Adaptimmune Therapeutics plc

Good day and thank you for standing by. Welcome to the Q3 2021 ADAPT Immune Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star 0. I would now like to hand the conference over to your speaker today, Julie Miller. Please go ahead.

Good morning, and welcome to Adaptimmune's conference call to discuss our third quarter 2021 financial results and business updates. Please review our forward-looking statements from this morning's press release as 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 with me for the prepared portion of this call. Other members of our management team will be available for Q&A. With that, I'll turn the call over to Adrian Rockliffe. Add.

Thanks, Julie. And thank you, everyone, for joining us. About this time last year, we laid out our 2252 strategy. We are now one year into that five-year strategy, and we've made substantial progress against each of the four pillars we set out then. The first pillar was that we wanted to have two marketed products targeting May J4, and the second pillar was to identify further indications for two additional BLAs for our Spear T-cell products. The first product we're targeting for approval is our first-generation TCR T-cell therapy targeting MAI-J4, Afamacel. In June, we presented initial data from the Spearhead 1 trial at ASCO, demonstrating that Afamacel is a life-changing therapy for people with synovial sarcoma and MR-CLS. We remain on track to file our first BLA next year for Afamacel, which we anticipate will be the first engineered T-cell therapy on the market for a solid tumor indication. Based on the data presented recently at ESMO from the SURPASS trial, we have shown that our next-gen MAJ4-targeted therapy, ADPA2N4CD8, is effective with responses in five different solid tumors, an overall response rate of 36%, and an 86% disease control rate. These data confirm the potential of a broader MAJ4 therapy franchise. In Q3, we announced that we initiated the Phase II Surpass II trial for people with esophageal and EGJ cancers. Today, we announced that we will start a second Phase II trial next year called Surpass III for patients with ovarian cancer. We continue to enroll patients in the original Phase I Surpass trial with a focus on rapidly identifying additional indications for late-stage development. Onto our third pillar, five new autologous products in the clinic from our extensive preclinical pipeline by 2025. We've reported substantial progress with additional HLAs, new targets, and next-gen programs, with our most advanced preclinical therapies being the next-generation engineered IL-7 TIL therapy in collaboration with CCIT Denmark, And our next-gen MAI-J4 targeted therapy incorporating IL-7 and CCL-19 developed in collaboration with Noil Immune. Additionally, the translational data we'll present at CTOS and CITC next week show the stellar quality of our translational science teams and how learnings from this research will help us develop better products to take into the clinic. Last but not least is our fourth pillar. to allogeneic products in the clinic by 2025. In this morning's press release, we confirmed that we plan to file our first IND in 2023 for a wholly owned allogeneic product targeting MAJ4. In Q3, we signed a fantastic strategic collaboration with Genentech that has now become effective and for which we will receive the upfront payment of $150 million in Q4. We also announced that we would open a dedicated allogeneic manufacturing facility next year. I believe that our allied platform represents a significant piece of the future of cell therapy for us and our partners, and this progress confirms we are amongst the leaders in the allogeneic T cell space. Looking forward, we will continue to deliver updates from our trials from a clinical and a translational perspective. Following the initial data presented at ASCO for our Pivotal Spearhead 1 trial, next week we will present a fuller data set at CTOS in an oral presentation delivered by Dr. Brian Van Tyne from Washington University. We will also present a poster highlighting translational scientific insights from this trial. At CITSE next week, we will present data demonstrating the positive impact of adding an AKT inhibitor to the expansion phase of our manufacturing process. It's a feature of developing cell therapies that epigenetic modifications during manufacturing have the potential to be as important as the genetic modifications we make to the cells themselves. In this same poster, we will present clinical translational learnings from patients in the SAFAST trial for whom we reported clinical data at ESMO, indicating that these manufacturing improvements, along with the next-gen enhancements, make an improved and more potent sphere T-cell product for people with cancer. These types of translational learnings are critical as we aim to bring forth further next-gen products and enhancements to better address solid tumors with our cell therapies. When looking across the pipeline of ongoing clinical trials with our 2252 goals in mind, we need to pursue our ambitions rapidly and efficiently and critically evaluate what is and is not a product. Today, we announced that we've ceased enrollment in our Spearhead 2 trial with Afamacel in combination with Pembrolizumab. Given compelling activity seen with our next-gen ADPHOM4CVA product across a range of solid tumors, next year we'll evaluate the combination of a checkpoint inhibitor with this therapy. We will not go into details today, but we'll update in due course about the best design and the path forward. We also announced that we have enrolled a sufficient number of patients in our Phase 1 trial with ADPA2-AFP for people with liver cancer, leading us to close screening. We presented data at ELCA demonstrating that ADPA2-AFP is an active product, with several patients receiving clinical benefits, including a durable complete response, and other patients with prolonged stable disease associated with a significant decrease in serum AFP. But the response rate to date is not what we had hoped for. We'll analyze data from the full patient population in this trial and determine next steps, including evaluation of alternative TCRs, manufacturing improvements, and potential next-gen enhancements. So far in 2021, we've delivered clear progress against our T252 strategy, and we will continue to deliver over the next four years. We're on track to file our first BLA. We're showing compelling data from Surpass, confirming the potential of the MAJ-A4 targeted franchise. And we're working quickly to pursue further late-stage trials, starting with the recently initiated Surpass 2 trial in esophageal and EGJ cancers and Surpass 3 in ovarian cancer, which we'll initiate in 2022. We're also planning to explore the use of checkpoint inhibitors alongside our NextGen product with the aim of identifying further treatment regimens for our cell therapies for people with cancer. Beyond our current clinical trials, we've continued to make progress with our autologous and allogeneic preclinical pipeline, including in collaboration with GSK, Estelas, and most recently Genentech. All of our progress this year brings us closer to achieving our vision of being a fully integrated cell therapy company. And you can really see this when you consider that we are filing a BLA and preparing for our first commercial product. while simultaneously building an allogeneic manufacturing facility for future generations of cell therapies for people with cancer. As we close out the year, I'm pleased with our progress and will provide further guidance for 2022 at the beginning of next year. With that, I'll turn it over for questions. Operator?

As a reminder, if you would like to ask a question, please press star, then the number one on your telephone keypad. Again, that is star, then the number one. And your first question comes from Mark Fram with Cowan & Company.

Yes, thanks for taking my questions. Maybe on the filing, other than, obviously, the presentation in about a week at CTOS, what's kind of gating to the filing going in? Is it just a little bit more follow-up on the last few patients, or are there still real discussions to be had on things like potency assays and exactly what needs to be included from that front.

Elliot, do you want to take on?

Yeah, sure. Hi, Mark, and thank you. Just with respect to the BLA filing, clearly the data still is not in its final format and needs to be presented in the appropriate way. The cohort that will support the filing, cohort one from the Spearhead 1 trial, you know, has completed. So, you know, all the patients are enrolled and data collected and, you know, we'll be, you know, finalizing that data set in the fairly near future. So while there's still work to be done, I don't think that that's necessarily, you There is also still work to be done with respect to demonstrating that our manufacturing and release testing are acceptable to the agencies. And that goes side by side with meeting the primary endpoint for efficacy and showing an acceptable safety profile. And while I don't think that there are issues that are insurmountable in either of those, there is still, in any of those, there's still work to be done. And that work will take us out into 2022, and we're on track to meet the timeline to file the BLA next year.

Okay, thanks. That's very helpful. And then maybe I... realize you're just opening SIRPAS 2 and SIRPAS 3 hasn't fully opened yet, but just given the increased demand for your trials you've seen over the last six months to a year, you have some broad outlines you can give on how quickly those trials might enroll and when we might be able to start seeing data from some of those expansions into tumor-specific cohorts.

We've not given guidance on timings for that, and we will give guidance on 2022 milestones and probably beyond at the beginning of next year, but it won't include specific guidance on rates of accrual in those trials.

Okay, fair enough. Thanks for taking my question.

Your next question comes from Michael Schmidt with Guggenheim.

Hey, guys. Good morning. Thanks for taking my questions. So I think you mentioned that you're, you know, initiating a new pembrolizumab combination study with the next-gen HF4 asset, which obviously makes sense. I was just wondering if there are any learnings from the initial trial that can be applied here in terms of the combination moving forward.

Yeah. So, hi, Michael. Thank you. There are certainly learnings. I mean, you know, we're – we should be learning from everything that we do as it informs, you know, our next steps. The real reason for us choosing to really change the focus of the combination to the next-gen product is based on really at this point having experience with the next-generation product, seeing its improved potency, efficacy, and wanting to put sort of the best combination forward. I think that's really the key point here.

I got it. And then, you know, the other question I had, perhaps related to the prior question, just on CMC for a family cell. I mean, we have seen a number of FDA, you know, BLA delays around manufacturing and CMC of T cell products. And, yeah, if you could maybe just provide some additional color in terms of what has to be done to really check the box on CMC for the BLA?

Yeah, this is John Lunger. I lead the CMC organization. So a couple things there. One is we are obviously going through all the activities we need to do to prepare the Section 3 of the BLA. The supply of our commercial product will come from the same supply chain that we've used for the Phase 2 trial. So there's no changes in there, which I think is a big plus for us. We had interactions related to potency assays and all the release assays, frankly, and those are progressing well, and we feel confident that we've got the right assays in place, and we'll have them in place by the time we file the BLA next year.

Okay, thanks. And then last one, just around the Genentech collaboration, obviously very interesting given their given their engagement with adaptive as well. But just wondering how we should think about potential news flow coming out of that collaboration over the next, you know, one to two years or so.

Yeah. Hi, Michael. It's Helen here. I'm taking Martin. Nice to speak with you again. We haven't disclosed specific, we'll have specific updates on the program, but clearly we anticipate that we will need to do that given the our position and the importance of this deal to us and its progress and the fact that it's on a very long-term nature. We've only just passed HSR clearance, so I think it's a little early to give guidance on when we will be updating, but we hope that certainly during the course of the next year we'll be able to sort of map out when we can provide more data and more information.

Great. Thank you.

Thanks, Mark.

Your next question is from Nick Abbott with Wells Fargo.

Hey, good morning. Thanks for taking our questions, and yeah, congratulations on a very good update, very solid. You mentioned earlier we have Cohort 1 at SPHER 2, but there's also Cohort 2. So can you provide any details on how that is enrolling?

Without providing specific numbers, it continues to enroll well. There's clearly interest in treating patients with a famicel who have synovial sarcoma. That's the answer to the recruitment question. It's not intended to be part of the hypothesis testing for the filing. but will be supportive from the standpoint of additional safety and efficacy, you know, considerations as well as looking at specific subgroups.

Thanks, Elliot. In your prepared comments, you mentioned CERPAS-3 in ovarian cancer. Is the intent, I mean, have you discussed the size of this trial with FDA? Is the intention to seek registration if it's positive?

I think it's early to push the boat out too far on exactly what the trial looks like and to disclose conversations with FDA. I think that that's the answer. Yeah, thanks.

Okay. And then just going back to... You know, the next set of trials or the next trial with next-gen of Famicel and a checkpoint inhibitor, I mean, in the prepared comments, that statement is tied to Spearhead 2. So I know you're not going to go into details, but is the plan here to test this in a broad range of tumors, or is it more as a replacement of Spearhead 2? Yeah.

Correct, Nick, without going into great details. It will likely be broader than just head and neck cancer, specifically what tumor types, you know, are in the study we haven't discussed, but it is intended to be across tumor types, not just a single tumor type.

Okay, perfect. Great. Thank you very much.

Thanks, Nick.

Your next question comes from Shomit Roy with Jones Research.

Hi, this is Dania. First question would be, can you provide at least some color on the Spearhead 2 as to since you ceased trial, how many patients have been enrolled and when we expect data update? So I think we

We have not enrolled any patients in that trial. And if we haven't, we just don't have. And that's one of the reasons why we're closing that now, so that we can get on to the more potent product in combinations with the more potent product.

Thank you. And can you provide any color on the soprastery? And we said that you provide for the details, but as you're moving on to ovarian cancer, are you going to focus on platinum resistance or can you provide any details on that?

Yeah. And do you want to touch on that? Yeah. So the We haven't really given details with respect to exactly what the patient population will look like. The current trial is enrolling patients who are platinum ineligible. So patients who are eligible to receive another cycle of platinum will typically get that from their physicians before being entered into a clinical trial.

Excellent. Thank you very much. Your next question is from Mara Goldstein with Mizuho.

Great. Thanks so much for taking the question. So I just wanted to maybe drill down a little bit into the ALO program. And I know you mentioned that you'll have manufacturing up. later in 2022. But maybe you could talk a little bit about, if possible, the particular focus. I know the agreement calls for you to look at five different targets. So maybe if you could speak to us a little bit about that, that would be helpful. And then I'm just curious, just on the allogeneic program, given what we've seen, obviously, with Allogene's program and how you think about that vis-a-vis approaching FDA with your IND.

Thanks, Mara. This is Helen Tate-Martin again here. Just talking to the ALOE program, obviously we've made reference to building our ALOE manufacturing facility, but primarily in the first instance that will be to support our internal May J4 ALOE program. That will be the first into the clinic and the the IAD we signaled late 2023, you know, the yellow facility will initially be supporting that, but obviously the capabilities and the space will also support collaboration programs. So I think that was the first question. And I think in terms of focus, there is obviously, we have a proprietary differentiation process from our edited stem cells to T cells that go through the process of scale scaling and NGMP transfer, so if there's work to be done, hence having our own facility will be important as a component of that. And I think in terms of the characterization work, which is really, I think, you know, where it's relevant to the allergene position, obviously that's a donor-derived product as opposed to a stem cell differentiated product. You know, Obviously, you know, it's a great team at Allergy, and we know that they'll be all over the evaluation and the interactions with the agency. It will be important not just for us but, you know, others in the field to pay close attention to that. I think we're quite – we have differences, though, around the stem cell characterization at every step of the editing process. That's always been important for our approach, and I think that that also gives you know, perhaps, you know, an advantage in some ways in terms of knowing exactly what the characterization in terms of edits has generated at each step of the clone and differentiation process. So, you know, obviously we'll pay a lot of attention and it will be quite, you know, important in our engagements with the FDA between now and our IMD filing.

Okay. And if I could just ask a different question, which is that as you're approaching the the filing for the synovial sarcoma, how are you planning to layer in a commercial organization as you approach that filing period?

So, thanks, Mara. Helen again here. So in terms of the preparation, as you would imagine, you know, given the plans on Spearhead, Spearhead 1 trial and the progress We have been laying the groundwork for every dimension of commercial readiness, obviously looking a long way out. That obviously includes the work to prepare and scale in John's organization, and I'm sure you can touch on that too. But we have also been looking very closely at... what type of team we need, where we need them, when we need them, and have been building accordingly. And there'll be more to come on that, I think, as we get closer to the VLA filing.

All right. Well, thank you very much.

Cheers, Rob.

And there are no further questions at this time. I will now turn the call back over to Adrian Rockliffe for closing remarks.

Thank you everybody for your questions on what has been a very busy quarter and we look forward to being a very busy next 12 months. It's notable that the questions that you asked covered the broad spectrum of the activities that define adaptivine from our BLA file all the way through our mid-stage trials and into the earliest parts of our allogeneic platform. and also interesting that there's an increased focus which I think is representative of the industry focus at this point in time on the CMC aspects and actually making the product which I think speaks to the investment that we've made consistently over the last five years as we seek to build an integrated cell therapy company to deliver these these potentially transformative therapies to patients. And with that, thank you for your time today and we look forward to future discussions.

This concludes today's conference call. Thank you for participating. You may now disconnect.