Hello, and welcome to Virtual Investor Conferences. My name is Anthony Kraus, and on behalf of OTC Markets, as well as our co-host, Zacks Small Cap Research, we're very pleased you have joined us for our next live presentation from Adaptimmune Therapeutics. Their session will be moderated by Michael Kim, Senior Analyst at Zacks Small Cap Research. Please note, you can submit questions for the presenter in the box to the left of the slides. You can also view a company's availability for one-on-one meetings through the Schedule Meetings tab found on the conference platform. At this point, I am very pleased to welcome Adrian Rawcliffe, Chief Executive Officer of Adaptimmune Therapeutics, which trades on Nasdaq under the symbol ADAP. Welcome, Adrian and Michael.
Thank you. Great.
Thanks, thanks, Anthony, and good afternoon, everyone. Thank you for joining us today. Again, I'm happy to have with us Adrian Rawcliffe, Chief Executive Officer of Adaptimmune, a company that we initiated coverage on earlier this year with a $3 price target. I'm sure Adrian will get into this, but Adaptimmune is a biopharmaceutical company focused on designing, developing, manufacturing, and delivering innovative cell therapies to treat cancers across multiple solid tumor types. So with that, Ad, great to see you. Thank you again for taking the time.
Good to see you, Michael.
Great. So we've got a few topics that I think are probably top of mind with investors, so with that, maybe just to start, for those who may be a bit newer to the story, might be helpful if you could provide a brief history of the firm, just in terms of the capabilities and the infrastructure that you've been able to build up over time, and then if you could maybe spend a bit of time discussing T- cell therapies and how you're positioned within that market.
Certainly. So Adaptimmune was founded about 16 years ago, and it was founded on the premise that cell therapy will revolutionize the treatment of cancers. But the challenges with other approaches, in particular the CAR-Ts, which have been very successful in the hemo space, is that they can't target targets that are routinely found in the solid tumor space. And since solid tumors make up over 90% of the burden of cancer, morbidity, and mortality, it seemed key that if cell therapy was to have this transformative effect, we needed platforms and approaches that could address solid tumors.
And our TCR, or T- cell receptor engineering platform, enables us to, to engineer the native targeting protein of the T- cell, the things that T- cell normally use to recognize what they want to kill in your body, which is normally foreign pathogens. And we can engineer that T- cell receptor to recognize targets that are routinely presented on a wide range of solid tumors, and by doing so, we can generate cell, engineered cell therapies that will target that wide range of solid tumors.
So it was also key to us that, in order to do that, in order to discover, develop, and ultimately deliver autologous cell therapy, so cell therapies made from the patient's own cells, it would be important to have a set of capabilities that were different to the capabilities in normal drug discovery and development, that was particular for cell therapy, and so we set out to build those. We started as a protein engineering house, and we built forward-integrated the capabilities necessary to develop preclinically and then clinically to manufacture cell therapies, and we built a pipeline of cell therapies using these engineered T-cell receptors that target a broad range of tumors.
And at the very front end of that pipeline is our most advanced product, which was approved by the FDA for the treatment synovial sarcoma in August this year, called Tecelra. And that is the first engineered cell therapy for a solid tumor, and the result of that investment in capabilities and pipeline over the last decade.
That's great. Very, very helpful. Appreciate the color there. Maybe just as it relates specifically to treating sarcomas, it seems like there haven't been a lot of new drugs that have come to market for quite a while. So patients, unfortunately, face a lack of options when it comes when first-line therapies prove ultimately ineffective. So perhaps you could speak to Tecelra's efficacy in terms of the clinical trials and differentiated treatment approach that have seemingly sparked a fair amount of interest within the sarcoma space.
Yeah. You're correct. Sarcomas and soft tissue sarcomas generally is a name that's given to actually a collection of quite a range of different types of sarcoma, types of cancer. synovial sarcoma is a cancer of connective tissue. It’s typically diagnosed in patients in their thirties, and you're correct, so it's a young person's disease. You're correct that what normally happens is a patient will be diagnosed, maybe they may be amenable to curative, potentially curative intent resection or surgery if the cancer is discovered when it’s localized. But if it’s spread, if it’s metastasized, then systemic therapies are required. And the first line of that is anthracycline-based chemotherapy.
That has a reasonable response rate, but most of those responses are transient. And then after that, there really has been nothing. The last drug approved in this space was a drug called pazopanib. And that was... that had a response rate that was measured from somewhere around 4% to about 14%. So it's in that sort of range. Now, it's important to note that Tecelra was not developed in a head-to-head study against pazopanib, because there really isn't an accepted standard of care in the second-line setting. Tecelra was developed in a single-arm trial with synovial sarcoma patients. And in that trial, we demonstrated a response rate per the label, the FDA analysis in the label, of 43%.
So very different to the historic standard conventional experience of those patients, which would be response rates in the teens. And those responses are really durable as well. Something like 40% of those responses continue longer than 12 months. And those in that clinical trial, and we published the data from that in The Lancet earlier on this year. Responders had a 2-year survival probability of 70%.
And this is a fantastic transformation for those patients. The last thing that I'll say about Tecelra, because I think it is critical to understand this for how patients view it, is it's a one-off treatment. You know, the patient's experience in the sarcoma space is of a series of debilitating treatments, be that radiotherapy, surgery to remove individual tumor masses, chemotherapy, various other debilitating clinical trial agents. And those need to be given frequently over periods of time. The patient experiences this constant engagement with the healthcare system or with therapies that make them feel really bad and have actually relatively marginal effect on their tumor.
You contrast that with the opportunity to get a one-off, essentially one-off cell transplant, almost, of engineered cells, and then to whatever benefit those patients experience over what can be quite a prolonged time, that's it. They're not having any other therapies to treat their cancer. That is a profoundly different experience, and I think that's why the efficacy, the fact that this is the first drug in this space for a very long time, is why there is so much excitement within the sarcoma community by both patients and physicians.
Yeah. Makes a lot of sense, for sure. You alluded to this a bit earlier, Ad, but I think another somewhat unique aspect synovial sarcoma is the patient profile. So could you maybe speak to sort of the target population in terms of underlying demographics, survival rates, and sort of the potential of the treatment market, if you will?
Yes, so I think synovial sarcoma receiving a diagnosis synovial sarcoma is pretty devastating. You have to imagine, you're probably in your twenties or thirties when you're diagnosed. About a third of patients are diagnosed below the age of thirty, so this is a young person's cancer, and typically, if you end up with a pain in your shoulder or limb, and you're thirty, I'm just about able to remember that myself, you sort of say, "Well, it'll probably go away." You probably do nothing, and by the time it doesn't go away, and you go to the doctor, and the doctor says, "Well, it's probably some sporting thing.
Here, have some physio." And it takes a long time for many of these patients to be diagnosed. Because you don't think, "I'm thirty, and I've got cancer." So when you are diagnosed with a scan, sometimes with a biopsy, then you're hit with this diagnosis synovial sarcoma, and you don't know a single person who's ever been diagnosed with that, and your doctor, your oncologist, probably hasn't seen a patient synovial sarcoma, if at all. Rare, they've seen rarely, if at all. And so it is imperative that these patients get treated in sarcoma centers of excellence, and most of them tend to make their way there. Once you are diagnosed, if you are diagnosed locally, yes, there is curative surgery. Most patients aren't.
Most patients are diagnosed with metastatic disease, and then five-year survival on diagnosis for metastatic disease is 20%. So it's a devastating diagnosis in a young population. Now, what that means for us is that is a very high agency population. These are patients who are incredibly motivated to be able to find effective treatments. There are about 1,300 cases, maybe up to 1,300 cases synovial sarcoma diagnosed each year. Of that, we estimate about 400 will have the correct biomarkers, the correct targets to be able to go after with Tecelra. So this is a rare disease, but it's a rare disease where there really isn't anything else, and so we anticipate being able to get to a very high percentage of these patients over time.
And this, therefore, is very much a rare disease commercialization model, and, where as opposed to a sort of more mass market approach, and there isn't really any competition. So we think that, with this therapy, and with the one that's following it by about 24 months, which is called lete-cel at the moment, which targets a slightly different patient population, there's about a thousand patients there that we can go after in our sarcoma franchise and who would benefit from those treatments. And we think that that has the potential to give us a franchise in the U.S. in these lead indications that's about $400 million, which is a nice, commercially viable franchise for a company like Adaptimmune, and one that we can address readily with the network that we have in place.
Yeah. So maybe just to follow on to that, to those points, what the narrative has certainly shifted now that the FDA has approved Tecelra. The focus is on commercialization, as you pointed out. Just curious in your mind, what some of the potential risks from an operational standpoint as it relates to the rollout? And then on the flip side, you know, might there be opportunities for potentially a quicker uptake, particularly given sort of the market dynamics and your position within the market that you alluded to? Ad, you still there?
Okay, well, appears we might be having a bit of technical issues. Please bear with us.
Hey, Ad.
Hi, Michael. Sorry about that. You dropped us-
No worries.
You dropped us.
No worries. I just asked, I don't know if you caught the question, but just maybe some perspective on the commercial rollout in terms of potential operational risks, and then on the flip side, you might there be an opportunity for ... for quicker uptake, just sort of your position in the market?
Yeah. So I think you're right. The perspective has certainly shifted. Now we are a commercial company. I think there's a few things that we think we have going for us. First is, this is a community, the sarcoma community, that we've been working with for approximately the last decade, developing medicines for sarcoma. And so, this is a very concentrated treatment community. There's something like 100 sarcoma centers of excellence. It's well understood if you have a rare sarcoma, that you should be treated in a sarcoma center of excellence. And so patients get referred to those sarcoma centers of excellence, and they within the centers, it's concentrated to the top end.
So we anticipate we will launch, in the first 90 days after launch, we'll be in six to 10 centers, and we'll grow that to a network of 30 treatment centers. And those 30 treatment centers are the treatment centers that cover about 80% of the patients in the sarcoma centers of excellence. So it's very concentrated. And these are centers that not only are they very experienced sarcoma centers, they're also leading cancer centers that you'll recognize. And if you go onto the website, Tecelra.com, you can see that we have seven centers on that website that are working to bring patients through. We have two centers fully up and running at this point in time. And so that's the starting point.
And these centers are also about half of the centers that we used in our clinical trials, in particular, in the SPEARHEAD-1 trial. So we know them well, and they know our product well. So that, that's one area, that concentration is one area of de-risking and why we think that we are well-placed to be able to commercialize this particular medicine. We understand the market, we understand the centers, and it's a relatively modestly sized footprint for us.
The other piece that I think a lot of companies with cell therapies have struggled with, and where a lot of the challenges sort of lie, is in the manufacturing of these cells. So these are autologous products. I take a patient's own cells, I engineer them, we return them to that patient. And so each patient is his own manufacturing run. This is obviously a logistically complex thing to do, and it's also scientifically complex as well.
We have been doing this in our center in the Navy Yard with Tecelra, previously afami-cel, in clinical trials. And so, at most this center was reviewed, audited, inspected by the FDA, and so we feel very confident in our ability to manufacture Tecelra for every patient that comes through from the 30 centers that we'll have up and running. I think the key is that we will with Tecelra get these centers up and running, and we're obviously have established all the processes to be able to do that. Then when lete-cel comes through, the interesting thing about lete-cel is that it will go into all of those 30 centers at launch.
And so, if we want to think about uptake of these products and commercial opportunities, I think there's definitely an uptake for strong, possible potential for stronger uptake of lete-cel because it would just be going through the full network that we will have established.
Yep. Okay, great. And then sort of beyond the number of treatment centers onboarded, I know you've pointed to the number of patients apheresis as a key leading indicator for the ramp-up of Tecelra sales. So, maybe if you could just talk a bit about the process in terms of timelines and what you might expect correlations to be as it relates to sales. And then related to that, just a question from the audience. Just curious if we will get information when first patients are to be treated commercially, which I think you've talked about, the fourth quarter as potentially the starting point.
Yeah. Yeah, so to talk about why we picked patients, apheresis. We think that's a fairly concrete point where the patient has already cleared the testing, the biomarker testing, and they will also have gained reimbursement for that, for their treatment. And so, and yet it will precede patient dosing by the manufacturing period, plus whatever period it takes to get the patient in, and then lymphodepleted and treated. There is, from the history of these products, some drop-off between apheresis and the number of patients dosed. There are some patients that the companies have been unable to manufacture for. In our clinical trial, we had manufacturing success rate north of 90%.
But we don't know what that will be with the commercial patient group, so there's that, and then there's the time element that you referred to. Our manufacturing time period is anywhere from four to six weeks. And then you've got a little bit more for the patients to be lymphodepleted and then treated. And so that's why we're saying that even though we launched in August, by the time we test the patients, get clearance for reimbursement, apheresis, manufacture, and dose, we anticipate the first commercial patients will be treated in Q4 this year, and that's when we'll have our first sales recognition.
And we look forward to being able to update on that, but I think for the first, given that patient dosing is when we're going to have sales, we will whilst we reserve the right to inform people about the first patient. Yes, we will wait until we've actually got those sales booked, and we'll be updating on sales on the quarterly basis. So until we start updating at our quarterly calls about sales, the patient's apheresis will be the surrogate for what's happening in that patient flow.
Yeah. Okay, great. Very helpful. Maybe shifting gears a bit to lete-cel, as you alluded to. Just curious to get your perspective on the commercialization opportunity. Seems like there's a lot of overlap and synergies with Tecelra. You talked about, you know, the distribution footprint. So any insights into, you know, potentially being able to drive a quicker ramp-up in sales once you do receive FDA approval?
Yeah. So we anticipate that lete-cel, lete-cel, which has completed its pivotal trial, the IGNYTE-ESO trial, and it completed that positively. It was positive, actually, at the interim read. The final read we will have, and we are planning to make available those data at CTOS this year, in November, for the full trial. But that has been a positive trial. That is a positive trial. And we anticipate that will form the basis of the clinical evidence for approval, which we anticipate in 2026. You're correct that the commercial footprint for lete-cel is almost exactly overlapping the commercial footprint for Tecelra. These are the same sarcoma centers of excellence. These are largely many of the same physicians. And so a lot of that commer...
Infrastructure that we built for Tecelra will be 100% applicable to the commercialization of lete-cel. Because we'll have all of those 30 centers in our network open at the point where lete-cel is launching, we anticipate that the patients will find access to that more rapidly than they will for Tecelra. We think that the opportunity for lete-cel, that lete-cel is probably about one and a half times the size, maybe a little bit more, than that of Tecelra. There's about 400 patients that are the addressable patient population for Tecelra, and about 600 patients, incrementally 600 patients, that are the addressable patient population for lete-cel. So still a rare disease, still dealable within the footprint that we will have built, and just a great opportunity for us in these rare sarcomas.
Yeah. Okay, and from an economic perspective, I know you mentioned the four hundred million target in terms of peak year sales here in the US for Tecelra and lete-cel. But just given sort of the manufacturing and distribution infrastructure that obviously has already been built up, as well as the lack of alternative treatments that you referenced earlier, just curious to get any perspective or insights into the potential slope of the sales curve as we look out over the next few years.
Yeah. So I think the way we think about this is we think about both products together. And we think about peak patient numbers approximately two to three years after the launch of lete-cel. And so you've got a slope between now and two to three years after the launch of lete-cel to between where we are now. We anticipate substantial penetration. We've talked about the pricing that we anticipate, and so if you think about that, it's clear that we're targeting at peak getting to around about half of the patients that are addressable in that space. So you know, could it be better than that?
Yes, it could be better than that, because 50% of the patients is a strong number, but I'll point out that Immunocore's Kimmtrak for uveal melanoma, which in many ways is a similarly sized population to one of these rare soft tissue sarcomas. That is already at more like two-thirds of the patients, maybe a bit more of the patients that are eligible for Kimmtrak are on drug or have received drug. And so we think that in these rare tumor types, because it is more of a rare disease model, it's more of a patient identification and getting them to a treatment center model, than it is a competitive sell against something else that also has robust efficacy because there isn't anything else.
So we anticipate fairly deep penetration, fairly steep curves over time. However, I do want to just temper that a little bit with, you know, this is a cellular therapy, and we will be growing and expanding the footprint over the next eighteen months or so, and so that will affect the front end of that slope going up.
Yeah. Okay, next question. It seems like there may be a bit of uncertainty as it relates to the recently announced collaboration with Galapagos in connection to uza-cel specifically. So maybe if you could just provide a bit of a high-level overview of the relationship just in terms of the roles for the two parties, in terms of clinical trials, different indications, and then maybe be helpful just to outline sort of the various structures as it relates to upfront payments versus incremental payments and the potential for royalties down the road.
Yeah. So we were absolutely delighted to partner with Galapagos earlier this year because it seems obvious to us and to them, and I think to anybody paying attention to this space, that the opportunity to pair a product like uza-cel that has shown incredibly robust response rates in very late-stage patients with very difficult to treat tumors, with a seven-day vein-to-vein manufacturing process, has the potential to really change the dynamic for what this cell therapy could represent to patients. And in particular, the starting point of head and neck cancer is a really good example of that. Because, you know, we've treated five patients with uza-cel, with head and neck cancer. Every single patient had a profound reduction in their target lesions. Every single patient.
Four of the five patients were bona fide RECIST responses, confirmed responses. This is therefore a highly active product, and yet at the same time, head and neck cancer patients develop and progress rapidly and sometimes precipitously. The opportunity to shorten the manufacturing time from the four to six weeks that we use on our platform currently, to seven-day turnaround time, seven-day vein-to-vein time, I think has the opportunity to make that available to many more patients and to get to those patients earlier. It's that opportunity that we are seeking to prosecute in the initially in the collaboration with Galapagos. What's going to happen is we are going to conduct a clinical trial, a phase one clinical trial using the using Galapagos distributed manufacturing platform, and uza-cel.
We'll conduct that in the U.S. and in Europe, and that will enable us to demonstrate the advantages of the short manufacturing turnaround and the efficacy of the uza-cel product. On the basis of that, Galapagos then has a choice about whether they want to take that forward, and they want to take that forward in head and neck cancer or in a range of other indications, and then they pay us money in order to be able to do that. We received $85 million upfront, of which $15 million was R&D expenses, and the remainder was an upfront payment. We'll get another $15 million when we dose the first patient in R&D expenses, and then there's up to $100 million in an option fee on positive proof of concept....
downstream milestones and royalties that go up to double digits. And so it's economically attractive for us, but most importantly, really importantly, is the opportunity to make this therapy, make the best version of this therapy, particularly in those cancers that rapidly progress. So that was the rationale for that deal. In the meantime, we have uza-cel on our platform in ovarian cancer. And that's quite advanced. That's in the SURPASS-3 trial. And in ovarian cancer, we've not seen the drop-off in patients. We've been able to manufacture for the patients that we are getting into that trial. That trial is recruiting quite well at the moment. And that has the potential to be a registrational trial.
We'll have first interim reads of that data once we've enrolled the full patient group, so at some point next year, and final data in 2026 for that. And uza-cel on our platform in ovarian cancer could be the, our third product to market after Tecelra and lete-cel.
Got it. Well, great, it's been very helpful. I appreciate the time. Look forward to continuing to follow the company's progress, and learning more about the great work you guys are doing. Thank you everyone for joining the conference today, and appreciate it. Have a great day.