My name is Ella Rosenblatt with the Jefferies Investment Banking team, and it is my pleasure to introduce you to Gavin MacBeath, Chief Executive Officer of TScan Therapeutics.
Great, thank you, and thank you to Jefferies for the opportunity to talk today. As many of you know, we are a publicly traded company, so I will be making forward-looking statements during this talk. Just by way of introduction, TScan is a fully integrated next-generation tcr-T-cell therapy company. We were founded back in 2018. We've been in business for over six years now. As I said, we're clinical stage, so we have two main clinical programs: a program in heme malignancies, where we're treating patients with AML, MDS, and ALL that are undergoing allogeneic bone marrow transplants. I'll go into quite a bit of the data that we've accumulated to date on that program in this talk.
Our second program is in solid tumors, where we're taking a unique approach in the industry, and that is to work towards treating patients with multiple agents simultaneously, or what we refer to as multiplex therapy. In the heme program, we have very promising data to date. We reported data at ASH in December last year, and at that time, we had treated 26 patients and seen only 8% relapses. Only two of those 26 patients had relapsed, compared to 4 out of 12, or 33%, in the control arm of this trial. I'll go into our steps forward with that program, including the design of the pivotal trial that we're going to launch this year. There are multiple catalysts this year, clinical catalysts that we expect. One is the launch of that pivotal trial.
We will present updated data on that heme phase I study by the end of the year, including long-term follow-up data, two-year data on the initial patients in that study. In solid tumors, we're also planning to provide our first update on safety as well as efficacy in the solid tumor trial by the end of the year. By way of introduction to the whole area of TCR-engineered T-cell therapies, this is very similar to CAR T therapy in that we are genetically reprogramming a patient's or a donor's T-cells to recognize the cancer in the patient. However, instead of using an artificial chimeric antigen receptor, we're using the naturally occurring T-cell receptor. This is the mechanism that T-cells naturally use to recognize and kill cancer cells.
One feature of T-cell receptors is that they are what are called HLA-restricted. In other words, they work in conjunction with a particular HLA type. Your HLA type is actually defined in chromosome six. You have six different class one HLAs, and they can be quite varied. The good news is that there are certain HLA types that are much more common than others. In particular, we as a company have chosen to focus on the six most common HLA types. Collectively, over 90% of people in the United States and 85% of people worldwide are positive for at least one of these six HLAs. Our strategy as a company is to focus on these six HLA types and build out a pipeline of TCRs that are able to treat a broad range of cancer patients. Our pipeline is really quite varied.
You can see at the top in yellow is our heme malignancy program. We have two different agents in phase I trials, or as I'll explain moving forward, we'll be moving one of those products into pivotal trials, TSC-101. We also have a planned IND this year to extend this heme program to other HLA types as well, including A*03:01. In solid tumors, we actually have seven different agents in the clinic right now. They're all in the same phase I clinical trial. It's in dose escalation right now. This is where we plan to update the street on both safety and efficacy by the end of the year. With that, I'm going to jump into the heme malignancies program and really focus on the data that we put out at ASH in December.
By way of introduction, the unmet need here is that patients with AML, MDS, and ALL, right now, the only potentially curative option for these patients is to get a bone marrow transplant or an allogeneic hematopoietic cell transplant. This is actually quite effective for patients, but unfortunately, particularly for patients that are getting a transplant with reduced intensity conditioning, there's about a 40% chance that the patient will relapse. If they relapse, the prognosis is very poor. In fact, about 80% of those patients will die within two years of relapse. The unmet need here is to make transplant more effective, to essentially treat any residual cancer and prevent relapse in patients undergoing transplant therapy. The way our program works is we focus on patients, shown at the top in pink, whose blood cells all express a particular antigen.
For this example, I'm focusing on the antigen HA-2. All of their blood cells, including their cancer cells, will be displaying this antigen. What we do is we pair them with a donor whose blood cells are negative for that antigen. In these diagrams, those are colored blue. If they get a transplant, they'll first undergo conditioning therapy to essentially wipe out all their white blood cells, and then they'll get stem cells from that donor. Those stem cells will now repopulate their entire white blood cell system. Now all their new healthy blood cells will come from the donor and will be negative for that antigen. That's why they're colored blue in this diagram. Any residual cancer cells will be pink. They're HA-2 positive.
In order to surgically remove or basically target those residual cancer cells, what we do is we take T-cells from the donor and we engineer them to recognize the antigen HA-2. Then about three weeks post-transplant, we treat the patients with those engineered T-cells. At that point, those T-cells will only recognize any residual cancer, but they're not going to touch any of the new healthy cells that come from the donor. It is a very clean way to target residual cancer without the side effects associated with targeting a large number of tumor cells. In our trial, we included a control arm in our phase I study. In the control arm, the patients are getting standard of care bone marrow transplants. This is the normal course of action. The patient would get screened, identified for a transplant.
They would then identify a donor for that transplant. The donor would get apherese right before the transplant, and then on day zero, the patient would receive those stem cells. What we're doing in our treatment arm is essentially the same procedure, except prior to that apheresis for the transplant, we apherese the donor to collect their T-cells, and we start our manufacturing process. You can see 21 days post-transplant, the patient gets a single infusion of those T-cells, and most of our patients have now received a second infusion 40 days after that first infusion. In our phase I study, as I said, we reported data on the first 26 patients treated, as well as 12 control arm patients. The patient characteristics were very well balanced between the treatment and control arm.
I won't go through all the details here, but if you focus on the last line, what you'll see is this is highlighting which are the high-risk patients in the study, which are the patients that are most at risk of getting relapses. They're either positive for disease, MRD positive prior to transplant, or they have adverse risk genetics. What you can see is in the treatment arm in green, 80% of the patients were at high risk of relapse, or 81%, and this compares to 77% on the control arm. Very comparable patient populations. This was a dose escalation study. We didn't encounter any significant safety issues, no dose-limiting toxicities in the study, so we proceeded very quickly through the first two dose levels.
At this point, most of the patients in the study have received dose level three, which is two infusions of the engineered T-cells. In terms of safety characteristics, again, very well tolerated product. We've seen very little product-related toxicity. We have, of course, seen toxicities related to the transplant itself. In terms of product-related toxicities, only one grade one event for CRS with TSC-100 and only one grade two event for CRS with TSC-101. No cases of ICANS in this study. How do we know that our product's being effective? The goal of this product is, as I said, to remove all those pink cells, any patient-derived cells, whether they're healthy or malignant cells. There are two assays that we perform on the patient's blood or bone marrow to determine if we've been successful.
The first is we take bone marrow biopsies and look to see if there's any minimal residual disease in the patient. Can we detect any cancer cells? If we can, that patient is called MRD positive, and they're obviously of higher risk of relapse, whereas if they're MRD negative, they are lower risk of relapse. The second assay we perform is what's called donor chimerism, where we're looking in their blood to see if there are any detectable patient cells, whether they're normal or malignant. If we can't detect any patient cells left, right, if it's all donor, then that's called 100% donor chimerism. That patient is at very low risk of relapse, whereas if they have mixed chimerism, they're at higher risk of relapse. Here's a summary of all the chimerism data that we've collected to date.
On the left in blue and purple are the patients that we've treated with cell therapy. On the right in yellow are the control arm patients. As you go down the rows, these are successive time points since they got their transplant. The yellow diamonds indicate when they got infusions of the engineered T-cells. If you see a blue checkmark, that means they have 100% donor chimerism. They're at very low risk of relapse. If there's a pink X, that means they're incomplete chimerism and are at higher risk of relapse. What you can see on the left is that all of these patients, once they received their first infusion of T-cells, have had complete donor chimerism, whereas on the right, the control arm patients, it's a very different picture. Many of these patients have incomplete chimerism.
In terms of relapses, on the left, there were two patients that we saw relapsed from their disease, whereas on the right, in the control arm, four out of the 12 patients relapsed. In terms of the MRD status, we take regular bone marrow biopsies. All of the patients have a bone marrow biopsy at day 60, day 100, at six months and at 12 months. On the treatment arm, they get a bone marrow biopsy right before they get their first infusion of T-cells. What you can see on the top in blue and purple is that every patient that received our product converted to MRD negativity and stayed that way throughout the course of the study, whereas on the bottom, the control arm patients, many of them did become MRD positive and went on to relapse.
By the way, these patients are very similar in the treatment and control arm. If you look at the far left, this is the MRD assay performed before they got their transplant. You can see in pink squares that about 50% of the patients were MRD positive in both the treatment and control arm prior to transplant. Very similar patient populations. I think visually, this is most easily represented by the Kaplan-Meier curve. This is looking at probability of relapse. You can see on the control arm, a much higher probability of relapse than on the treatment arm, where we've dropped the probability of relapse down to 8%. Similarly, if you look at event-free survival, we see, again, a very favorable hazard ratio. Overall, very well tolerated products. All of the product has persisted. We've tracked the engineered T-cells in the patients.
Every patient that's made it past a year, we can still see their engineered T-cells in circulation. Overall, the data are clearly favoring the treatment arm relative to the control arm. Based on that, we've made the decision as a company to move forward with a pivotal trial, which we intend to launch this year. We've already met with the FDA last year to discuss the clinical trial design. For a start, in terms of our strategy, as I said, there were two products that we looked at in this phase I study, TSC-100 and TSC-101. It turns out that the TSC-100 patient population captures about 24% of patients in the US who would be eligible to receive the product, whereas TSC-101 is 42% of patients who would be eligible to receive that product. In fact, it's largely overlapping patients.
Most of the patients that are eligible for TSC-100 are also eligible for TSC-101. Based on that, we've elected to just move the TSC-101 product forward. They're essentially equivalent in terms of their mechanism of action. The study design that we agreed on with the FDA is really quite unique. For a start, very simple study, two-arm study. The treatment arm, patients will be getting standard of care bone marrow transplants coupled with TSC-101, just as we did in the phase I study. For the control arm, we reached agreement with the FDA that the control arm would be what's called a synthetic control arm. It turns out in bone marrow transplant, every patient that gets transplanted in the U.S., all their data goes into a database managed by CIBMTR.
There are literally hundreds of thousands of patients' worth of data in this database. The study design is that for every patient that we treat on the treatment arm, we will find three patients in the CIBMTR database that have the same disease and have very similar patient characteristics, similar age, similar risk genetics, similar treatment regimen. That becomes a control arm for the study. Based on that design, we'll continue with the patient population of AML, MDS, and ALL. We're powering the study for a hazard ratio of 0.6. Right now, we're outperforming that on our phase I study. To be conservative, we're powering the study to reach a hazard ratio of 0.6 with 85% power. We estimate that this will require about 140 patients on the treatment arm and that we'll get readout on this study in 24 months.
We're going to launch this study in the second half of this year, which means we'll have a top-line readout on this pivotal trial in the second half of 2027. This study is powered for the primary endpoint of relapse-free survival, which we've reached agreement with the FDA will support full approval of the product. This is not an accelerated approval path. This is a full approval path. This is what the TSC-101 data look like for relapse-free survival as of the December 2024 data cut. Obviously favoring the treatment arm relative to the control arm. In terms of the addressable patient population, as I said, right now, we can address a subset of patients that are undergoing transplants. About 7,350 patients a year in the U.S. alone get allogeneic transplants.
Our trial will focus on the 42% of patients that are AO201 positive, but also the patients will be receiving a transplant with reduced intensity conditioning and with a particular type of donor, either a haploidentical donor or a mismatched unrelated donor. With those as the enrollment characteristics, we estimate there's about 1,000 patients a year in the U.S. plus Europe that meet all of the enrollment characteristics of the pivotal trial. However, we believe that if our trial is successful, this will, of course, if it's successful, reduce relapse rates by about 50%. That means that the outcomes, if you get our therapy, will be substantially better than if you don't get our therapy, including with different donor types. A lot of transplant centers prefer matched unrelated donors relative to haploidentical donors, but those two types of transplants actually have very similar outcomes.
However, if you were to have a 50% lower chance of relapsing with our therapy, which requires a haploidentical donor, then we anticipate a change in clinical practice where physicians who would normally use a matched unrelated donor would instead favor haploidentical donors. We actually anticipate a change in practice that would enable on-label use of our product for a broader set of patients, up to 2,400 patients per year in the U.S. plus Europe. Similarly, right now, myeloablative conditioning has a better outcome than reduced intensity conditioning, but it comes with a much higher risk of non-relapse-related mortality. In fact, 16% of patients will die from the conditioning regimen, usually of infection, as opposed to 2% with reduced intensity. If we can drop the relapse rates by 50%, it would be more favorable to get reduced intensity conditioning with our product.
Again, we anticipate a change in clinical practice. Depending on the extent of change in clinical practice, we anticipate the addressable market to be somewhere between 1,000 and 5,000 patients a year. If we look at current drug pricing for TCR-engineered T-cell therapy, most recently, TECELRA was approved with a pricing of $727,000 for that therapy. If we're anywhere in that range, then this represents a potentially multi-billion dollar opportunity. One way in which we anticipate expanding this program is by extending our therapy to other HLA types. As I said, right now, TSC-101 addresses patients that are positive for A*02:01, which is 42% of people in the U.S., about 47% of people in Europe. To extend to other HLA types, we've actually developed a universal way to move forward with other HLA types.
That is to use the target CD45 as the source of antigen. CD45 is a very well-expressed protein in all lineages of heme cells, but it is not expressed in any tissue outside of heme. Because we are finding donors that are negative for the antigen based on finding donors that are negative for that HLA type, this represents a general way to move forward with other HLA types. Right now, we have already got a TCR that recognizes an epitope from CD45 that is expressed on the HLA type A*03:01. We anticipate filing an IND on that in the second half of this year. We are going to then open up phase I to move that product forward. We also have a TCR coming along for A*01:01, again, a different epitope from CD45. This is a way to expand this program to other HLA types as well.
Based on that, we believe we can double the addressable patient population as we expand to other TCRs that address other HLAs. That is where the heme program sits. Again, update on data by the end of this year for the ongoing phase I patients, as well as an anticipated IND for TSC-102- AO301. At this point, I'm going to turn to solid tumors, which, as I said earlier, is a very different strategy as a company. Here, we're addressing what we believe is the key unmet need in solid tumors. That is that solid tumors are intrinsically heterogeneous. Not every tumor cell in a tumor expresses a given antigen, which means that if you treat a solid tumor with a single agent, you often address many, but not all of the tumor cells, and the patient will ultimately relapse.
Whereas if you can come in with multiplex therapy, right, with more than one agent at a time, this has a better chance of addressing that heterogeneity. In fact, the whole history of cancer therapy has shown that combination therapy always outperforms single-agent therapy. For example, if you look at this tumor image, we have imaged this tumor for two of the an``tigens in our pipeline, PRAME and MAGE-A4. PRAME positive cells are stained in red, MAGE-A4 positive cells are stained in green. What you can see is that this tumor has some green cells, some red cells. In fact, there is very little overlap between the green and red cells. If you were to treat a tumor like that with just a PRAME TCR, you would kill all those red cells, but all those green cells would be untouched.
That patient could show a partial response, but then would relapse. However, if you came in with a combination of a PRAME and a MAGE-A4 specific TCR, you have a much greater chance of addressing that tumor and getting a complete remission or even a cure. Our strategy has been to build a collection of TCRs that address different targets and are specific for different HLA types. We call this collection our ImmunoBank. When a patient comes in, we get a sample of their tumor, we test the tumor to see what antigens are expressed in their tumor. The strategy is to go to that ImmunoBank and select the best two or three TCRs for that patient that best matches their particular tumor. We call this Customized Multiplex TCR T-cell Therapy. That is the vision that we have.
This is what we've been working towards as a company for some time now. Right now, we've actually got seven TCRs that we've successfully taken through IND. They've been cleared by the FDA. They're all in the same phase I clinical trial. The goal of this study, which we call the PLEXI-T study , is to start treating patients with multiple TCRs simultaneously. To do this functionally, we have two separate protocols. We have a screening protocol in which we identify patients that would qualify for our therapies while they're still currently on effective frontline therapy or second-line therapy. Once we know that a patient would qualify for our study, we keep that patient in a database. If they progress on their cancer, we already know that they qualify for our product, and we can move them very quickly into our phase I clinical study.
In yellow then, the treatment protocol, the patient would come in, we would apherese the patient to collect their T-cells, manufacture their product. They go through standard lymphodepletion, and then on day one, they get their first infusion of engineered T-cells. Then 28 days later, they get a second infusion of engineered T-cells. The strategy that we reached agreement with the FDA on is that we would first treat each patient with single plex therapies, so single TCRs at two different dose levels to make sure that each TCR-T is safe on its own. Once a TCR-T has cleared dose level two, it becomes eligible to be combined with any other TCR that's cleared dose level two. At dose level three, the patient can get two different TCRs, so two successive infusions on the same day.
This is where we also introduce the repeat dose 28 days later, where they will again get two successive infusions of the two TCRs. Dose level four is an escalated number of cells relative to dose level three. We did enable on this protocol the ability to do single plex therapy at dose levels three and four. Same total number of T-cells, but with just a single TCR, so that we can see a comparison between multiplex therapy versus single plex therapy. In December, we gave an update on how this trial was going. At that point, we had treated eight patients in the study with four different TCRs, an HPV16 TCR, a MAGE-C2, a PRAME, and a MAGE-A1 TCR.
At that point, we'd actually already cleared dose level two for two of those TCRs, the HPV16 TCR and the PRAME TCR. What happened at the end of last year is we actually introduced a seventh TCR, the MAGE-A4 TCR, into the study. The first half of this year, we've been focused on moving the MAGE-A4 TCR through dose level one and two so that that would enable multiplexing with now a clinically validated target. TECELRA was, as I said, recently approved, which is a MAGE-A4 specific TCR. What we've been guiding to in our public guidance is that we will treat our first patient with multiplex therapy in the first half of this year. We anticipate putting out a press release when that occurs.
In the second half of this year, really trying to move this trial forward as quickly as possible to treat as many patients as we can with multiplex therapy so that we can get an interpretable data set by the end of this year. We are still guiding to reporting both safety and efficacy data on the study by the end of the year. We made a decision also to focus this study on a defined set of cancer indications. We had sort of an all-comers approach in the first two dose levels. As we get to effective dose levels, and we believe that dose level three and higher are now efficacious dose levels, we would focus this study on HPV- positive patients, head and neck cancer, cervical cancer, and anal and genital cancers. These are all caused by HPV16 infections.
For HPV negative patients, really focus on non-small cell lung cancer, sarcoma, and head and neck cancer. You will notice what is missing here, and that is cutaneous melanoma. We feel this is a very crowded space. Obviously, there are a lot of therapies available now. AMTAGVI was recently approved. Dual checkpoint therapy is very effective in melanoma. We feel that the real opportunity here is to move our products forward in lung cancer, sarcoma, and head and neck cancer. I just want to also highlight the addressable patient population with multiplex therapy. As I said, with the addition of the MAGE-A4 TCR, we have done a calculation now. This is based on our own data from our screening study where we have screened several hundred patients now for expression of these various antigens.
What we're finding is that, for example, with head and neck cancer, 40% of patients with head and neck cancer would qualify right now to receive at least two of the TCRs out of the seven that we currently have in this clinical trial. At least 25% of patients with non-small cell lung cancer qualify to get multiplex therapy. For anal and genital cancer, 60% of patients. This is now a really substantial percentage of patients in each of these indications that would get two or more TCRs in our current clinical study. If this program's successful, we'll continue to build the ImmunoBank with more TCRs addressing other HLA types so that we can further increase these numbers over time. I just want to end by reiterating our publicly stated milestones. In blue at the top is the solid tumor program.
We're still targeting treating our first patient with multiplex therapy this month. We are updating the street on safety and response data for multiplex therapy by the end of the year. In the heme program, we've obviously opened our expansion cohorts at dose level three already. We are planning to launch a pivotal study in the second half of this year, file an IND for this HLA expanded TCR in the heme program by the end of the year, and provide an update on data in our phase I study, including two-year data on our initial patients in the study by the end of this year. I want to thank the organizers for inviting me here today. I'm happy to take any questions in the last minute and 40 seconds.