Adaptimmune Therapeutics plc

Hello and welcome to the Adaptimmune Therapeutics third quarter 2024 results conference call. As a reminder, all participants are in listen-only mode and the conference is being recorded. After the presentation, there will be an opportunity to ask questions. To join the question queue, you may press star then one on your telephone keypad. Should you need assistance during the conference call, you may signal an operator by pressing star then zero. I will now turn the call over to Dan Odd-Cohen, Investor Relations for Adaptimmune. Dan, please go ahead.

Thank you, operator. Good afternoon, everyone, and welcome to Adaptimmune's conference call to discuss our third quarter 2024 financial results and business updates. I would ask you to review the full text of our forward-looking statements from this morning's press release. We anticipate making projections during this call, and actual results could differ materially due to several factors, including those outlined in our latest filings with the SEC. Adrian Rockliffe, our Chief Executive Officer, is here with me for the prepared portion of the call, and other members of our leadership team will be available for Q&A. With that, I'll turn the call over to Adrian Rockliffe. Over to you, Ed.

Thanks, Dan, and thank you everyone for joining us today. So I'd like to start by addressing the announcement we made in today's press release regarding our new strategic business plan. This plan has three main objectives. One, to streamline operations to focus on our commercial sarcoma franchise. Two, to prioritize the R&D programs that have the best return on capital, and the best opportunities for transformational medicines for patients. And three, to set the company on a course to operating breakeven during 2027. The plan was a result of a thorough review of the entire company and investments across the organization. And it follows the successes we've had in the initial stages of the Decelera launch, which is progressing very well against our objectives and which I'll discuss later. It also follows the successful primary analysis data from the Pivotal Ignite ESO trial with Leticel that we announced earlier today. The positive results from this pivotal trial, which has met its primary endpoint, demonstrated even better outcomes than the interim results we announced back in June. And it will form the basis of the BLA submission for Leticel starting next year. Based on these data and our successful approval of T-Cell in August, we have increased confidence that Leticel has a high probability of approval and will become an important medicine for people with both synovial sarcoma and MR-CLS. Now that we have a very clear path towards a successful sarcoma franchise with potentially two FDA-approved products, we have even greater conviction in our projection of $400 million in combined U.S. peak revenue for Tisara and Leticel. As such, We believe that maximizing the value of this sarcoma franchise is the highest priority for the future of the company, for its shareholders, and for the patients we serve. And we also felt that now was the right time to make these tough business decisions to achieve this objective. So to that end, we will reduce our cost structure to ensure we achieve operating cash flow break even during 2027. we'll reduce our headcount by about 33% and compared to our estimated 24 cost base, we'll reduce our total operating expenses by approximately 25% next year and over 30% in subsequent years. In total, this represents a saving of $50 to $60 million in 2025 and in the range of $300 million in the period from 2025 to 2028. before one-time restructuring costs. These savings substantially reduce the financing needs of the company between now and the transition to cash flow positivity. As a result of this restructure, we will reduce our UK footprint and research functions and suspend clinical trial activities with user cell for ovarian cancer, which will remove the associated CMC and development costs in the coming years. The Galapagos collaboration on user-self head and neck cancer and other indications is going well and will not be affected. And we will be continuing with our lead preclinical assets, PRAME and CD70. And we'll suspend investments in other earlier stage pipeline programs. We continue to seek strategic partners for PRAME and CD70, as well as our leading IPSC allogeneic platform. So following the successful launch of T-Celera and the great letter cell data we're presenting at CTOS, the company is now fully focused on building a successful business with a cost-efficient commercial infrastructure focused on what we anticipate will be two FDA-approved products in sarcoma, achieving our cash flow break-even objective in 2027, and substantially reducing the need to bring in additional capital before becoming cash flow positive. This strategy, whilst involving difficult choices to reduce costs, is in the best interest of our stakeholders and of the patients who need our transformative cell therapies. Now, moving on with an update on the T-Cellera launch, which is tracking very well against our plan. T-Cellera is the first FDA-approved engineered cell therapy for a solid tumor and was approved in August for treating synovial sarcoma. So we're now about three months into the launch. With previously available treatment options providing low response rates and a five-year survival rate of only 20%, we're finding that T-cellular has been embraced by the sarcoma community as a transformational treatment option for this devastating disease. We now have nine authorized treatment centers or ATCs accepting patients and referrals from healthcare providers and that can initiate the T-cellular treatment journey across the U.S. This is at the upper end of the guidance we provided previously of six to 10 centers within the first 90 days. Furthermore, we have an additional four sites that have signed contracts and a further 15 sites that are in active contract negotiations. Our ultimate goal has consistently been to have a network of approximately 30 ATCs offering T-cell retopatients within two years of launch, since those ATCs would cover an estimated 80% of the patients treated in sarcoma centers of excellence. We are confident we can now activate our full network of ATCs by the end of 2025, two to three quarters ahead of our previous projections. This is a testament to the team's focus and to their execution, but also to the high level of engagement of each of our targeted sites. On the payer side, T-Cellular is approved for a rare and serious form of sarcoma with demonstrated clinical benefit for patients. We've seen significant engagement by insurers And currently, insurance plans representing over 67% of commercial lives formally cover T-cellular. And this continues to increase as planned. For these types of therapy, the insurance approval process is almost always conducted individually for each patient by the treatment center and the patient's insurer. And our adaptamine assist team is involved in every step of the process to support the centers and the patients to navigate through financial and logistical needs and to make sure that they have a seamless treatment experience. On the patient side, we're also very pleased to have A4 East our first patient, and manufacturing is currently ongoing. There are now approximately 15 patients that have been confirmed as double positive following biomarker testing, meaning they've tested positive for the right HLA and for MAGE A4. Furthermore, there are at least an additional 25 patients in various stages of biomarker testing before this. Whilst not all of these patients will be eligible for or will opt for T-cellular treatment over a particular timeframe, we provide these metrics so you can see where our level of excitement and confidence is coming from. It is now very clear that we have a robust flow of patients that will progress to treatment with T-cellular in the remainder of 24 and 25. The patients are there, and the commercial model that we've built is working. to make T-cellular available to appropriate patients. Going forward, though, we're unlikely to continue to provide this level of detail regarding launch metrics, and all of this is in line with our previous guidance of expecting our first commercial revenues in Q4 of 2024. Just as a reminder, revenues recognized when the treatment center receives T-cellular So, we don't expect meaningful revenues in Q4 of this year, but as we progress into 2025, we'd anticipate modest revenue in the first two quarters that will continue to accelerate throughout the year as patients flow through our expanding network of treatment centers. With the commercial launch tracking to plan, along with extremely encouraging feedback from centers and from physicians, we're very excited about TESOLA's potential to improve and extend the lives of people with synovial sarcoma. But this is only the first foundational medicine in the sarcoma franchise. And in a separate press release this morning, we announced the results from the primary analysis of the full data set from Lettercell's IGNITE-ESO pivotal trial, which met the primary endpoint and are even more positive than the interim data we released back in June. The full analysis of IGNITE-ESO reinforces the achievement of the primary endpoint for efficacy in the full dataset of 64 patients treated, with a 42% response rate overall. And this included six complete responses, which is a complete response rate of almost 10%. These responses are very durable, and although this dataset is not fully mature, the median duration of response in the MR-CLS population is currently just over a year, and in the syrenovial sarcoma population, the median duration of response is just over 18 months. The full data set will be presented at the Connective Tissue Oncology Society, or CTOS, meeting on November the 16th and will serve as the basis for the BLA filing planned in 2025. We expect Leticel to expand our reach beyond T-Cellera and into NY-ESO-expressing synovial sarcoma and MR-CLS patients. This will more than double the number of treatable patients, and we estimate that Leticel will eventually make up over 60% of the combined sarcoma franchise revenue. Since the commercial footprint and the ATCs for Leticel are essentially identical to that for T-Celera, we will have significant operational, channel, and cost synergies when we launch this second product. Following CTOS, on November the 18th, we will hold a virtual investor event to further elaborate on these findings from the Pivotal IGNITE ESO trial and expand upon what it means for the treatment landscape in sarcoma. The event will feature Dr. Sandra D'Angelo, sarcoma medical oncologist from Memorial Sloan Kettering Cancer Center. She was an investigative clinician in both the Spearhead 1 clinical trial, the Pivotal trial for T-cells, and the IGNITE ESO clinical trial, the Pivotal trial for letter cells. Details are available in today's press release and on our website, and we hope you join us. Moving on to the financial results, at the end of Q3, we had approximately $186 million in total liquidity after further drawdown of $25 million from our debt facility following the FDA approval of Tesara. In the third quarter of this year, our total operating expenditure was $55.6 million. And for Q4, we expect our run rate operating expenses to be broadly consistent with the first three courses of 24. And the impact of the cost reduction initiatives I spoke about earlier will take effect starting in 2025. In closing, Adaptimmune has successfully discovered, developed, and is commercially delivering the first ever engineered cell therapy for a solid tumor. And we now have clear line of sight to our second approval and commercial launch of a wholly synergistic product in this franchise. We've achieved this with the expertise and commitment from our entire team. Now, we've made difficult decisions that are necessary to set the company on the path to cash flow positivity as we bring the benefit of this cell therapy franchise to the sarcoma community. And we will continue to make decisions to enable us to provide therapies with transformative benefits to patients, thus delivering long-term success and value to the company and to its shareholders. And with that, leadership team is happy to take questions. Operator?

Thank you. To join the question queue, you may press star then one on your telephone keypad. You'll hear a tone acknowledging your request. If you're using a speakerphone, please pick up your handset before pressing any keys. To withdraw your question, please press star then two. First question is from Mark Fram with TD Cohen. Please go ahead.

Thanks for taking my questions. Maybe just to start off with on the launch, can you just kind of remind us how long that process takes, kind of from a physician first expressing interest for a particular patient and getting to that 15 patients who have now cleared HLA and MAGE testing? And then how should we think about the timeline from getting that double positive result to you know, actually kind of working through the process of negotiating contracts and all that to then, you know, ultimately ghost the patient.

Yeah, thanks, Mark. So, yeah, so we provided details in my prepared comments that I think it's the first time we've provided those, which was that there's 15 patients that have tested positive for both biomarkers, and an additional at least 25 that are in various stages of biomarker testing. And I think it's important to understand that whilst we're super happy to see that patients are having the opportunity to be identified and testing, we think that primarily confirms the unmet need that's there and the pent-up demand for T-Cellera. it's important to note that testing can happen at any time during the treatment journey. So not all of those patients will necessarily flow through to become treated with T-cellular in any specific time period. But we do expect the majority of double positive patients to continue their journey and be treated with T-cellular in the first two quarters of next year. And obviously, the the patients that are coming through the other stages of testing will flow through in proportion to their testing positivity and then over that sort of similar timeframe and subsequently. We previously stated that we thought that the period from the very start of a physician first wants to test the patient through to being treated with T-cellular could take approximately three to four months. And I think that's important, but that also assumes that the patient is being tested and then going straight into treatment, not being tested really early on in their diagnosis process. So that three to four months, I think, is a reasonable estimate as we start at launch of T-cell. So I think the long and short of that is that we don't expect meaningful revenues. We do expect first commercial revenues, but we don't expect those to be huge in Q4. But we do expect them to ramp into 2025 as those 15 patients come through in Q1 or the majority of those come through in Q1 and Q2 and then subsequently. And I think the other thing to note is that we've currently got nine ATCs up and running. accepting referrals. And we expect that to continue to escalate as well to get to the full network of approximately 30 plus or minus by the end of next year. So as that ramps as well, patients' access to T-cell or through the expanding treatment centers will be increased. So all of that together, I think, makes us really confident about the shape of the funnel of eligible and potentially eligible patients, and that that will continue to grow and come through as we look at the patient flow into 2025. And we therefore feel quite confident the patients are there and quite confident in both the revenues coming through in 2025 and, of course, ultimately of the peak sales of the sarcoma franchise. which is driven off essentially the same funnel and process.

Okay, very helpful. And then maybe just on the decision around Surpass 3, can you maybe speak to the data that's evolved in there and just maybe how much of this decision was driven by the data evolving in a way that was a bit different than what led you to start Surpass 3 in the first place, the prior data that led into it, versus... you know, just the kind of treatment landscape and ovarian just being kind of in flux?

Yeah, so I think the way we thought about that decision was we looked at the entire portfolio and we looked at it from a capital allocation perspective. And what you've got if you look at that is you look at a sarcoma franchise that has, you know, capital requirements but is, super close to being commercially real for us and produce producing sales one product on the market one product with these latest data with a clear route through and the sort of hugely synergistic commercial front end on that and and that that seems that seems a very high return on invested capital and at the other extreme of the pipeline you've got a a couple of opportunities in CD70 and PRAME that are absolutely enormous upside. So despite the fact that they're early and have, you know, some capital requirements, more limited capital requirements over the next few years, there's a massive potential opportunity in both of those. And then we have UserCell. And UserCell, obviously, we did the partnership with Galapagos, which we feel really good about. And we have ovarian cancer remaining. So we looked at the requirements and the investment requirements over the next few years for UserCell, where we've got to effectively qualify an entire manufacturing process, et cetera, and get a BLA file for what will ultimately be a single indication, because all the other indications have the potential to go on to Galapagos' platform. And that just didn't stack up relative to the other opportunities, so it's really a purely a purely capital allocation portfolio prioritization decision for us as opposed to either, you know, we still believe very strongly in the CD8 next generation construct as evidenced by the push that we have with Galapagos to put it on their platform. And we also, I think, still are confident that the user cell is producing meaningful responses in patients, but from a total capital allocation and portfolio prioritization perspective, it just didn't make the cut.

Okay. Thank you.

The next question is from Tony Butler with Rodman and Renshaw. Please go ahead.

Thanks very much. Adrian, a few questions. I'll ask them all if I could because some are connected The first is around Leticel. And it's a question around bridging studies that may need to occur. What's the risk to that? And how does that apply to CMC? And importantly, would you anticipate the cost of goods of Leticel to be higher or the same as that for a Famicel? And then finally, back to Usacel. I wondered if, in fact, you simply go to Galapagos and offer them whatever data you have and for ovarian cancer, platinum resistant ovarian cancer, and that could be, you know, in lieu of some capital that comes back your way. Thanks very much.

Thanks, Tony. So, with respect to Leticel, So we are going to, we have a commercial process for Leticel that was established by GSK and the Ignite ESO trial, the 64 patients that I referred to were all manufactured with that commercial process. That process was conducted by Milteni Biotech and we plan on going to market with Milteni Biotech's process manufactured at the same site that was manufactured for a lot of the NETICEL patients in that pivotal trial. And as such, whilst we will need to conduct normal validation work that was not conducted by GSK in the run-up to the BLA, we don't anticipate that we're changing manufacturing sites in order to go to market on that. So that's one element of de-risking. With respect to the cost of goods, I think we'd say two things. One, there isn't a meaning, there isn't a massive difference between the cost of goods we anticipate for Leticel and for T-Celera. And we would just point to the previous guidance of 70% cost margin at peak sales as sort of how we think about that for the sarcoma franchise. But it doesn't differ dramatically for Leticel and T-Celera. With respect to UserCell, I wouldn't want to prejudge. It is worth pointing out, though, that the approach that we took with Galapagos was that the proof of concept trial that we're doing with UserCell on the Galapagos distributed manufacturing platform is in head and neck. They then have the opportunity to option a range of other indications up to and including all indications associated with UserCell on their platform. And I wouldn't want to judge what other discussions might happen with respect to the UserCell data.

Thank you.

Thanks, Danny.

The next question is from Michael Schmidt with Guggenheim. Please go ahead.

Hi, this is Paul. I'm for Michael. Thanks for taking our questions and for all the details on the launch. I have a couple of follow-ups on the apheresis. First, have there been patients who have been confirmed double positive so far but opted not to receive apheresis for whatever reason and left the patient journey? And then what's your sort of baseline expectation for conversion rate of getting a patient who does test positive for both HLA and MAGE to that apheresis step? And then secondly, you know, you mentioned one patient has been in the third quarter. Has there been any additional progress here or patients near that stage in the fourth quarter, given that we're about halfway through the quarter?

Thanks. So, with respect to the patient sort of conversion rate and what we would anticipate, and to the question about whether there are patients who have not opted to move forward with T-Celera. I think it's just way too early for us to be able to put metrics on that. The one thing I think I would say, though, is just to put it in context, there's some variation in obviously in the timing of when patients get tested in their journey. And we will be pushing in order to get patients tested as early as possible. In some cases, way before they're actually eligible for T-Celera, which requires prior chemotherapy. But it would be very useful to know for those patients whether they would be eligible when, as invariably happens, the chemotherapy ceases to work. So, we'll be pushing that to be early. So, I think the discussion on where the patients are moving forward into T-cell rate is too early and we haven't really got good data on the timings and the flow of those patients. It is worth pointing out, though, that T-cell rate is just so much better than the standard of care. that our assumption is that the majority of those patients who would be tested in double positive will at some point move forward into being treated with T-cellular. It just may take a little time. But we do anticipate the majority of those 15 patients to move forward in the first two quarters of next year and be treated in the first two quarters of next year. And with respect to the apheresis, we have one apheresis to date. So, we have lots of other patients at various stages of the pipeline, but that one apheresis was as at this point in time. Great. Thanks very much. Thank you.

The next question is from Jonathan Chang with the Rink Partners. Please go ahead.

Hi, this is Yander Lee for Jonathan Chang. Thanks for taking my questions. So first question, I have a follow-up on the SURPASS-3 study. Can you comment on the accrual rate for ovarian cancer patients in this study? And did this factor into your decision to discontinue enrollment? And additionally, when can we expect the data from the patients who already enrolled? Will the timeline for 2026 data readout still be the same?

Thank you. So, in terms of accrual rates, actually that trial was accruing reasonably well in 2024. We'd previously planned on the interim analysis in 2025. That interim analysis would be on the basis of 13 patients. First interim analysis is based on 13 patients per arm of that study, so 26 patients in total. And I think we were on track to be able to do that. We will probably release the data that we have accumulated at some point over the course of the next 12 months when it's reasonable and meaningful to do so. But we are terminating that, so we won't have the full data set that we were previously considering in 2026.

Understood. Thank you. So I have another follow-up question. So you mentioned that the pre-concord development for PRIM and CD70 is ongoing. And how will these two early stage programs be impacted by the headcount reduction and the cost-saving plan you just announced? Thank you.

Yes, so we will be focusing the headcount, the resources that we have in the early phase pipeline on those two programs and moving them as quickly as we can into the clinic. And we anticipate IND for PRAME now next year and CD70 following that. So I think that will become the key focus for our teams in the early stage, our research and early development teams.

Understood. Thanks for taking the question. Thank you.

The next question is from Craig Sivanovich with Mizohu Securities. Please go ahead.

Hey, good afternoon. Thanks for taking my questions, and congrats on the great data for NYE. So I've got three questions, if I could. Just first, I think I heard Adi say this earlier in the call, but can you just remind us on when There is a time in the future where Letticelle is perhaps on the market. How you would think about the shape of the uptake or trajectory curve vis-a-vis what you are currently anticipating for T-CellRest, so just comparing and contrasting kind of a view of revenue trajectories for each of those products. That's the first question. Then second question, just on the cost savings. any color around how to think about the splits between SG&A and R&D in terms of those cost savings. And then lastly, just on the PREM opportunity, you know, really interesting target. I think we've seen a little bit of mixed success thus far in terms of targeting PREM, because just maybe remind me how you are viewing your level of confidence in either the target itself or perhaps the constructs that you're advancing to get, you know, optimal efficacy and safety. Thank you.

Thanks, Greg. So I'll take questions one and three and then I'll ask Gavin to comment on the split of the cost savings. So in terms of the shape of the uptake curve, I think there's one element that will be the same that's driving that, and then there's one element that we think will be quite different. So the element that will be the same is that the process of testing a patient, aphorising a patient, manufacturing a patient, the negotiations with the insurance company, and then returning that. We think that will be roughly the same for both for T-cell and for letter cell when it comes to market. But the thing that will be quite different is that by the time we have Leticel approved, we will have stood up the full network of approximately 30 ATCs. for a famicel. And so therefore we anticipate that we'll be able to engage and have many, many more of those sites active from day one for Leticel than the current ramp for a famicel, which we're very happy with at nine so far and on our way route to 30. But you can clearly see that if we could go through the full 30 from day one, which we will be able to do, we believe with Leticel, That would be a significant advantage. And that would translate into a faster uptake relative to T-cell rot. With respect to PRAME, we feel that PRAME is a fantastic target for us doing what we do, engineered TCR T-cells. There probably is not a broader, more broadly expressed cancer testes antigen out there. And the data that we see where people targeting it seems to demonstrate that PRAME is a good target. And I think the cell therapy data that we've seen, I think, gives clear indications that it's possible to see substantial and prolonged responses in the melanoma space, in particular And we think that that bodes very well for cell therapy treatments that target PRAME. And we think this sort of demonstrates as well why cell therapy has the potential to be the gold standard of efficacy for targeting these types of targets versus bispecifics or other types of targeting. With respect to why we are so confident about our our program, we think we're very good at designing T cell receptors. We've made, this has been our life's mission. And we have taken everything we know about designing T cell receptors to be able to engage T cells to target cancer. And we've put that into our program into ADP600. And we have a, we've previously shown, a very highly sensitive TCR. And we believe that this will drive, based on all of our knowledge about how these things work and all the experience with MAI-J4, we believe this will drive a clinical benefit in patients and will potentially also drive the ability to target at concentrations that are exhibited across a much broader range of tumor types than currently current therapies are showing efficacy. And so that's why we believe that there's an opportunity for a best-in-class program, particularly when you then combine that with next-generation approaches and other engineering to further enhance the program. And then the last thing I'll say is there are really two Maybe there's a couple of others in preclinical development as well. But a very small number of PRAME cell therapies that are credible programs moving forward into development. And for such a huge potential target, a massive unmet medical need, we feel this space is wide open relative to almost any other target out there. So we're quite excited about the opportunity to put ADP600 into the clinic next year.

Gavin.

Yeah. Hi, Greg. So in terms of the $50 to $60 million worth of savings we expect next year in 2025, the split of those savings is roughly 60-40 R&D to SG&A. As we look at a little bit further, as we think about the $300 million worth of savings we anticipate over the next four years, actually the split is probably slightly more heavily biased in the out years to R&D. And that's because we continue to invest behind the commercial team and the success of bringing T-cellar and SSL to market. Thank you. Thanks, Greg.

I'm sorry. The next question is from Arthur Hugh with HC Wainwright. Please go ahead.

Hey, good afternoon, Adam's team. So I had two quick questions. So one is, during the screening for the MAGA4 and HLA type for the semi-cell, so how's the rate you guys see the real-world screening versus the previous guide at 1740?

Yeah. So, I'm going to start by saying impossible to tell at the moment, and then I'll explain a little bit why. So, the HLA test that we developed is, there's nothing particularly special about it, and there are many, many ways of testing for HLA. And indeed, we anticipate that sites will use a wide range of HLA tests. And the uptake on our HLA test indicates that they are indeed using a wide range of HLA tests. So we don't get to see the vast majority of the HLA testing that gets done. But given that the HLA prevalence has been sort of relatively well characterized, including in our clinical trials, which were, after all, conducted at almost exactly the centers that we're going into, we feel reasonably confident about the 40% to 45% range that we've put out there before and don't really see any reason why it would be different. On the MAI-J4 testing, we have had significant uptake of our test. However, I don't think that the rate there is quite high at the moment. And we anticipate that that's actually because maybe some of the patients coming into that MAEJ4 testing have previously been tested with MAEJ4 and found to be positive, but they want it confirmed with our IHC diagnostic. And so I don't think we're really in a position at the moment where we have sufficient data and sufficient time to be able to confirm or deviate from the previous estimates, which, you know, I will point out those previous estimates were conducted on pretty decently sized populations during the clinical trial. So I'm not sure we would anticipate much deviation from that anyway.

Got you. Thanks for that, Colin. Very helpful. And my second question is regarding the lettuce cell data. I noticed that for the synovial sarcoma for lettuce cell, the duration of response is about more than 18 months. It's significantly higher than the semi-cell. Is there a reason or we can figure or in terms of patient baseline or something else you guys can tell us more color on that?

So I'm going to answer that very briefly, and then I'm going to ask Dennis Williams to comment on that. So my brief answer would be that I think those data are somewhat immature. The duration of response is great. It's worth noting that in the Lancet article the duration of response was about 12 months based on that data cut. The median duration of response numbers are quite volatile when you're dealing with relatively small numbers of patients, but we're very pleased that we have 18 months at this data cut, and we look forward to presenting that data for the BLA. Dennis, do you have additional color you could provide on that?

Hello? Well, I would say that there's sort of, in some ways, comparing apples to oranges. I mean, it's difficult to compare in duration of responses, particularly a subpopulation in Ignite ESO, to another trial. I would say in both cases, the median duration of response is very impressive. It's very different looking than you would typically see for available second-line therapies. But I expect when CTAS, when the data gets presented this weekend, there'll be some discussion around that, and I would love to hear what the scientific community thinks about it.

All right. Thank you for taking my question. Thanks.

The next question is from Yanan Zhu with Wells Fargo. Please go ahead.

Hi. Thanks for taking our questions. This is for Yanan. So our question is around what are the remaining items need to be done before you can file the rolling BOA, start the rolling BOA?

Thank you. Three things that we need to get the BLA, one, clinical data, positive clinical data from the pivotal trial, which we now have the full primary analysis of, and so we'll be rolling forward to file that as the first part of the rolling BLA. Secondly, the CMC parts of that, of the file, which we will be working to, analyze that, validate that process, et cetera, and be able to file the Module 3 of the BLA in due course. And then lastly, I think you've got to remember that we are going to be having a parallel file with the NYISO diagnostic, so we're working already with a partner to be able to develop and then have that diagnostic registered. And those are the principal components that will go into the approval package for Leticel.

Got it. Thank you for that. And assuming a patient is eligible for both E-Celera and Leticel, how do you think a patient would choose between these therapies? And is there a possibility of sequential dosing of these two therapies? Thank you.

Yeah, really good question. So, the MAEJ4 and NY-ESO are both significantly expressed in synovial sarcoma patients. Both have fairly high levels of expression. It's worth pointing out that the MR-CLS population NY-ESO is very, very highly expressed in that population. And obviously, we don't have an indication for that for T-cell at this point. And so, that would be entirely additive sales. For synovial sarcoma, I just mentioned that the sales projections that we've put forward assume that only the NY-ESO positive MAEJ4 negative patients would be treated with Leticel. And so it's entirely based on incremental patients. And it's therefore, as you pointed out, maybe a little conservative because there's a bunch of patients who are dual positive and a significant proportion. And there is the opportunity maybe in due course for sequential treatment as people build familiarity with that and as data comes out on on patients that have been, that have received both of these therapies or sequential treatment with MYESO and MAEJ4 targeting cell therapies. And in terms of how patients will choose, I think that sort of remains to be determined, how patients and physicians will choose. Obviously, we anticipate that potentially target expression will play a part. but also physician and physician familiarity with the treatments. And ultimately, I think what is clear is that we are launching two therapies into this patient population who currently have no options. And therefore, for eligible patients, treatment with one or more of one or both of these is going to be transformative for them compared to the existing second-line treatment options. And so, you know, that I think means that this just means that there's an opportunity here to provide cell therapies to more patients with synovial sarcoma and now MR-CLS.

Thank you for all the callers. Thank you.

The next question is from George Farmer with Scotiabank. Please go ahead.

Hi. Thanks for taking my questions. A couple from me. You know, I actually just get on the topic of double positive synovial sarcoma. You know, according to the FAMSA label, it looks like the duration of response is six months. You're seeing 18 months of lettuce cells. Shouldn't the choice be obvious about which cell therapy one may want to select?

So, I think you've got to, to Dennis's point that Dennis mentioned, I think the duration of response of six months for T-cellerate in the label, slightly different to the data set that was published in the Lancet, which had 12 months. That was down to the fact that there were a couple of patients included in the FDA's data analysis, a couple of responders that had shorter duration of responses that were incremental to the data that was in the Lancet. I think that shows you the variability of the median duration of response data. What is clear is that for Leticel and for Famicel, about 40 plus percent of patients had durations of responses that were more than a year. And so, there's some very fine lines that are being dealt with here. And I think that would be a factor to consider, but I'm not sure that that would be the only factor to consider as patients make that choice. And if it is, if they do choose that they would like T-Cellera, then that's great. And does not change our overall sales projections for our sarcoma franchise because whether they get a famosa to sell or letty cell we still benefit from The sale and that patient still benefits from an adapt immune cell therapy for this rare disease Okay Yes, it does thank you and also You know the ASCO presentation

earlier this year, there was a single grade five adverse event. Have you seen any since then in this expanded safety analysis? Dennis, do you want to comment on that?

No, that's correct. There was a one grade five T cell related event, and that will be discussed at the presentation this weekend.

So there were additional grade five adverse events? over and above what was presented at ASCO?

There has not been new Grade 5 events since ASCO.

Okay. That's great to hear. And then finally, in this restructuring process, is there any impact on current executives?

So we are still working through the impact on the organization, and we'll communicate that when those decisions are taken.

Okay. Great. Thanks very much.

The next question is from Michael Kim with Zaks Small Cap Research. Please go ahead.

Hey, everyone. Good afternoon and thanks for taking my questions. First, in terms of the increased confidence in reaching 400 million in peak sales, peak year sales for the sarcoma franchise, I know you talked about the early success you're seeing with Teselra as well as the strong results coming out of the Let It Sell pivotal trial, but anything beyond that that is maybe driving higher conviction in that number? And then related to that, any shift in the timeline for hitting peak sales as part of that step up in confidence?

So I think, I mean, we started the year guiding the 400 million peak year sales number, I think all that's happened since then has just increased that confidence. So, walking through, we got T-Cellera approved, you know, the first engineered cell therapy for a solid tumor, by no means a given in the marketplace. And the launch of that is going really well. The discussion about, well, how many patients are there, are the patients there, I think have been thoroughly, our view has been thoroughly vindicated by our experience in the screening and testing process in the first period of time. So the fact that we have now sitting here 15 double positive patients and a further 25 at some stages of testing at least, given that we don't see all of the testing that's ongoing, That's just what we can see. I think it gives us really good confidence in the sales uptake for T-Celra. And also, I think, helps validate our underlying assumptions about the incidence prevalence rate. Not exactly. We can't be super precise on it. But I think it helps give us confidence that the patients are there and that they are flowing through the system and that they are addressable by us. And then the data at CTOS, I think, just confirms the efficacy profile that you can anticipate in these rare sarcomas from cell therapy. And just as note, the fact that this data has continued to improve as we go through the clinical trial. from the first interim readout, the second interim readout, and now the final, the primary analysis data set, I think just says that this is a building confidence in the efficacy profile. And the relationship to the 400 million, I think, is also the fact that the efficacy profile in MR-CLS is very similar to the efficacy profile in synovial sarcoma with a more than 40% response rate and really strong durability. And obviously, that's key because the MR-CLS population is an important addition in order to get to the 400 million sales. So all of that together, I think, adds up to that increasing confidence.

Got it. That's very helpful. Appreciate that. And then maybe just to follow up on the capital front, I know you mentioned drawing down on the $25 million tranche as it relates to the loan with Hercules. But can you just update us on where things stand as it relates to the other tranches that are, I think, built into that agreement?

Yeah. Happy to. Gavin, do you want to touch on that?

Yeah, so there's further three tranches that should drawable, $5 million, which is drawable on certain criteria associated with famicel and Leticel, $30 million on approval of Leticel, and then $40 million on terms to be decided between both parties.

Got it. Okay. I appreciate that. Thanks for taking my questions.

Thank you. You're welcome.

The next question is from Peter Lawson with Barclays. Please go ahead.

Peter Lawson Great. Thanks so much. I guess a couple of quick questions. When do you expect the next patient to be A4Es? And then with current cash and the loan, what's your projection for the cash runway?

Dr. Peter Lawson I think the answer to that is soon. First question is will be soon. But, you know, and we anticipate that those patients that are currently double positive to start flowing through 2024 through the ordering process and into 2025. And I think that's really underlying our confidence in the ramp of sales as we go through 2025. What, in terms of cash runway guidance, I think We closed the quarter with $186 million in liquidity. We have announced the restructuring and the cash impact, the impact on the expenditure next year relative to our guidance in 2024. And I think it's important to remember that as of the last Q call, we stopped providing forward cash runway guidance and the principal reason for that was because smart people like yourself, Peter, could easily calculate from our expenses base and runway guidance what our forward sales projections were and we are not interested in giving forward sales projections until we have significantly more experience under our belt. sometime probably next year, late next year sometime. So because of that, we're not providing cash runway guidance, but we have 186 million in liquidity and a restructuring program that is designed to shape our P&L and get us to cash flow break even on an operating level in 2027.

Thank you. And you think you'll provide revenue guidance next year?

I think once we've got a few quarters of sales under our belt, I think that's when we'll be able to be more useful to you in providing forward-looking guidance.

Okay. Thanks so much.

This concludes the question and answer session. I'd like to turn the conference back over to Adrian Rockliffe for closing remarks.

Thank you ever so much for joining us to hear about the launch of T-Celera and the great progress there and the data from the Leticel Ignite ESO Pivotal Trial and the restructuring that will enable us to deliver a profitable sarcoma franchise and cash flow break even in 2027. Look forward to updating you in due course as we execute on these things. Thanks for your time.