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Ladies and gentlemen, thank you for standing by. Welcome to T-Scan Therapeutics Strategic Update Call. At this time, all participants are on a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star-one-one on your telephone, and you will then hear an automated message advising your hand is raised. And to withdraw your question, please press star one-one again. Please be advised that today's conference is being recorded. I would like now to turn the conference over to Gavin McBeth, Chief Executive Officer of T-Scan Therapeutics. Please go ahead. Thank you, everyone, for joining us this morning. So this morning, I'll be providing a major strategic update to the company that we announced this morning and just as a reminder, we are a publicly traded company, so I will make forward-looking statements during this presentation. So, as many of you recall, in the history of T-Scan, one of our core objectives has been to deliver TCR-engineered T-cell therapies to patients with cancers, in fact, cancers with both heme and solid tumor malignancies. And last October, in October of 2025, we announced that we were pausing the solid tumor program in order to develop an in vivo engineering platform for solid tumors. So I'm excited today to announce that this program has actually made tremendous progress over the last year. And in fact, we have now, as of today, advanced two product candidates in this program into IND enabling activities. So we've developed an in vivo lentiviral platform that efficiently delivers the genes for these TCRs into T cells in vivo. T-cells get engineered and are able to clear target cancer cells in mouse models. So our strategy moving forward is to focus this program on our two most active TCRs from our previous clinical trial, a TCR directed at the antigen PRAME and a T CR directed at the antogen MAGE A4. And we'll be moving both of those products forward into IND enabling activities. So, over the coming two years, this program is going to create significant value inflection points. For example, we will be presenting preclinical data on our final constructs that we've moved into IND-enabling activities, as well as regulatory updates in Q1 of 2027. We are planning to file our first IND in Q4 of 27, and then finally to launch a phase one trial in Q3 of 2027. Sorry, file the first ING in Q2 and launch the pivotal trial in q4. I'm also pleased this morning to update on data in our heme program. We actually have very strong clinical data with our now commercial-ready manufacturing process in which we enrolled patients and treated them with this process, a cohort of patients that we refer to as Cohort C. As we previously disclosed, we've reached agreement with the FDA on a phase three study and, in fact, launched that study. And we've, in effect, enrolled our first seven patients on this study. However, unfortunately, we have not been able to secure sufficient funding to complete that clinical trial. It's obviously a large study and requires a significant amount of capital to complete the trial. And so we made the very difficult strategic decision to pause the phase three study and allow the data in these 21 patients to mature, to get longer-term follow-up on these patients. At the same time, we remain committed to establishing our manufacturing process at an external CDMO that has the capabilities of providing product in a commercial setting. And for this program, we are now actively seeking strategic partnerships. So the key value inflection points for this program moving forward is that we remain committed to presenting six-month data on these 14 patients in Cohort C in Q4 of this year at a major medical meeting. And then we will present updated data on all 21 patients, the patients in Cohord C plus the seven patients that we've already enrolled in the pivotal trial. We will present data on those patients in Q2 of next year. At that point, all of the patients in the study will have had over one year of follow-up. And then finally, again, key strategic inflection point for us is to secure a strategic partnership that can fund this program moving forward. And dann finally, for our autoimmune program, we have previously disclosed that we've discovered targets in HLA-B7-driven autoimmune diseases, such as ankylosing spondylitis. We are, with the strategic reorganization, halting further development of this program, pending partnerships. And so, obviously, a value inflection point for us would be to secure a strategic partnership in autoimmunity. So, with that as background, our updated pipeline slide now really focuses on the solid tumor effort. As I said, we'll be moving two products into IND-enabling activities, one directed at PRAME, the other directed at MAGE-A4. And then we, in fact, have other TCRs in late-stage discovery that continue to build out on these targets. For example, we have a product that has now reached the end of discovery that recognizes PRAME presented on a different HLA, the HLA-A2402. So we continue to build out our products to provide better HLA coverage in these well-validated targets of PRAME and MAGE A4. As you can see on the bottom of the pipeline slide, we are pausing for the development in the heme program as well as autoimmunity and are actively seeking partnerships for these programs. And we believe that this strategy is the best strategy to move our products forward and bring the most value both to patients and to shareholders with this new reorganized company. So I just want to spend a few moments walking through the Solid Tumor Program and what we're trying to accomplish with this program. And just by way of introduction, really needs no introduction, but solid tumors represents an incredibly large unmet medical need. Over half a million patients every year in the United States die from solid tumor indications. And in fact, just looking at melanoma alone, over 8,500 patients die from melanoma, despite the fact that there are about 20 approved therapies in this space. And about 125,000 patients die annually from non-small cell lung cancer, despite there being over 50 approved therapies. in this space. So there's still a very keen need for effective therapies that address these deadly diseases. So we are developing TCR-engineered T-cell therapies for very prevalent cancer-specific antigens that are uniquely addressed by TCR engineered T-cel therapies. PRAME, as many of you know, is expressed in over 90% of melanomas. And then MAI-J4 is actually quite prevalently expressed in a variety of different cancers, including non-small cell lung cancer, head and neck cancer, and ovarian cancer. So these are the primary targets for the two products that we are moving into IND-enabling activities. So just by way of introduction to in vivo engineered technology. So in vivo engineering really solves some of the key challenges of autologous TCR T-cell therapy. So for a start, traditional autologious therapy requires manufacturing product for patients one at a time and often is plagued by out-of-spec issues, significant cost of goods. In vivo program, that completely eliminates those issues. The lentivirus is made as a large batch, and that same product is essentially an off-the-shelf product that can be delivered to patients without delay. There's no vein-to-vein time issues for treating patients, and there's no need for lymphodepletion prior to administering the product. So far, T-cell-targeted lentiviruses are clearly the way to go for this type of in vivo therapy. We believe that the lentiviral approach is particularly appropriate for oncology because it enables permanent genetic integration of the gene of interest, the TCR, into the T cells of the patient, which means that these cells can now continue to propagate in the patient. They can form memory cells, driving long-term immune surveillance. And with this method, you actually see higher levels of engineered T-cells in patients based on other studies that are being performed, as well as greater expansion of these engineered T cells than you typically see with an ex vivo engineered product. And in fact, this last year has seen an incredible explosion in the area of in vivo engineered CAR-T programs. So, for example, just highlighting three companies here that have had really remarkable results, Colonia, Eso Biotech and Legend. All three of those companies have delivered engineered CAR T therapy using lentivirus into patients. And in all three cases, we've seen 100% response rates in patients, albeit a relatively small number of patients treated so far, but really remarkable results with this approach. So as a company, we're asked, how can we build on this type of work, but really bring these therapies to solid tumors? And TCR, engineered T cell therapies, really provide the mechanism for delivering engineered T-cell therapy to solid tumors. So traditionally, it's been very challenging to treat solid tumors with CAR-T therapy, and we've seen much better results in the clinic with TCR engineered T cell therapies. So what I'm showing you here on the left is an example of a tumor sample that we collected as part of our previous Plexity study. And you can see very robust expression of PRAME in this cutaneous melanoma sample, showing essentially all the tumor cells expressing PRAME at a very high level. PRAME is an intracellular protein, so not addressable by CAR-T therapy, and yet a T cell can recognize this target PRAME because the tumor cell is presenting an antigen derived from PRAME, shown in the figure on the right here in pink, an antgen derived from PRAME displayed on a class one HLA molecule, in this case, the most common HLA, HLA-A0201, which represents about 42% of the US population. So the T cell is able to recognize this target and mount an anti-cancer immune response, kill that tumor cell, and so ultimately shrink tumors and the goal, obviously, to completely cure the patient. We have previously disclosed in our corporate deck that we've got some early data. This is not with our current construct. This was with an earlier version of our construct, in which what we showed is that mice that have been engrafted with human PBMCs and then treated with our lentivirus are able to control tumor growth. growth. This is a non-small cell lung cancer model in this mouse, and do so just as effectively as an ex vivo engineered product that targets the same antigen, in this case, antigen derived from MAGE A4. What's important to note in this experiment is that the in vivo product is actually producing the same results as the ex vivo product, but at less than 10% of the dose that we're using with the ex vivo product. So much more efficient, much more potent product delivered using this in vivo approach. Well, since generating these data several months ago, we've now finalized our lentiviral construct that we're moving into IND enabling activities. And so just to walk you through the components of this. So on the left, what I'm illustrating is a modified lentivirus that has three key proprietary elements. So the first is that the lentivirus has been modified to have a non-targeting fusogen. A normal lentivavirus would have a fusogen that specifically targets CD4 T cells. So this is a non targeting fusogen and then we've added to this lentiviruses two different antibodies that both recognize targets on T cells so they direct this modified lentivirus directly to both cytotoxic and helper T-cells. So we're using a dual targeting approach with our lentivirus. And then finally, inside the lentiv virus is the transgene. This is our proprietary TCR gene, both the beta and alpha chain of the TCR, as well as the alpha and beta chains of the co-receptor CD8 that enables us to engineer both cytotoxic and helper T-cells. So these antibodies on the surface simultaneously target and activate T-cels. The fact that they activate T cells while transducing them means this enables rapid expansion of the T- cells in vivo, and the non-targeted fusogen mediates entries exclusively to T-celes and not to any non-target cells in the patient's circulation. So the update here is that we have these dual targeting products that efficiently transduce human PBMCs in mice, induce expansion in vivo, and we have shown that these engineered T cells are able to completely control tumor growth in mice at, again, less than 10% the equivalent dose of ex vivo engineered T-cells. So we will be sharing preclinical data from both our PRAME and MAGE-A4 programs at a major medical meeting in Q1 of 2027. So, just as a sort of high-level timeline of this program, we actually met with the FDA back in Q2 of this year through the Interact mechanism. Got very helpful feedback on what would be required for an IND and so have been following that plan since Q2. In Q3, we identified our lead candidates. We finalized the lentiviral construct and we've now advanced our first two products to IND-enabling activities. In Q1 of next year, we intend to present preclinical data on this program, as well as provide a regulatory update. In Q2, we plan to initiate GMP production of the lentivirus. In Q3, we plant to file our first IND, and then in Q4 of next years, we'll be able to file the first INP. And then in the next year initiate phase one clinical development. So very exciting to be able to move this program forward and to really build on the initial success we had in our ex vivo clinical trials to now bring that to this in vivo program. I want to shift at this point to an update on our heme malignancies program, where, as I said, we're sharing this morning updated clinical data, as well as the strategic decision to pause this study to allow data to mature and to actively seek partnerships for this program. So, just as a reminder, this program is really spearheaded by the product TSC-101, which is designed to treat residual disease and prevent relapse in patients undergoing hematopoietic cell transplantation, or otherwise known as bone marrow transplants. And so the way this works in the clinic is that patients that are qualified to get a bone marrow transplant come into the clinic. We identify a suitable donor for that patient. And for our product to be effective, the patient has to have the HLA type AO201, gain about 42% of the U.S. population. and we need to pair them with a donor that's A2 negative, which we can do about 80% of the time using either a haploidentical or a mismatched unrelated donor. The patient then undergoes a regular transplant, a regular standard of care transplant, but then immediately following the transplant, typically about three weeks post-transplant, they receive their first infusion of our engineered product, which is designed to target residual disease and prevent relapse. They then, 40 days later, receive a scheduled second infusion, which is typically done in the outpatient setting. Originally, when we launched this study three years ago, we included both a cohort of patients treated with the product, which we now call cohort A, as well as a control arm. And then more recently, we have enrolled an additional cohort of patients, cohort C, where patients in this cohort have all been treated with our new commercial-ready manufacturing process. And so what this is showing is that the patients have been generally well-balanced across these three arms of the study. However, if anything, cohort Z actually represents a much higher risk patient population. So in fact, every patient in cohort C has some factor that makes them a very high risk of relapse. And I'm highlighting here in pink the fact that 12 out of the 14 patients in cohort C had minimal residual disease positive biopsies immediately prior to transplant. So if you're MRD positive prior to implant, that puts you at a very higher risk of relapsed. And just to emphasize this point, what I'm showing on this slide is two different published studies, both in AML, the study on the left. It's a retrospective analysis of 392 patients with AML that underwent transplant. And what you can see on the bottom is that the patients that were MRD positive prior to transplant, as shown in blue, had a very high risk of relapse. In fact, ultimately, 55% to 60% of those patients relapsed following transplant compared to, in the black line, patients that were MRD-negative prior to transplant. So being MRD positive prior to implant is a very significant risk factor for patients undergoing transplant. On the right is another study, in this case of over 1,100 patients with AML who received their first allotransplant, and again, very high relapse risk in these patients. In fact, 55% of these patients that were MRD positive prior to transplant, the far right column of this chart, relapsed at one year compared to only 17% of the patients who were MRD negative. And in fact, the relapse-free survival rate at one-year was only 32% for the MRD-positive patients. So now if you look at our cohort of patients, Cohort C, this included 14 patients that were treated with our product. what you can see on the left here in these squares, the pink squares represent MRD positive bone marrow biopsies prior to transplant. And you can say that 12 out of the 14 patients were in fact MRD-positive prior to transplants, putting them at very high risk of relapse. There were two patients, patient one and patient five, that were MRD negative. However, you'll also see that those patients also had a very high-risk factor. Both of those patients had mutated p53, which is prognostically very bad in patients undergoing transplant. So really, all 14 of these patients were very high-risk patients going into transplant. Yet despite that, we have seen very encouraging data so far. What you're seeing in the chart in the bottom right here is that we've only seen two patients relapse out of the 14 patients on the study to date. This is now with six months of median follow-up on all these patients, and we're currently seeing a 79% relapse-free survival rate among this cohort of patients. But I think even more remarkably, we have been tracking donor chimerism as a measure of how effectively we're eliminating the cancer cells in these patients. And in this chart, complete donor chimerism, in other words, no detectable patient-derived cancer or normal cells in the patient, that's indicated by a checkmark. And if you look across this chart all 14 patients in cohort C have now shown complete donor chimerisim at their last assessment. So some of these patients initially showed incomplete chimerizim, but over time and following infusions of our engineered T-cell products, as shown with the yellow diamonds, all of these patients have now converted to complete donor chimerism, including the two patients that relapsed. So another way of looking at these data is shown on this slide, in which we're providing the actual quantitative measurements of chimerisim. So anything above the assay cutoff of 0.2% indicates incomplete chimerisme. So just by way of example, if you look at the patient in the top left, patient one. This was a patient with P53 mutated AML, very high risk of relapse. The patient initially following their transplant had 4.5% donor chimerism. In other words, 4. 5% of their blood cells were still patient-derived. Many of those blood cells were disease cells that could lead to relapse, the patient received two infusions of engineered T cells. Immediately, their chimerism dropped below the limit of detection of the assay, so below that cutoff of 0.2%. And that patient has, in every subsequent reading, had complete donor chimericism. This patient is now 220 days post-transplant and still completely disease-free. But now, as you look across all of these patients, you can see that every single one of these patient is showing complete donor Chimerism. And I think there a couple of remarkable stories here. Patient number three was a patient with a MECOM rearranged AML. That's a very high-risk type of cancer that was also MRD positive. They initially achieved complete chimerism. The chimerizm then started to rise. They received a third infusion, and following that third inf fusion, their chimerazm has now dropped again below the limit of detection of the assay. This was in the absence of any other therapy going on for that patient at the time, really illustrating the potential of these cells to eliminate any remaining cancer and prevent relapse in the patient. Patients nine and 10 are the two patients that did actually experience a relapse. And yet in each case, in the case of patient 10, they received a third infusion of product along with a commonly used maintenance therapy. And again, are now showing complete donor chimerism. Patient nine also, following their relapse, received commonly used maintenance therapy that is not known to induce complete responses. And yet, our engineered T-cells were still circulating in that patient. This patient is now showing complete donor chinerism. So very exciting data on the study. Obviously, with six months of follow-up, we'd like to continue to track all of these patients, ensure that these data continue. And so our strategy as a company is to continue to crack all the patients in cohort C, as well as the seven patients that we've enrolled into the pivotal trial, treated the same manufacturing process. So those 21 patients will continue to be tracked over time, so that by the time we get to mid next year, all of those patients will have over a year's worth of follow-up, and we'll have a very, very clear picture as to how effectively we're preventing relapse in these patients. And then I just want to end by pointing out that this product is incredibly well tolerated. We have not had any major safety concerns from the product. The adverse events that we've observed on this study are all consistent with the typical adverse events you see from bone marrow transplants alone. We haven't seen an increase in any concerning adverse events in the patients treated with our product relative to the control arm patients that receive transplant alone. And so, as I said earlier, because of this very well-tolerated safety profile, our product is now routinely being delivered in the outpatient setting, at least for that second infusion and sometimes for the first infusion as well. So, with that, I want to sort of reiterate that the strategic shift that we're making today is to really focus on the solid tumor program to advance that program forward as rapidly as possible so that we can initiate clinical trials in Q4 of next year on the heme program to pause further development of that study, allow the data to mature, and then actively seek strategic partnerships to continue to advance the program forward. Now, along with this strategic shift. We are unfortunately also ongoing a large reduction in force. The result of that is that over the course of our coming year and a half, we'll be saving $55 million from our anticipated runway. And so this now provides us with runway all the way into Q4 of next year, which is when we plan to initiate the phase one trial with our two TCR products that target MAI-J4 and PRAME. And so with that, I want to pause and open up for any questions from the analysts. As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, Please press star 11 again. And the first question will come from Tara Bancroft with TD Cohen. Your line is open. Thanks very much. This is Nick on for Tara. Thanks for taking our question. What sort of preclinical data should we expect to see in Q1 next year to support the development path of both of the in vivo candidates? And what have you seen so far, specifically with your updated lentivirus that gives you confidence in this prioritization? Thanks very much? Yeah, so what we've seen so far, we've been comparing different targeting arms for the lentivirus to find the best possible targeting antibodies that will direct the product to T-cells as well as appropriately activate the T- cells, activate them sufficiently to enable rapid expansion in vivo, but not activate them too much to lead to exhaustion. So that's where the tweaking has been going on. So the preclinical data that we'll be sharing will largely focus on in vivo mouse data, in which we will show the degree to which our T cells get transduced in vivo, the degree To which the T cells expand, and the degree to which the t cells target and eliminate cancer models implanted in those mice. So really sort of the typical, you know, pharmacological models in mice demonstrating in vivo engineering of the T cells and in vivo efficacy. Thank you very much. It's helpful. Thank you. And the next question is going to come from Sam Slusky with Lysa Capital. Your line's open. Hey, thanks for taking the questions. Two for me, I guess on the in vivo TCR approach, just remind me on timelines, once you're in the clinic, kind of how quickly you expect to get to expected efficacious dose levels. And then just comparing, contrasting in vivo PCR versus, you know, so-called like a CD3 bispecific, like what are some of the advantages that come to mind for you? Thanks. Yeah, thanks für the question. So one of the beauties of the solid tumor program is that things do move very quickly once you're in the clinic. So obviously, we no longer have to deal with the challenges of patient-specific manufacturing. So we would, you know, intend to move relatively rapidly through dose escalation. One of the advantages we have is that there has now been quite a bit of experience in the clinic with in vivo engineered programs. So we can target our initial doses appropriately based on other people's experience in the space. So we tend to move relatively quickly through dose escalation, get to an efficacious dose, really by dose level two, if possible. And then you get very rapid feedback. We will be taking CT scans, obviously prior to the first infusion, and then every six weeks following that. And so even as early as six weeks, we could start to see preliminary efficacy data on patients treated with the product. So I'd say within six months of initiating the trial, you could actually have meaningful data to evaluate as that sort of preliminary look as to how well the product is doing. Your second question, oh yes, relative to bispecifics. So both engineered T-cells, in vivo engineered cells and bispecifics both take advantage of the patient's existing T cells to mediate an anti-cancer response. However, I think one of the key advantages of in vivo engineered T cells is that you are permanently genetically engineering those cells so that they are able to expand in vivo. They're able to undergo the normal T-cell biology of target-mediated expansion, activation, cytotoxicity. And then more importantly, those cells are able to form memory T-cels. And so those memory T cells will graft in the patient and essentially be ready for immune surveillance throughout the rest of the patient's life. So really, it's a one-and-done therapy as opposed to a bispecific that is a transient effect and requires constant redosing. Thank you. And the next question will come from Maxwell Score with Morgan Stanley. Your line's open. Great. Thank you for the question. I was wondering if you could elaborate a bit more on what are the most important milestones or specific data sets over the next six to 12 months that could help advance partnering discussions for autoimmune programs? Thank you. For autoimmune, I would say, you know, we've put together a package already. We've identified several targets in these B27-driven autoimmune diseases that we believe are, you Know, biologically relevant targets. We've disclosed in a previous meeting that one of these targets discovered from a patient with ankylosing spondylitis, if you take that protein and inject peptides from that protein into a mouse, you actually recapitulate the disease phenotype. You see spinal fusion in that mouse over time. So we feel we've identified the key targets. we've shown that they're actually biologically relevant. One of the key pieces of data that we're working on is to show that those targets are prevalent in different patients with those diseases. So really understanding how common those targets are, how commonly you generate T-cells against those targets, and then how effective you would be in eliminating T- cells that recognize that target. But that's sort of the key component necessary to engage a strategic partner around this program. But right now, a lot of those data have been collected, so it's really a matter of finding an appropriate partner that wants to move this program forward. Great. Thank you. Thank you, as a reminder, to ask a question, please press star 11 on your telephone. And the next question comes from Andres Maldonado with H.C. Wainwright. Your line is open. Hi, everyone. Thanks for taking my questions. Just two from us. Just curious from a competitive landscape perspective, as you look at PRAME and MAE-J4, can you just give us some context on if either of those targets represents an easier path to development and some commentary on how you're thinking about perhaps patient selection for either of those targets. And then a quick follow-up to that would be for TSC-101, I guess, what else would you like to see to potentially strengthen that case for a partner funding the phase three? Thank you very much. Sure. So I'll start with the PREM and MAE-J4. So those are both areas where the prevalence of those targets is very well understood. PRAME is most famously expressed at very high levels in cutaneous melanoma, as well as uveal melanoma. And so, you know, that is clearly an obvious area to go into. In that case, over 90% of tumors express PRAME at a high level, which means it may not even be necessary to pre-screen patients to identify patients that are PRAME positive, since this is the majority of patients already. But one of the advantages of our program is that we've already been there, right? We've already done this in our Plexi-T trial. And so part of that was we already developed assays, clinical trial assays that can be used to prospectively select patients whose tumors are expressing these targets. And in fact, we implemented as part of the Plexi-T trial, a screening protocol in which we screened over 900 patients, acquiring biopsies, doing the immunohistochemistry assays in order to identify patients prospectively before enrolling them in the trial. So we can build on all of that success to move this program rapidly into key areas of unmet need. Obviously, cutaneous melanoma for PRAME is kind of the easiest testing ground for that TCR, but there's many other diseases that also express PRAME. And then from AJ4, just the level of expression in non-small cell lung, head and neck, and ovarian cancer, as well as various types of soft tissue sarcoma, is very attractive areas to initiate studies as well. So our plan is not to go broadly with 8, 10, 12 different indications in our phase one, but to take a much more targeted approach and go to the areas where we've seen success in the past with ex-Viva engineered products or with bispecifics to really test the platform that it is as effective or hopefully much more effective than these other approaches of addressing the targets. and then in terms of the question around heme i believe the question was um what data um are we looking for that would make this program more partnerable um you know so really uh as i said very excited about the most recent translational data on these cohort c patients all of them being in complete donor chimerism these patients have six months of median follow-up what we've heard from a lot of people is that we really need to see one year's worth of follow-up or, you know, at least one year worth of following-up on patients to really believe that we are, you know, preventing relapse, that this isn't a transient effect that then leads to relapse. So what we need, honestly, is time, right? As more time goes on and as patients continue to remain in complete chimerism with no evidence of disease, the program becomes more and more convincing with time. We're going to take those seven patients that are already enrolled in the pivotal study and follow those patients as well, essentially break the blinding of the pivotal study so that we can look at those patients, as well as the 14 patients in cohort C, so now a largest set of 21 patients, track them over time. And if we see continued data that clearly demonstrate greater than 50% reduction in relapse rates, right now we're well beyond that, that becomes a very compelling story for a strategic partner. So I think at this point, it's really time and continued success with the patients that we've already seen success with. thank you thank you i'm showing no further questions at this time i will now turn the call back over to gavin for closing remarks great uh thank you uh thank everyone for uh joining again today um and you know uh happy to follow up uh with people following the call uh this presentation will be available on the investor section of our website. And so, just looking forward to moving these new and exciting products forward into the clinic. Thank you. This concludes today's conference call. Thank you for participating, and you may now disconnect.