Great. Thank you very much. I'm Maxwell Skor, a biotech analyst with Morgan Stanley. I'm happy to have TScan with us today and the CEO, Gavin McBeth. Before we dive into it, I have to read some quick disclosures. For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. For those in the audience who are new to TScan, Gavin, can you briefly introduce TScan's next-generation TCR-T therapies and highlight any key takeaways you'd like us to know going in? Sure. Thank you for having me today. For those not familiar with TScan Therapeutics, we're a fully integrated TCR-T cell therapy company. We were founded in 2018 out of Harvard Medical School and founded based on the technology that enables us to discover the targets of any T cells. What we did in the early years is use that technology to figure out what T cells naturally recognize in patients that are responding to immunotherapy, patients with cancer responding to immunotherapy. Based on that information, we built a pipeline of TCR-engineered T cell therapies. TCR therapy is very similar to CAR-T therapy. We're basically genetically reprogramming a patient's T cells. Rather than using a chimeric antigen receptor, we're using the naturally occurring T cell receptor. Over the years, we've built two main clinical programs. Our lead program is in hematologic malignancies. This is addressing patients with AML, MDS, or ALL that are undergoing a bone marrow transplant. The key unmet need here is that patients that get transplants, if they relapse, the prognosis is very poor. Our therapy is designed to prevent relapse in patients undergoing bone marrow transplants. The second program is in solid tumors. Our core hypothesis is that you'd get deeper and longer-lasting responses if you treat a patient with more than one TCR-T cell therapy at a time. Basically, mimic what nature does, where nature provides a polyclonal response to cancer. We're working towards what we call multiplex therapy, where we treat a patient with more than one TCR-T cell agent at a time. In the solid tumor program, we actually have seven different TCR-Ts all in the same clinical trial working towards that goal. Okay, great. Can you walk us through the most recent clinical data for the heme program that you presented at ASH in December and how that compares to the standard-of-care? Yeah. As I said, the heme program is focused on patients undergoing bone marrow transplant therapy. We had two products in that trial, one addressing a target called HA-1 and the second addressing a target called HA-2. Very similar types of targets here. At ASH, we presented data on 26 patients that we had treated either with TSC-100 or TSC-101. Those are the agents targeting HA-1 and HA-2, respectively. We also included a control arm in our Phase I study. We had 13 patients in the control arm. What we showed is that out of the 26 patients that we had treated with our cell therapy product, only two of those patients had relapsed, so 2 out of 26 or about 8%. On the control arm, 4 out of 12 patients or 13, depending on how you count, so about 33% relapse rate on the control arm. Clearly, a very strong difference between the patients treated with our cell therapy product versus a very comparable patient population undergoing standard-of-care transplant alone. Based on those data, we have made the decision to move forward with a pivotal trial. We've been in discussions with the FDA and have designed a pivotal trial that we're looking to launch first patient in this year and with a readout in about 24 months post first patient in. Looking to get a top-line readout on our pivotal study by the end of 2027. Okay. Do you have any expectations for the two-year relapse data on the initial Phase I patients by, I believe, you're guiding to year end? For this particular patient population and the type of transplant they're receiving, the historical relapse rate has been about 40% at two years. We're looking for a 50% reduction in relapse rates, so we're looking for about a 20% relapse rate. If we can be seeing about a 20% relapse rate or better in the patient population at two years, that gives us confidence that the trial that we've designed for our pivotal study would read out positive. That's what we're looking for at the end of the year. Okay. Can you talk a bit more about just the patient makeup, the inclusion criteria? How should we think about these patients overall? Yeah. For patients with AML, MDS, and ALL, really the only curative therapy for them is to get a transplant. Right now, about 9,000 patients in the U.S. with AML, MDS, and ALL get bone marrow transplants every year. We are focusing specifically on patients that will get a transplant with reduced intensity conditioning. There are really two types of conditioning therapy for transplant. For young, very healthy people that can tolerate very strong chemotherapy and radiation, they would get what's called myeloablative conditioning. About 1/3 of transplants get myeloablative conditioning. Two thirds of transplants get reduced intensity conditioning, and that's where the relapse rates are higher. We think the core unmet need in this space is for patients undergoing transplant with reduced intensity conditioning, where you have a high risk of relapse and where a cell therapy product that reduces relapses would increase the rate at which patients are actually cured by the transplant. Are these generally older patients that can't handle the more intensive? Yeah, generally, older patients would get reduced intensity, yes. Is there a higher bar in regard to safety that you have to meet then? What we found so far in our Phase I study is that our cell therapy product is incredibly well tolerated. We're not actually seeing any imbalance in adverse events on the treatment arm relative to the control arm. Obviously, patients that are undergoing transplants have various adverse events associated with the transplant, but our cell therapy is not actually increasing the rate of adverse events. The only thing we've seen that is directly attributable to our cell therapy product out of 26 patients, we've seen one grade I CRS and one grade II CRS. Obviously, very well tolerated product. No ICANs or any other typical adverse events associated with cell therapy. Great. Maybe drilling down a bit more on 101, can you describe the pivotal trial and what's unique about the trial design? Yeah. Our trial design is to actually take advantage of the fact that in the transplant space, there's a very large, well-curated database of every patient that undergoes a transplant in the United States. Every transplant, all the data is input into the CIBMTR database. In fact, there's about 700,000 patients' worth of data in that database right now. This provides an ideal setting for a real-world evidence study, where for every patient that we treat on the treatment arm in our study, we'll find three patients in the CIBMTR database that match that patient. Exact match on the disease. If it's an AML patient, there will be three AML patients in the database. Then propensity score match on the most prognostic variables that influence outcome. That would include patient age. It would include mutation status, such as p53 mutations or FLT3 mutations. It would include the exact conditioning regimen that they're receiving. It really provides a much better way to get a balanced control arm for a fairly heterogeneous patient population. In fact, an even better way than if you were to do a randomized controlled study, where you can only stratify on two or three variables rather than propensity score match on 8 - 10 variables. Okay. What are you looking for in the pivotal study? What are the thresholds in regards to hazard ratio and reduction in relapse rates that might affect the patient population potentially? Basically, what would be considered a win in this case? Yeah. We recognize that the data that we presented at ASH was unusually good data. We were seeing hazard ratios of 0.2 at the time. That is still based on relatively small numbers. We do not want to dilute ourselves if the data is going to continue to be as pristine as we originally saw. We powered the study to have a hazard ratio of 0.6 for relapse-free survival. We got agreement with the FDA that the primary endpoint of relapse-free survival, which includes either relapses or deaths, would be sufficient to support full approval for the product. An RFS hazard ratio of 0.6 is in line with what other studies in this space have typically powered for. A 0.6 hazard ratio with an 85% power would require about 140 subjects treated with the product and a 1 - 3 randomization with the control arm. Based on that study design and the anticipated enrollment rate that we've been seeing in our Phase I, we estimate that we would get to a top-line readout on that study in about 24 months. Okay. Based on your interactions with KOLs, could you just comment on physician feedback in regards to the overall profile of TSC-101? Have you heard anything regarding the ease of use? Yeah. Physicians are actually extremely excited about our program. They've been actually competing to get slots on the study because they believe in the product so much. What we found is that there's actually a fairly low bar in terms of what they would consider clinically meaningful. Physicians have said that if you could reduce the relapse rates by 15% - 20%, they would start to use the product. We're aiming to reduce relapse rates by 50%. Certainly meeting any bar for clinical meaningfulness. We've also been talking to insurance companies. Payers definitely would reimburse if we meet the primary endpoint on our study. There's been a lot of excitement about the product. Really, any patient that would qualify, and to qualify, you need to have the HLA type A0201 and be paired with a donor that's A0201 negative. Other than that, physicians would enroll any patient that they have that would meet those criteria at this point. Okay. Can you touch on your plans to expand into other HLA types? Yeah, any commentary there? Yeah. We recognize that the key way in which we mismatch on the antigen is through mismatching on the HLA type. Based on that, we launched a program to expand to other HLA types, now focusing on epitopes that are derived from the protein CD45. The reason we've settled on CD45 as sort of a general solution to this problem is because it's a large protein. It's abundantly expressed in all lineages of heme cells, but only in heme cells. This meets the ideal criteria for a protein that we would derive targets from. Based on that, we now have a TCR that's in IND-enabling activities for an HLA type A0301. We actually, just in our 8K this morning, also showed an update to our pipeline that we have a TCR for A0101 as well for CD45, now in IND-enabling activities. In late-stage discovery, we have a TCR for A2402, which is the most prevalent HLA type in the Asian population. We are really expanding to three other HLA types with this program. That would obviously require a separate pivotal study. We are looking to launch a Phase I with those products next year, start to accumulate data. That provides a way to essentially double the addressable market with those three additional TCRs. Okay. Now let's pivot over, I guess, to the solid tumor program. What is your ImmunoBank of TCRs, and how does it enable multiplex TCR cell therapy? Yeah. We feel very strongly that one of the key problems to address in solid tumors is the problem of heterogeneity. Not every tumor cell in a tumor is the same. There is a lot of heterogeneity among tumor cells. In particular, not every tumor cell expresses a given target. What we found, if you stain tumors for some of the targets in our pipeline, like PRAME or MAGE-A4, is that some, but not all, of the tumor cells are expressing PRAME. Other cells are expressing MAGE-A4. If you were to treat a patient with just a single TCR, you would typically address some, but not all, of their tumor cells. That patient would potentially relapse relatively rapidly. If you could treat a patient with more than one TCR at a time, you would stand a much better chance of getting a complete response or a long-term remission. Based on that, we have built a collection of TCRs that address different cancer-specific targets and address different HLA types so that ultimately, the vision is that when a patient comes in, we would test their tumor to see what targets are expressed in their tumor. We would go to that collection or that ImmunoBank of TCRs and select the best two or three TCRs for that patient based on which antigens are expressed in their tumor. To work towards that goal, we have now introduced seven different TCRs into the Phase I trial. These address five different cancer-specific targets and currently four different HLA types. The targets that are included right now are MAGE-A4, MAGE-C2, MAGE-A1, PRAME, and we also have a program addressing the E7 protein of HPV16. Those five targets are all currently in the clinical trial. We have TCRs spanning four different HLA types across those five targets. That's helpful. What are you looking for in the initial safety and response data? I believe it's expected in the first quarter? Yeah. We recently changed our guidance around this. We were expecting to deliver data by the end of this year. We've shifted that out a quarter to Q1 of next year just based on some challenges that we've been seeing and typical challenges associated with Phase I clinical development. We're looking to get our first patients treated with multiplex therapy soon. The data that we're looking to release in Q1 is data on approximately 8 - 10 patients treated with multiplex therapy. I think that will give us the key data that we need to determine, is our core hypothesis correct or not? Are we getting deep responses with multiplex therapy? Obviously, how durable those responses are will take time to determine. The data we'll release in Q1 should get us the first meaningful read on, is this product being effective? All the patients treated with multiplex therapy are what we would consider an effective dose. Every patient that you see data on with multiplex therapy should, in principle, respond to our product. Okay. Can you elaborate a bit more on the patients enrolled in this study? Yeah. We're focusing on, it is a basket study. We're including multiple indications, but we're trying to focus somewhat on which indications to address. We're basically focusing on head and neck cancer, soft tissue sarcomas, and non-small cell lung cancer. Those are the key indications for the various MAGE and PRAME family of targets. For HPV16 positive patients, that includes head and neck cancer, cervical cancer, and anal and genital cancers, the cancers that are basically caused by HPV infection. That's the list of indications. You'll notice that cutaneous melanoma is not on that list. We think that space is very well served right now. There's quite a crowded space with dual checkpoint inhibitors, with Iovance's product, with the MADx's very promising data with their PRAME program. We're really focusing on the areas that aren't being addressed currently. Okay. Before jumping into financials, maybe you can just highlight what the catalyst path ahead looks like for maybe the next 12 - 16 months and maybe what the market's missing overall with the TScan story. Yeah. The core catalyst for us is first on the heme program. We'll have updated data at a major medical conference in hematology at the end of the year. That will include the longer-term follow-up study on those initial patients as well as additional patients we've enrolled into that trial. Another key milestone for us is to get our end-of-phase meeting with the FDA and our pivotal trial launched, then continued expansion of the program with additional IND filings in the CD45 program. On the solid tumor front, the key catalyst is Q1 of next year for our initial look at safety and efficacy data on patients treated with multiplex therapy. We actually have a program that we haven't talked about yet. Just as a teaser, you'll recall that the core technology of the company is target discovery. We've actually been doing a lot of target discovery work in the area of autoimmunity. We have an ongoing partnership with Amgen to discover the targets of T cells in patients with Crohn’s disease. Outside of that partnership, we also have internal programs to discover the targets of T cells in other autoimmune disorders. We'll actually present some of our exciting target discovery efforts at a medical conference later this year. Okay. Maybe next year, we'd expect an R&D day or something like that. Yeah, I think that's very appropriate to sort of talk in more detail specifically about the autoimmune work that we've got ongoing. Okay, great. With approximately $218 million in cash and cash equivalents at the end of the second quarter, and runway into the first half of 2027, how are you prioritizing capital allocation for programs across your pipeline? Our core is we really want to fund the pivotal trial, make sure that that gets launched and is up and running. On solid tumors, we've funded the program up to this data readout. How that data reads out in Q1 really determines sort of the future financing strategy for the solid tumor program. Right now, the capital that we have is really allocated to launch that pivotal study and get us on track through a commercial product. Great. Okay. Now I'm going to move to a couple of survey questions we've been asking most of our companies. With China's rise in biotech innovation, how are you thinking about your competitive position here? Will this influence your R&D or potentially BD strategy? Yeah. We've seen a lot of interesting development in T cell therapy coming out of China. I would say the majority has been in the T cell engaging space, a little less so in genetically reprogrammed or engineered T cell therapy space. We sort of feel like we're still more or less in a fairly small class of companies pursuing TCR-T cell therapy. We keep a close eye on that. In particular, there's been some interesting developments on platform development, for example, in vivo engineering. We've seen some platforms coming out to enable genetic reprogramming of T cells in the patient rather than outside in the lab. That's something that we're moving forward with as a company as well. We have some efforts ongoing to develop a potential in vivo engineering platform as well. Would that be via CRISPR, potentially? No. Typically, the DNA is delivered either in a modified lentivirus in vivo or in lipid nanoparticle formulations. That's what we've been focusing. How are you, if you are, how are you currently leveraging AI or thinking about AI's future disruptive potential? Yeah. I sort of joke with some of my colleagues that we invest a little more in RI than in AI. By that, I mean real intelligence versus artificial intelligence. I would say a lot of our programs don't necessarily lend themselves to AI innovation, although we have invested in an enterprise version of ChatGPT so that internally, we use that mostly in our discovery efforts. I think there is a lot of opportunity to use AI to sort of optimize clinical trial site selection, clinical trial design. That is one area that we're looking into, but we haven't implemented at this point. Okay. Last question, what has been most impactful from a regulatory perspective? Would it be the FDA changes or MFN or tariffs? Granted, that might be a little bit early in regards to your case. Yeah. The tariffs haven't affected us that much. Most of the materials that we use for our manufacturing are U.S.-derived. There are some exceptions to that, but that hasn't really affected us that much. I would say the biggest effect has been that uncertainty at the FDA. I think all companies have been, and the whole biotech space has been, a little bit disrupted by really just the uncertainty around it. I wouldn't say there's anything particularly negative for us. Cell therapy is still very much a core valued highly at the FDA. Vinay Prasad has been very optimistic about cell therapy. It's more been just the uncertainty and the changes in senior leadership that affected the overall biotech space. Nothing specific. Nothing specific. OK. I guess the last, last question would be, is there anything I've missed in regards to what we've covered today? Anything investors are calling out or anything you'd like to emphasize? No, I think we've actually covered everything very well. Okay. I appreciate your questions. Thank you very much, Gavin. Really appreciate it. Thank you, everyone. Thank you.