Autolus Therapeutics plc (NASDAQ:AUTL) Q2 2023 Earnings Call Transcript

Autolus Therapeutics plc (NASDAQ:AUTL) Q2 2023 Earnings Call Transcript August 6, 2023

Operator: Hello, ladies and gentlemen, and welcome to the Autolus Therapeutics Second Quarter 2023 Financial Results Conference. At this time, all participants are in a listen-only mode. After the speakers’ presentation, there will be a question-and-answer session. [Operator Instructions] Please be advised that today’s conference is being recorded. I would now like to turn the conference over to your host, Julia Wilson, Communications Consultant. Please go ahead.

Julia Wilson: Thank you, Corey. Good morning or good afternoon, everyone, and thank you for joining us to take part in today’s call for Autolus’ second quarter 2023 financial results and operational highlights. I’m Julia Wilson, Communications Consultant for Autolus. 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, we will make statements related to our business that are forward-looking under federal securities laws and safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These may include, but are not limited to, statements regarding the status of clinical trials and development and regulatory timelines for our product candidates, and our expectations regarding our cash runway.

Photo by National Cancer Institute on Unsplash

These statements are subject to a variety of risks and uncertainties that could cause actual results to differ materially from expectations, and reflect our views only as of today. We assume no obligation to update any such forward-looking statements. For a discussion of the material risks and uncertainties that could affect our actual results, please refer to the risks identified in today’s press release and our SEC filings, both available on the Investors section of our website. On Slide 3, you will see the agenda for today’s call, which is as follows; Christian will provide an overview of our operational highlights for the second quarter of 2023. Lucinda will then discuss the company’s second quarter 2023 financial results, before Christian will conclude with upcoming milestones and any other concluding comments.

Finally, we will, of course, welcome your questions. Over to you, Christian.

Dr. Christian Itin: Thank you, Julia. Good morning to you all. Thank you for joining us. It’s my pleasure to review our progress for the second quarter of 2023. Moving to Slide 4, we had a very productive second quarter with the ASCO and EHA data presentation of our pivotal FELIX study as the highlight. obe-cel has shown an excellent profile in adult patients with relapsed/refractory acute lymphoblastic leukemia. The ORR, based on complete remissions with either complete or incomplete hematological recovery was 76%, up from the interim analysis, which came in at 70%. The safety profile, which was remarkable with low levels of high-grade cytokine release syndrome in ICANS, and the data tracked very well on persistent and duration of response with our prior ALLCAR19 study where we have seen 35% of treated patients and long-term remissions without any need for additional anti-leukemia therapies.

Next follow-up is planned for ASH with several obe-cel-related abstracts submitted to the organizers this week. Critical for the successful outcome of the FELIX study was our robust product delivery platform with high manufacturing success rate, short vein to delivery time, and high percentage of patients dosed with obe-cel. Key focus now is on the completion of the validation of the commercial manufacturing facility, which we call the Nucleus. We’re on track for a filing of a biologics license application with the FDA at the end of 2023, and a market authorization application with EMA in the first quarter of 2024. As the program is progressing towards the regulatory review, we’re also actively preparing obe-cel for launch, with critical activities underway in medical affairs, completion of value dossiers, and onboarding of clinical centers.

On Slide 5, we have a short overview of the key pipeline progress. First, we continue to expand the obe-cel opportunity. In non-Hodgkin’s lymphoma, in our ALLCAR19 study, we demonstrated very high levels of metabolic complete remission rates in patients across B non-Hodgkin’s lymphoma indications, with an attractive high level of sustained CRS in DLBCL patients. We have also notably taken the decision to develop obe-cel in autoimmune disease, starting with a small Phase 1 dose confirmation study in SLE patients, which we expect to start early in 2024. We believe the excellent safety and efficacy profile we have seen for O obe-cel in ALL and on Hodgkin’s lymphoma patients will translate well into B-cell-mediated autoimmune diseases, and together with our established commercial manufacturing and delivery base, plus attractive COGS, will drive a well-differentiated expansion of the obe-cel opportunity.

Looking into obe-cel lifecycle, the pediatric ALLCARPALL study with AUTO1/22 was updated at the EBMT meeting in the second quarter, and continues to show an impressive level of clinical activity and a very favorable safety profile. Also, in the second quarter, we presented longer follow-up of the peripheral T-cell lymphoma patients treated with AUTO4 showing complete remissions now sustained beyond one year. Finally, and also in collaboration with UCL, AUTO8 is progressing well in the Phase 1 multiple myeloma MCARTY study, with the first data planned for the end of the year. And finally, AUTO6NG Phase 1 study in neuroblastoma is expected to start in the third quarter. Turning to Slide 6 and to tell you a bit more about how we’re strengthening the Autolus team.

We had a very busy second quarter with great additions during the second quarter. I’d like to start out with Dr. Robert Iannone, who joined our Board of Directors in June. Rob brings to Autolus a wealth of experience in the life science industry, having worked across a broad range of therapeutic areas and phases of development, including immuno-oncology programs at Jazz Pharmaceuticals, Immunomedics, AstraZeneca, and Merck & Company. Rob is a great addition to the board and brings obviously very relevant experience as we’re going through the regulatory review process in the US and elsewhere, and obviously is really instrumental in the further development and positioning of the product. In July, we announced that Rob Dolski will be succeeding Lucinda Crabtree as Chief Financial Officer.

Rob has more than 20 years of a very diversified experience as a life science financial executive and joined Autolus from Checkmate Pharmaceuticals where he served as the CFO and was a key member of the team driving the sale of the company to Regeneron. Prior to that, Rob had key leadership roles and operational roles at Moderna, Human Genome Sciences, and Amgen. Rob is on the call with us today and I’ll ask him to give a quick introduction later in the call. At the same time as we announced Rob’s appointment, we also announced that Dr. Veronica Hersberger had been appointed as Senior Vice President, Medical Affairs. Veronica joined Autolus from TargImmune, a private Swiss oncology company where she served as the Chief Medical Officer. She brings a long career in oncology development, medical affairs, and a long, remarkable level of experience across a wide range of products.

During her time at AstraZeneca, Veronica was a global product leader for both Calquenceand Lumoxiti. And prior to that, she served as the global head of medical affairs for the hematology franchise at Roche, where she was also involved over the years in the development of a wide range of oncology programs. Finally, Miranda Neville was promoted to Senior Vice President, Project Management, heading up the obe-cel program. Miranda has served in various roles at Autolus, most recently as Vice President, Head of Program and Portfolio Management. Miranda has over 20 years of experience in project management, engineering capital projects and operations. Prior to leading the obe-cel program, Miranda ran Autolus’ commercial manufacturing capital product, delivering the Nucleus facility in record time.

Prior to Autolus, Miranda supported several consulting projects for large biopharma companies, as well as clinical stage gene therapy programs at companies like Human Genome Sciences and others. And particularly at Human Genome Sciences, Miranda led the BENLYSTA program in SLE through the successful BLA, and then obviously resulting regulatory approval and launch of the product. So, we’re expanding the team with a very experienced set of industry leaders in their respective fields, and obviously all of them are having a significant impact already, and will continue a lot of contributions in the future. With that, I’d like to actually switch over to Obe-cel, and we’re moving to Slide 8. Here, I would like to take the opportunity to really give you a quick update and summary of the key data that we presented both at ASCO as well as at EHA from the FELIX data.

As you remember, the patients that we enrolled were relapsed/refractory patients that had been – extensively gone through extensive lines of therapy prior to actually being eligible for this study. The primary endpoint we’re looking for is overall response rate based on CRS and CRis, and then we’re obviously looking at secondary endpoints that look at duration of response, event-free survival, as well as overall survival and the ability to convert patients into an MRD negative status. Now, we have enrolled 112 patients in the study. We infused 94, so 84% of the patients enrolled were actually dosed with the product. And you can see in the slide also the difference between the enrolled and infused patients and kind of what the key characteristics were.

Now, when we look at the baseline characteristics as indicated, these are clearly a very advanced patient population. We have somewhat older patients. When you look at the average age of 50 years, that’s somewhat above of what we’ve seen in prior studies in relapsed/refractory ALL, and certainly not an easy population to work with. We see obviously well balanced between gender have the usual type of level of Philadelphia chromosome-positive patients and prior types of therapies. I think what I’d like to point out that at the bottom is obviously the patients did have high levels of tumor burden in their marrow, and also we had a significant proportion of patients that had Extramedullary disease, which are known to be very difficult to treat and to manage.

Moving to Slide 10, this is the overall response rate. As you can see, we had an overall response rate of 76%. 54% of the patients achieved CR 21% at Cri, and we have seen a very high level of patients achieving not just the complete remission, but also an MRD negative status with a sensitivity of 10 to the minus four. Now, when we look at duration of response, obviously this is still early in terms of follow-up, with a median follow-up of 9.5 months. And you can see that the overall curve tracks very nicely with what we had expected and seen prior. But you can also see there’s still a significant number of patients in the earlier part and the upper part of the curve, which tells you that there is still quite a bit of observation that we need for this study to actually for this curve to fully stabilize.

At this point, 61% of the responders are in ongoing remission. Now, when we look on Slide number 12, into sort of the – a bit more into sub-analysis of kind of what’s driving or impacting the overall response rate, we do see obviously key drivers here. What I’d like to point out, as indicated before, patients that have Extramedullary disease, tend to have a poor outcome, as are patients that have very high levels of disease in the marrow. In fact, if you have patients that have more than 75% tumor burden in the marrow, you see a reduction of the overall response rate to the range of about 60%, whereas patients with disease burdens below 75% in the marrow, and in fact, any level below, were in that range of somewhere between 80% and 85%. I think it’s also worthwhile pointing out and not a surprise that obviously if you have patients that had a very significant number of prior lines of therapy, they tend to do less well than patients that had been less exposed to therapy before.

And overall, obviously some limited impact that we can see on either prior Ino or prior blinatumomab therapy. However, those are also overlapping. So, from a confidence interval, not clearly differentiated. So, with that, moving to safety. As you can see on Slide 13, quick summary on the immunological toxicity that we have observed. We looked obviously specifically for cytokine release syndrome and neurological toxicities as measured by ICANS, and I think it’s remarkable when you see overall that we have a remarkably safe product. On the overall CRS level, we had about 3% of patients that had experienced high-grade CRS, which is very low compared to any other, I think, therapeutic approach that utilizes T-cells, including blincyto. When we look at the ICANS, we also see that the level of higher grade ICANS is low.

It’s 7%, which is also below any of the other therapies that are redirecting T-cells. I think overall we do see somewhat of an impact on tumor burden on ICANS, but we don’t see much of a difference in terms of tumor burden on cytokine release syndrome. On ICANS, you can see that the patients that have more than 20% tumor burden, that the ICANS are elevated. We have about 10% of patients that have ICANS. If you’re below 20%, you have a very low probability of experience to high-grade ICANS. What was quite remarkable was that most of the patients that experienced the high-grade ICANS, which was a total of seven patients out of the 94, six actually had more than a 75% tumor burden at the time of lymph depletion. So, this is after bridging therapy and everything else you could do to contain the disease prior to dosing, that’s still an excess of 75%, and that’s the group of patients that actually have the highest risk, which also actually gives you very important information ahead of dosing the patient on what to expect and how to manage the patients going forward and (affect towards) the physicians in control of this therapy rather than basically finding themselves in a position where they’re frankly being taken for a ride.

Now, moving to Slide 14, as you can see, one of the key parameters that we’ve been looking at is obviously the behavior of the T-cell in the patient. And as you do remember, one of the unique properties that we have with obe-cel is that it is obviously a product that has a very unique design. The design allows us to get a very physiological engagement of the target cells, rapid recognition, rapid kill, and then a rapid disengagement after that kill has occurred, and an ability for those cells to recycle back into action. But as they’re cycling back into action again, they not only actually continue in a serial killing mode, which actually is at much, much lower level of toxicity overall, they also actually give a very strong signal to proliferate.

And so, one of the things that we do see across all of our patients is a massive expansion of the CAR T-cells in vivo, which gives us this enormous peak that you see on the left hand side on Slide 14, which in fact matches very nicely the peak of expansion or total number of CAR T-cells formed over time. That matches very nicely with what we have seen in our prior study, the ALLCAR19 study. When we look at the area under the curve for the first 28 days, also very nicely matching. If you look at the half-life, very nicely matching our prior experience. And as we’ve seen with ALLCAR before, we do see a sustained level of CAR T-cells over time. And this is important because this – as we go to Slide 15, as a quick reminder, what the observation was in the ALLCAR19 study, you can see on the right hand side is that very similar behavior of rapid expansion, but then sustained levels of CAR T-cells over time.

And you can see we look here up to four years in the ALLCAR19 study. And we also did observe that all of the patients that had long-term remissions without any additional therapy, which are the patients at the top part on the swim plot on the left-hand side, all of those patients had sustained persisting CAR T-cells. So, we believe actually having seen a replication of the cellular properties in our FELIX study tracking what we have seen in the ALLCAR study gives us a high degree of confidence that we’re on the right track in terms of a longer-term follow-up as well. Moving to the summary on slide 16, obviously we’re very excited with the outcome that we have seen in this study. Remember, as a backdrop, this study was conducted through the peak of the pandemic.

We were not able to go onto the sites. Everything was done remotely. And as you can see, and it’s also reflected in the patient population, we have a wide range of patients with extraordinary risk factors, which actually normally wouldn’t see recruited into studies like the FELIX study. So, we have very much a real-world patient population that we’ve treated here. And to see the outcome, both on efficacy, as well as on safety to be so consistent with what we’ve seen before, gives us a lot of confidence in the property of the product, but also with our ability – in our ability to deliver the product reliably at high level of quality and in time for these patients, which is really critical. When we then look at the engraftment as we just talked about, obviously we’re tracking what we have seen in our prior experience with the program, and that obviously gives us a lot of confidence in the further analysis and follow-up of the study.

Now, I’d like to spend just a two, three minutes on manufacturing, moving to slide 18. And I just want to briefly talk about what are some of the critical success factors on product supply. The first is, when you are dealing with patients with acute leukemia, you actually start with a very challenging starting material, because many of these patients do not only have disease in their bone marrow, but also actually have disease that actually gets into the blood and basically leads to very high tumor burden also in the blood. So, when you’re collecting cells from the blood in a leukapheresis, you have patients where you have the predominant cells that you collect, up to 95% of the cells can be leukemic cells. And as you can imagine, that’s an incredibly difficult starting material because you have to first get rid of those cells before you can even think about manufacturing, and which means that your manufacturing process has to be able to handle a wide range of very complex and challenging starting materials.

So, we spend a lot of time optimizing the manufacturing product process to actually achieve the level of robustness that is required for reliable product delivery here. The other aspect is that you need to have a very consistent turnaround time, which means you have a consistent production time, and then you need a consistent product release time, which is the analytics that leads you to a full batch record that allows you to release the product. That actually is a very, very important part if you take in overall turnaround times. And what actually allows us to actually be consistent and also manage our overall costs has to do with the fact that we’re operating with a fully enclosed system that actually allows us to operate in a lower grade clean room environment than what you typically see in the space.

And that actually is a massive – leads to massive reduction in the time that it takes for people to get in and out of those particular rooms. So, that’s actually directly impacting costs, but it also has much less running costs involved. And it also simplifies the whole approach because it allows you to build on a semi-automated level of semi-automation, which also reduces the actual handling steps substantially. And with that, increases robustness, but also decreases cost. Now, people are critical here and I think we shouldn’t underestimate the importance of the piece that you have to build here, and the people you have to train. The people that actually operate in a facility like our manufacturing facility in Stevenage, are not people you can hire at this point from the market.

They do not actually exist. You have to actually train them. So, actually creating a highly trained and motivated workforce is absolutely critical. And one of the key things that we have to do is actually establish a full-fledged training program to make sure that our operators are fully trained, fully capable, and skilled to deliver this type of an operation, this type of an outcome. And then the culture of continuous improvement is extremely important. If you have processes that have a large number of steps, that gives you opportunity to improve frankly, every single one of them. And that ultimately will translate, not only in robustness, but also in increased efficiency, and with that, continued ability to decrease cost of goods over time, as well as reduce turnaround time.

And then finally, the scale of the operation, you have to actually be able to deliver and serve the market that you’re launching in. And that’s been one of the critical issues that we’ve seen in the spaces that the capacity available at launch was completely outstripped by the demand. And that creates a lot of problems, a lot of disappointment, and it’s something that is really important to get right. This is why we chose to actually design a facility that allows us to actually treat two thirds of all relapsed/refractory patients in the US and in Europe from the facility from which we launch or plan to launch the product. So, those are important aspects. You also don’t want to actually over-engineer or over-design the capacity, because if you go too high, you have too much excess capacity.

You have a very significant adversarial impact on cost to goods. So, with that, moving to slide 19, I already mentioned the whole series of aspects that matter in terms of the actual product. We’re working with the Miltenyi Prodigy machines, which have proven to be extremely robust and reliable equipment, and are really kind of the workhorse frankly, on which we do the manufacture. You can see actually on the lower part of the chart, you see looking at the actual manufacturing success rate, the transduction efficiency rate to delivery time. And what we chose to do also as part of the presentation at ESCO and DHA to show frankly every single batch manufactured for the pivotal study. And that is important because this is an area where I think confidence in the manufacturing and the consistency is extremely important.

That’s why we chose to present the data in this quite unusual way in our field. Now moving to Slide 20, just a brief word on the manufacturing facility, the commercial manufacturing facility. We’re well on track to run a complete evaluation of this facility. It was a very unusual project. We built this product or project in record time. We went from groundbreaking in November ‘21 to get the first clean room up and running in November ‘22. And we expect to file the BLA by the end of this year. So, roughly from groundbreaking to BLA filing, the timeline of 24 months. And that includes all the build, the full validation of facility and getting all of that obviously into shape so that you can actually submit for registration. So, it’s been a remarkable project.

There’s a lot of different areas that we’ve done quite differently than what’s normally done, but I think what it ultimately gets us to is it goes back to the team, the ability, the goal-setting. But as you can see also on the right-hand side, what’s really important is then actually to demonstrate that this type of facility can operate at high level of frequency and actually do that without breaking on either equipment on the infrastructure, be it pressure, temperature, et cetera, or just on the flow of materials, goods, and people through the facility. So, what you see on the right hand side is actually a capacity challenge we conducted in the second quarter where you see literally every one of the Prodigy machines running in parallel at that point in time in the facility, which obviously leads us to maximal use – maximal amount of people in the room, maximal flow, pressure on flow, et cetera, of materials, good, et cetera, through the facility, and really gives you the ability to pressure test, identify where you have issues or stress in the system, and then actually address that and keep improving from there.

So, it’s been a very successful operations that we had. And the final comment I’d like to make here is that obviously our range delivery time through all the challenges and logistics during the pandemic was 21 days. We expect that to go down to 16 days at launch, and that actually has to do with the commercial operating model that I’ll mention on the next slide, but also on a set of release assays that actually allows to accelerate and which were all implemented and were implemented as part of the pivotal study and will come to full effect at the time of launch. So, preparing for commercial launch, going to Slide 22, obviously there are a number of things that we need to sort of really focus on. One is obviously the data and the path to approval, which we have talked about already.

Expect to file a BLA application by the end of the year and then early next year for the European side. Manufacturing obviously needs to be ready. It needs to be all put together. And in particular, when we then look into commercial side, we need to obviously have a lot of work ongoing on the medical affairs side working on the completion on the HDS dossiers and the central onboarding, which are really core activities that you need to have in place, and it has substantial amount of lead time, with then obviously a focus in 2024 to really focus on the actual launch, prep, and execution, and also, obviously considerations around commercializations in Europe. Now, one of the things that we did report on, on Slide 23, is the fact that we have selected Cardinal Health as our US distribution partner.

And that is important because actually it allows us to have some of the commercial infrastructure components to be supported and supplied by our partner. And that allows us to sort of focus our activities on the specific bespoke aspects of what we need to do. So, distribution is obviously important because the actual way on how these products move are not really moving technically with change of custody to a distributor and then on forth, but it goes directly ultimately from us to the center, but there still has to be obviously an invoice generated. There has to be – the center has to be checked and make sure that everything is fulfilled, and also there has to be reporting to the government. And those are areas where Cardinal will help us and will support us.

Same is related to order-to-cash activities. But I think what’s probably more from an operational and ultimately success perspective important is the depot model where we’re going to be actually be able to ship products that are manufactured for patients in the US can actually ship them before they’re fully released, while they’re still in our custody, moving physically from the UK to the US, get fully released in that time. And as soon as the full release is then, the product can then actually be moved from the depot to the center. And that obviously allows us some parallel processing and that cut time out of the range of delivery time, which is one of the key contributors to the reduction range of delivery time that I pointed to in my prior slide.

Now, when we look then on Slide 24 and 25 is, where do we go from here? Obviously, obe-cel in ALL is well on track. It’s the primary focus of the company, but obviously there is quite a lot of opportunity that we see for obe-cel, and we see it in several directions. What this slide summarizes is that the way we think about obe-cel is not just as a single product in ALL, but it is an actual opportunity to develop a franchise around obe-cel. And that is true for o obe-cel itself, but also from a lifecycle management perspective, actually leading in two follow-on products. The two follow-on products are AUTO1/22, which is a dual-targeting approach addressing the challenge of relapses driven by loss of CD19 antigen. And the second is a dual-targeting approach for multiple myeloma, possibly also for autoimmune disease, with an approach that has combined CD19 and with a very sensitive BCMA targeting chimeric antigen receptor.

So, what we’ve done basically here is we’re taking the CD19 CAR, which we believe is the best-in-class CD19 CAR in the business, from obe-cel, and we’re combining it in those two additional products with CARs that are highly sensitive for CD22-expressing cells, and in fact, tailored to actually give us activity against those cells that have very low levels of CD22 expression, as well to make sure that we have a very efficient engagement on cells, that even if they’re trying to sort of down-modulate CD22 expression. Quite similarly, in multiple myeloma, many of the cells, when you analyze patients, you do see that the expression of BCMA can be extremely low. It can be 10, 20, 30 receptors per cell, not thousands, but actually 10, 20, 30 receptors per cell.

And that obviously requires a very sensitive chimeric antigen receptor to tackle those cells and make sure they can be efficiently recognized and taken out. So, here, the optimization also was on that side similar to what we’ve done with the CD22 CAR. And we’re combining both of those CARs with the CAR from obe-cel. And that gives us a very interesting set of products and it gives us applications both on the hemato-oncology side, but also applications that we can choose on the autoimmune side as well, where we’re looking to sort of get rid of C of autoreactive B-cell-producing plasma cells. So, moving to the next slide on – this is Slide 26. This is a slide you’ve seen before, summarizing the non-Hodgkin’s data published at the end of last year.

We’ll keep updating that data. Obviously, it gives us a very high level of activity with obe-cel. And just as a reminder, obviously in a non-Hodgkin setting, we’re actually dosing patients with a single dose and do obviously have a very significant level of clinical activity. Almost all patients achieve metabolic CRSs and many of them sustained over extended period of time. Very interesting, obviously what we’re seeing in DLBCL where we actually see sustained responses and have no relapses so far, which is quite remarkable. And also what we’re seeing is good levels of persistence. Also, non-Hodgkin’s lymphoma, which is something that hasn’t been quite as consistent across the field. The safety has been excellent in all of these indications, and we believe that the safety profile should allow obe-cel to actually be used in outpatient settings in those respective indications as well.

Moving to the next slide, Slide 27. A quick word on the opportunity we see for obe-cel in B-cell mediated autoimmune disease. Many of you have seen the really pioneering work by Erik (indiscernible) and Andreas Mackensen from the University of Erlangen, that was published obviously in several papers now, that looked at utilizing a CD19 CAR approach in patients with refractory SLE as the initial study and then expanded into an additional set of related B-cell mediated autoimmune diseases. The outcome was quite remarkable because what we basically observed is that the patient lost the autoreactive antibodies, as well as clearly the underlying producing cells within a very short period of time. The antibodies typically got cleared within about month, and that clearance actually was sustained over time.

So, the patient did recover as a consequence of that removal of the autoreactive antibodies, and went from very high composite scores to basically baseline. And these are refractory patients. So, the outcome was very remarkable, very different from I think anything we’ve seen in the field based on monoclonal antibodies. I mentioned the fact that Miranda ran the BENLYSTA program. So, there’s quite a bit of understanding within the company also of autoimmune diseases, so the B-cell-mediated. This is a different quality of outcome, and you’ve seen a number of companies start to look at that, et cetera. We believe we’re actually extremely well positioned with our product because we obviously do have, as far as we can tell, based on our data today, is that we have the safest and probably the most active CD19 CAR in the business.

We also have a commercial manufacturing base, and we have an ability to deliver these products reliably and at attractive cost of goods. I think all of these components I think are incredibly important if you want to position a CD19 CAR program or any of the related B-cell-mediated autoimmune diseases. We will start out with a dose confirmation study. We’ll do that in SLE patients, and we will use that then as the basis to discuss the design of a pivotal study with the agency. So, that’s where we are with the program. We expect to get started early next year in dosing patients, and we’re really excited, obviously about the opportunity here. Just as a quick reminder then on the two other programs that are beyond obe-cel in the franchise. I mentioned AUTO1/22, looking to find a way to mitigate CD19-mediated – CD19 loss mediated relapses.

Obviously, we’ve tested this product AUTO1/22 again in patients that are ineligible for Kymriah, including patients that had actually relapsed after Kymriah therapy with CD19 negative disease. And we can show very high level of clinical activity that gives us a good level of sustained activity, as well as an excellent safety profile. So, this product, obviously, is, I think, doing what we expect it to do and provides sort of an interesting opportunity for investment going forward. AUTO8 is the program targeting multiple myeloma. Also, that program is in the clinic. We expect first data at the end of the year. And clearly has a design principle that should allow us to get at B-cells that have very low expression of BCMA, but also having the CD19 component and just following obviously the conversation on immunity and fact are plasma cells that are CD19 positive.

There is also hypothesis that in fact, those cells that are CD19 positive plasma cells are the driving cells in multiple myeloma. That’s been a hypothesis that was postulated in actually the mid-90s by Dr. Matsui at Johns Hopkins, and it’s been one debate that’s been going on for a while in the field, but we believe also with the data that we see now in SLE, there’s a good chance that that actually has an ability to potentially give us sort of a deeper form of remission and also more sustained presence of the cells that is driven through the CD19 side. Now, finally on the – moving beyond obe-cel, obviously we’ve provided an update at the Lugano Lymphoma meeting on AUTO4, have seen an excellent continuation of the data. The key data really that we were interested in is to see what the complete remissions that we were able to induce in these patients where they were sustained over time.

And in fact, we have now two of those patients that have crossed one year, and that starts to give us a lot of confidence in the clinical effect and benefit that we can actually induce with the seratherapy. And obviously there’s more data, data that we’re sort of working on that we’re also looking to sort of publish the data in a peer reviewed journal as well. Now, moving just quickly through the pipeline slide on Slide 32 obviously there is a significant amount of our programs as you can see we do in collaboration and work on collaboration with UCL and sort of the broader translational program we’re running, which has been a very successful collaboration, and also gives us an opportunity to really generate clinical data for future investment decisions so that when we actually are making decisions beyond what we’re going to do beyond obe-cel and beyond the initial indications, really can be based on clinical data and doesn’t have to be based on preclinical data, which we believe unfortunately in this field, do not provide a lot of confidence in terms of the ability to translate the outcomes into patients.

So, with that I would like to hand over to Lucinda for the financial results.

Dr. Lucinda Crabtree: Thanks, Christian, and good morning or good afternoon to everyone. It’s my pleasure to review our financial results for the second quarter ended June 30, 2023. Cash and cash equivalents and restricted cash at June 30, 2023, totaled $307.8 million. This compares to cash and cash equivalents and restricted cash of $382.8 million at December 31, 2022. Total net operating expenses for the three months ended June 30, 2023, were $47.9 million as compared to total net operating expenses of $46.5 million for the same period in 2022. Research and development expenses decreased by $1.5 million to $36.7 million for the three months. Ended June 30, 2023 from $38.2 million for the three months ended June 30, 2022, primarily due to the following; a decrease of $5.9 million in clinical costs and manufacturing costs, primarily related to our obe-cel clinical product candidate, a decrease of $0.6 million in legal fees and professional consulting fees in relation to our R&D activities, a decrease of $0.5 million in depreciation and amortization related to property, plant, and equipment and intangible assets, a decrease of $0.1 million in material transportation costs.

These were offset by an increase of $3 million in salaries and other employment-related costs, including share-based compensation expense, which was mainly driven by an increase in the number of employees engaged in R&D activities, an increase of $1.7 million in facilities costs related to our new manufacturing facility, the Nucleus, which is based in Stevenage, UK, as well as increases in cost related to maintaining our current leased properties, and an increase of $0.9 million related to IT, infrastructure and support for information systems related to the conduct of clinical trials and manufacturing operations. General and administrative expenses increased by $2.8 million to $11.1 million for the three months ended June 30, 2023, from $8.3 million for the same period in 2022.

And this was primarily due to the following; an increase of $1.5 million in commercial readiness costs due to increased commercial readiness activities being undertaken, an increase of $1.2 million in salaries and other employment-related costs, including share-based compensation expenses, which was mainly driven by an increase in the number of employees engaged in G&A activities, an increase of $0.2 million related to IT, infrastructure and support for information systems related to the conduct of corporate and commercial operations, an increase of $0.1 million in depreciation and amortization related to property and equipment and intangible assets. And these were offset by a decrease of $0.2 million, primarily related to reduction in directors and officers liability insurance premiums, and legal and professional fees.

Other income or expense net increased to an income of $0.5 million for three months ended June 30, 2023, from an expense of $1.3 million for the same prior period in 2022, respectively. The increase of $1.8 million is primarily due to the strengthening of the pound sterling exchange rate relative to US dollars for the three months ended June 30, 2023 versus three months end June 30, 2022. Interest income increased to $3.4 million for the three months ended June 30, 2023, as compared to $0.1 million for the same period in 2022. The increase in interest income of $3.3 million primarily relates to increased account balances and yield associated with our cash and cash equivalents during the three months ended June 30, 2023, compared to the same period in 2022.

Interest expense increased to $5 million for the three months ended June 30, 2023, as compared to $1.8 million for the three months ended June 30, 2022. Interest expenses primarily related to the liability for future royalties and sales milestones associated with our strategic collaboration agreement with Blackstone. Income tax benefit decreased by $4 million to $3.5 million for the three months ended June 30, 2023, from $7.5 million for three months ended June 30, 2022, due to a decrease in qualifying R&D expenditures, and a reduction in effective tax rate related to the UK research and development tax credit regime under the scheme for SMEs. Net loss attributable to ordinary shareholders was $45.6 million for the three months ended June 30, 2023, compared to $42.1 million for the same period in 2022.

The basic and diluted net loss per ordinary share for the three months ended June 30, 2023, totaled $0.26 compared to a basic and diluted net loss per ordinary share of $0.46 for the three months ended June 30, 2022. Autolus estimates that its current cash and cash equivalents on hand and anticipated future milestone payment from Blackstone will extend the company’s runway into 2025. So, before I hand back to Christian, I wanted to say what a pleasure it has been to work with all the talented people at Autolus, with a very special thanks to my direct team and the management team. I wish them and the company every success. Over to you Christian.

Dr. Christian Itin: Well, thanks, Lucinda, and thanks in particular for all your contributions over the last few years. You will definitely be missed, and wish you success with your next steps. Welcome, Rob. We’re in a fantastic situation that with Rob Dolski, we have a great successor to Lucinda in the role of CFO. And I would just like to briefly introduce Rob, and then also ask Rob to introduce himself as well. So, first off, obviously, as I mentioned earlier, that Rob joins us from Checkmate Pharmaceuticals, obviously have been going through an interesting phase of the company, including the sale to Regeneron, which obviously gives him sort of a very nice and kind of rounded experience on that kind of last part of his experience.

But his experience is much broader than that. And in fact, Rob brings a very unusual combination of financial experience, but also operational experience, including deep understanding of manufacturing, commercial aspects, launch-related issues, et cetera, which are really important in where we are now, and I think will set us up really well for the next steps that we’re going to take with the company, and I think will help us drive the strategy, planning, execution, as well as then the next steps and expansions that we’re all looking forward to as we’re sort of taking our steps and becoming a commercial entity. So, with that, I’d like to hand over to Rob just to ask you, Rob, to introduce yourself directly.

Rob Dolski: Thank you, Christian, and good morning, or afternoon to everyone. I’m delighted to be joining Autolus at such an important time. With the upcoming obe-cel BLA filing and the expansion of the manufacturing and commercial efforts, it’s going to be a very busy time, and I certainly look forward to interacting with our analysts and investors over the coming months. I’ll now hand things back to Christian to wrap up with a brief outlook on expected milestones. Back to you, Christian.

Dr. Christian Itin: Thanks, Rob. So, to summarize, and we’re moving to Slide 36, we think we have an exciting time ahead of us. Key focus, obviously, is getting obe-cel into the regulatory process and review, which is really the primary focus of the organization. We expect the BLA filing towards the end of the year, followed by a filing in Europe in the early part of next year. Next up, obviously are the plan to have FELIX data presentations at ASH. So, we submitted as indicated a few abstracts and also, we’re looking forward to obviously providing you update and more insights in the study. In addition, we’re also preparing for commercial product supply and launch readiness as a very significant workstream associated with that.

And we also expect to provide updates on the pipeline programs with additional data and follow-up during the year with our key programs, which at this point, obviously are on patent, and also gives us opportunity for conversations on that side. Moving to Slide 37, we believe we’re at very attractive and interesting point with the company. We’ve taken a significant amount of risk out of the program with the successful data presentations for the FELIX study at ASCO and EHA. And I think that puts us into a position where we believe we have an opportunity to go through a fundamental value step with the lead program and thus the business. And obviously, we’re looking forward to really driving this program through that process and hopefully onto the market with, I think, a very strong belief that the product has an ability to be transformational for a very challenging indication.

And I think patients definitely need access to safer and more efficacious therapies. Alongside those opportunities that we have in ALL, and that we’re obviously driving with a lot of focus, as indicated at today’s call, we see the obe-cel opportunity substantially broader, and we see it as a franchise opportunity that gives us access to a range of indications with the program over time, and then expanding into the additional related programs with AUTO1/22 and AUTO8 as well. So, with that, I’d like to stop here and looking forward to your questions. Thank you.

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Q&A Session

Operator: [Operator Instructions] Our first question comes from the line of Matt Phipps at William Blair. Matt, your line is open.

Matt Phipps: Hello, thanks for taking my questions and all the updates. Christian, on the SLE study, just curious if you can say at this point if you’ll test multiple dose levels, how the dose might compare to the FELIX indication. Do you think there’s any reason to look at different lymphodepletion regimens? And just real quick, any update on the FELIX MRD cohort just given some real-world data that CARs has shown a lot of use in patients who are MRD negative. Thank you.

Dr. Christian Itin: Thanks, Matt. Excellent question. So, first on SLE, clearly we believe that for the SLE indication, the dose that we need in that indication is substantially lower than what we need for acute lymphatic leukemia patients, because obviously there is – the amount of cells that has to be removed is very, very different. And we expect to be able to confirm a dose that is substantially lower in this indication. We don’t expect to run a dose escalation, but I think we’ll pick a dose with an ability to escalate or deescalate should that become necessary. But we actually do not expect that that actually will be necessary. So, we think we’re pretty clear what the dose needs to be, but we need to also want to have that confirmed in a small number of patients so that we have a basis for conversations with regulators for design of future studies.

We don’t think there’s a change that we want to play around with lymphodepletion. You could do that, but there is – I think we’ve seen a lot of work that went into the conditioning of the marrow to accept cells. A lot of that work comes from the original work in stem cell transplants that was adapted for the cell therapies and particularly also for CAR T therapies. And there’s a good reason I think why we have a good level of consensus utilized across a wide range of indications and programs. I do not believe that that’s an area where I go back and reevaluate. That would take substantial amount of time, and we do not believe the benefit actually warrants that type of high investment. With regards to MRD, that’s an area we’ve also been very active in.

We’ll certainly provide update on low disease burden patients and MRD patients, which is an obvious thing to look at because clearly patients with lower disease burden have obviously less work factor for the CAR T-cells to accomplish. But also, it will help to further improve the already very, very attractive safety profile of the program, and should also allow us to consider at least patients with low disease burden and patients who are in relatively good shape to consider actually dosing patients, ultimately in a hospitalized patient setting as well, which I think will further, I think, support access and facilitate access to obe-cel as a therapy.

Operator: Thank you. Please stand by for our next question. Our next question comes from Asthika Goonewardene of Truist. Your line is open.

Asthika Goonewardene: Hi, guys, good morning, and thanks for taking my questions. I want to build on Matt’s previous question on SLE. Can you tell us how long the dose – the DLT monitoring will be required on this Phase 1 in SLE? I’m just trying to get an idea of how quickly you will be able to get this study recruited in 2024. And then if we just think back on the data presented from the FELIX study at ASCO, you showed that tumor burden is quite associated with the incidence of ICANS, and that’s very predictive and probably very useful in the physician’s hands. We also know adult ALL is a rapidly progressing disease. So, I’m wondering what shaving off that five days from the vein to delivery time on FELIX versus what you expect to go – when you go into commercial mode, would you be able to get more patients before they’ve reached that 20% bone marrow blast threshold?

Dr. Christian Itin: So, really good question, Asthika. First off, the question related to the Phase 1 study design at the DLT period, I think what we’re seeing in the work that was done by Andreas and (indiscernible) also would indicate that you could consider a relatively compact DLT period in their hands they’re using a 10-day period for the patients. So, that’s something that we’re looking into, but it’s clearly also – obviously, we’re operating with a lot of clinical data from our experience in ALL and NHL. So, we have a lot of safety experience with the product, and we believe that that can be relatively compact. The question then related to obviously the tumor burden aspect and how that could be impacted by the vein to delivery time.

So, first of all, I think a shorter vein to delivery time always helps because the disease can be quite explosive in growth. So, anytime you shave off between frankly identifying the patient and treating the patient, is going to be helpful. But I think what is really important is that you want to actually make sure ultimately that if you’re not running the patients to – or waiting with the patients until they’ve actually reached very, very high levels of tumor burden before you actually identify them and involve them for therapy with a CAR T therapy. That’s not a good idea. It’s obviously what can happen. And the beauty of the data is that we’re highly active across the entire range of tumor burden and disease state and severity of disease, which also gives us an awful lot of confidence around the program.

But just from a very practical perspective, if you have an opportunity to identify the patients earlier, again the patients relapse, and a lot of that is done by monitoring patients’ tumor burden based on the PCR or FACS or NGS, that actually gives you an opportunity to identify the recurrence of disease earlier, and that actually increases your chances of a successful therapy, and also gives you an ability to minimize toxicity of this. So, it’s clearly an aspect you look at, and I think the shorter vein to delivery time overall helps, also because a lot of these patients are very immune -suppressed and there’s always a risk that the patients could actually pick up an infection, which would then actually could delay the dosing because that infection needs de first be taken care of before you could dose the type therapy.

So, speed is helpful. I think we’re at an excellent spot in terms of the time and dose, which is a highly competitive position.

Asthika Goonewardene: Great. Thanks for taking my questions, guys.

Operator: Thank you very much. One moment for our next call. Our next call comes from the line Kelly Shi at Jefferies. Your line is open.

Kelly Shi: Thank you for taking my questions. I have two quick ones. The first is regarding the subgroup analysis at ASH of this year. What kind of patient stratification are you going to use for this analysis? And also, what is the reason for 30% of the patients receive transplant while still in remission? Thank you.

Dr. Christian Itin: Hi, Kelly. Thanks a lot for the questions. The first is with regards to kind of the subgroup analysis. I think there’s obviously quite a lot. It’s a very rich data set. And this is one of the larger studies that actually have been conducted. If we take the Phase 1 component, it’s one of the largest studies conducted in relapsed/refractory patients. So, we have a very rich data set and that allows us to look at aspects in more detail of impact of tumor burden, impact of risk parameters on outcome, both on efficacy and safety outcome. And those are clearly key areas of focus that we’re sort of looking, expecting to provide updates on. So, it’s a very rich data set. What we’ve seen at ASCO is obviously just scratching the surface of the data that we’ve collected.

And we’re looking forward to obviously providing these much more detailed views, which also I think are some of the key reasons for the level of confidence in the consistency of the data that we have sort of articulated in the last few months. The patients that we had in the study, 30% of the patients did receive a stem cell transplant. That is pretty much kind of the range you sort of would expect based on clinical practice. I think if you have a patient – as an example, you have a patient that’s a younger patient, still relatively fit, that has an ability or capacity to actually tolerate a stem cell transplant, or may not have had one before, I think in those cases, certainly until you have long-term follow up in the study. I think physicians will have to make a choice whether or not to follow the patient and follow the persistence, follow the dysplasia and indicators for continued pressure on the leukemia.

Or if they think they have a good match for the patient, how to make a decision whether or not to potentially transplant. This is truly a physician decision. As you can see, it is a low percentage of patients that where that actually was a decision that was chosen to be taken. But it is clearly one of the options that is available to physicians. And it’s very much a very specific and very, I think, detailed analysis that the physicians actually make for the particular patients on whether or not to consider a transplant. And what we also certainly did see in the UK also where the physicians have more experience with the product. And the longer experience with the product is that while the first patient on the ALLCAR study received a stem cell transplant, actually that user transplant decreased quite a bit after that.

And in fact, the patients that actually were transplanted certainly in the early findings, suggests that the patients unfortunately didn’t do any better. And so, that’s obviously also one of the key questions as well, is whether indeed it’s beneficial, because one of the things you do when you move a patient to transplant after CAR T therapy is that you also eliminate all the CAR T-cells prior to the transplant. So, that’s a tricky decision to make because if the CAR T-cells are still active, you actually may have taken away a substantial component of your opportunity for longer term success in the patient. And at the same time, there is obviously not insignificant amount of risk, particularly if it’s a second transplant, that you have complications related to the second transplant, including treatment-related mortality.

So, it’s a very – it’s a much more nuanced conversation. And I think as we have more data and longer-term follow up in the study, I think that’s certainly an area we’re going to look into whether or not patients that have received a second – or a second transplant have received a transplant after obe-cel, how they’re doing and whether they actually are doing better or worse than patients who did not receive it.

Kelly Shi: Super helpful, thank you. And I also have one quick one regarding the lupus trial. So, does the manufacturing process require additional steps to increase purity compared to oncology CAR T product? Thanks.

Dr. Christian Itin: That’s a really good question, Kelly. And the answer is actually, the lupus patients are a lot simpler to manufacture because you do not have the contamination by higher levels of leukemia cells floating in the blood. So, the starting material you collect from these patients is a much better starting material. And it’s also – because of that, we believe that also will allow us to actually shorten the manufacturing process for these patients because we need less cells and we actually have a much better – much more homogeneous starting material. So, it’s actually just the other way around. It is an easier material to work with than what we’ve done in ALL, which we believe is probably the single most challenging patient population from a production perspective.

Kelly Shi: Great. Thanks.

Operator: Thank you very much. Please stand by for our final question, and please remember that management will follow up with everyone directly who didn’t get to ask the questions. Our next question comes from Eric Joseph of J.P. Morgan. Your line is open.

Noah Burhance: Hi guys, this is Noah on for Eric. Thanks for taking our question. We were wondering regarding the SLE trial what clinical parameters will inform an optimal dose selection. Thanks.

Dr. Christian Itin: Hi, Noah, thanks for joining. Really good question. So, what you want to see is the two parameters that you’d like to see and that I think you can actually get out of this study. The first one is you want to see that therapy at the level you dose gives you a very profound B-cell aplasia removal of B-cells in these patients, and a rapid decline of autoreactive antibodies in that patient. And then you also want to see that the lupus-related composite scores actually track down, and you would expect most of those to actually go to baseline. At the same time, you want to see that that clinical activity can be induced without triggering any significant level of toxicity to the patient. So, it is both the safety that obviously will be important, as well as the pharmacodynamic parameters, as well as then the disease parameters that will be following that will inform the understanding of the dose and activity relationship.

Operator: Thank you very much. At this time, I would now like to turn the conference back over to Christian Itin for closing remarks.

Dr. Christian Itin: Well, thank you very much for joining today. Obviously, this was a full presentation. There’s a lot of updates that we had in this quarter. I think an exciting stage for the company. I think it’s fair to say we’re kind of moving flat out across the entire organization to deliver a BLA by the end of the year, which requires obviously the completion of the work on the manufacturing facility, and then also all the work that’s going on, on the clinical analysis – the analysis of the clinical data from the FELIX study. So, an exciting time, very intense, but also I think very rewarding because we’re feeling that we’re working with a product that has a very unusual profile, and I think that promise to really have a big impact on patients’ lives going forward. So, with that, I’d like to thank you all for joining today and looking forward to keeping you updated as we go through the second half of the year. Thank you.

Operator: Thank you. This concludes today’s conference call. Thank you for participating. You may now disconnect.