thank you. Gil, I appreciate it.

Your next question comes from the line of Asthika Goonewardene from Truist. Your line is open.

Hi. Thanks for taking our questions. This is Bill on for Asthika. We were wondering if the MRD cohort, would that data be ready for the first half 2023 update? And then also subsequently, we are just wondering in your hands and your experience, on average, how many multiple myeloma cells are double positive for CD19 and BCMA? Thanks.

Thanks for joining Bill. First question related to data becoming available from the MRD cohort, whether that’s going to be coinciding with the main data release from the morphological cohort, that’s something we need to look at. Obviously, we will have a range of follow-up on these patients, and one of the determinations we will need to make is how much of a minimal follow-up we want to have in that patient group. But there may be possibility to include some of that data, at least on the initial experience in that group from a safety and a basic activity perspective. So, we will see how that progresses. I think there is an opportunity, but in general, what you would like to have at the MRD cohort is a longer follow-up, and actually see how these patients do over time. Not only in terms of the initial response you can induce, and their safety profile associated with that treatment.

Thanks. And the CD19 and BCMA double positives, in the multiple myeloma population.

Right, so there are two aspects of that. So, BCMA is the main target that you would find on multiple myeloma cells. The interest from CD19 is sort of twofold. Number one, there is what is believed to be a driving population of multiple myeloma that is CD19 positive. That’s one aspect. So, it’s a smaller number of cells, but having a key role in driving the disease. And secondly, the fact that if you have your therapy and you have an ongoing activation of your compartment using – with the de novo generation of CD19 positive cells, not myeloma cells, but generally positive cells, that that probably is going to be helpful to actually sustain activity of the CAR T-cells over time as well. So, there are likely two elements there that play into the rationale for choosing the targets.

Thanks so much.

Thank you.

Your next question comes from the line of Kelly Shi from Jefferies. Your line is open.

Hi, Good morning. This is Dave on for Kelly Shi. Just a couple of questions for me. One is on futility analysis, can you provide more color, whether it’s safety or efficacy analysis, or how many patients were in that analysis? And second is dual CAR, what kind of bar do you think will be suitable to move that program into next step? Thank you.

Alright. Thanks a lot Dave. Appreciate it. So, the futility analysis, that was a predesigned analysis point, obviously for the study, and as you typically do in futility analysis, you look at primary aspects of the program. One is the likelihood of the program to succeed. And that’s basically a certain statistical power, you want to see that the program is going to succeed. And secondly, also as you look at the overall adverse event profile and you want to make sure that the profile of that product is as expected. And you do not pick up any undo adverse events in the program. So, that was pre-specified and ultimately it’s driven by the statistical analysis on your likelihood of success in the program as well. With regards to AUTO1/22, obviously the start of the Phase 1, as indicated in Kymriah eligible patients is obviously the initial dataset that we are getting. Ultimately, this type of product, you would like to position at the same level of Kymriah, so you do not actually want to have sequential CAR-T therapy that would not be a smart thing to do, but actually have a product that has an ability to overall improve the ultimately event free, as well as overall survival, in that patient group, by minimizing relapses, due to antigen loss. And that’s ultimately what you would be looking at. When you look at the space, you see that about the event free survival, at 1 year for pediatric patients, is around 50%, so that’s the number that you would like to actually look to improve and see improved, in a product now with a dual targeting approach in pediatric patients.

Got it. Thanks. And just to follow-up on the BCMA CD19 CAR, so what would be the bar for that product, because of this changing treatment paradigm of the multiple myeloma?

Right, you have to really postulate a very high bar for the program to proceed into the next steps of development. We do see obviously a very good profile for the JNJ program, and we see good, sustained activity on the BMS program. I think what you would want to see is, you want to see very deep molecular CRs that you can induce. And you also would like to see an improved pattern with regards to persistence, as well, in the product. I think those are two parameters that I think are give you – can be picked up relatively early in the evaluation of the program. And I think those are certainly two of the parameters we would be tracking very carefully.

Got it. Thank you.

Thank you.

Your next question comes from the line of Simon Baker from Redburn. Your line is open.

Thank you very much for taking my questions. I have three, if I may, generally of some more general nature. I just wondered if you could give us your latest observations on the normalization of enrollment rates as we start certainly in parts of the world to emerge from the pandemic. Are we close to normal or is there still some distance to go? Secondly, on the Stevenage facility, you talked about the capacity of 2,000 batches per year. is that from second half 2023, or is there a ramp up? And could you give us some idea of the scope to expand? You talked about the option, I wonder if you could give us an idea of how much it could be expanded by. And then finally, a couple of weeks after your full year results, the FDA published their draft industry guidance document on CAR-T development. I just wondered if you could give us your perspectives on that document, and the direction the FDA is moving in, now that you had a good chance to review it. Thanks so much.

Thanks for joining us, Simon. So, the first question was related to the enrollment and frankly, the ability of clinical trials centers to support clinical trials. And as I think many of us have seen, obviously, during the peak of the pandemic, many of the institutions were impacted heavily. Not only by a lot of workload, but also as a consequence of losing a substantial amount of staff, or a number of staff, that are particularly in those individuals were active in the ICU entities, etcetera. So, that’s been certainly a significant issue. We have seen a lot of that normalize. There is still some geographic differences, but the vast majority of centers are back in a normal mode of operation, certainly for patients that have the level of medical need, as we are seeing here with obe-cel, in patients with acute leukemia that actually do have to get treated, you cannot wait to treat those patients, and we are seeing a normalization, certainly for those patients. I think for some of the less life threatening diseases that may still actually take a bit more time. But I think that’s where we are. A big chunk is actually – or a big aspect is going to be the training of nurses and frankly, both the hiring and training of nurses, which will take time. And it certainly will be a significant effort, we see all across both the U.S., as well as Europe and UK. Second question was related to the capacity at Stevenage. The capacity at scale at the new facility will be 2,000 batches. We are obviously going to ramp up that capacity operationally as we are rolling out the product and as we are sort of growing the product. It doesn’t make sense to actually have a full standing operation for that level of capacity and then not fully using that. So, that needs to be an adapted approach, as you go up the design of the facility, set-up of the facility, supports, about 2,000 products a year. The scope to expand actually would allow us to actually expand physically the facility, and with that increase the capacity overall. And then, the last question was related to the CAR-T guidance document that was coming out from the agency. I think an important aspect is that obviously we are in a relatively new field still. There is a lot of learning going on. And I think having that type of learning and best practices sort of starting to be consolidated and sort of agreed upon, I think is very helpful. And so we are I think – glad to see that we are seeing some of that guidance to be more formalized as it is outlined now in that directive.

Great. Thanks so much.

Thank you.

Your next question comes from the line of Eric Joseph from JPMorgan. Your line is open.

Hi. Thanks. This is Sean on for Eric Joseph. So, sorry, my line was dropped for a little bit. I apologize if it’s a repeat of the question. So, we are basically wondering of the follow-up question on the futility analysis. So, whether you can talk about some more details on the statistic assumption of patient numbers comprising that analysis, and having passed it, is there a minimum CR rate or duration of response that can be inferred from that?

Thanks for joining Sean. And yes, indeed, the question has been asked before. So, the futility analysis again, is basically my thought is we obviously haven’t communicated, but a difficult one to know is whether the study actually is in a position to reach the design primary endpoint that you have set, and the statistical outcome that you have set for the overall study. And that is what you want to make sure that indeed the program can reach that outcome. And, that’s typically what you do in your futility analysis, and as indicated, it’s primarily based on the clinical activity side. And in our case, the primary endpoint being the complete remission rate. But then also, obviously, looking at the overall safety, which is obviously going to be taken into account as well. So, those are kind of the key parameters, we haven’t actually given more detail and more resolution on that. Obviously. we nicely passed that point, and we are progressing well with the program.

Alright. Thank you.

Thank you.

There are no further questions at this time. I would now like to turn the conference back to Mr. Christian Itin.

Alright, well, thank you very much all for joining today. Obviously, an exciting first quarter. We are really looking forward to the second quarter with seven abstracts to be presented in the upcoming weeks. And we also will take the opportunity in particular, to write the EHA data, to give you a more in-depth update around the conference as well, and also put the data in context as well, outside of just a pure clinical data perspective. Alright. With that, I would like to thank you all for joining and wish you a great day. Thank you.

Ladies and gentlemen, this concludes today’s conference. Thank you for your participation and have a wonderful day. You may all disconnect.