Adaptimmune Therapeutics - Q3 2023
November 8, 2023
Transcript
Operator (participant)
All participants, please stand by. Your conference is ready to begin. Good morning, ladies and gentlemen, and welcome to the Adaptimmune's Q3 Financial and Business Update conference call. I would now like to turn the meeting over to Ms. Juli Miller. Please go ahead, Ms. Miller.
Juli Miller (VP of Corporate Affairs and Investor Relations)
Good morning, and welcome to Adaptimmune's conference call to discuss our third 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, and Dennis Williams, our Senior Vice President of Late-Stage Development, are 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?
Adrian Rawcliffe (CEO)
Good morning. Thanks, Juli, and thanks everyone for joining us. In the first part of 2023, we set out to transform Adaptimmune. Specifically, we set out to accomplish five key goals. One, complete a large organizational restructuring to significantly reduce our cost base. Two, submit our BLA for Afami-cel, putting us on the path to being a commercial cell therapy company. Three, recover Lete-cel and PRAME from GSK. Four, complete the strategic combination and subsequent integration of TCR². And five, prioritize our clinical portfolio on the basis of data throughout the year. Midway through Q4 2023, we've made significant progress in each of these. In relation to the reorganization, while these things are always difficult, we achieved it with limited disruption to the company and to its momentum.
On the second goal, Afami-cel, we showed data last week at CTOS, demonstrating clear, lasting benefit for people with synovial sarcoma who respond to Afami-cel, and we'll complete the submission of the BLA this quarter. I want to ask Dr. Dennis Williams, who's been responsible for the development of the Afami-cel program, to comment on its current status. Dennis?
Dennis Williams (SVP of Late Stage Development)
Thank you, Ad. I want to echo Ad's excitement for our Afami-cel data. I attended the annual meeting of the Connective Tissue Oncology Society, or CTOS, where Dr. Brian Van Tine presented updated data, and they are transformational for people with synovial sarcoma. One of the primary goals of CTOS is to advance the care of people with sarcoma, and doctors who treat people with synovial sarcoma are eager to have Afami-cel as a therapeutic option. We share this eagerness, and completion of the BLA has been our top priority. As part of the rolling submission, we submitted the first of three modules, the preclinical module, at the end of last year. In quarter one, we completed submission of the clinical module. Since that time, we have been focused on completing submission of the CMC module.
All BLA CMC validation work is complete, including assay method validation and process performance qualification. Completion of the final section of the BLA is imminent. We are in the final stages of dossier preparation. This includes activities such as the comprehensive review of the dossier, labeling and summary document finalization, and regulatory submission publishing. We have RMAT designation and have taken advantage of frequent interactions with the FDA. Meetings have been positive, and we have taken significant steps to de-risk our file. Last year, at the pre-BLA meeting, Adaptimmune and FDA agreed on the planned content of the BLA. We have also received what we believe is favorable FDA feedback in July on the commercial T-cell potency assay, including agreement on the potency dataset for inclusion in the submission.
The agency also agreed that data from Cohort 2 of the SPEARHEAD-1 trial can serve as confirmatory evidence for full approval. This cohort is fully enrolled, with mature data readouts expected late next year. We know that Afami-cel has the potential to transform the way synovial sarcoma is treated, and bringing this product to market is very important to us and the sarcoma community. With that, I will turn it back over to Ad. Ad?
Adrian Rawcliffe (CEO)
Thanks, Dennis. Returning to the other accomplishments in 2023, the third one relates to the recovery of Lete-cel and PRAME from GSK. The rights to PRAME are fully recovered, and the Lete-cel transfer is in an advanced stage, with the IND set to transition shortly. We recently reported data from a planned interim analysis of the pivotal IGNYTE-ESO trial with Lete-cel, showing 18 responses by independent review out of 45 people with synovial sarcoma or MRCLS. Therefore, the trial will meet its primary endpoint for efficacy, which required only 16 responders out of 60 patients in this cohort. I would note that all 60 patients have been treated, and we will have further data readouts next year. We're excited about how Lete-cel and Afami-cel complement one another.
Our initial assessment is that Lete-cel could increase the addressable market by two to three times and could be delivered with essentially the same commercial organization. We will continue to evaluate how Lete-cel fits into our pipeline, and I'll update you on our plans for our expanded sarcoma franchise early next year, after the transition from GSK is complete and after we have submitted the BLA for Afami-cel. For the fourth goal, related to the combination with TCR², we completed the transaction in Q2, and the business integration is now also complete. On the fifth goal, the prioritization of the clinical pipeline based on data. Today, we announced we are stopping further development of the two mesothelin-directed TRuC programs, Gavo-cel and TC-510.
We have reviewed the data from the phase II trial of Gavo-cel and the phase I trial of TC-510, and the magnitude of the clinical benefit in either program does not justify further development. Although it's difficult to stop a program when it is evident some patients are getting benefit, we do not see a rapid route to market with either of these assets, and we are committed to focus our resources on cell therapies where this path is clear. With respect to other pipeline priorities, we are narrowing our next-gen ADP-A2M4CD8 SURPASS trials to focus on ovarian, head and neck, and bladder cancer, and we showed data supporting this prioritization at ESMO. In our focus indications, there was a 50% response rate, which improves to 75% in patients who received three or fewer prior lines of therapy.
Based on this encouraging data, the SURPASS phase I trial will only enroll patients with head and neck and urothelial cancer in earlier lines of treatment and in combination with checkpoint inhibitors. Enrollment of patients with other indications in this trial has been discontinued, and we have also initiated the phase II SURPASS-3 trial in platinum-resistant ovarian cancer, which we intend to be registrational. This has been a transformational year for the company, and we will achieve each of the goals we set out in 2023. Data readouts demonstrate that our engineered cell therapies work across multiple solid tumors, and we continue to prioritize our resources on those products that have the greatest chance of commercial success. In closing, I want to focus attention on three events in the short term. One, the completion of the submission of the Afami-cel BLA this year.
Two, transfer of Lete-cel IND from GSK this year. And three, updating you in the new year on the path to deliver our expanded sarcoma franchise. And with that, I'd like to turn it over to the operator for questions. Operator?
Operator (participant)
Thank you. We will now take questions from the telephone lines. If you have a question and you are using a speakerphone, please lift your handset before making your selection. If you have a question, please press star one on your device's keypad. You may cancel your question at any time by pressing star two. Please press star one 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 Mara Goldstein from Mizuho Securities. Please go ahead.
Jerry Gong (Associate)
Hi, this is Jerry Gong on for Mara Goldstein. Thanks for taking our questions, and congrats on the quarter. I guess starting off with, you know, SURPASS and [ADP] trial, there was better activity seen in earlier line patients. Can we expect that to be an increased focus, you know, in the SURPASS and SURPASS-3, enrolling patients earlier in their disease course And I guess secondly, with ADP-600, which is that PRAME TCR, I know it's early, but has a starting dose been planned yet? And how quickly, if so, do you think you can, you know, progress to a therapeutically active dose? Thanks.
Adrian Rawcliffe (CEO)
So, I'm gonna ask Elliot to talk about the implications of the earlier line observation on our development plan in head and neck, bladder, and what we're doing in ovarian cancer, and then we'll come back to PRAME.
Elliot Norry (CMO)
Yeah, thanks very much. So I think, you know, you, you stated it correctly. The focus of the treatment of patients in the SURPASS phase I trial will be solely on patients who have either head and neck cancer or urothelial cancer, with particular attention to patients who have had fewer prior lines of therapy. In addition to that, we plan to dose the patients that we can, with checkpoint inhibitors in combination. And that—it's our intent to really optimize the data that we have coming out of that study in the next 6-12 months to demonstrate how the product works, particularly in that patient set. As it relates to SURPASS-3, that study is being conducted in patients with platinum-resistant ovarian cancer, which is a fairly well-defined patient entity.
That being said, we do restrict the number of prior lines in that study, and pleased to say that that study is open and enrolling, and we really do expect to see a robust enrollment of the trial in 2024.
Adrian Rawcliffe (CEO)
Then with respect to PRAME, I think it's a little early to say. We're very excited about the opportunity with the PRAME program, both ADP-600, the TCR itself, and the second gen approaches that we have in the hopper. But it's a little too early to say what the dose escalation and the starting dose is gonna be.
Operator (participant)
Thank you. Our following question is from Marc Frahm from TD Cowen. Please go ahead.
Marc Frahm (Biotechnology Equity Research Analyst)
Hey, thanks for taking my questions. As the durability data continues to evolve in sarcoma, just how is that impacting your kind of view on pricing for that product as we get towards an approval? And then on the earlier stage with the PRAME, just with the increased sensitivity, you know, I guess, how would you expect that to manifest in a clinic? Would that do you think that's more likely to drive a response rate benefit, a duration benefit, or, you know, is it just maybe somewhat broader eligibility criteria?
Adrian Rawcliffe (CEO)
So I think it's a little too early to comment on the pricing strategy that we have for Afami-cel. The only thing I will comment on is that the efficacy that we are clearly seeing, the duration of response, the clear benefit to the responders on overall survival and on time to next treatment, is clearly the type of evidence that one needs to support pricing in a rare tumor type like synovial sarcoma. And we look forward to a, getting the product approved, and b, the commercialization of that as our first product. With respect to PRAME, I'm gonna ask Jo to comment on the expectations that we have for that highly sensitive TCR.
Joanna Brewer (Chief Scientific Officer)
Yeah. So with the greater peptide sensitivity, we would expect it to be able to tackle tumors with lower antigen expression. So we're hoping to be able to treat a broader range of antigen expression, and we would expect the effect to show up both in the overall response rate and in the duration of response. So it would, it should affect both metrics in a positive way.
Marc Frahm (Biotechnology Equity Research Analyst)
Great. Thank you.
Adrian Rawcliffe (CEO)
Bye. Thanks, Mark.
Operator (participant)
Thank you. Our following question is from Michael Schmidt. It's from Guggenheim Partners. Please go ahead.
Paul Jeng (VP of Biotechnology Equity Research)
Hi, this is Paul on for Michael. Thanks for taking our questions. I have a follow-up on the PRAME. Just on the competitive landscape, given that there was some updated data this morning from Immatics with plans to move forward in melanoma and some signals in ovarian and uterine. You know, what is your view on the clinical landscape so far for PRAME? And what's your confidence in potentially being able to address, you know, cancer types beyond those listed like lung and breast cancer with the enhanced sensitivity TCR? That's my first question. Second one is just quickly on Lete-cel. Can you help put that interim data from IGNYTE-ESO in context with what you've shown with Afami-cel, and any view on how that might translate over to a survival benefit? Thank you.
Adrian Rawcliffe (CEO)
Certainly. So maybe I'll just touch on the PRAME with the competitive landscape. I think we're quite delighted to see the data from Immatics' PRAME program today. I think that really is a very strong validation, if any were needed, of the opportunity for TCR-based therapies in the solid tumor space, particularly those targeting cancer testis antigens like PRAME, like MAGE-A4, like NY-ESO. And I think this is just further validation that the future, or at least a significant part of the future of cell therapy and solid tumor, lies through these approaches. So we're very happy about that. And really, in the cell therapy space, there are only really two significantly advanced PRAME programs with specific engineered TCRs.
I think, therefore, that there's a lot of opportunity for product development in that space to leverage what we believe from our perspective will be a best-in-class program. And I've, I just point out that the... You compare the competition there to the competition against almost any other cell therapy target, I would refer you to CD19 and BCMA by way of example. And the space is wide open, and these are, these are clearly the two leading programs in that space.
With respect to Lete-cel, and the data, I think I'm just gonna take that comment and just in a short, summarized fashion, say the data at the moment looks to be quite comparable to the data with Afami-cel, although obviously it's in a larger, broader population because it includes MRCLS. But a 40% response rate and a decent but slightly immature durability, I think, is consistent with what we've seen with Afami-cel. And so we look forward to getting that program back, considering it, and I'll update everybody in the new year about our plans for that.
Paul Jeng (VP of Biotechnology Equity Research)
Okay, thanks very much.
Adrian Rawcliffe (CEO)
Thanks, Paul.
Operator (participant)
Thank you. Following question is from Jonathan Chang from Leerink Partners. Please go ahead.
Dylan Drakes (Equity Research Associate of Emerging Oncology)
Hi, guys. Thanks for taking my questions. This is Dylan Drakes on for Jonathan Chang. It seems you had a bit of a step up in R&D expense this quarter. I was wondering how we should think about spend going forward with the Afami-cel going to commercial stage, the TCR² asset being discontinued, and the PRAME program entering the clinic?
Adrian Rawcliffe (CEO)
... So, Gavin, our CFO, do you want to take that question?
Gavin Wood (CFO)
Yeah. So the step up this quarter in R&D was down to two reasons. One was first quarter of TCR², R&D expenses included, and secondly is a reduction in the R&D tax credit due to a change in the tax regime here in the U.K., which means the offsetting tax credit is declining. That legislation is actually under review. In terms of going forward, clearly, we've got, you know, we've got Afami-cel with commercial launch. We've got great data we've seen on Lete-cel, and we'll be updating all our development plans early in the new year.
Dylan Drakes (Equity Research Associate of Emerging Oncology)
Great. Thanks so much. If I could just ask one follow-up. How are you guys currently thinking about your second gen versus your, versus your first gen product candidates? And do you plan on utilizing the CD8 co-receptor transduction with your ADP-600 candidate as well?
Joanna Brewer (Chief Scientific Officer)
Yes, we are planning multiple next gen approaches with the PRAME candidate with ADP-600. And we do think that those next gen approaches will be part of broadening the franchise out to multiple tumor types. It may not be that CD8 is optimal in all of them, although that will certainly be one of the ones that we're using. But we're using some other approaches as well. So one, particularly to tackle longevity, but so to hopefully increase the duration of response. But also we're looking at a switch receptor as well, thinking that maybe in different contexts, you will actually have greater success with different candidates.
Dylan Drakes (Equity Research Associate of Emerging Oncology)
Great, thanks so much. I appreciate that.
Operator (participant)
Thank you.
Adrian Rawcliffe (CEO)
Thank you.
Operator (participant)
The following question is from Yanan Zhu, from Wells Fargo Securities. Please go ahead.
Yanan Zhu (Senior Analyst of Biotechnology Equity Research)
Great, thanks for taking our questions. First, a question about MAGE-A4. So you're enrolling head and neck and urothelial patients in earlier line setting in SURPASS-1. I was wondering, how many patients do you aim to enroll in those indications? What would be a bar for success? Obviously, you had great data in your previously reported patients, but going forward, what's your bar for success for the additional patients to be enrolled? And when we might be able to see data from those additional patients? Thank you.
Elliot Norry (CMO)
Yeah, thanks so much. So, we haven't specifically guided to, you know, the exact number of patients that we would intend to enroll. I think that we've seen a small to moderate data sets in head and neck and bladder cancer, with four patients having been... four patients in the dataset with head and neck and seven with urothelial. And I'd like to see us, you know, get closer to the size data sets that we have seen in phase I with ovarian cancer, to be able to make the most informed decisions about how to prosecute those two indications going forward. With respect to when you would see that data, it certainly wouldn't be in the early part of next year, and we haven't provided specific guidance.
But we're enrolling those patients actively now, and we'll hope to be able to provide additional information, you know, in the future.
Yanan Zhu (Senior Analyst of Biotechnology Equity Research)
Got it. In terms of key metrics for success, would the new data be held to the same kind of a level as the few patients reported? Or, you know, where does the bar start in terms of positive signal?
Elliot Norry (CMO)
Well, you know, I think that for the, for response rate, what we've seen in phase I is really quite remarkable in the number of patients that we've dosed. I would love to see with a larger data set that kind of response rate is maintained. Although, for example, in head and neck cancer, if it doesn't turn out to be 75% responders, but something slightly lower than that, I think we'd still be thrilled.
The truth is that we'd be ultimately, from the standpoint of being able to provide meaningful benefit to patients, I think that, you know, response rates for the spaces that we would likely pursue need to be, you know, north of 35% or so, and durations of response, you know, need to be at least in the five to six month range, for us to be able to think about later stage programs. But we're incredibly enthusiastic about the data that we've seen. And I think that we just need to consolidate that with additional clinical information to move forward.
Yanan Zhu (Senior Analyst of Biotechnology Equity Research)
Great. If I may, sorry, add one question on urothelial cancer here. You know, there was recently practice-changing data out of the, I think, EV-302 trial for the ADC plus PD-1 in a frontline setting. Does that have any impact, you think, to the positioning or how you conduct the study for the urothelial patients?
Elliot Norry (CMO)
So, of course, I think we have to take that into consideration with respect to positioning, and that data is fantastic for patients with urothelial cancer. You know, received standing ovation at ESMO. So, we of course have to consider that. I think that the idea that pembrolizumab and PADCEV are being moved, you know, clearly toward the first line space opens up a lot of opportunity in second line plus treatment. So, from the standpoint of bladder cancer, in the patients that we enroll, we do expect that some of them will have potentially been treated with that type of treatment regimen going forward.
But, if we're able to demonstrate with a single therapy, the kind of a one-time therapy, the kind of response rate that we have in patients with very advanced disease, we think that the movement of pembrolizumab into first line and chemotherapy out of first line treatment, you know, likely opens up the space for more opportunity, if nothing else.
Yanan Zhu (Senior Analyst of Biotechnology Equity Research)
Very helpful. On the PRAME announcement, I just have this curious, a couple of curious questions. How does the sensitivity of this TCR to PRAME compare with your MAGE-A4 TCR sensitivity against MAGE-A4? And then I was just curious about the positioning of potentially two cell, you know, T-cell therapies in melanoma. There's TILs in late-stage review by FDA, and obviously looks like the melanoma data today from a competitor. It looks also quite encouraging. Hopefully, you would, you know, also show even, you know, a demonstration of differentiation, even from the competitor. But how do you think about how these cell therapy, T-cell therapies position against each other in a melanoma setting? Thank you.
Adrian Rawcliffe (CEO)
Okay. I'm gonna ask Jo to take the question on sensitivity relative to MAGE-A4. I'll then comment briefly on the emerging field of cell therapy in solid tumors, and of course, we're happy to set up a follow-up call for any other questions you might have as well. Jo?
Joanna Brewer (Chief Scientific Officer)
Yes. So the PRAME TCR peptide sensitivity is very similar to the MAGE-A4 one, actually slightly better. So we anticipate, you know, that's one of the things that makes us very confident in this TCR. Obviously, every tumor antigen is slightly different, so it does depend on how the protein is expressed and how well it's processed. So you can't—they don't read exactly one to one in that sensitivity analysis. So I think we're, we're very confident that it will react to relatively low levels of antigen, which is, is really positive.
Adrian Rawcliffe (CEO)
With respect to the competitive landscape, I would put both the TIL therapy and the opportunity for PRAME and melanoma actually in a much broader context. You know, this is. If you think about what's happened in the last year or two, it's become clear that cell therapies in solid tumors can demonstrate incredible response rates in very late stage patients. And that gives, I think, confidence that this as a modality of therapy is here to stay. If you roll forward a year from now, the high probability that you will have two therapies, two cell therapies in the solid tumor space on the market, Afami-cel, or Afami-cel and obviously, the TIL program. Coming behind that could be Lete-cel. Coming behind that could be our CD8 program in ovarian cancer.
Coming behind that is head and neck and bladder cancer. Coming behind that is perhaps Immatics' PRAME program in melanoma. And I just think you're seeing a move to establish cell therapy in these spaces as a modality that can have significant benefits for patients who have very few other options. And I'm looking forward to initially the TILs and subsequently the engineered cell therapies presence in spaces like melanoma, because I think, unlike sarcoma, which is a relatively rare focused indication, these are much larger indications, and I think establishing them in those much larger populations will be really important for the field.
Yanan Zhu (Senior Analyst of Biotechnology Equity Research)
Great, thank you for all the color.
Adrian Rawcliffe (CEO)
Thank you.
Operator (participant)
Thank you. Once again, please press star one at this time if you have a question. Following question is from Peter Lawson from Barclays. Please go ahead.
Peter Lawson (Managing Director of US Biotech Equity Analyst)
Great. Thank you for taking the questions. Just on, on the ovarian cancer program, would we potentially get interim analysis to that in the second half of 2024? Just if you kind of give us any timelines around the data sets and kind of how many patients we'd see for ovarian cancer, but follow up?
Adrian Rawcliffe (CEO)
So, I'm not gonna give specific timelines. The only thing I am gonna do is say that we will likely be in a position to disclose the interim data analysis once we have completed enrollment of all of the patients in that study. You know, as previously stated, we do intend for this study to be registrational, and we do not want to introduce any bias into the patient enrollment. So, that will be the earliest point as when we give interim analysis in interim data sets.
Peter Lawson (Managing Director of US Biotech Equity Analyst)
Perfect. Thank you so much. And then on the PRAME, I apologize if I missed this, but there are the components you're gonna be engineering into the T-cell, whether it's CD8, or if you're using the TCR² approach?
Adrian Rawcliffe (CEO)
Jo, do you want to talk about how we think about that?
Joanna Brewer (Chief Scientific Officer)
So we're really thinking about doing those, as individual kind of test products. So we're looking at the merits of each of those next gens individually to see how well those will perform.
Peter Lawson (Managing Director of US Biotech Equity Analyst)
Okay. So it kind of be almost like a bake off of, of those various components-
Joanna Brewer (Chief Scientific Officer)
Yeah.
Peter Lawson (Managing Director of US Biotech Equity Analyst)
-of the CD8.
Joanna Brewer (Chief Scientific Officer)
Yeah. Yeah.
Adrian Rawcliffe (CEO)
I think, Jo, you commented earlier that it might be that in different settings,
Joanna Brewer (Chief Scientific Officer)
Yeah.
Adrian Rawcliffe (CEO)
-different, next generation approaches are more or less useful.
Joanna Brewer (Chief Scientific Officer)
Yeah.
Adrian Rawcliffe (CEO)
So we'll be taking that into account as well.
Peter Lawson (Managing Director of US Biotech Equity Analyst)
Okay. Thank you so much.
Adrian Rawcliffe (CEO)
Thank you. Thanks for this.
Operator (participant)
Thank you. We have a second line from Peter Lawson from Barclays. Please go ahead.
Adrian Rawcliffe (CEO)
Peter, you have other questions?
Peter Lawson (Managing Director of US Biotech Equity Analyst)
No.
Operator (participant)
So I believe-
Adrian Rawcliffe (CEO)
I think that was a repeat.
Operator (participant)
Duplicate.
Adrian Rawcliffe (CEO)
Operator.
Operator (participant)
Yeah, exactly. Thank you. So we have no further questions registered at this time, so I would now like to turn the meeting back over to you, Mr. Rawcliffe.
Adrian Rawcliffe (CEO)
Thanks very much, and thanks everybody for your time today and the questions across the breadth of the portfolio we are now developing. I am looking forward to updating you on the three key things in the course of the coming months. One, the submission of the BLA for Afami-cel. Two, the transfer of the Lete-cel IND, and in the new year, the plans for our sarcoma franchise. In the meantime, if you have any questions, please do reach out. Thanks for your time today. Take care.
Operator (participant)
Thank you. The conference has now ended. Please disconnect your lines at this time, and we thank you for your participation.