Adaptimmune Therapeutics plc

Good day, and thank you for standing by. Welcome to the afternoon second quarter earnings conference call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during this session, you'll need to press star 1 on your telephone. Please be advised that today's conference is being recorded. I would now like to turn the conference over to Julie Miller, Investor Relations. Please go ahead.

Hello and welcome to Adaptimmune's conference call to discuss our second quarter 2021 financial results and business updates. Please review our forward-looking statements from this afternoon'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. Adrianne Rockless, our Chief Executive Officer, is 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 Rockliff.

Thanks, Julie. And thanks, everyone, for joining us. So last year, we set out our 2252 strategy for the next five years. And at the beginning of this year, we identified the milestones in 2021 to start to deliver that strategy. From a clinical perspective, these milestones were, one, to present initial data from our Pivotal Spearhead 1 trial with Afamacel at ASCO with a fuller data set to follow at CTOS. Two, present data from our AFP trial at ILCA. And three, present data from our Surpass trial with our NextGen program targeting MAI-J4 at ESMO. I'm pleased to say that in Q2, we delivered on the first of these with excellent Afamacel data at ASCO. and we're positioned to deliver on the next two in Q3 at ILCA and ESMO as anticipated. I want to say a little bit about each of these milestones in turn. As you can see from the press release, we had a busy Q2. In June, we presented initial data from our pivotal Spearhead 1 trial at ASCO. With a disease control rate of approximately 85%, an overall response rate of approximately 40%, and very encouraging initial durability. These data demonstrate that Afamacel has life-changing potential for people with synovial sarcoma and MR-CLS. We plan to update data from this trial at CTOS later this year. We're working hard to file our BLA next year and achieve the first element of our 2252 strategy to have a product on the market targeting MAJ-A4. we're preparing for a successful commercial launch working with key industry leaders, Agilent for companion diagnostic, Milteni for our lentiviral vector supply, as well as developing our in-house capabilities to support commercial delivery for a famicel. For the second and third clinical milestones this year, we are on track to update in Q3 on our AFP and surpass programs, at ILCA and ESMO, respectively. At ILCA, on September the 5th, Dr. Bruno Sangro will present data from our AFP Phase 1 trial. He'll present data on 13 patients who have been treated in Cohort 3 and Expansion, 11 of whom have had at least one post-baseline scan. We'll issue a full press release around these data, and we'll update regarding this program going forward. At ESMO, we'll present an update from the SURPASS trial with our NextGen program targeting May J4. You'll remember that last year, we reported data at CITSE from six patients in the dose escalation cohorts of this trial, with two confirmed responses in patients with EGJ and head and neck cancer, as well as tumor reductions in three other patients with esophageal, ovarian, and EGJ cancers. As I said in the Q1 call in May, enrollment in the first half of 2021 in this trial has gone very well. As of the data cut for the ESMO presentations, we've treated 25 patients in this trial, and 23 of these patients have at least one post-baseline scan. And we are very much looking forward to sharing this data update as planned at ESMO. The poster will be available online on September the 16th. Again, we'll issue a full press release, and provide an update on the future for the development of this therapy. A couple of other updates on this program. The SURPASS trial was initially in a wide range of MAGE-A4-expressing tumors, but was subsequently amended to recruit in four focus indications, lung, bladder, head and neck, and gastroesophageal cancers, where we had seen anti-tumor activity and responses with our MAGE-A4-targeted therapies previously. Based on emerging data in several patients with ovarian cancer treated in the SURPASS trial, we will add ovarian cancer back to the list of focus indications. So going forward, the SURPASS trial will continue to enroll patients with lung, bladder, head and neck, gastroesophageal, and ovarian cancer. In addition, our SURPASS II trial which is the phase two trial with the NextGen product targeting MAI-J4 for patients with esophageal and EGJ cancers, is on track to initiate as planned in Q3. We've designed a protocol to account for the evolving standard of care in this setting and identify a patient population that is most likely to benefit from this type of therapy. We are committed to identify more indications for late phase development with the 2252 goal of having an additional MAI-J4 marketed product in the next five years. Our clinical data, our translational learnings, as well as our preclinical pipeline, including our industry-leading allogeneic program, move us closer every day to our goal of cell therapy products that are both curative and mainstream. And with that, I'd like to turn it over to the operator for questions.

Thank you. To ask a question, you'll need to press star 1 on your telephone. To withdraw your question, press the pound key. And our first question comes from Tony Butler with Roth Capital. Your line is open.

Good afternoon. Thanks very much for taking the questions. There are two, one with two parts. Adrian, you mentioned the companion diagnostic development with Agilent, and I I'm assuming that you're going to see CLIA validation. So the question is, can you provide some information around the number of patients that you may need to see to provide to the FDA? And importantly, will that cause any delay, or do you think it will cause any delay in the BLA filing based on Spearhead 1? And Part B of that question, would you use this particular validated diagnostic and surpassed two in esophageal cancer in EGJ. Question two is around the program that you have with Astellas. And I recall that one of the, I believe it was one of the hit programs, Astellas had taken, if you will, a ownership or joint venture in. They'd also taken a second program. And I wondered if you would speak to that, and if you don't want to reveal the program, fine, but how far along are the development of both? Thank you. Thanks, Tony.

So we have not provided details on the development pathway for the companion diagnostic. I can confirm that there won't be any delay to, we don't anticipate any delay to the BLA file on the basis of that. Could you repeat the question on the Surpass 2 trial?

Yes, sir. You're going to use that companion diagnostic in the Surpass 2 trial, and therefore that trial may actually be somewhat delayed in enrolling, even though you said it's going to be in Q3.

Thanks. So the answer is no, we're not using that diagnostic in that trial, and we don't anticipate that that will be delayed in enrolling. With respect to the ASTELLAS collaboration, I'm going to ask Helen to comment on the status of those programs.

Thanks for the question, Tony. Can I just repeat it back to you? I think you were double-checking on the second program, but the first one we named mesothelin as a target for one of our HLA-independent or HIT programs. and we are co-developing that one together. The second one has been selected but is not named and won't be named foreseeable, if that's the question.

It is, Helen, and thank you. The issue was how far along has that progressed since they have decided to take that program under their wings as well.

I wouldn't be at liberty to say exactly how far it's progressed, but it is moving along the timelines that we anticipated for selecting the target. So I think early, basically, but not that far behind the measles healing program.

Thanks very much. Thanks, Tony.

Our next question comes from Mark Pham with Cowan & Company. Your line is open.

Hi. Thanks for taking my questions, and congrats on getting all these patients in and ready for presentation. Maybe, Adrian, your comment about adding a focus on ovarian within Surpass, just to be clear, is that based on, I think that you had a little bit of tumor, you had some tumor shrinkage in one ovarian patient as of the last update. Is it based off that, or is it really that you've seen more in additional patients that have happened subsequent to that update?

We are going to comment on any of the data that is in the surpassed trial pending the ESMO data release. I think that question will be much better answered when we can all look at the same amount of data and have that discussion then.

OK. And you may get a similar answer here. But can you give us a flavor? You know, you gave the kind of patient numbers, but can you give a flavor of kind of the spread of tumors that are going to be in there? You know, should we be thinking about any of these tumor types starting to get to that kind of high single-digit, 10-patient type of threshold you've historically talked about that's useful for kind of establishing proof of concept or utility, if that were the case?

You're correct. You're going to get the same answer as for the previous question, but I do admire your persistence on this. We haven't guided and we're not going to guide. I think it's best it's only a month away. Everybody can look at the data set when we put it out there at ESMO and we can talk about it from an informed perspective at that point.

Okay. And then maybe turning to the planned BLA, You're continuing to enroll a second cohort of patients in Sphere Head 1. Will the filing just have the first cohort, you know, that we've already kind of seen the response rate data, plus the couple incremental patients, or do you expect that filing to have the complete trial, including some of these patients who are enrolled into the second cohort?

Yeah. Hi, Mark. It's Elliot. The plan is to file the BLA based on the data in cohort one.

Okay. Thank you. Thanks, Bob.

Thank you. Our next question comes from Michael Schmidt with Guggenheim. Your line is open.

Hey, this is Kelsey on for Michael. I just had two quick ones. Could you just provide some color on where you stand with the launch prep and commercial readiness? And then the second one we saw in the press release that the radiation sub-study was officially closed. Maybe just a little bit of color there on why it stopped. And that's it for me. Thank you.

Thanks, Kelsey. I will ask... Elliot to touch on the radiation sub-study, and Helen, do you want to just pick up on where we are with commercial readiness and prep?

Yeah, sure. I'll kick off with the answer to that one. I mean, I think we're in reasonably good shape. We've been planning for this for quite some time. We've had internal folks focus on the key things around market access, marketing, and broad commercial planning and now we're beginning to turn our attention to dig deeper and also obviously into the outward customer facing roles so as you would imagine we're working very closely with KOLs, et cetera, and then getting feedback and beginning to sort of map out all kinds of materials, pathways, and roles on that side. And then, you know, I know that John could quite easily comment on the prep that's going on to put our commercial manufacturing and our operations, technical operations in place, ready for a different level of delivery of products to complement what we do on the clinical side. So, yeah, that will say more in due course, I'm sure, but at this stage, I think we're pleased with how it's tracking.

John, do you want to pick up on the CMC aspects of this?

Sure. We've said before that our commercial launch will come out of the same facility here in Philadelphia that we've been using for the clinical trials, and we have the capacity that we need for that launch. So supply-wise, we're in good shape, and then we're obviously going through all of the activities that you need to prepare for the BLA filing, the process characterization work, and those type of things, which is proceeding well.

Elliot, do you want to touch on radiation sub-study?

Yeah, sure. So we decided to end enrollment in the radiation sub-study, you know, really for multiple reasons. single center sub-study of the phase one, a famicel multi-tumor study, and really the only part that was remaining open. The study was significantly affected from an enrollment standpoint by the COVID pandemic and really presented a very challenging enrollment scenario with the single center and also with expanding into other centers. And when we look back at the trial design as well, based on how it had been organized, it was really unlikely to provide sufficient answers as it relates to differentiating the addition of low-dose radiation to cell therapies. So while there's still, I think, scientific promise the idea of using low-dose radiation to improve T cell trafficking, and we'll sort of retain the option to reintroduce that at a later time if it makes sense. This study really did not make good sense for us to continue to enroll. The real focus is for those same tumor types that are expressing MAEJ4 to really be put into the CD8-alpha program and continue to enroll for PASS.

Got it. Okay, thank you.

Thanks, Cassie.

Thank you. Our next question comes from Jonathan Chang with SVB Learing. Your line is open.

Hi, guys. Thanks for taking my questions. First question, what do you see as the go, no-go bar for advancing the next J4 program into later stage development for the different indications beyond the Phase I SURPASS study?

Sure. So maybe I'll take a stab at that. So I think I don't want to get into speculation about individual tumor types. I think we'll let the data speak for itself at ESMO. But I think I'd just refer everybody to the discussions that we've had previously about what efficacy and cell therapy is. in very late stage populations such as those that we're studying in this phase one trial would look like. And I think we've consistently said that three out of ten patients responding with benefit to patients of six months, give or take, would probably be the ballpark that we're looking to see. Now, obviously, that does vary depending on individual settings and tumor types, but I think we need to understand the data a little bit more before we can discuss that and look forward to doing so. from asthma onwards.

Got it. And maybe a similar question in the same vein. What do you see as the go, no-go bar for picking a particular indication to be a focus indication in the ongoing SURPASS study?

But that one was a bit more, a bit simpler in that we selected those indications some time ago, the four that we had previously. And obviously, I'm not going to comment on the rationale behind putting ovarian in. As I commented earlier, we'll talk about that when we get down to ESMO. But more generally, you might recall that we had an analysis of all of the patients that were treated with MAEJ-A4 targeting therapies in both the dose escalation portions of the SURPASS study and then also the phase one trial for a famicel that recruited a number of non-sarcoma patients, you may recall. And the indications that we selected as focus indications then, lung, bladder, gastroesophageal, and head and neck, were indications where we had seen either confirmed responses or very substantial anti-tumor activity in the case of bladder or urethelial cancer. We didn't have any responses there, but we had seen very significant anti-tumor activity and really was a way of focusing down that trial from the sort of 10 indications that it routinely expressed MAI-J4 down to something a bit more manageable to try to get to patient numbers where we could make development decisions.

Understood. Thanks for taking the questions. Thanks, Jonathan.

Our next question comes from Mara Gladstein with Mizzou. Your line is open.

Thank you. Hey, it's Mara Goldstein. Just two questions. On Surpass 2, you spoke to in your prepared comments about making some modifications to sort of conform to evolving standard of care, and I'm wondering if you can just speak to that at this point in time. And then the second is I'm just curious. We've heard from a couple companies within the cell therapy space around vector supply constraints, and you also kind of alluded to a little bit around sort of supply constraints. Maybe you could speak to that specifically as it relates to you guys and what you're doing.

Certainly. Thanks, Mara. So I'm going to ask Elliot to talk about the SURPASS-2 study and the standard of care evolution there, and then I'll ask John to pick up the discussion on our strategy around vector supply. Thank you.

Thank you.

Yeah, hi, Mara. Just very briefly, you know, the standard of care for really the gastroesophageal cancers has evolved from being a chemotherapy approach in first line followed by PD-1 inhibitor in most scenarios. There are some other drugs that play in in specific settings, but those drugs are now being used fairly commonly as a combination first-line approach, which does two things. I mean, first of all, it improves the standard of care for those patients, but it also opens up the space for second-line therapy in many patients in that the patients don't just receive, they don't receive, you know, first chemotherapy, progress, then PD-1 inhibitor, then progress, then be open to third-line treatments. They're really compressing those two treatments still into first-line. That being said, there's still tremendous unmet need in this population, and that the response rate and duration of response with that combination, although better and an advancement for patients, there's still quite a long way to go to help this really devastating tumor type the patients with those diseases.

So the modifications you'll expect to make will be essentially to move sort of closer to a second-line therapy? Is that what I'm understanding?

The study does allow for the drug to be used in second line behind combination chemotherapy. We've made some other changes with respect to patient selection and whatnot based on what we've learned in in the phase one program, but that's the most significant change.

Okay, all right, thank you.

Yeah, and on the vector, you probably recall back in 2017, we made the decision to pursue a vector strategy that had two main elements. One was an external partner that could work with us through commercial, and Ed mentioned Milteni earlier, which we've used, worked with Milteni for the vector supply for our Spearhead trial and other trials. So that's the material that we'll use going into commercial. But secondly, we decided to also develop the internal capabilities. So we have done that, and we're supplying our other trials with material produced internally from our facility that's in the Cell and Gene Therapy Catapult Center in the UK. So we've kind of executed on the plan to have two sources of vector available to us, one internal and one external.

Okay. All right. Thanks a lot.

Thanks, Lauren.

Thank you. And there are no other questions in the queue. I'd like to turn it back to Adrian Rockwell for closing remarks.

Thank you, everyone, for your questions and your continued support for the company. We look forward to updating everyone on the data in September and keeping you up to date with continued progress. With that, we'll close the call. Thanks a lot.

This concludes today's conference call. Thank you for participating. You may now disconnect. Everyone, have a great day.