Word count: 2,971
TWST: Let’s start with an overview of the company, its history and how it has evolved over the years.
Mr. Rawcliffe: Sure. So Adaptimmune is an integrated cell therapy company. We’re focused with a platform derived from affinity enhanced T-cells and we’re targeting solid tumors. And that’s different. We also have a pipeline of clinical products with a first BLA — Biologics License Application — to be submitted this year for a rare tumor type called synovial sarcoma. We presented data at ASCO this year on that. And we think that will be the first transformative medicine for patients with metastatic synovial sarcoma for several decades, actually.
Behind that we have a pipeline of affinity enhanced T-cells, the most advanced of which other than the one that’s being submitted for the BLA, is across a range of tumor types in a family of trials called SURPASS. And it targets a target that’s present on head and neck, bladder cancer, lung cancer, gastroesophageal cancers. And we’re in mid-stage trials in those indications with the intention to take future products towards the market in due course, and we’re presenting data from the Phase 1 SURPASS trial at ESMO this year. So we are an integrated cell therapy company, submitting a BLA this year, broad platform coming, broad pipeline coming behind that.
And in terms of how we’ve evolved? I think we’ve evolved consistent with the space and our leadership position in it. We, as a company — we’ve been a company for 14 years. So we’re long standing in the cell therapy space. And we’ve seen that space evolve from science projects to real products on the market. And the next frontier, the holy grail for cell therapy is the ability to get cell therapy to work in solid tumors. And that’s where we’ve been focusing all our energy. And we are absolutely at the leading edge of that with the first engineered T-cell therapy in a solid tumor space, with a BLA submission this year.
TWST: I know you have different terminologies here, so I just want to make sure. Is that a part of SPEAR or is that something separate?
Mr. Rawcliffe: So a SPEAR describes the underlying technology platform. It stands for Specific Enhanced Activity Receptor. So it describes the fact that we engineer the T-cell receptors on T-cells to be able to recognize cancer, specific targets on cancer with enhanced affinity. And that overcomes the main thing that happens with your immune system and cancer, which is your immune system just can’t recognize cancer with enough specificity to go ahead and kill it.
And so we engineer the T-cell receptor, which is the business end of the T-cell. It’s the thing that T-cell uses to recognize what it wants to kill. And we engineer that so it can see cancer targets. And then when it does, the T-cell does its job; it kills those targets, and it brings in the rest of the immune system as well to attack that cancer. So the way to think about these cells is like they’re the stormtroopers kicking in the door; if these cells can attack cancer cells, then the rest of the immune system piles in behind to eradicate the tumor.
TWST: And where are you in terms of clinical trials?
Mr. Rawcliffe: So our lead product, or afami-cel, for synovial sarcoma has completed the hypothesis testing cohort for its pivotal trial. We announced that the trial was positive last year with a clear separation between the responses that we see, the response rate that we see and historical controls. And we have RMAT designation with the agency — that’s Regenerative Medicine Advanced Therapy designation — that gives us access to talk to the agency — the FDA — about the program and we’ve talked to the FDA about the pivotal SPEARHEAD-1 trial, and its design and that will be the basis of the BLA that we will submit this year. So that’s the most advanced program.
Then behind that, the next-generation T-cell, with the same target as afami-cel, but with enhanced potency is in Phase I and Phase II trials. The Phase I basket trial we call SURPASS, which is across a broad range of tumors — that’s really a signal-finding study in late-stage patients to try to see where we see responses. And that’s the data that we are putting out at ESMO later this year. And then as we see responses in particular tumor types — we’ve seen responses in head and neck, bladder, and gastroesophageal and ovarian cancers so far.
Based on data in gastroesophageal and ovarian cancers, we initiated a Phase II trial last year in gastroesophageal cancers and plan to initiate another Phase II trial this year in ovarian cancer. And subject to the data, we aim to put those on a path to registration and ultimately becoming a commercial product.
TWST: Is there anything else you have in the pipeline that you’re expecting to be able to present soon?
Mr. Rawcliffe: Yes, so the other very exciting thing that we’ve got is that all of the stuff that I’ve been talking about before and all of our clinical pipeline is what’s known as autologous cell therapy. An autologous cell therapy basically means they’re your cells, and we take them out from each individual patient, we engineer them for our enhanced T-cell receptor, our SPEAR T-cell receptor in there, and we send them back to you. And so it’s a personalized treatment for you, with our engineered T-cell receptor. And that as a process takes time. And it’s obviously patient specific and what we have been working on for six years now.
There are a number of other companies in the space all trying to get a universal cell, donor cell that could go into any patient. That’s very difficult to do. And that’s called allogeneic. So you’ll hear the autologous platforms and allogeneic platforms, and we have both. Our allogeneic platform is in the research phase, is yet to go into the clinic. We plan on filing an IND for that next year. But that’s super exciting for us and for the field.
And if successful, that has the opportunity to have an off-the-shelf cell therapy. So rather than having to go through this complex manufacturing process, which although well-established now and we were good at it, as are the other cell therapy companies in the autologous space, it does take time and it is costly. You would have an off-the-shelf product available immediately for a patient when they received the diagnosis and wanted a cell therapy treatment. And that’s to say our first IND for that will be filed next year.
TWST: I was curious, how did the pandemic impact your research, your work? And where are you now in that process?
Mr. Rawcliffe: I think the interesting thing about the pandemic was, and this is true not just for us and for other biotech companies, I think it was true for the majority of society, is the realization of just how much you can do completely remotely. And at the same time, after a period of time, we’ve found that there were some very important things that it was difficult to do entirely remotely, that some level of face-to-face contact was necessary.
So from a sort of operations of the company perspective we were actually quite successful through the pandemic. We were able to very effectively take everybody remote and then bring them back, and actually our style — our approach to work remotely or in the office — has changed and alongside many others we’re implementing a hybrid model based on specific roles. So I think that is a significant change brought about by the pandemic, that increased flexibility.
The other thing for us, obviously, is clinical trial recruitment. And as well as the operations of Adaptimmune, you’ve got the operations of the hospitals that were also hit, not just in terms of their processes in place to combat COVID in their workplace, which I think puts additional constraints on patients seeking help, but also the fact that many of the hospitals were overrun at certain points in time with large numbers of COVID cases and prioritized those and obviously didn’t prioritize even late-stage cancer patients. And so, there was a definite period of time where recruitment slowed.
I think one of the advantages that we’ve had is that we are running our trials both in North America — U.S., Canada — and in Europe. And actually, when you chart the waves of COVID backwards and forwards, it was rare that all those locations were shut down at the same time. So by and large, we were able to continue to recruit the trials, but there were definite effects on — for example, MD Anderson Cancer Center in Texas was one of our major recruitment sites and went through phases of having very strict COVID responses and a lot of cases, and so on a site-by-site basis, that was significant.
I think, overall, we’ve come through that, I think, quite strongly. I think that’s true of the sector, as well as not just of Adaptimmune. I mean, it’s notable that during the pandemic we recruited our pivotal trial almost entirely during the pandemic. That went fine. We raised a quarter of a billion dollars on the basis of ASCO data that we put out in 2020. And we did that entirely virtually. And we executed a very large deal with Roche Genentech, which we signed at the tail end of last year, so late 2021, but most of that was negotiated through the pandemic, through various waves of the pandemic. So I think we’ve managed to come through it stronger on the other side, although COVID clearly had a significant impact.
TWST: Can you talk about the deal with Genentech and why it’s important?
Mr. Rawcliffe: So I referred earlier to an allogeneic platform. And this is a genuine platform. So whilst we can use it to develop our products, and the first product we will put into the clinic is targeting MAGE-A4 and is wholly owned, which is the same target as afami-cel, but this will obviously be an off-the-shelf version. The applicability of that platform is much broader. And so we’ve had a strategy for some time to make that platform available to partners and to leverage and monetize that platform to some extent, so that they can pursue their own programs and targets of interest on an allogeneic stem cell derived allogeneic platform, which is what our platform is.
And so in 2020, we did a deal with Astellas that enabled them to have a number of targets that we’d work on closely and move through. And then last year, we did a much larger deal with Roche Genentech. They paid us $150 million upfront and they will pay us another $150 million over the five years subsequent to the signing of that. And there’s development milestones downstream, and I forget the exact biobucks number we put out there, but it was — I think it was $3 billion of biobucks associated with the program. But more importantly it’s real validation by an acknowledged scientific leader in the space, Roche Genentech, that Adaptimmune platform can be the basis of a long-term set of products.
And Genentech’s interest is very long term. The deal has two parts to it — one part of which is a very long-term approach to a personalized off-the-shelf therapy that we’re working with our partner Genentech. So it’s super exciting, super validating, and part of the strategy to leverage that platform because it has potential way beyond what we could possibly hope to do with it.
TWST: I was wondering, what are your priorities for the next 12 months to 24 months? And what would make that timeframe a success?
Mr. Rawcliffe: We have four very clear priorities. And particularly in this biotech market, it’s really critical that we’re focused on those. So number one, we are submitting our BLA for afami-cel. That is a gargantuan task. There have only been five successfully filed cell therapy products in history. And so we plan on being the sixth or possibly the seventh. And so there isn’t a roadmap, there’s a lot of stuff that we’re working through with the FDA as we go and we plan on submitting the BLA this year. And subject to regulatory review, that product will then be available commercially in late 2024. So that’s a key priority. And so the BLA itself and standing up a small focused targeted effort to commercialize afami-cel for patients with synovial sarcoma.
Secondly, the SURPASS family of trials. This is the opportunity to make cell therapy mainstream in the solid tumor space because the SURPASS product has shown activity across a broad range of tumors, and prosecuting those trials into late-stage development and towards the market is going to be key to demonstrate the value of our platforms.
Thirdly, is the allogeneic platform that I referred to. Focusing on that and delivery of the IND for MAGE-A4 and progression of the partnerships with Genentech and with Astellas.
And then lastly, we have believed for the longest time that to be successful in cell therapy, you have to own your manufacturing. There’s a whole set of rationale about why that’s particularly important in autologous cell therapy versus in monoclonal antibodies or other therapy types. And we’ve invested significantly in that over the years, and it’s really paid off. The capabilities we have to be able to manufacture ourselves, I think puts us in a very strong position, both when it comes to executing on clinical trials and as we move forward to commercialize that product out of the same facility where we did the clinical trials, actually.
And so, investment in that so that we can supply both the commercial demand for afami-cel in synovial sarcoma, and the late-stage clinical trial demand — that investment in the CMC space is a fourth priority for us.
So, what does success look like? We will be one of the very, very few biotech companies that’s actually commercialized its own product that it discovered eight years ago in the clinics in Oxford and has developed all the way through clinical trials. And we will now be putting that on the market. Not only will we be one of that select group, which is a small group, but we will have done the first engineered T-cell therapy in a solid tumor as well, which is another major first. And we will have established the potential of cell therapy in solid tumors, and that will be a similar step to the one that, for example, Kite Gilead took when it established that you could do CAR T therapy for B cell malignancies for the lymphomas and leukemias. It will show that we have been able to do that for solid tumors, which I think is a huge step for the field.
TWST: I was wondering what are some of the challenges you face? What keeps you up at night?
Mr. Rawcliffe: So, this is a very complicated space. And as is true with all new modalities of therapy, new types of therapy, there’s no playbook for a lot of this. And so what we’ve had to do is build a team who all come with their own skill sets from different places, but who have integrated around getting cell therapies to market and that knowledge to be very different. So that, I suppose it’s unknown. If you’re not comfortable with ambiguity in this space then being the cell therapy CEO is not a good place to be. So I think you’ve got to be comfortable that we’re doing stuff that just hasn’t been done before.
I think there’s not that much that keeps me up at night. I think that historically there has been, and it was when we weren’t sure what the benefit for patients was from our therapies. But the reality is at the moment that everywhere we look in our trials, we see — most of our trials are not blinded – so I see patient data as it comes through, sometimes in semi real time. And so everywhere we’re looking at the moment, we are seeing the positive effects these cells are having on patients. And once you’re convinced of that, all the ambiguity is manageable. Because you can see that scan and that patient had a huge tumor at baseline, and it’s gone now. And so you can see that your cells are doing something.
And so, you know, the road may be unknown, it may or may not be navigated before with certainty. But I think if you believe that you’re doing something profound for patients there’s a hell of a lot of ambiguity you can deal with elsewhere.
TWST: What’s the most important thing a potential investor should know about the company?
Mr. Rawcliffe: Adaptimmune is the leader in engineered T-cell therapies in solid tumors. We’ve built a successful, integrated, completely dedicated and specific company to advance cell therapies. And that’s what’s going to make us successful, establishing these as a mainstream therapy in solid tumors. And the field is enormous. If you think that monoclonal antibodies are a big space, a big target market, a big economic potential, big upside, cell therapy will dwarf that in time. And Adaptimmune is right at the forefront of getting that access.
TWST: Was there anything you wanted to mention that we didn’t discuss?
Mr. Rawcliffe: I think the only thing that is what I just said about where we’re positioned relative to the field. I think that’s the take home for Adaptimmune at the moment. BLA this year, everything to play for.
TWST: Thank you. (CJ)
Adrian “Ad” Rawcliffe
351 Rouse Boulevard
Philadelphia, PA 19112
(215) 825 9260
(215) 825 9459 — FAX
Eyepoint Pharmaceuticals (NASDAQ:EYPT), GeoVax Labs (NASDAQ:GOVX), Telesis Bio (NASDAQ:TBIO), Organovo Holdings (NASDAQ:ONVO), TRACON Pharmaceuticals (NASDAQ:TCON), and Abivax: Six Biotech Companies, Six Strategies
April 18, 2023