Great. Thank you very much, thank you very much for joining the conference. My name is Li Chun and I'm a Quarterly Research Associate with DuckTao. Our next presenting company is TScan Therapeutics. With us today is Mr. Gavin McBeth, CEO of TScan. It's a clinical stage biotech company focused on the development of TCRT cell therapies for cancer treatment. Please go ahead.
Great. Thank you very much, and thank you to the organizers for giving us the opportunity to present this morning. I do want to remind people that TScan is a publicly traded company and we will be making forward-looking statements this morning. Just by way of introduction, for those that aren't familiar with TScan, we are a fully integrated next-generation TCRT cell therapy company with multiple assets in the clinic right now. In particular, we have two main clinical programs: a program in heme malignancies, where we're targeting residual cancer to prevent relapse in patients undergoing bone marrow transplants, and a program in solid tumors, where we are working towards delivering multiplex therapy, in other words, more than one TCRT therapy simultaneously in order to address the key problem of heterogeneity in solid tumors.
Our lead program is the heme program, and we have very promising clinical data, which we presented in December at ASH last year, in which we showed that in a treatment arm comprising 26 patients, we had only seen two relapses out of 26 patients, or 8%, whereas in a control arm, a very well-matched control arm, we saw 4 out of 12 relapses, or 33%. Based on this substantial reduction in relapse rates, we are moving that program into a pivotal study, and I'll go through that program in my presentation. We have multiple clinical catalysts coming this year. We'll be presenting updated data on our heme phase one study at a medical conference at the end of the year, as well as we aim to launch our pivotal study, so dose our first patient this year. We also have upcoming data on our solid tumor program.
We intend to present data on our initial patients treated with multiplex therapy in Q1 of next year. Finally, as I said, we are a fully integrated company, and that includes manufacturing. We have our own GMP manufacturing suite, but for our lead program in heme malignancies, we've engaged an external CDMO for commercial manufacturing, and we'll be using that CDMO as well as ourselves in our pivotal study. We ended Q2 with $218 million in cash, and that gives us the runway into Q1 of 2027. Just a little background on TCRT cell therapy. If you're not familiar with TCRs, essentially every cell in your body has class I HLAs on their surface, and these class I HLAs, it's their job to present to the immune system peptides derived from proteins in the cell. In this diagram, the tumor cell is presenting a peptide in pink.
In this case, the example is a peptide derived from the protein PRAME on a class I HLA, which is pictured in green. The way T cells recognize these foreign antigens is through the T cell receptor. In blue is the T cell receptor of the T cell. It recognizes the class I HLA and that peptide and then mediates a cytotoxic response to kill that tumor cell. Everyone has six different class I HLA genes. They're all encoded on chromosome six. The challenge here is that there are literally hundreds of different types of HLA genes. The good news is that certain genes are much more common than others. In fact, if you focus on the six most common HLA types, it turns out that over 90% of people in the United States and 85% of people worldwide have at least one of these six HLA types.
In order to provide a therapy for the vast majority of patients, we're developing a broad pipeline of TCRT cell therapies targeting different antigens and different HLA types. Right now, our pipeline includes nine different TCRTs that are currently in clinical trials in phase one. You can see at the top two different TCRs in our heme program and in the bottom seven different TCRs in our solid tumor program. We did just update our pipeline yesterday to reflect the fact that we now have two different additional TCRs in IND-enabling activities in our heme program, both targeting epitopes derived from CD45. I'll explain a little more on that later. With that, I'm going to dive into our heme program, give you a little bit of background about what the unmet need is and how we're addressing it.
In heme malignancies, in particular in patients with AML, MDS, and ALL, really the only curative regimen for these patients is to get a bone marrow transplant. In fact, bone marrow transplants are highly effective. Most patients are cured by a transplant. In fact, about 60% of patients are completely cured. Unfortunately, for the 40% or so of patients that relapse, the prognosis is very poor. In fact, if you relapse, there's an 80% chance that you will die within two years. The key unmet need in this space is can we make transplant more effective? Can we prevent relapse and cure more patients that undergo this therapy? The mechanism of our product is as follows. If we identify a patient, and in these diagrams, the patient cells are depicted in pink and the donor cells are depicted in blue.
If we identify a patient who has the HLA type AO201, that means that all of their blood cells, including their leukemia cells, will present the antigen HA2 on the surface of the blood cell. If we pair that patient with a donor who doesn't have that HLA type, who's AO201 negative, then none of their blood cells will present that antigen. If that patient undergoes a transplant, they will first start by getting conditioning therapy that wipes out all of their blood cells, and then they get stem cells from the donor so that once their white blood cell count recovers, all of their new healthy blood cells are donor-derived, so they're HA2 negative. That's why they're depicted in blue here. If they have any residual cancer, that still comes from the patient, and those cancer cells are HA2 positive, and we'd like to selectively eliminate those cancer cells.
What we do is while the patient's undergoing the transplant, we apherese the donor. In other words, we take T cells from the donor. These T cells are HA2 negative, and we engineer them with a T cell receptor that recognizes HA2. As soon as their white blood cell count has recovered post-transplant, which is typically about 21 days post-transplant, we give them their first infusion of T cells. At that point, those engineered T cells will only target the residual cancer because that's HA2 positive, but won't touch any of those new healthy blood cells that come from the donor. A very clean way to eliminate residual cancer and prevent relapse in these patients. The design of our phase one study actually included a control arm in our phase one so that we could see in a similar patient population what the relapse rates are.
In the control arm, subjects are first identified through screening, then a suitable donor is identified. The donor undergoes apheresis to get their stem cells, and then day zero, they receive those stem cells. Very similar process on the treatment arm, except in addition to the apheresis to get the stem cells from the donor, just prior to that, we apherese the donor to get their T cells, start the manufacturing process, and then you can see on day 21, and then again 40 days later, on day 61, the patient receives an infusion of those engineered T cells. Very little burden on the patient. They're getting just two 30 to 60-minute infusions of T cells, typically now done in an outpatient setting, and then very little burden on the donor if they just undergo one additional apheresis prior to the transplant.
These are the patient characteristics of the 26 patients on the treatment arm and 12 patients on the control arm that we presented at ASH last year. In green are the sum total of all the patients that received either TSC-100 or TSC-101, very similar products. In yellow is the control arm patient. You can see very similar characteristics, same age, very similar gender breakdown. I would point you to the last line of this table, which is really the critical line, and that is what % of these patients were high-risk patients, in other words, at high risk of relapse. You can see in the treatment arm, 81% of the patients were considered high risk, either because they had detectable disease or because they had adverse risk genetics like p53 mutations or FLT3 mutations. On the control arm, very similar %, 77% were considered high risk.
This was a dose escalation study, and we used a dose escalation scheme called an i3 plus 3 design that enabled us to treat just a single patient at each dose level, assuming there were no DLTs. We advanced very rapidly to the third and highest dose level in which the majority of patients were treated. Dose level one, they only got a single infusion of T cells. At dose levels two and three, they got two infusions of T cells. The product was very well tolerated. In fact, we saw essentially no imbalance between adverse events on the treatment arm compared to the control arm. These patients do experience adverse events related to the transplant itself, but we did not see an increase in adverse events on the treatment arm relative to the control arm.
The only adverse events that we noted that were clearly attributable to the product, one patient experienced a grade one CRS, one patient experienced a grade two CRS, highly manageable, no cases of ICANS. During this trial, we used a number of assays to determine how well our product was working. The goal of this product is to eliminate all the patient-derived cells in the patient, so all the pink cells. There are two key assays that we perform on these patients post-transplant. The first is a bone marrow biopsy to determine minimal residual disease. Here we're specifically looking for cancer cells in their bone marrow. The patient is MRD positive. That means they're at higher risk of relapse, whereas MRD negative patients, it's below the limit of detection of the assay. They're at lower risk of relapse.
The other assay we do is performed on peripheral blood, and here we're looking at all patient-derived cells, whether they're malignant or normal. The goal of the transplant is to eliminate all patient-derived cells. If you have complete donor chimerism, that means you cannot detect any residual patient cells. That's very good news for the patient because obviously it's the patient-derived cells that would lead to the relapse. If they exhibit mixed chimerism, they are at higher risk of relapse, although it's not a guarantee that they would relapse. These are the data, the chimerism data that we presented at ASH last December. On the left, in blue and purple, are the patients treated with either TSC-101 or TSC-100, respectively. On the right, in yellow, are the control arm patients. If there is a blue checkmark, that means they have complete donor chimerism.
A red X indicates incomplete chimerism, and the yellow diamonds indicate when they received their T cell infusion. Standing back for a second and looking at this chart, it's very obvious that there is much more complete donor chimerism exhibited on the treatment arm on the left relative to the control arm on the right. I'd also draw your attention to the relapse rate. You can see on the left, two patients relapsed, one passed from their relapse, whereas on the right, out of the 12 control arm patients, four of those patients relapsed. Two of them at that time had passed away from their relapse. We have continued this year to enroll patients into this trial.
At a major medical conference at the end of the year, we intend to update everyone on data from this trial, which will include additional patients treated with TSC-101, as well as additional control arm patients. More importantly, we will show longer-term follow-up on these initial patients. Turning to the MRD assay, this is performed on bone marrow biopsies. In pink, it indicates MRD positive, whereas in blue, squares indicate MRD negative. You can see on the far left that about 50% of the patients prior to transplant were MRD positive, and that's 50% on the treatment arm as well as the control arm. Again, very good balance between these arms.
At the top, you can see that all the patients that were either MRD positive or MRD negative achieved MRD negativity and sustained MRD negativity post-infusion of T cells, whereas at the bottom, you can see a very different picture on the control arm. Overall, we observed a substantial reduction in the rate of relapse, which is why, based on these data, we are now taking this program into a pivotal trial. We have met with the FDA both last year and again this year. We have an end-of-phase meeting scheduled sometime before the end of the year in which we intend to achieve agreement on a pivotal trial design with the FDA. With that in mind, I just want to highlight how we're moving this program forward. In particular, as I said, there were two different products in our phase one study, TSC-100 and TSC-101.
TSC-100 addresses about 24% of patients, whereas TSC-101 addresses about 42% of patients. Since they're both targeting the same HLA type, it really doesn't make sense for us to move both products forward since most patients that we can treat with TSC-100, we can also treat with TSC-101. Our pivotal trial design is to move TSC-101 forward, and it's a very simple study. We have a treatment arm in which patients will receive transplant plus TSC-101 in the same manner as you saw on the phase one study. The control arm, we're aiming to have a synthetic control arm in which for every patient that we treat on the treatment arm, we will find three patients in the CIBMTR database that match that patient. Exact match, the disease state, and propensity match a number of variables that are all known to be prognostic of outcome in transplant.
We think this is the best way to achieve ideal balance between the treatment and control arm in the study. For those not familiar, CIBMTR is a large curated database of every patient that undergoes transplant in the U.S. and abroad. It includes over 700,000 patients in that database. We're powering the study to achieve a hazard ratio of 0.6 with 85% power. Based on our current enrollment rates in the sites that we intend to have participate in this study, we anticipate that we can fully enroll the study and get to a top-line readout on relapse-free survival within 24 months of first patient in. We're aiming to complete this study and present top-line data by the end of 2027. Just a quick word on the addressable market here.
Right now, about 9,000 patients with AML, MDS, and ALL undergo allogeneic transplants every year in the United States and about a similar number in Europe. Our product is designed, obviously, there's specific enrollment criteria in our pivotal trial. It is designed for patients with the HLA type A0201 that have an A2 negative donor. We're also focusing on reduced intensity conditioning. The majority of transplants are conducted with reduced intensity conditioning. Finally, the donor type, we're focusing on patients with haploidentical or mismatched unrelated donors. Right now, the current practice shows that there's about 1,300 patients in the United States plus Europe combined that meet those enrollment criteria. However, right now, the donor choice in a transplant is very site-specific. Some physicians prefer to use matched unrelated donors, whereas others prefer to use haploidentical donors, but with very similar outcome.
If we can really change standard of care, reduce relapse rates by 50%, then a patient will have a much better outcome if they get a haploidentical transplant with our product than if they had a matched unrelated transplant and didn't get our product. We anticipate, and we've seen it already in our phase one study, a shift in clinical practice where more patients will undergo transplant with haploidentical donors in order to get our product. If a full shift occurred, that would lead to about 3,400 patients a year. If we see a shift in the use of myeloablative conditioning to reduced intensity conditioning, this would further expand the market to, in principle, over 5,000 addressable patients a year in the United States plus Europe combined. We do have a way to extend this program to other HLA types.
We talked about this a bit at the end of last year, and that is to target epitopes derived from CD45, which is a lineage-specific protein in heme cells, to other HLA types. We now have two products in IND-enabling activities, one targeting the HLA type A0301, a second targeting A0101, and in discovery right now, TCR is targeting A2402. With expansion of HLA types, we believe we can essentially double the addressable market once we get three more TCRs through pivotal trials. There are additional expansion opportunities, which we believe would enable us to address over 15,000 patients a year. In the few remaining minutes, I want to touch briefly on our solid tumor program as well as some exciting new news in autoimmunity. In solid tumors, we believe that the key unmet need is that solid tumors are heterogeneous. Not every tumor cell expresses a given antigen.
If you look at the staining of a lung cancer tumor on the left, you can see in red cells stained for PRAME, in green cells stained for MAGE4, and there's very little yellow cells, right? These are actually distinct cells expressing these two different antigens. If you were to treat a solid tumor with just a PRAME TCR in this example, you would only kill half the tumor cells, and that patient would relapse. If you treat this tumor with two different TCRs, one for PRAME and one for MAGE4, you have a much greater chance of achieving a deeper response or even a complete response in this patient. That's the logic behind our strategy.
Overall, our vision is to build a collection of TCRs so that when a patient comes in, we determine what antigens are expressed in their tumor and then go to that collection and pull out the best two or three TCRs, and that becomes a customized multiplex therapy for that patient. Our progress towards this right now is that we have seven different TCRs in our phase one study. The design is that we first test each TCR at two different dose levels to make sure that they're safe on their own. Once a TCR has cleared dose level two, it becomes eligible to be combined with any other TCR that's cleared dose level two. That's where we introduce the concept of multiplexing. We'll also continue to enroll patients with singleplex therapy at that dose level.
Right now, we have cleared dose level two for three of our TCRs, HPV, MAGE4, and PRAME, and we are looking to dose our first patient with multiplex therapy very soon and present data on multiplex therapy in Q1 of next year. I just want to end with a quick word on autoimmunity. The core technology that TScan Therapeutics was founded on is a target discovery technology in which we're able to identify the target of any T cell. Earlier, about two years ago, we entered an agreement with Amgen to use this technology to determine the targets of both pathogenic and protective T cells in patients with Crohn's disease. That program is ongoing. In addition, we've also done internal work in which we've been studying other autoimmune disorders.
We have recently identified a number of very compelling targets in several autoimmune diseases, and we are looking to present those initial data at a medical meeting later this year. With that, I just want to end on this pipeline, this milestone slide. Again, reminding you that we intend to launch our pivotal study this year with TSC-101, file INDs for our expansion TCRs, and at the end of the year, update on data, two-year data in our phase one study. In the solid tumor program in blue, we intend to report initial safety and response data on patients treated with multiplex therapy in Q1 next year, and finally to present internal data on our autoimmune work at a conference later this year. Thank you for your attention. I'm happy to take any questions.
Great. Thank you for the presentation, and thank you for everyone's presence. Have a great day.