Adaptimmune Therapeutics PLC (ADAP) 2023 Q2 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to the Adaptimmune's Q2 Financial and Business Update Conference Call. I would now like to turn the meeting over to Ms. Juli Miller. Please go ahead, Ms. Miller.

Good morning, and welcome to Adaptimmune's conference call to discuss our second quarter 2023 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 Rawcliffe, our Chief Executive Officer, is here with me for the prepared portion of the call. Other members of our management team will be available for Q&A.

With that, I'll turn the call over to Adrian Rawcliffe. Ad?

Thank you, Juli, and thanks, everyone, for joining us. In this morning's press release, we confirmed data and catalysts that we anticipate over the next 18 months. For the next few minutes, I want to highlight achievements from this past quarter with a particular focus on our top priority, the afami-cel BLA. Over the course of this year, Adaptimmune has made substantial progress towards filing a BLA for afami-cel for people with synovial sarcoma. When approved, this will be the first commercially available engineered T-cell therapy for a solid tumor indication.

We've already completed submission of the preclinical and clinical modules, and we've been working towards submission of the final CMC portion of this rolling BLA submission. We've made significant progress with the CMC module and its requirements, and we've taken full advantage of the opportunities for interaction with the FDA afforded by our RMAT designation.

In recent months, we've had 2 Type B interactions with the agency to derisk key areas of the file. The first was to gain alignment with the agency that the confirmatory evidence requirements to convert this file from accelerated approval to full approval would be met with data from Cohort 2 of the SPEARHEAD-1 trial. Cohort 2 has fully enrolled and will complete dosing shortly. Cohort 2 is trending similarly to Cohort 1, and we believe we'll have a mature data set from this cohort next year, which will support conversion to full approval.

The second Type B interaction with the FDA was to discuss our plans for cell release, including the parameters for our commercial potency assay. Again, we received very constructive feedback from the FDA, with confirmation of the adequacy of our data required for the BLA.

Recently, several other critical milestones have been completed. We've demonstrated comparability of afami-cel drug batches manufactured with clinical trial supply vector and commercial supply vector. In collaboration with Agilent, our companion diagnostic partner, we've completed submission to the FDA of the premarket application for the companion diagnostic. We've completed method validation for lot release assays, including the potency assay, and we've completed vector process performance qualification, or PPQ.

Looking forward, we have the following elements to complete to enable submission of the final CMC portion of the BLA.

We are close to completing T-cell PPQ and we'll shortly complete all remaining wet work, with the last few experiments set to finish in coming weeks. We will submit the vector comparability package to the FDA for review prior to submission of Module 3, which we previously agreed with the agency that will not delay overall submission. And finally, we will complete the write-up and review of all the sections for Module 3 of the submission.

We have updated our guidance to reflect that we now anticipate that the submission will complete in Q4 2023. We feel confident that we have substantially derisked the submission time line. We have alignment with the agency on key judgment areas and have completed the vast majority of the wet work associated with Module 3. We are set for a submission in 2023 and a potential approval in Q4 next year of the first engineered T-cell therapy for a solid tumor.

We also have the opportunity to treat even more people with sarcoma with the return of lete-cel from GSK later this year. As a reminder, lete-cel has been evaluated in the pivotal trial, IGNYTE-ESO, in synovial sarcoma and myxoid/round cell liposarcoma, and we anticipate data later this year. This could be another near-term commercial opportunity for Adaptimmune as well as an additional treatment for people with sarcoma.

Behind afami-cel and lete-cel, our pipeline continues to progress with the aim of delivering commercial cell therapies for people with cancer. We have initiated the Phase II registration-directed SURPASS trial in platinum-resistant ovarian cancer. This trial is recruiting patients into a monotherapy and a combination therapy arm with nivolumab, with enrollment ongoing through 2023 and 2024.

We have received RMAT designation for the treatment of platinum-resistant ovarian cancer on the basis of the excellent clinical response data from the Phase I SURPASS trial with ADP-A2M4CD8 in that setting. And we plan on taking full advantage of the opportunities offered by our RMAT designation to engage with the agency to advance this product to approval as quickly as possible.

Lastly, we have completed our strategic combination with TCR2 to form what we believe is the preeminent cell therapy company for solid tumors. Through this strategic combination, we've added 3 programs to our pipeline, along with platform technologies in TRuC, TCR T-cells and next-gen enhancements. We have retained almost 40 colleagues with critical capabilities and added $85 million to our total liquidity, confirming our cash runway into 2026.

In summary, our top priority is to launch our first commercial product, afami-cel, next year. The PDUFA clock will be based on successful filing of the BLA, and we've taken significant steps to derisk critical elements. Behind afami-cel, we have lete-cel, which is in the process of transitioning back from GSK and could offer another near-term commercial opportunity for the treatment of synovial sarcoma and MRCLS.

We have progressed our next-gen MAGE-A4 targeted products with the initiation of the registration-directed SURPASS-3 trial in platinum-resistant ovarian cancer, for which we also have RMAT designation. We have a deep pipeline, as outlined in this morning's press release, with numerous data catalysts over the next 18 months, and we look forward to updating across our pipeline on the basis of clinical data later this year.

Lastly, we're funded into 2026. And with that, I'd like to turn it back to Maude for questions. Operator?

(Operator Instructions) Our first question is from Michael Schmidt from Guggenheim Securities.

This is Kelsey on for Michael. I just had a few, mainly on ovarian cancer. I guess maybe for SURPASS-3, I guess what kind of efficacy profile do you think would ultimately be required to make A2M4CD8 a standard of care treatment option there? And then maybe building off of that from the TCR2 program, could you maybe set expectations for the gavo-cel data in ovarian cancer later this year? And maybe how we should think about responses compared to the Adaptimmune program? And maybe could you speak to the rate of co-expression for MAGE-A4 and mesothelin?

Okay. So I'm going to ask Dennis to talk about SURPASS-3 and the data that we have and our expectations for a profile on that, and then we'll come back to the questions on TCR2 after that. Dennis?

Yes. Thanks, Ad. In general, for accelerated approval for platinum-resistant ovarian cancer, one would desire to have response rates in the 30% to 40% range and those responses to be durable. What does durable mean? Somewhere in the 6-month range or longer would be the ideal durability. We clearly want to have a population where we have the opportunity to follow patients for durable responses, not dissimilar to what we've done previously for afami-cel.

And with respect to TCR2 and the gavo-cel data, Elliot, do you want to update on what we're going to have at the tail end of this year?

Yes, sure. Thanks. So with respect to the treatment of ovarian cancer with gavo-cel in combination with nivolumab in the Phase II trial, we have, at this point, enrolled all the patients that we would need in order to make an interim assessment of the data that would be anticipated later this year. At this point, we have paused further enrollment in that program until we have the opportunity to assess that data. And I think that the expectations for what would be required to advance that product are similar to what Dennis had outlined for SURPASS-3.

With respect to MAGE-A4 and mesothelin co-expression, I don't have a formal analysis of that, but MAGE-A4 is expressed in approximately 25% of patients with ovarian cancer, while mesothelin is expressed in considerably more, closer to the 60% to 70% of patients with platinum-resistant ovarian cancer. So I expect that there would be some overlap biologically. I don't think that they're related. So it's probably just close to a mathematical equivalence, but we haven't specifically studied that.

Our following question is from Tony Butler from EF Hutton.

Adrian, this is more big picture. You've outlined U.S. submissions and I very much appreciate that. What's Adaptimmune's view on opportunities ex U.S., if any? Importantly, has there been discussions about some -- any partnering opportunities where a potential partner may wish to develop or help develop a product in the EU and/or otherwise?

So I think conceptually, we've thought about the opportunity to take cell therapies in the space global, and -- but we also recognize that we are unlikely to be the right people to do that in all geographies. And so you can imagine that we are obviously interested in opportunities to partner in geographies where we are not going to be able to be the primary commercialization agent. I think there are challenges, obviously, associated with registration and with pricing in some of those jurisdictions. But I think those challenges are solvable, particularly when you are at some level of manufacturing volume when your cost of goods is commensurately lower.

And so we fully anticipate that afami-cel and the other products in our pipeline will be available in due course in a -- on a broader basis than the United States. I can't speak specifically to partnering opportunities at this point in time. And I would anticipate that we will launch afami-cel in the United States and gain significant traction with that and other parts of our portfolio before there is much traction ex U.S.

Following question is from Marc Frahm from TD Cowen.

Maybe first on the BLA submission. With the Cohort 2 serving as confirmatory and being kind of essentially enrolled as of today, should we think of that as being data that's likely to get provided to the FDA during the review and ultimately be part of the original, just a regulatory decision?

Dennis?

Yes. Thanks, Ad. Cohort 2 data is going to be in the BLA from a safety perspective. We have not discussed with the FDA to provide updated efficacy data, including Cohort 2 data, during the course of the review. That would be atypical like during the course of a BLA review. That's not something that's been on the table to date. So at this point, it's not deemed to be needed, right, for this initial approval. I guess as these discussions evolve with the FDA, we can discuss options if that were to come up. But at present, we would want to come in with Cohort 2 data when the follow-up for DOR is sufficiently mature.

Okay. That's helpful. And then maybe following up on Tony's questions. You've given, Ad, some of your comments there about COGS and scale. Do you think that next year some of those partnerships in other territories require either data from or just a broader deal around your second-generation products and/or other targets in addition to just MAGE-A4?

I think it would be inappropriate for me to comment on the specifics of discussions and what deal constructs might look like. I think it varies depending on who the potential partner is and what their interest is. And I think we will deal with that in the coming years.

The following question is from Jonathan Chang from Leerink Partners.

First question, can you help set expectations for the upcoming SURPASS update at ESMO?

Certainly. I will ask Elliot to update on -- to answer that on our incremental update at ESMO. Elliot?

Thanks, Jonathan. First of all, we're pleased that we've been granted an oral presentation at ESMO for this update for the SURPASS trial. As you may recall, last year at ESMO, we presented data from 43 evaluable heavily pretreated patients and shortly after, updated that data, demonstrating a 52% response rate across our 3 areas of focus: ovarian cancer, urothelial cancer and head and neck cancers. And the overall response rate in -- across all indications was 37% with median duration of response around 5 months.

This year at ESMO, we will provide an incremental data update showing more mature data from that data set in the original monotherapy arm, as well as a few additional patients in that arm. We amended the trial previously to look at combination therapy with checkpoint inhibitors. And we will show early data from approximately 10 patients in the combination arm. And remember that this is also in late-stage patients who have been heavily pretreated.

There will also be presentation of translational data and translational insights. And going forward, as we said previously, as a result of these Phase I results, we initiated SURPASS-3 registration-directed trial in platinum-resistant ovarian cancer with RMAT designation. And we will also be focusing the trial going forward on earlier line treatment of head and neck and urothelial cancers, again, in combination with checkpoint inhibitors.

Got it. And second question, I appreciate all the color around the progress towards the afami-cel BLA submission. Can you provide any more color around what specifically the BLA submission delay can be attributed to?

Certainly. I think the first important thing to understand is that it isn't one specific thing or item. And I think the purpose of me talking through the interactions with the FDA and the wet work that we've done was to demonstrate that we have substantially derisked the filing itself and that the reason that we've taken the extension into Q4 is that there have been a -- as we've gone through that derisking, there have been a number of elements that have just taken a little longer than we anticipated. Not each one, not by much, each one not hugely significant, but obviously, you need to do these things in sequence. You need to validate the assays before you can do the PPQ, for example.

And so the effect of the sequential changes to those individual time lines means that, although we've discharged most of the risk associated with that time line, we are now confident that to submit a quality file in 2023, it will take us to Q4 2023 to do that. So not one specific thing and actually a lot of areas of potential risk removed, but it is going to take us to Q4 to get this done.

Our following question is from Mara Goldstein from Mizuho.

I wanted to ask, now that the TCR2 acquisition is closed and you did suggest that you'll be reviewing the data not just from TCR candidates but other candidates, does the guidance assume full development of gavo-cel and 510? Like how should we think about that should indeed some of those programs not progress?

Yes. So I'll ask Gavin to talk about the guidance and how it covers a range of scenarios. Gavin?

Mara, yes, so as we think about our guidance, we've got a variety of programs and products that we want to bring forward, and we'll be making resource allocations across that portfolio as we do each year. And therefore, whilst we're excited about each of the pipeline and products that we have, we haven't actually finalized which ones we will be taking forward as we exit this year and begin to write plans for next year.

Following question is from Peter Lawson from Barclays.

This is Alex on for Peter. Just two for me, a quick follow-up on the ESMO update from SURPASS. Do we -- in those 10 patients, the 10 combination patients, should we expect to see ovarian cancer patients specifically?

Elliot?

I don't think that we've guided specifically to the types of patients that we would present, but those 10 patients are across all indications, that they were not selected particularly for one tumor type versus another. So there are a range of tumor types in the trial, ovarian cancer being one of them. And I think that's all we can say at this point.

Okay. That's helpful. And then just on the BLA, a follow-up here. If you could just reiterate what the confirmatory evidence that will be required here in terms of your agreement with FDA? And then do you expect a priority review?

Dennis?

Yes. Thanks, Ad. I'll answer the second question first. The answer would be yes, we would expect a priority review. We have RMAT designation as an expedited designation and certainly the application would justify a priority review. As far as the confirmatory evidence, the proposal was to utilize Cohort 2, complete Cohort 2 data with sufficient follow-up for duration of response. Just as a reminder, right, the durability of this -- of response in afami-cel is quite long. So we have to follow patients for the appropriate amount of time to come in with mature DOR data, or duration of response data. So what we discussed with the FDA is the full Cohort 2 data set, which is slightly larger than what we did for Cohort 1 for synovial sarcoma in SPEARHEAD-1. And we discussed broad timings for when that may come in with the FDA, and they agreed that this would be an appropriate plan.

We have no further questions registered at this time. I would now like to turn the meeting back over to Mr. Rawcliffe.

Thanks, everyone, for your time today. We look forward to updating you further later on in 2023 on our BLA progress as well as on our other programs. In the meantime, please don't hesitate to reach out with any questions. Thanks again.

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