Adaptimmune Therapeutics PLC
NASDAQ:ADAP
Adaptimmune Therapeutics PLC
NASDAQ:ADAP
Price:
1.195 USD
-3.63%
Market Closed
Updated:
May 16, 2024
Section:
Earnings Call Analysis
Summary
Q3-2023
Q3-2023
Adaptimmune Advances SAR Programs, Narrows Clinical Focus
Adaptimmune, midway through Q4 2023, has made significant strides in restructuring to cut costs, and advancing Afami-cel towards commercialization with a BLA submission expected this quarter. Interactions with the FDA have been positive, with consensus on BLA content and favorable feedback. Lete-cel and PRAME have been reacquired from GSK, with Lete-cel potentially tripling the addressable market. The merger with TCR2 has been completed. The company stopped further development of Gavo-cel and TC-510 due to insufficient clinical benefits. Focus has narrowed to ovarian, head and neck, and bladder cancers in the SURPASS trials, with promising response rates leading to a registrational Phase II SURPASS-3 trial in ovarian cancer.
You don't have any saved screeners yet
Good morning, ladies and gentlemen, and welcome to the Adaptimmune 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.
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?
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 5 key goals: one, create 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, whilst 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 will 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?
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 3 modules, the preclinical module at the end of last year. In quarter 1, 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 been -- and we have taken advantage of frequent interactions with the FDA. Meetings have been positive, and we have taken significant steps to derisk 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 data set 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?
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. And 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 2 to 3x 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. And on the fifth goal, the prioritization of the clinical pipeline based on data. Today, we announced we are stopping further development of the 2 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 improved to 75% in patients who received 3 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 3 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 Instructions]
Our first question is from Mara Goldstein from Mizuho Securities.
This is Jerry Dong on for Mara Goldstein. I guess starting off with SURPASS and ADP that trial, there was better activity seen in earlier line patients. Can we expect that to be an increased focus in the -- in 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 progress to a therapeutically active dose.
So I'm going to 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.
Yes. Thanks very much. So I think 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 it's our intent to really optimize the data that we have coming out of that study in the next 6 to 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.
And 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 going to be.
Our following question is from Marc Frahm from TD Cowen.
Even though 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 some approval and then on the earlier stage with the PRAME, just with the increased sensitivity, I guess how would you expect that to manifest in the clinic, would that -- do you think that's more likely to drive a response rate benefit, a duration benefit? Or is it just maybe somewhat broader eligibility criteria.
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 on -- 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 going to ask Joe to comment on the expectations that we have for that highly sensitive TCR.
Yes. 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 should affect both metrics in a positive way.
Our following question is from Michael Schmidt from Guggenheim Partners.
This is Paul on for Michael. 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, some signals in ovarian and uterine, what is your view on the clinical landscape so far for PRAME? And what's your confidence in potentially being able to address 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 spot benefit?
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, very happy about that.
And really, in the cell therapy space, there are only really 2 significantly advanced PRAME programs with specific engineered TCRs, and I think therefore, 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'd just point out that 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 clearly the 2 leading programs in that space.
With respect to Lete-cel and the data, I think I'm just going to -- I'm going to 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.
Following question is from Jonathan Chang from Leerink Partners.
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 into commercial stage, the TCR2 assets being discontinued and the PRAME program entering in clinic.
So Gavin, our CFO, do you want to take that question?
Yes. So the step-up this quarter in R&D was down to 2 reasons. One was a full 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 -- we've got Afami-cel commercial launch. We've got the great data we've seen on Lete-cel, and we'll be updating all our development plans early in the new year.
Great. If I can just ask 1 follow-up. How are you guys currently thinking about your second-gen versus your first-gen power candidates? And do you plan on utilizing the CD8 coreceptor transaction with your ADP600 candidate as well?
Yes. So we are planning multiple next-gen approaches with the PRAME candidate with ADP600. 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 real approaches as well. So one particularly to tackle longevity, but to hopefully increase the duration of response, but also we're looking at a switch receptor as well, thinking that maybe in different context, you will actually have greater success with different candidates.
Following question is from Yanan Zhu from Wells Fargo Securities.
Great. First off, 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.
Yes. Thanks so much. So we haven't specifically guided to the exact number of patients that we would intend to enroll. I think that we've seen small to moderate data sets in head and neck and bladder cancer with 4 patients having been -- 4 patients in the data set with head and neck and 7 with urothelial. And I'd like to see us 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 2 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 in the future.
Got it. In terms of key metrics for success, would it -- would the new data be hold -- held to the same kind of a level as the few patients reported? Or where does the bar start in terms of positive signal?
Well, I think that 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, 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 response rates in the spaces that we would likely pursue need to be north of 35% or so and durations of response need to be in -- at least in the 5- to 6-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.
Great. If I may, sorry, add one question on urothelial cancer here. There was a recently practice-changing data out of the, I think, EV-302 trial for the ADC plus PD-1 in frontline setting. Does that have any impact, do you think, to the positioning or how you conduct the study for the urothelial patients?
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, 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 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 -- onetime 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 likely opens up the space for more opportunity if nothing else.
Very helpful. On the PRAME announcement, I was just happen to be 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 T-cell therapies in melanoma, there's TIL's in late-stage review by FDA and obviously, it looks like the melanoma data today from a competitor, it looks also quite encouraging.
Hopefully, you would also show even a demonstration of differentiation even from the competitor. But how do we think about how these cell -- T-cell therapies position against each other in a melanoma setting.
Okay. I'm going to ask Joe 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 are happy to set up a follow-up call for any other questions you might have as well. Joe?
Yes. So the PRAME TCR sensitivity is very similar to the MAGE-A4 one, actually slightly better. So we anticipate that's one of the things that makes us very confident in this TCR. Obviously, every tumor action 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 1 to 1 in that sensitivity analysis. So I think we're very confident that it will react to relatively low levels of antigens, which is really positive.
With respect to the competitive landscape, I would put both the TIL therapy and the opportunity for PRAME in melanoma, actually in a much broader context. This is -- if you think about what's happened in the last year or 2, 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 is a modality of therapy is here to stay.
If you roll forward a year from now, there's high probability that you will have 2 therapies, 2 cell therapies in the solid tumor space on the market, 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 established 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.
[Operator Instructions]
Following question is from Peter Lawson from Barclays.
Great. On the ovarian cancer program, would we potentially get interim analysis to that in the second half of '24. Just if you can kind of give us any time lines around the data sets and kind of how much -- how many patients would we see for ovarian cancer, I have got a follow-up.
So I'm not going to give specific time lines, but the only thing I am going to 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, we -- 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 and so that will be the earliest point as when we give interim analysis in interim data sets.
Perfect and then on the PRAME, actually I'll apologize if I missed this, but where are the components you're going to be engineering into the T-cell, whether it's CD8 or if you're using the TCR2 approach?
Joe, do you want to talk about how we think about that?
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.
Okay. So its kind of being almost like a big option of those various components of the CD8.
Yes. Yes.
And I think, Joe, you commented earlier that it might be that in different settings, different next-generation approaches are more or less useful. So we'll be taking that into account as well.
Then we have the second line from Peter Lawson from Barclays.
Peter, you have other questions? No?
So I think that was a repeat, operator.
Yes, exactly. Thank you.
So we have no further questions registered at this time. I would now like to turn the meeting back over to you, Mr. Rawcliffe.
Thanks very much. And thanks, everybody, for your time today and the questions across the breadth of the portfolio we now are developing. I am looking forward to updating you on the 3 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.
Thank you. The conference has now ended. Please disconnect your lines at this time, and we thank you for your participation.