Good morning, everyone, and welcome to H.C. Wainwright 26th Annual Global Investment Conference. My name is Arthur He, Senior Biotech Analyst at the H.C. Wainwright. Thanks for joining us for having a conversation with the management of Adaptimmune Therapeutics. A little bit about Adaptimmune. Adaptimmune is a newly minted commercial-stage biopharmaceutical company focused on developing novel T cell therapies based on its proprietary T cell receptor platform to treat cancer. Most recently, the company received its first FDA approval for Tecelra, the first-ever engineered T cell therapy for solid tumor. Joining me here are Mr. Gavin Wood, Chief Financial Officer, and Ms. Cintia Piccina, Chief Commercial Officer, and Dr. Karen Miller.
Cheng
... Cheng. Senior VP of Early Stage Development.
So, Gavin, Cintia, and Karen, welcome.
Thank you.
So maybe, to help set the stage for our audience who are not so familiar with Adaptimmune, could you guys give an overview of the Adaptimmune pipeline?
Yeah, maybe I'll kick off, and then guys can jump in. So, Adaptimmune, as Arthur just said, is a engineered T cell innovator, and we've just had our first product approved by the FDA, which is Tecelra, which is a cell therapy against synovial sarcoma. We're a company of about 500 people. About half those people are based over here in the Navy Yard in Philadelphia, where we do our manufacturing and manage most of the clinical trials from, and also here in up in Boston. And we've have a pretty significant R&D function based over in the UK. Our pipeline is advanced. Behind Tecelra, which we've just launched, is a product called lete-cel, which is clinically de-risked, and we'll be looking forward to approval of that later in twenty twenty-six.
We will also behind that have a phase II trial in ovarian, which is also phase III, and that's in platinum-resistant ovarian cancer, and that's with a second-generation product. Further behind that, we have a preclinical program in PRAME as well as in CD70.
Yeah. Thanks. Thanks, Gavin. So maybe, Karen, I know you guys developed all these TCR T-cells based on your SPEAR T-cell platform. Could you help us understand how they are differentiated from the CAR-T therapy?
Sure.
Yeah.
CAR-Ts use an artificial cell surface receptor in order to get their signals, where TCR therapies utilizes the T-cell's own natural receptor. I think the biggest differentiator between the two therapies is that CARs can only recognize proteins that are bound to the extracellular membrane, whereas TCRs, because of the mechanism of action, they can recognize both cell surface receptors and proteins that are generated internally and then subsequently expressed on the cell surface through that TCR, so it gives you a wide range of targets that you could interrogate.
Yeah. Thanks, Karen. So Cintia, I know it's still way early, but could you give us some color on the drug launch so far for Tecelra?
Yeah, absolutely.
Yeah.
It has been really exciting. So we got approval in early August, and we were ready to go at approval. At the same time that the product was approved, we also had the approval of the two biomarker tests that are required to identify the patients that are eligible for Tecelra. And so we have been. Our few teams were ready to go even before we had the full medical affairs and commercial teams deployed. And so right now, patients can be tested anywhere in the country. The testing platform is available. We are offering sponsor tests to facilitate that journey as well, and we have six authorized treatment centers on our website. So patients, when they are diagnosed and positive, they can go to a treatment site and get treated.
And all the interactions so far have been really very exciting with the whole sarcoma community because it's a rare disease that really didn't have a lot of innovation over the last several years.
Yep. Yep. Thanks, Cintia, and so you mentioned about the biomarker screening.
Right.
Could you tell us more about your effort you have already put on to kind of support and then boost the screening for the target patient?
Yeah. So a couple of things that we did. So there are two tests. One is just the HLA typing that is a little more traditional. The test that is new now with the approval of Tecelra is MAGE-A4, which is the antigen that Tecelra targets. That was developed by Agilent. We've partnered with Quest to be able to offer the test across the country, and through regular commercial route, but also sponsored. So it could be no cost to the patients, and they can get tested anywhere they are. They don't need to go to a treatment center to be tested. They can initiate the testing online, ship the tumor, get it tested, and when they're positive, then they can go to the treatment center.
We also have an internal team that's called Adaptimmune Assist, that has a group of navigators that will help the physician or any healthcare provider to, and the patients directly as well, to navigate through the journey, from the testing all the way to be able to travel and get to a treatment center, and also how the entire treatment journey progresses.
Ah, gotcha. Thank you. Thanks, Cintia. For the near to medium term, when we're looking at the launch, what sort of launch metrics should we focus on?
Yeah, so we are focusing on the number of authorized treatment centers that we're gonna continue to report. We are on track to onboard about at least ten for this year and continue to grow. We believe we need about thirty, and we'll get there sometime next year, and the other metric that will be important for us during this time period will be apheresis patients. It takes a little for our patients to be able to be dosed. They are being tested as we speak. There is all the logistics around the testing, and then they need to be apheresis, then there is the manufacturing turnaround time, that is about thirty days. So we really don't expect to dose patients until late in the year, so that's why we're gonna be providing information around apheresis patients.
I see. So, Karen, so we know right now that afami-cel is getting the accelerated approval. So could you tell us what's the process for converting this accelerated approval to the full approval? What's the requirement from the FDA?
Yeah, absolutely. So the study that was the basis of the FDA approval for afami-cel or Tecelra was called SPEARHEAD-1, and the data that makes up the initial BLA application is cohort one from that study. We had opened a second cohort of the study to enroll additional patients, and through the approval process, we had agreement from the FDA that that second cohort, which is already enrolled completely, can serve as the confirmatory evidence for this application.
Sure, yeah, and do they have any requirement for the durability for the... or just to-
They would like to see similar results, of course, but no specific requirements were made. I would like to say that the other big win, and I know that I'm saying this, but the other big win from the approval is that we do not have a REMS associated with this study, because the safety profile was different than I think what it would have seen in most CAR-Ts, very low levels of grade one and two CRS, that were quite manageable. So I'm very lucky to not have a REMS.
Sure. So let's switch gear a little bit for the... So you have lete-cel upcoming. So could anybody tell us about the regulatory pathway for lete-cel, and what's the gating step for the filing?
So the pathway for lete-cel will be very similar to that of afami-cel. We will, we'll follow the same steps. Now that we've had one and done, you know, we certainly have lessons learned that we can apply. So we are in the process of, you know, collating and generating that data. As you know, that program came back to us from GSK, so, you know, we are in the midst of program transfer and getting the application together, but it will take some time. I think the gating part for this is going to be. Honestly, I think it's just the nature of having data transferred and making sure that we have all of the data that we need in order to support this application.
So I guess you guys tried to, based on the afami-cel and the lete-cel, to build out a sarcoma franchise. So I guess-
One question I get more, mostly is, how do you guys think the afami-cel and the lete-cel can be synergistic to each other? And, what about, how should we think about the market potential for these two products?
Yes. So lete-cel is also indicated for sarcoma. So the target centers and the specialty that we are currently working with afami-cel is exactly the same. So the commercial footprint that we have put in place for afami-cel is gonna be exactly the same that we're gonna need for lete-cel, the same treatment center, same physicians, exactly the same. lete-cel gives us a couple of incremental opportunities. So lete-cel targets a different antigen, which is NY-ESO-1 instead of MAGE-A4. And in addition to that, we have data for lete-cel, in addition to synovial sarcoma, for MRCLS, which is another type of soft tissue sarcoma. So with lete-cel, we are able to reach a completely new indication and to be able to treat also synovial sarcoma patients that express NY-ESO-1 and don't express MAGE-A4.
So when you look at them in combination, the approval of lete-cel would enable us to reach about two and a half more patients than we can reach with afami-cel alone, and that's just looking into incremental patients, right? And so it is a significant opportunity in an area that has a really important unmet need.
Thanks, Cintia. So, another question for the sarcoma franchise is, how do you think... If both afami-cel and lete-cel get approved, what's the optimal treatment position for each, so?
Yes. So you mean in the entire treatment? So the products, so afami-cel was approved for patients that have already been exposed to chemotherapy. So post-chemotherapy is where patients can go, and it will be similar for lete-cel. So we expect that as soon as a patient progresses after chemotherapy, that they're then eligible for either product.
... and then in terms of the expression, then if it is an MRCLS patient, it would be a lete-cel patient, and then depending on the antigen expression, a physician would choose whether to go with afami-cel or lete-cel.
Gotcha. So let's move on to the uza-cel, your kind of advanced version of the afami-cel. I know you guys had forged the partnership with Galapagos. So could you tell us more about the strategy for the development of the uza-cel in your hand?
Yeah, so I can answer that for you. So, uza-cel, as you said, is the advanced version of MAGE-A4, so it's a MAGE-A4 plus a CD8 in the TCR that we think provides more active... not more active, but it helps us to overcome some resistance mechanisms in solid tumors. Currently, we have a study called SURPASS-3, that was mentioned earlier, that is ongoing in patients with platinum-resistant ovarian cancer. And that study is ongoing. It has been up and running for some time and is recruiting well at this point, and we're looking forward to seeing that data in the future. When we made this, the partnership with Galapagos, that study was already well on its way.
So the strategy for the development of the partnership with Galapagos was that it made more sense to go after a different indication rather than try to catch up where we already were with ovarian, on our platform. So the first study that we're doing with Galapagos will be in patients with head and neck cancer. We think this is an excellent indication for Galapagos's decentralized manufacturing platform because they allow, you know, around a seven-day vein to vein time, and patients with head and neck cancer, who we've previously had on study and who tend to respond really well, often progress very quickly and need a product faster than the traditional TCR manufacturing platform.
So we think this is an indication where we can hopefully make a difference for patients, and it'll be very interesting to see what the products that are produced on this decentralized platform look like and how they differ from those produced on a traditional platform.
Thanks, Karen. So just to follow up a little bit on the pipeline. So I know you have two, I guess, two more in the-
Yeah.
Pretty, pretty late stage.
Could you help to highlight those programs to our audience?
Yes. So we have a program which is called ADP- 600, which is our PRAME TCR. Our wonderful research group developed this TCR that we believe is more potent than TCRs that are currently under investigation. We're moving towards IND with that study and are really anxious to get that in the clinic. I think that'll be one of the next new INDs that comes through for us. And then the second product is called ADP- 520, which is a CD70-targeted asset, and that has the potential to address bigger markets. Two of the highest expressing indications are renal cell carcinoma and also AML, which are definitely unmet needs and a sizable population. That's also in research currently, but is moving towards IND.
Sure. So, Karen, the last question regarding pipeline, and so we all know a lot of cell therapy company kind of pivot to, from the oncology to-
... autoimmune disorders. I'm just curious, do you guys have a plan to explore any opportunities in autoimmune disease? And, maybe you can tell us more, how does your approach can differentiate from the rest of the crowd?
So I think, first of all, you know, our mission has always been to be a solid tumor cell therapy company, and I think for the time being, that strategy will remain in place, and we are not looking, at this point in time, to expand, to things like autoimmune diseases, though, there has been, you know, very exciting data and significant process using CAR-Ts in that space. Maybe something we consider in the future, but we're gonna stick with solid tumors for the moment.
Sure, I keep my eyes on that. So, Gavin, I guess, to close our conversation, could you remind us, what's the major catalyst coming up for Adaptimmune in the next twelve months?
Yeah, I think we've touched on many of them. Clearly, as Cintia said, demonstrating the execution of the commercial launch is gonna be really important to us and to the community. I think the measures to look for there is the number of patients being apheresed and the number of ATCs that we stand up as leading indicators. Clearly, as the commercial launch progresses, we'll begin to be able to talk to revenue numbers, but we're probably 12-18 months away from trying to guide there. So those two clearly are important things. I would point to the upcoming lete-cel data that we'll be presenting at CTOS, which will be the first full data set from the IGNITE-ESO trial. So that's shortly.
As we move into next year, clearly looking at how the ovarian trial is developing. We won't be able to say too much about that until it's fully enrolled. It's dual arm. And then, of course, we'll be updating, probably from Q1 onwards, as progress against the BLA on lete-cel. We just touched on the PRAME or ADP-600, moving into the clinic, and a little bit behind that CD70. So there's a rich pipeline of things to be talking about over the next twelve months.
Sure. How about your cash position?
At the end of Q2, we had $250 million on the balance sheet, and that's a good position to go forward from.
Awesome. So thanks, Gavin, Cintia, and Karen, for-
Pleasure.
Thank you.
Thank you guys for coming down to talk to our audience.
Thank you
... and, thanks.