Adaptimmune Therapeutics - Q1 2023

Transcript

Operator (participant)

Hello, welcome to Adaptimmune's first quarter call and business update. I would now like to turn the call over to Juli Miller. Juli, please go ahead.

Juli Miller (VP of Investor Relations)

Good morning, and welcome to Adaptimmune's conference call to discuss our first 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, 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 it over to Adrian Rawcliffe. Ad.

Adrian Rawcliffe (CEO)

Thank you, Juli. Thanks to everyone for joining the call. My comments today will be brief, and we can go directly to questions. We've started 2023 at pace, and it promises to be a year of change for Adaptimmune. We completed the prioritization and restructuring in Q1, cutting costs whilst remaining focused on our priorities. The afami-cel BLA, the CD8 program in ovarian, bladder, and head and neck cancers, PRAME, and our allogeneic platform. A strong pipeline of cell therapies for a wide range of solid tumors. Adding to that strength, we announced that we entered into a strategic combination with TCR². We are two companies that have spent our entire histories focused on solid tumors, with experienced teams who've advanced strong clinical pipelines with significant value-creating near-term catalysts.

Add to that the compatibility of our technology platforms, including an innovative next-generation toolbox and a cash runway into 2026, and taken together, it's clear that this combination will create a preeminent cell therapy company to treat solid tumors. We expect the transaction to close in Q2, 2023, subject of course to shareholder approval at the end of this month. Both companies are very actively planning for integration. We will update further once the transaction is closed. We are also on track to have a commercial product, afami-cel, which would be the first engineered T-cell product on the market for a treatment of a solid tumor. We announced that we completed part two of the BLA submission in Q1. Part three is in progress for completion in mid-2023. Afami-cel is an incredibly exciting drug and the need for new marketed treatments for synovial sarcoma compelling.

Recently, we had the privilege of hosting a young woman who is surviving synovial sarcoma at an internal meeting. Hearing her personal account of misdiagnosis, harsh treatments, and a plea for new and innovative therapies was inspirational for all of us here and highlights further how important afami-cel is for this patient population. She also described the loss of young lives to this cancer and the experiences of her peers in the sarcoma community. We hope to share stories like hers in the future and continue to raise awareness for synovial sarcoma and the high unmet need in this cancer. Continuing with afami-cel news, we will present updated overall survival analysis for afami-cel in June at ASCO. It's clear that this is a powerful treatment for this rare and deadly cancer.

Beyond afami-cel, we remain focused on developing our MAGE-A4 franchise with our next-gen CD8 therapy and progressing more products to market. To that end, we are initiating the phase 2 SURPASS-3 trial in combination with nivolumab for platinum-resistant ovarian cancer. This trial has the potential to become registrational and is supported by RMAT designation with the FDA. We are also initiating additional cohorts in the phase 1 SURPASS trial in combination with pembrolizumab to treat patients in earlier line settings for head and neck and urothelial cancers. Last year, we announced we have PRAME back from GSK. We believe that this is another powerful target for solid tumors with increasing validation across the industry. We're progressing PRAME to be IND ready by the end of this year and plan to initiate trials next year.

We also announced in Q1 that we're in the process of transitioning lete-cel back. We will receive approximately $37 million from GSK in relation to the transition of the ongoing clinical trial. We anticipate lete-cel data in synovial sarcoma and MRCLS later this year and will evaluate this opportunity accordingly. In closing, this has been a significant first quarter for us and will undoubtedly prove to be a year of change as we move towards our first BLA and marketed product. Behind that, we have an unparalleled pipeline of cell therapies for solid tumors that will continue to prioritize development in a thoughtful, data-driven fashion. I look forward to reporting out on future progress. With that, I'll turn the call over to Q&A. Operator?

Operator (participant)

Thank you. We will now begin the question-and-answer session. 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 are using a speakerphone, please pick up your handset before pressing any keys. To withdraw your question, please press star then two. We'll pause for a moment as callers join the queue. Our first question comes from Marc Frahm of TD Cowen. Please go ahead.

Marc Frahm (Biotechnology Equity Research Analyst)

Hi, yes. Thanks for taking my questions, and congrats on the progress. Adrian, you made the update of, part two being in of the BLA. On the part three there, do you now have everything you need in-house, and it's, you know, it's a question of packaging it all up appropriately and submitting it? Or are there still data points that you need to gather for that portion?

Adrian Rawcliffe (CEO)

I think there's still a lot of work going on, to complete the BLA on time. I'll ask Dennis, who's leading that program, to comment a bit further.

Dennis Williams (SVP for Late Stage Development)

Yeah. Hi. Yeah, as Adrian said, I mean, we're in the final stages of method validation and some of the other activities related to the dossier preparation. We continue to look forward towards our goal. We're excited to have 2/3 of the application already down at the FDA.

Marc Frahm (Biotechnology Equity Research Analyst)

Okay. That's helpful. Maybe just on the pipeline, the ADP-A2M4CD8 program, just any data presentations we should be looking forward to, maybe in the second half of the year?

Adrian Rawcliffe (CEO)

We said that we will provide an update on the monotherapy cohort in late-line patients and the patients that we've dosed in combination with nivolumab at another appropriate congress later on this year.

Marc Frahm (Biotechnology Equity Research Analyst)

Okay, great. Thanks.

Adrian Rawcliffe (CEO)

Thanks.

Operator (participant)

Our next question comes from Tony Butler of EF Hutton. Please go ahead.

Tony Butler (Senior Managing Director)

Thanks very much. Adrian, I just wanted to discuss some of the trials with checkpoint inhibitors. I want to make sure that is Adaptimmune paying for the checkpoint inhibitor? That's point one. Number two is the notion here that the combinations. I mean, let's be clear, the combinations may evolve greater activity, but I guess in the absence of a total control arm, how do you actually separate the two when you're, when you're simply, if you will, doing a phase two study or at least a study that's exploring the combination? How do you think through that if you were to move to a regulatory trial? Thank you.

Adrian Rawcliffe (CEO)

The short answer on the question of where, of who's paying for the checkpoint inhibitors, the answer is that Adaptimmune is currently paying for the checkpoint inhibitors. On the question of the trial design, I think we focus on the SURPASS-3 trial since that's the one that we are, that is a phase 2 trial progressing simply towards registration. I'll ask Dennis to comment on that trial design and how we consider that in platinum-resistant ovarian cancer.

Dennis Williams (SVP for Late Stage Development)

Sure. In SURPASS-3, it's a randomized trial in that there's a monotherapy arm, and then there's another combination arm with nivolumab. Both arms are compared against historical response rates for non-platinum-based chemotherapy in platinum-resistant disease. You know, your point's well taken. In the checkpoint inhibitor space, both as monotherapy and in combination with chemotherapy and platinum-resistant disease, the efficacy is very well described. For us, it'll be very obvious that if the combination arm shows something, it'll allow us to compare that against the monotheraphy arm to make some inferences if we see perhaps greater depth and durability. We certainly will be able to determine that that's not solely due to the checkpoint alone because as we know, checkpoints alone don't have appreciable activity in that disease.

We feel very confident that the results of that trial will be quite interpretable.

Tony Butler (Senior Managing Director)

If I could just ask one follow-up, Dennis, on this topic. I thank you very much for the commentary, but the other is, do you limit the number of previous therapies that a patient may undergo? That, in part because it seems that, at least the response rates in a number of tumors were better when it was, I think, two or less, at least for monotherapy. I'm just curious how you may balance that in combination also with the checkpoint inhibitor. Thank you.

Dennis Williams (SVP for Late Stage Development)

Yeah. For SURPASS-3, we do limit the number of prior lines of treatment. You know, the data we presented about baseline characteristics and how they relate to response, among them being the number of lines of prior therapy, that's across, you know, the basket experience we have in the phase 1 SURPASS trial. Of course, some of those prior lines of therapies differs notably depending on which cancer that patient has. In the platinum-resistant space, since platinum-based therapy is quite effective until they become resistant, we do allow a number of prior prior platinum treatments. We would expect patients to receive bevacizumab if unless they were otherwise unable to receive that.

We would also expect patients to have received, you know, a prior PARP if that was indicated. We do intend to have a more homogenous phase 2 population and among that, to limit the number of prior lines in this trial.

Tony Butler (Senior Managing Director)

Thanks very much.

Adrian Rawcliffe (CEO)

Thanks, Tony.

Operator (participant)

Our next question comes from Mara Goldstein of Mizu. Please go ahead.

Speaker 11

Hi. Thank you for taking our questions. This is Paul from Mara. Two small ones first. When are you going to get that $37 million payment from GSK? It says on the release that there'll be the vote on the 30th. Is that TCR or is that Adaptimmune's vote?

Adrian Rawcliffe (CEO)

I will comment on the vote, and I will ask Helen to comment on the payments received from GSK. The votes on the 30th are both the TCR2 and the Adaptimmune votes happen on the same day. Subject, of course, to that vote, we plan to close the transaction very shortly thereafter. Helen,

Helen Tayton-Martin (Chief Business and Strategy Officer)

Yeah. Thanks for the question. This is Helen Tayton-Martin. In relation to the money, the income from the GSK transition, the majority of that will be in line with the transition of the programs, which is anticipated, the lete-cel program, which is anticipated during the course of 2023. There is some very small amount which will come in 2024, but we haven't disclosed it. It'll come in stages, basically, but the majority of it will be during this year, and hence it being built into our runway and projections.

Speaker 11

Got it. Just to follow up on afami-cel launch. I was wondering if you can certainly we can share regarding the payor discussion, how that's going and any color on the pricing strategy would be helpful. Thank you.

Adrian Rawcliffe (CEO)

I think the discussions with payers are going well at this point in time. We are obviously a year or so away from launch, and we will have more to say on pricing strategy as we approach approval.

Speaker 11

Got it. Thank you so much.

Operator (participant)

Our next question comes from Michael Schmidt of Guggenheim. Please go ahead.

Speaker 10

Hey, this is Paul on for Michael. Thanks for taking our questions. My first one's on PRAME. As you look towards a future phase 1, how are you currently thinking about expression thresholds for PRAME and potentially enriching for certain tumors upfront versus sort of a broader signal finding approach? Maybe just a read through from the recent PRAME updates across the landscape. Seems like some of the responses have mostly been in particular tumor types, melanoma, ovarian. As you're moving towards the IND, you know, what gives you confidence in the broader opportunity? Are there any sort of particular indications and focus for you?

Adrian Rawcliffe (CEO)

I will ask Jo Brewer to comment on that and our thinking as regards PRAME expression, our TCR and what indications we are considering.

Jo Brewer (Chief Scientific Officer)

Thanks, Ad. It's a great question, and I think we're really excited about having PRAME back in our hands, because it's a fantastic target, and we're very excited about the opportunity that this will give us. You're right. We'll likely look at more than one indication. We are making, you know, informed decisions about our clinical strategy at the moment. We're still deciding exactly where we will go. There are obviously synergies in ovarian with our other trials as we're looking, you know, working with the right people in that area. There are, there's great expression profiles in other tumor types as well, and PRAME is a large opportunity for us. I think we will use, you know, some of our learnings from MAGE-A4 most definitely. We'll look at working with sites that we know well.

We will see. We're still in the pre-clinical phase here, getting ready for IND. Obviously, we're discussing those right now. I think in terms of PRAME out there, it's obviously a well-validated target. There's been some great data recently from Immatics, and we're very mindful of that. Our TCR is engineered as you would expect. We have a higher affinity engineered TCR where we've been optimizing the TCR for binding and function. We're quite confident that this is gonna give an edge with our PRAME product. We're also looking at our next-gen opportunities with PRAME as well, based on work we've done with the MAGE-A4. We're transferring that across to PRAME. We will be looking to make the most of PRAME as a target with products coming forward.

I think, you know, it's still early days for the PRAME space and we intend to be in there, doing the best that we can and hopefully bringing forward some great products.

Speaker 10

Great. Maybe just a follow-up on lete-cel. Just wanted to get your updated views on that program and how you might expect that program to transfer in the third quarter to perhaps impact your OpEx. You know, for that data later this year, is there a particular response rate threshold you're hoping to see to support a potential commercialization decision? Thank you.

Adrian Rawcliffe (CEO)

I think your-- implicit in your question is the correct consideration that we're making, which is, as I've touched on before, we view lete-cel's return as essentially a pre-option on what has the potential to be quite a late stage product. Indeed, I think that trial was designed to support at least in part registration. We look forward to getting those data back in-house, and it will be very much tail end of this year. We will make rigorous data-driven decisions. The, I think the standard for activity in this space has been set by afami-cel, with a response rate approaching 40%.

I think if we look historically at what we've said about the required response rates in this space, I think if we're not at, you know, 30% in this space, I think it's, it'd be challenging to think about development. That's been our historic benchmark, and it probably ends up being our future benchmark at this point in time for this, for that particular asset too.

Speaker 10

Great. Thanks so much.

Adrian Rawcliffe (CEO)

Thank you.

Operator (participant)

Our next question comes from Jonathan Cheng of SVB Securities. Please go ahead. Go ahead.

Speaker 12

Hey, guys. This is Dylan Drake on for Jonathan. Thanks for taking my question. First of all, I just wanna ask how you guys are thinking about strategic priorities for your pipeline programs following the merger, particularly when you think about your approach to ovarian cancer and how you plan to address any overlapping major mesothelial patient populations.

Adrian Rawcliffe (CEO)

Let me. Let me say a little about that. Obviously, we're limited in what we can say because we have yet to conclude the transaction. At the moment, TCR² and Adaptimmune are continuing as independent companies. The best way of thinking about our focus at the moment is that we're focused on our priorities for Adaptimmune as a company, which I went through afami-cel, DLA, CD8, PRAME, and our allogeneic platform. However, clearly, we, as we bring this pipeline together, we will need to address two angles. One is how do you develop these programs in a synergistic fashion, a synergistic and efficient fashion. There's pros to...

There's benefits to the fact that we have both assets in ovarian in terms of execution, clinical execution, and experience in the ovarian space. There's also considerations like overlap between the antigen that we need to think about how one would deal with. All of that is driven by data. I think we are looking forward to the data that has been accumulated by TCR² of gavo-cel combination with nivolumab, and we look forward to making data-driven decisions on the entire portfolio as we go through this year and into next year.

We are very clear that we will need to be thoughtful and rigorous about the prioritization across the portfolio in order to develop the best medicines out of what is the best pipeline with the broadest range of targets and the deepest base of assets in the cell theraphy industry at this point in time.

Speaker 12

Follow up on that. How do you see the allogeneic pipeline progressing, and how do you guys think about prioritizing both the allogeneic and autologous programs in the future?

Adrian Rawcliffe (CEO)

I'm gonna touch on that just very briefly, then I'm going to invite Jo to comment as she is leading the allogeneic platform work. I think one of the things that's become clear in the industry, in fact, I think this is why there's a resurgence of interest in the autologous space, is that it's been clear to us for a long time that the allogeneic promise is definitely there. The idea of an off-the-shelf cell theraphy product is incredibly attractive. It's also quite a long way away, I think the next decade, in particular in the solid tumor space, is the decade of autologous solid cell therapies.

I think you can see in the investments that people are making in the CAR-T space, that I think this is becoming an industry perspective. It's unfortunate that some of that is because of the inevitable challenges that have arisen as you try to develop a new modality, i.e., allogeneic T cells. What I mean, there's now, I think, gonna be quite a gap. Autologous is not simply a bridge to allogeneic. They will be different products, and the allogeneic products will be, I think, quite a way behind the autologous products, particularly in the solid tumor space. As such, our focus is on developing our autologous pipeline of products which have near-term potential, near or medium-term potential to benefit thousands of patients who have deadly cancers.

Then I think the evolution of the allogeneic platform will then determine two things. One, the extent to which there is direct overlap or the extent to which there is complementarity between these platforms in due course. We're very pleased that we have a foot in both camps, and in particular with the allogeneic platform with our partner, Genentech. We see a very, very significant solid business in the autologous space. In solid tumors before there's any allogeneic players out there, including our own. Jo, anything that you'd like to add to that?

Jo Brewer (Chief Scientific Officer)

I think you covered that pretty well, Ad. As Ad said, we're still really committed to the allogeneic platform, and we are making progress there. It's one of those working through unknown unknowns. You know, what comes up in these programs, they're new challenges that need to be solved. The team's been working very hard on this for a long time now, and we've made a huge amount of progress. We have to react to an ever-changing landscape around us as well. The regulatory bar for allogeneic programs is very different to autologous. The way that the autologous programs are progressing in terms of, you know, business model and ability to supply patients is also making that bar harder for allogeneic products as well. You know, it's becoming.

We're getting better at supplying and treating patients with autologous products, which means that the allogeneic products have to try much harder to be improvements on that. We're still completely convinced that that is the long-term future, and we're keeping all of that in mind. We're still putting a huge amount of effort into our allogeneic platform because we do see that as our long-term play for the future. That's why we're very happy to be partners with Genentech, who view it in a similar way to ourselves, in that this is a long-term play for good gains at the end of it. I think we've not been talking about it much recently because we're just carrying on. It's, it's great, but right now the transformative data is in the autologous space, and we're commited to that as well.

We're making a valid business, with strong data and treating patients. Allo will come in time, but for now, there's important work to be done in autologous as well. Important products that we can bring forward.

Speaker 11

Great. Thank you. I appreciate that.

Operator (participant)

Our next question comes from Peter Lawson of Barclays. Please go ahead.

Speaker 9

Hey, good morning. This is Alex on for Peter. Thank you for taking our questions. Just another question on the PRAME program. I was wondering if you could clarify just the timing of the IND, if that's mid 2023. When would you be in position to start a phase 1 study here? Kind of related, you know, in terms of manufacturing for the PRAME program, are there any synergies in terms of, you know, being able to leverage your current manufacturing footprint or know-how processes for manufacturing for that program? Thank you.

Adrian Rawcliffe (CEO)

I will comment briefly, and then I'll ask John Lunger, Chief Patient Supply Officer, to comment on the manufacturing approach for the PRAME program. I think you might be confusing our BLA timing of mid 2023 with the discussion that we've had on PRAME, where we said we would be IND-ready in 2023 with the clinical trial to follow shortly thereafter. We anticipate being in the clinic with PRAME in 2024. John, would you like to talk about the manufacturing for PRAME?

John Lunger (Chief Patient Supply Officer)

Yeah. Thanks, Ad. Hi. Yeah, absolutely, we're leveraging our capabilities that we built in manufacturing. It's definitely one of the advantages of building the integrated capabilities that we have. As soon as PRAME began to come back, we started to look at our network. We have the ability to make the lentiviral vector that we would need in our facility that's in the U.K., and we have the capacity for drug product in the Navy Yard. The flexibility that that's enabled to react is fantastic, and we'll certainly leverage that.

Adrian Rawcliffe (CEO)

Okay.

Operator (participant)

This concludes the question and answer session. I would like to turn the conference back over to Adrian Rawcliffe for any closing remarks.

Adrian Rawcliffe (CEO)

Thanks everyone for your time today. We've been very pleased to share our progress with you, we look forward to updating later on in 2023 after we have concluded our transaction with TCR². In the meantime, please feel free to reach out with any questions. Thank you again for your time. Bye.