Adaptimmune Therapeutics plc

Good morning, ladies and gentlemen, and welcome to the Adaptimmune Q1 2024 Financial and Business Update Conference Call. I would now like to turn the meeting over to Ms. Julie Miller. Please go ahead, Ms. Miller.

Good morning, and welcome to our conference call to discuss our first 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 Brockliff, our Chief Executive Officer, is here with me for the prepared portion of the call, and other members of our management team will be available for Q&A. With that, I'll turn the call over to Adrian. Ad?

Thanks, Judy. Thanks, everyone, for joining us for our Q1 call. I plan to provide Some brief comments before we go into Q&A. The comments are going to be brief because a couple of weeks ago we held an investor day, and we provided a fairly comprehensive update on the regulatory status of Afamacel as we move towards the PDUFA date of the 4th of August. And we also talked about how important this is for the field as the first approved engineered TCR T-cell therapy for a solid tumor indication. We also discussed our preparations for the commercial launch of Afamacel in some detail. We said that we'd be ready to do this on approval of Afamacel and that this would be the beginning of a commercial sarcoma franchise that we feel has significant and underappreciated value. In this morning's press release, we provided a further update on the BLA progress. And our head of late-stage development, Dennis Williams, is here for the Q&A portion of this call. In short, our interactions with the FDA are progressing as planned, and we're looking forward to our late-cycle review meeting in the second half of this month. Thus far, the FDA has not requested an ADCOM or a REMS program. We look forward to the labeling discussions and also to commercialization in due course. And I'm happy to confirm that our customer facing commercial and med affairs team are now fully in place. Cynthia Pacina, our chief commercial officer, is here for the Q&A as well. As I said, we are on track to be ready to launch on approval. We have a focused team starting at six to 10 treatment centers and ramping up to approximately 30 in due course. And if you revisit the Investor Day presentation by Dr. Mihaela Druta, which is available on our website, you will see that the expectations and anticipation for a famicel within the sarcoma community are very high. I think that sense of anticipation was reinforced by Philip Leder, patient advocate and president of the Sarcoma Alliance, who lost his sister to sarcoma. And he, I think, very eloquently highlighted the demand for novel therapies in this space. So we are scaling our manufacturing to be able to meet what we anticipate to be the launch volumes for Afamacel in the second half of 2024. And in summary, all is on track for the launch of Afamacel on approval. And that's expected around our PDUFA date in August and is highly anticipated by the sarcoma community. And obviously, we are very eager to get this product into the hands of this community that has worked so hard with us over the last decade to develop medicines for sarcoma. Behind the Famicel, we are also progressing the development of Leticel, and I'll point you towards a presentation of the interim data analysis from the pivotal IGNI ESO trial in synovial sarcoma and MR-CLS that we previewed at a high level last year. These data look very similar to a famicel, other than, of course, they are in both synovial sarcoma and myxoid rounds of liposarcoma, and will be presented at a platform presentation at ASCO by Dr. Sandra DeAngelo. This will be an important milestone for people's understanding and the de-risking of this cell therapy as we continue to move towards having a BLA in place in 2025 with anticipated approval for Leticel in synovial sarcoma and MR-CLS in 2026. You'll have seen another press release from us this morning announcing that we've secured up to $125 million in debt financing with Hercules Capital, with the first tranche of $25 million available on closing and an additional $25 million available on Famicel approval. In addition, you will have seen that in Q1, we raised approximately $30 million off the ATM based on significant inbound inquiries. We've taken these steps to secure our financial position and have cash runway into late 2025. And with this runway, we have the funds necessary to execute on our priorities. The launch of Afamacel, followed by Leticel, and also executing on the other pipeline projects, such as the Phase II trial with user cell for platinum-resistant ovarian cancer. And Gavin Wood, our chief financial officer, is here for the Q&A as well. So with that, I'd like to turn it over to the operator for questions. Operator?

Thank you. We will now take questions from the telephone lines. If you have a question, please press star 1 on your device's keypad. You may cancel your question at any time by pressing star 2. Please press star 1 at this time if you have a question. There will be a brief pause while participants register for questions. We thank you for your patience. Our first question is from Jonathan Chang from Lering Partners. Please go ahead.

Hi, guys. Thanks for taking my questions. First question. Can you talk about the impact of the debt agreement announced today on your cash runway guidance? I'm just trying to better understand what's assumed in the current guidance.

So, Gavin?

Yeah, hi, Jonathan. So, a number of things have changed since we last gave guidance at the start of the year. Clearly, we had the termination of the Genentech agreement, and we're still working through the terms of that termination agreement. We've made significant progress on at Famicel and at the broader development of the broader sarcoma franchise. As Ad just mentioned, we've raised money under the ATM, and we've also executed a new debt facility at Hercules. Putting all those moving pieces together, we thought it prudent to bring in our cash runway by about a quarter to late 2025. Got it.

And what assumptions are there for how much of the debt is being drawn down.

We drew down 25 at close, 25 million at close, and there's 25 million available at the PDUFA date.

Got it. And then second question, just can you help set expectations for the upcoming ASCO Ignite EZO presentation? Thank you.

Dennis, do you want to say that? Yeah, sure. So for the ASCO presentation, we're going to be presenting results on the interim analysis of the Pivotal IGNITE ESO trial. So this is 45 patients in that trial, followed for at least six months. It's evenly comprised of patients with synovial sarcoma and myxoid round cell lapar sarcoma. So we'll present the efficacy data and safety data that were available at that interim analysis.

Got it. Thanks for taking my questions.

Thank you. Our following question is from Mark Fromm from TD Cohen. Please go ahead.

Thanks for taking my questions. First, it's nice that you're giving these details along the way of the FDA review and the late cycle review meeting coming up. Can you review what your closure strategy is going to be around some of the information that may be or gleaned by you guys at that meeting.

So, why don't I take a stab at that? So, we're actually running pretty hard towards both the late cycle review meeting and the discussions on labeling that we anticipate and on post-marketing commitment. You know, we're going to be focused on that in the run-up to the PDUFA date. And I think if there's anything material that comes out from that, we will be disclosing. Otherwise, we're pushing hard for the discussions with the agency and getting to PDUFA and then being able to launch.

Okay. And then as you get into the . I mean, what do you view as the kind major kind of questions that need to be answered about, you know, indications and things like that, and things to include or not include in the label.

Dennis Williams Yeah. So, hi. This is Dennis Williams. I think it's like I mentioned at the Investor Day, some of this really comes down to individual sort of wording that goes in the label. Like, for example, I'll give the follow-up on the example I gave at Investor Day, how we manage static high-release syndrome, right? about how that information should be structured in the label, how we give tocilizumab, or how we would recommend that product, and for what grade CRS. So sometimes it's really about the finer points of how the words are in the label. We have had no discussions to date with the FDA around the indication statement, and we feel very confident that the indication statement we proposed is more or less a few words is what we're going to end up with at the end of this review. Okay, thanks. Very helpful.

Thank you. Our following question is from Tony Butler from Rodman and Renshaw. Please go ahead.

Yes, good morning. I'm very respectful of the focus on FAMASEL and to a lesser extent on LETI, but I wanted to ask about USASEL and whether or not, at least in the calendar year, there was any anticipation of a follow-up on the past three either in ovarian or in the phase one with bladder, et cetera. Thanks very much.

So, why don't I cover that with what we're thinking about for user cell. With the past three in platinum resistant ovarian cancer, That's designed with the potential to end up as a registrational trial, and therefore, we won't be putting out any data on that until we have at least enrolled all of the patients in that trial. There are interim reads for futility analysis, but we won't be communicating the data until we've at least enrolled all of the patients in that trial, which we anticipate being a 2025 event, full enrollment of that trial. So with respect to the other indications, so we've now focused down onto ovarian cancer in SPAS3 and the two other indications in head and neck and bladder. And the objective is to gather data in a phase one setting. in a range of patients potentially in combination with checkpoint inhibitors as well. And what we've said there is we anticipate giving an update on the basis of the data that we've gathered at the tail end of this year about how we anticipate moving forward with those, which would include the data themselves.

Thanks very much.

Cheers, Tony.

Thank you. Our following question is from Craig from Mizuho Securities. Please go ahead.

Good morning. Thanks for taking my question, and congrats on all the progress. I just wanted to go back to the FDA review process, and in particular, also in light of the great analyst or investor that you had down in Philly, Just curious if there have been any other perhaps progress or maybe any additional inspections by FDA on the manufacturing facilities. Do you expect any other visits prior to approval? Just wanted to get a better handle on how things were shaping up there as it related to, you know, CMC manufacturing and your facilities.

Yep. Hi. This is Dennis Williams again. So, yes, I think at this point all the inspections are expected to be completed, right? So, we, both manufacturing facilities that we utilize, so our own manufacturing for a famicel drug product, the lentiviral manufacturing facility that we, for the vector that supplies for drug product has been inspected, that's had a good outcome. And all the clinical trial sites that were inspected also are completed. they all had a very good outcome. And as I mentioned during Investor Day, the AVR facility here from a GCP standpoint was also inspected. So at this point, we think all the inspections are complete. I guess there's always a scenario where another clinical site could be inspected, but at this point, I think at this stage in the review, the inspections are completed.

Okay, thank you for that clarity. And just with regards to earlier comments about not anticipating or not expecting perhaps an ADCOM or a REMS program, maybe just on the latter with regards to a REMS. Just from a calendar perspective, is this something that a discussion would naturally have happened by now, or is it still part of a potential discussion between now and the PDUFA? Thank you.

Yep, sure. So, we did not submit a REMS in this. BLA application, and we've had discussions with the FDA during the review. And I think at the time I had this discussion at Investor Day, the FDA review was ongoing, and there was no decision about a REMS at that time, and they certainly had not asked for one at that time. You're correct that had a REMS been requested, that time would have elapsed already. That would have occurred within the few weeks of that mid-cycle meeting. I can just say, in general, the conversations we've had with the FDA, we don't anticipate a REMS for this product.

Okay, thank you. And maybe just the last question, if I could, just if you could remind us all, assuming an on-time approval, how we should be thinking about the shape of the uptake curve, particularly from a revenue perspective.

So, why don't I touch on that, which is the, what we're basically guided to is that we've not given guidance on the specific numbers of patients that we anticipate coming through in the early part of the launch. And what we have said is that it's important to understand that because this is an autologous product that's manufactured, it needs to be screened for targets and then manufactured and then returned to patients. Whatever you think that uptake curve looks like, it's essentially frame shifted by, and we're guiding to, about a quarter from, so the first revenues from a FAMSAO the first patients would not be dosed, treated, and the first revenues recognized until Q4 this year, even though we anticipate approval and we anticipate starting to enroll patients from the PDUPA date in August.

Okay. Thank you.

Thank you.

Thank you. Our following question is from Michael Schmidt. from Guggenheim. Please go ahead.

Hi, this is Paul. I'm for Michael. Thanks for taking our question. So on the FMSA launch, you talked about targeting about six to ten sites for that early launch. But looking beyond this year, what's your current thinking on strategy for scaling up to all 30 ATCs across the country, and how many of those centers have had experience with FMSA in the clinical trial setting?

I'll ask Cynthia to talk to that, Cynthia.

Thank you. Yes, so we are, as Adrian said, we are targeting about six to ten sites during the launch period, meaning the first quarter after launch, and we are already starting to engage beyond those with the expectation to have up to the 30 sites available about 18 months after launch. Out of these 30 sites in total, 16 of them, which will be the priority sites, have clinical experience with Afamicel. And some additional sites that are part of the 30 also have experience with Leticel. So all of our 30 ATCs in the future, all of our clinical sites from Leticel and Afamicel will be part of those sites. And again, we know that those sites see the majority of the synovial sarcoma patients in the country.

Great. Thanks for that. And maybe just to follow up, as you look ahead to the launch, can you give a sense of what kind of metrics you're planning to sort of disclose in the early months to give a sense of how that launch is progressing? This has been an area of focus for the MTAG-B launch for our advance, so just curious if we can expect updates on, you know, number of patients identified versus infused, or if you're likely to provide more qualitative updates in the early months. Thank you.

So we plan on updating that at our next Q call.

Gotcha. Thanks so much. No problem. Thank you.

Thank you. Our following question is from Archer He from H.C. Rainwright. Please go ahead.

Hi, Ed and team. Thanks for taking my question. I guess I just had a broad picture question. So, as we see the sterile therapy industry moving to the autoimmune disease area, could you help educate us the potential from your platform aiming for the autoimmune disease? I know you guys are laser-focused on the launch, but I'm just curious on the potential there. Thanks.

Sure. So, as you've said, we are laser-focused on the launch. We have, if you dig into the history of the company long enough, we have explored the opportunity to develop TCR-targeted therapies for autoimmune disease, mostly focused on Treg programs. But I think in the short term, our focus is on, obviously, the launch of AfamSR and the sarcoma franchise. But also, in between that and the very long-term future in autoimmune and maybe other indications, just the massive unmet need that can be addressed with TCR T-cell therapies in the oncology space. And if you look at the rest of our pipeline, you'll see that as we, over the coming years, we will very quickly move from a sarcoma-only franchise with two products and 400 million of sales into much larger patient populations. And there's an opportunity with user cell in, obviously, ovarian, bladder, and head and neck. And then beyond that, with PRAME, given the recent interesting data with that target, and with CD70, both of which are in the late preclinical pipeline. And the opportunity there to address over 100,000 patients that are currently dying from their indications with the right target and the right HLA type. And so we see this in terms of horizons, short-term sarcoma, longer-term, broaden that out, making cell therapies potentially curative and mainstream across a broad range of tumors, and then taking cell therapies into other spaces where patients could benefit in other non-oncology indications in the long term. Thanks for the call.

Thank you. Our last question is from Peter Lawson from Barclays. Please go ahead. Mr. Lawson, your line is open. You may proceed with your question.

Great. Thank you so much. Thanks for taking my question, and thanks for the update. I wanted you to talk around the turnaround time, kind of time it would take between kind of approval, booking the initial revenues, as we can just think about the turnaround time, your end, also the turnaround time with the hospitals and the patients, and just any variables that we should be thinking about. Cynthia, do you want to talk to that?

Yes, absolutely. Yeah, so when we think about the turnaround time from the patient journey perspective, we need to consider that the patients, when they are identified, the first step is that they need to be tested for HLA in May J4, which is a process that can take a few days. Then we go through the aphoresis process, scheduling aphoresis, And then when we receive the aphresis material from a manufacturing turnaround time, then that would be of about 30 days, and then shipping it back to the sites. So that's why at launch, the companion diagnostic test will be approved at the same time, that's our expectation, at the same time that a family cell is approved. So we would expect to see, as Adrian mentioned before, first patients dosed during the fourth quarter of the year.

Okay, thank you. And then after the patients identified and the apheresis, what's the general timeline you expect around that? I imagine there's a fair amount of variability.

Yeah, hi, this is John. I'm leading manufacturing. So the turnaround time from Typical time from the collection of the apheresis material until the release of the product to send it back to the site tends to range between four and six weeks.

Okay. Are there things we should be thinking about the front end and the back end that are outside your control and kind of the sense you get how long it takes patients to kind of get through that funnel from being identified by the diagnostic test for HLA? and then the other end once it gets to the hospital and actually gets infused.

Yes, so a couple of things to consider before will be patient identification, the testing, then depending on where these patients are, they will have to be referred to a treatment center that can take a few days. Reimbursement is also something that will be checked at that very early part of the journey. Then from aphoresis all the way back to infusion, it's mostly straightforward. We could have potentially the patient condition getting worse or other things that are out of control, but then it's mostly a little bit more straightforward.

Okay. Just, I guess, a final question just around the surpassed data. I guess it's later this year we get head, neck, and bladder. Just to around the number of patients we should see and kind of what you regard as a positive coming out of those datasets.

Elliot?

Yeah, thanks. You know, we haven't guided to specific numbers that we would anticipate as it relates to patient dosing. We have said that we anticipate having sufficient data to make directional decisions regarding both of those indications by the end of the year. Great. Thanks so much. Thanks.

Thanks, Peter. Thank you. We have no further questions registered at this time. I would now like to turn the meeting over to Mr. Roklas.

So, thank you, everybody, for your time today. Thank you for your questions. Look forward to seeing those of you at ASCO who are attending, and look forward to updating you as we move towards approval and launch of our FAMASAL later on this year. Thanks a lot. Take care.

Thank you. The conference has now ended. Please disconnect your lines at this time, and we thank you for your participation.