Hey everyone, welcome to H.C. Wainwright Second Annual Cell Therapy Virtual Conference. My name is Arthur He, a Senior Biotech Analyst at the firm. Thanks for joining us to have a conversation with Mr. Adrian Rawcliffe, the CEO of Adaptimmune Therapeutics. Adaptimmune is a clinical-stage biopharmaceutical company focused on developing T-cell receptor cell therapies to treat cancers. To discuss Adaptimmune's pipeline and learn about the company's development strategy in 2024 and beyond, I'd like to invite Adrian to this virtual. Good morning, Adrian.
Good morning, Arthur.
First of all, to help set the stage for our audience, could you give us an overview of Adaptimmune's pipeline?
Certainly. We have a wholly owned pipeline of engineered TCR T-cell therapies, and they're exclusively focused on solid tumors. This has been the focus of Adaptimmune since its inception over a decade ago. At the very front end of that pipeline are afami-cel and lete-cel. These are two assets focused on synovial sarcoma and myxoid round cell liposarcoma, and they've both completed their registrational studies. Afami-cel is currently with the FDA with a PDUFA date of the 24th of August. Lete-cel is a couple of years behind, but they're both clinically de-risked and have shown to be effective in those indications. Behind that is uza-cel. Uza-cel is a next-generation version of afami-cel, which targets MAGE-A4 as a target.
That's in development in ovarian cancer in a phase II trial, could surpass III, and then head and neck and bladder cancer, where we're showing really encouraging high levels of response rates in a phase I study. Behind that are preclinical opportunities targeting PRAME and CD70, two of the largest solid tumor cell therapy targets for the field, and ones that we're highly excited about. Those are going to the clinic in the coming years.
Nice. Congrats on the priority review for the afami-cel. First, could you help highlight the afami-cel's clinical data supporting the BLA for us?
Certainly. So afami-cel, which has RMAT designation with the FDA, was studied in a trial called SPEARHEAD-1. This was a single-arm study in synovial sarcoma predominantly, and of the 44 patients in the first cohort, which is the hypothesis testing cohort of SPEARHEAD-1, we showed a 40%, 39% response rate. Those responses are deep and durable, with a median duration of response of approximately 12 months. And if you respond, then it makes a difference. We've shown that responders have not yet that population has not yet reached median survival for responders, but with 70% of them estimated to be alive at two years. So what's this compare against? Well, it was a single-arm study, but historic controls agreed with the FDA was an 18% response rate.
But in reality, many of these patients have many of the treatments that are used in second-line plus in synovial sarcoma have a high single-digits, low teens response rate. Those responses are not typically durable, lasting a few months, and overall survival for these patients is poor, with sort of estimates around between 9 and 12 months for second-line and decreasing beyond that. So clearly, afami-cel has shown itself to be, we believe, a transformational asset for these patients, MAGE-A4-positive patients with synovial sarcoma.
The clinical data are really impressive. And so I would like to ask, if the afami-cel got approved, how would you think the treatment fitting into the current treatment landscape, and what's roughly the market potential for an afami-cel initially?
Yeah. So for afami-cel and I'll talk about afami-cel, I'll talk about lete-cel because it's actually important to think about both of them together or carve out an afami-cel at the end. So afami-cel will be, we believe, indicated in treatment of patients who have received prior anthracycline-based chemotherapy. So that's used in the front line. That typically produces response is in maybe a small majority of the patients. Those responses are typically not particularly long-lived. So we anticipate approval in that second-line plus setting. These are typically young patients. The median age of diagnosis is in the early 30s. Five-year mortality is about 80%, so five-year survival about 20%. So clearly, the opportunity to go in there, this is an area of very high medical need.
And so we anticipate that there are something like 400 patients each year in the United States that are MAGE-A4 and HLA-A2-positive who have synovial sarcoma, for whom an afami-cel would be an appropriate treatment. So this is a rare indication. Lete-cel coming behind targets a different target. Targets NY-ESO-1, an afami-cel targets MAGE-A4. NY-ESO-1 is also expressed in synovial sarcoma, and that trial for lete-cel was done in both synovial sarcoma and another rare soft-tissue sarcoma called myxoid round cell liposarcoma. As I said, that trial has met its primary endpoint for efficacy, and we anticipate registering that. That would increase the patient population from about 400 patients to about 1,000 patients. And the beauty for us is that that goes through essentially exactly the same commercial footprint.
So we'll build this commercial footprint for afami-cel, add on lete-cel with essentially the same infrastructure, but be able to access approximately 2.5 times as many patients with both of these products.
Wow. Thanks for that, Ad. And just to try to stick a little bit longer on the afami-cel. So I guess the folks who would be the what's the next regulatory milestone? Should we expect an AdComm meeting, or how is the discussion between you guys and the FDA?
Yeah. So as I pointed out right at the very beginning, we have RMAT designation with the FDA. That means we were eligible for and received priority review when the BLA was filed, which happened on the 31st of January. That gives us a PDUFA date of the 4th of August. However, RMAT designation also means that you have the opportunity to have in-depth interactions with the FDA in the run-up to the submission. We took advantage of that, trying to understand in each case what the FDA's needs were so that we were confident that we would submit a file that would meet their requirements. Once we got onto the BLA being filed, we're very much on the FDA's clock.
So all of the normal inspections and meetings that you would anticipate have been scheduled, and we're working through those and the request for information from the FDA as we speak. We will give an update on where we are at our investor day on April the 18th, which I would encourage people to come to if you can. It's in Navy Yard in Philadelphia, opportunity to see the manufacturing facility tour, but also to understand directly from physicians and patient organizations about synovial sarcoma and the opportunity to understand Adaptimmune's plans to transform the synovial sarcoma space with our commercial planning and infrastructure build.
I'm very much looking forward to the investor day in Peru. Just to follow up on your comments earlier, could you tell us more about your preparation for the potential afami-cel launch, and particularly regarding the, I guess, more interesting is on the pricing strategy for the therapy?
Yeah. So I think the launch of afami-cel reflects the fact that this is a very concentrated treatment group, prescriber group. So sarcoma is typically treated, particularly in the metastatic setting, in sarcoma centers of excellence and concentrates to the top end of those sarcoma centers of excellence. These are centers where we have largely been conducting our clinical trials. So they're centers we know well. We anticipate that with 30 centers nationwide, 30 treatment sites nationwide, we would have good coverage. And we anticipate that patients will travel to these treatment centers. As I said, this is a one-off therapy with a young and highly motivated patient group. So we think 30 centers is about right for this patient population. We will start with 6-10 in the launch window and grow it to 30 treatment centers over a period of 18 months to 2 years.
To do that, we need to have the commercial and medical affairs organization set up. We've made great progress on that. We're approximately two-thirds of the way through the build of that. It's not the largest organization in the world. The entire commercial plus medical affairs is about 30 people. About half of those are in the field, and those are split roughly equally between med affairs and what you'd think of as commercial account managers. We won't have significant traditional sales. This isn't that sort of market. So this is a rare disease market, and the objective is to identify as many of these patients as possible and get them to treatment centers because they should be on afami-cel.
In terms of pricing, obviously, we haven't announced how we're going to price it, but we will be looking at pricing that reflects the rarity of the indication and the transformative efficacy and the value proposition that we think we've got for these patients, for the hospitals, and for payers as well. So more to come on that when we get approval.
Awesome. Thanks for the additional color. And just the last one, a touch on the afami-cel. I guess manufacturing for cell therapy is always one of the major focuses by their investors. So could you give us a little bit overview on the manufacturing process of the afami-cel and also tell us more about the progress that Adaptimmune has made, especially on the TCR-T therapy manufacturing?
So our T-cell manufacturing process looks reasonably similar to a CAR-T manufacturing process. We start with patient cells from an apheresis. We transfect those cells with a gene encoding our high-affinity T-cell receptor using a lentiviral vector. We then expand or grow those cells, incubate them, and then we harvest them and pack them and ship them back to the patient. So individual patient cell therapy, autologous cell therapy, and that process for each patient. That process takes a minimum of a little less than 4 weeks, but it can take up to 6 weeks turnaround time by the time you've got shipping on each end, etc. So 4-6 weeks process. We grow between 1 billion and 10 billion transduced cells. So the doses are slightly higher than the CAR-Ts where you're used to a few hundred million gene-encoded cells.
We took the view going back to actually before I joined the company that the manufacturing of these therapies was absolutely key. It was a key area competence that if you aspire to be a cell therapy company that discovers and develops and delivers these things, then you have to focus on the delivery. It's where all the challenges have been. We've focused on that primarily internally for cell manufacturing. We built and opened in late 2017 the facility in Navy Yard, our cell manufacturing facility here. That facility actually manufactured every single patient in the SPEARHEAD-1 trial out of this facility using the same process. We then use this facility to do the BLA qualification work and submit the BLA. We will launch from this facility, and this facility can provide up to the Peak sales.
That continuity of process and of manufacturing site and skill set is incredibly helpful for us as we navigate what is a very, very complicated manufacturing process. There's a reason why this has been the challenging area for most of the cell therapies that have been produced, and that's why we made the investments we did in the manufacturing that will bear fruit as we move into commercialization.
Nice. I'm looking forward to some first-hand experience at your facility on April 18th. So let's switch gears to lete-cel. I guess one interesting question I'd like to understand is, how did the lete-cel end up back with you guys? And I know there's still some milestone payment hanging there. Could you tell us more about what's the tie-in to the milestone for those payments?
No. So lete-cel was back when we IPOed. Lete-cel was our lead product, and it was under option to GSK. And GSK had signed a deal with us in 2014 that gave them the right to option that at proof of concept. Well, we reached proof of concept in 2017, and GSK decided that they would like to option that in. So we transferred it to them. And GSK then subsequently changed the manufacturing process. They moved it from our manufacturing process, which is similar to the one we use for afami-cel, to a manufacturing process based on Miltenyi's Prodigy device. So probably more scalable for larger indications. GSK then completed an enrolment and dosing in a pivotal trial called IGNYTE-ESO of lete-cel in synovial sarcoma and myxoid round cell liposarcoma.
We were very pleased to find out late last year that at the interim analysis of that trial, that trial has already met the criteria to meet its primary efficacy endpoint, even at this interim analysis. There's a 40% response rate across these two indications, pretty evenly split between these two indications. And that looks very similar, essentially, to afami-cel in synovial sarcoma. So we're really optimistic about that. GSK decided in late 2022 that they were going to get out of cell therapy. You may remember they made this announcement, and they terminated all their partnerships with us and with other companies as well. And so we transferred that with GSK. We transferred it back into Adaptimmune. And in-flight pivotal trial and all of the appropriate relationships that go along with that came back in. And the IND moved over in Q4 last year.
As part of that transfer back, GSK agreed to make certain payments back to us. The total of those was $35 million, $5 million for some manufacturing obligations they had, and then $30 million for other elements of the clinical obligations. We've received some of that last year, and the final payment for that we anticipate receiving in Q2 this year as part of our financing runway. Then that will be when the transfer is completely complete and all of the sites have moved over, etc.
Thanks for that additional color. So I guess for the lete-cel, one last question is, could you tell us more how the afami-cel and the lete-cel especially synergistic with each other in the sarcoma franchise?
Yeah, very much so. So afami-cel for synovial sarcoma, lete-cel for synovial sarcoma, and myxoid round cell liposarcoma. So an afami-cel doesn't have an indication for myxoid. So in the synovial sarcoma population, an afami-cel and lete-cel overlap. So an afami-cel targets MAGE-A4. That's in about 70% of patients. Lete-cel targets NY-ESO-1. That's in about 80% of patients. So clearly, there's some overlap. They're pretty independent variables. So the best way of thinking about it is that by the time lete-cel gets to the market, an afami-cel will have been on the market for a couple of years and hopefully will have got good penetration into the MAGE-A4 positive patients. So what we're really interested in is, what are the incremental patients that we would get? And of the 30% of patients that do not express MAGE-A4, we estimate that about 80% of them will express NY-ESO-1.
So we mop up. We get the remainder of those patients. And then we get all of the myxoid round cell liposarcoma patients that express NY-ESO with lete-cel as well. So there is a question, what happens to the patients that express both MAGE-A4 and NY-ESO? And we want them to get the best possible therapy. So we anticipate their doctor will make that decision, maybe on the basis of looking at the prevalence of the antigen in both antigens. But there's also the possibility over the longer term for sequential or maybe even combination therapy to go beyond the $400 million of peak sales that we anticipate with afami-cel and lete-cel in launch indications. And as we broaden out that sarcoma franchise, you could think about combinations or sequencing.
I see. So just to wrap up our conversation here, which program you want to highlight for us besides the afami-cel and the lete-cel in your pipeline?
So I'd highlight uza-cel. And uza-cel is the reason I'd highlight that is because I think that is the demonstration that engineered TCR T-cell therapy is not simply for rare sarcomas. So with uza-cel in a phase one trial across a basket of all indications, we showed a response rate of 35% in very, very late-stage, heavily pretreated patients with ovarian cancer, bladder cancer, head and neck, gastroesophageal cancers, melanoma, lung cancer, etc. That's a phenomenal response rate for that patient population. When you look at three indications, ovarian, bladder, and head and neck, there's a 50% response rate in those patients. Now, on the basis of what we saw in ovarian cancer, we're moving forward into a we have a phase two trial up and running called SURPASS-3 that has the potential potentially to be registrational.
For head and neck and bladder cancer, we're still signal finding in phase 1, maybe in earlier lines of therapy. But this is the opportunity to take engineered TCR T-cell therapy mainstream into a much wider range of cancers. The data is really encouraging. I still believe it is the best multi-cancer cell therapy data in the solid tumor space.
Awesome. Thanks for that. And so to close our conversation, could you remind investors your upcoming catalyst as well as your cash position, I don't know?
Certainly. So cash position at the end of Q4 was $150 million, just less than $150 million. We have another $150 million of non-dilutive financing from partnerships and other sources. That gives us a runway into early 2026. In terms of catalysts, I will make another plug for the Investor Day in the Navy Yard. We have the PDUFA date of August 4th for afami-cel. We have the first commercial patients for afami-cel, which we anticipate dosing in Q4 this year. And we will have full pivotal dataset for lete-cel out later on this year, certainly a headline, and the confirmatory evidence dataset for afami-cel later on in 2024 as well.
Then very lastly, we will make decisions on head and neck and bladder cancer in uza-cel right at the very end of this year on the basis of the data collected out of the phase 1 trial. Rich catalyst set over the next 12 months or so.
Nice. Nice. Very nice. So let me see if there's any question from the audience. So there's one question. How is Adaptimmune incorporating patient advocacy organizations and the patient themselves in the launch and the market access strategy?
Yeah. So there's a small but very fiercely vocal group of patient advocacy organizations in the sarcoma space, for example, Sarcoma Foundation of America. And we've been working closely with them throughout the development of afami-cel. And we believe that the demand for this from the patient groups and from the treating physicians, many of whom have been engaged with bringing this very first engineered cell therapy to patients in the solid tumor space, they feel very strongly about the potential benefit of afami-cel. And so I think we will have a groundswell for the adoption of this product that will ultimately make its way into guidelines and treatment guidelines, etc. But initially, from a highly active patient population, young, highly motivated, high-agency patient advocacy groups, and the small group of high-treating physicians there, there's a lot of demand for afami-cel going into launch.