Conference Transcript - TCRX 2026-04-15

Gil, Analyst — Needham

Good afternoon, everyone, and thank you for joining us the third day of the Needham Healthcare Conference. It is my pleasure to have with me today Gavin McBeth, CEO of T-Scan. Gavin, it's great to have you on. I think this is a good time to speak with you guys, especially ahead of some pretty important clinical updates. So maybe just to set the stage with everyone, And maybe a brief introduction, kind of discuss T-scan support technology platform and how do you view this strategy as different compared to, let's say, CAR-T's.

Gavin MacBeath, CEO

And thank you, Gil, for having me on. I appreciate the invitation. So T-scan Therapeutics is a fully integrated clinical stage T-cell therapy company focused on bringing TCR-engineered T-cell therapies to patients with cancer. And so I would say the biggest thing that differentiates us from other approaches, such as CAR-T therapy, is really exemplified by our lead clinical program, which is designed to treat patients with myeloid malignancies. And so right now, there is no good CAR-T solution for myeloid malignancies. CAR-T is very effective at treating B-cell malignancies as well as multiple myeloma, but a patient cannot live without their myeloid cells. So you cannot take the same approach and completely obliterate a patient's myeloid cells. So instead, our approach is to really home in on what is the only truly curative therapy for a patient with AML or MDS, and that is to get a bone marrow transplant. So right now, transplants are very effective. In fact, about 60% of patients are completely cured by a transplant. The problem is that if you aren't cured, if you have a relapse, the prognosis is very poor. In fact, 80% of patients that relapse will die within two years of their relapse. So the key unmet need here is can we make transplant more effective? Can we fully cure patients that are undergoing transplant therapy? And so the way we're doing this is we are targeting antigens that are present in the patient's blood cells, but are not present in the donor's blood cells. And so when you get a transplant, you completely replace the patient's blood cells with donor blood cells. But the relapse occurs if there are any residual cancer cells that are present following the transplant. And so what we're doing is we're making an engineered T cell product in which we engineer the donor's T cells to express a T cell receptor that will recognize antigens present on the patient cells, but not the donor cells. And then immediately following the transplant, we infuse the patient with these engineered T cells, and that targets any residual cancer in the patient, but it doesn't touch any of their new healthy donor derived blood cells because those come from the donor and are not expressing that antigen. So that's really the sort of key difference between the approach we're taking and approaches like CAR-T therapy that, you know, are really designed to completely obliterate an entire subset of cells in the patient.

Gil, Analyst — Needham

Thank you for that introduction, Gavin. So this scan has already shown some pretty impressive clinical data. Could you walk us through some of the earlier results?

Gavin MacBeath, CEO

Yeah, so we've been running a phase one trial with our lead program, TSC-101, for about three years now. So it's called the ALOHA study. And the most recent update from that study, we presented at ASH in December of last year, December 2025. And at that update, we showed data from 19 patients treated with our product. So those patients all received an allogeneic transplant and then got one or two infusions of our engineered T cells. But we also included a control arm in our phase one study. Those are patients, very similar patients, but receiving transplant alone without our cell therapy product. And what we showed is that we are reducing relapses in these patients by more than 50%. So we showed a relapse-free survival hazard ratio of 0.5 compared to the control arm in our study. We also showed that our product is long-lived. Every patient that's received our product, those T cells, those engineered T cells are still detectable in their blood. Out past two years now, even a patient that's now out past three years, we can still detect the engineered T cells in those patients. And those responses are long lived. So the three patients in our study that are out at two years, all three of those patients are still on study and completely disease-free. And that compares to only one out of four patients in the control arm that made it to that two-year mark. So what we're showing is robust reduction of relapses, as well as long-lived responses in these patients.

Gil, Analyst — Needham

Maybe it's worth reminding the audience also, what is the total addressable market here, given the HLA restrictions?

Gavin MacBeath, CEO

Yeah, so we're about to launch a phase three study with this program, which we intend to launch by the middle of this year. And the plan is that it'll be a two-year study, so that should read out in mid-28, with the commercial launch in mid-2029. And so at the time of commercial launch, we project that about 6,200 patients a year with AML or MDS would receive an allogeneic transplant in the United States. We actually think that number is probably going to be higher. We're just getting new data from 2024 numbers from CIBMTR, and it looks like that number is going to increase. But let's say conservatively 6,200 patients a year get transplanted. to qualify for our therapy, you need to have the HLA type AO201, which is about 42% of the U.S. population. And then you also need to be paired with a donor that's A2 negative. And our experience has shown that we can find an appropriate donor for each patient about 80% of the time. So if you take 42% and 80% of that 6,200, that's about 2,100 patients a year across the United States that would qualify for our therapy when we launched this product in 2029.

Gil, Analyst — Needham

So just to spend a second on the requirements for transplant here, I'm assuming you're restricted to one type of transplant as it relates to matching. And can that be expanded at all, or this is just going to be what it is?

Gavin MacBeath, CEO

Yeah. So just to sort of clarify what Gil's getting at here. So in order to qualify for our therapy, the patient, the donor has to be AO201 negative. And the way you would find a donor that's A2 negative for a patient that's A2 positive is that the type of donor has to be either a haploidentical donor or a mismatched unrelated donor. So a haploidentical donor is someone who is a close family member of the patient, such as a son or daughter of the patient, and they would be half matched on HLAs. And so that's how you could have an A2 negative donor with an A2 positive patient. The other way you can find a mismatch is if the donor is unrelated to the patient, but has a very close HLA match. So nine out of 10 HLAs match, but they're mismatched on just that one HLA AO2O1. So right now, our phase one study includes both types of donors, both haploidentical and mismatched unrelated donors. That's the plan for the pivotal trial as well. But yes, ultimately to use our product, we would just need to select a donor that's either haploidentical or mismatched unrelated. Right now, the other choices for a transplant would be a matched related donor, which means a close family member that's 100% matched on HLAs or a matched unrelated donor. So unrelated to the patient, again, you know, know, completely matched on HLAs. There's very similar outcomes in terms of relapse rates, irrespective of the donor type. So really, the choice of donor really comes down to other factors for the transplant center. But if we are successful, if we can reduce relapse rates by 50%, that makes this a much more compelling transplant to undergo, because you, you know, would have a much lower chance of relapsing and ultimately dying from your cancer. And so we believe that there would be a significant shift in clinical practice to favor haploidentical or mismatched unrelated donors in order to qualify for our therapy.

Gil, Analyst — Needham

A bit of a silly question, but doesn't this engineering improve the chances of preventing post-rejection or graft rejection?

Gavin MacBeath, CEO

So graft rejection really has to do with the transplant itself. And if you're getting a standard allogeneic transplant, the risk of graft rejection is actually very low. So about 2% possibly around that of transplants have graft rejection. We're not interfering with the standard transplant process at all. We have not seen any graft rejection in our clinical studies with all the patients that we've treated to date, including patients treated with TSC100, which is a product that we're no longer moving forward. So over 30 patients, we've never seen graft rejection. In terms of the engineered T cells, when we administer those, those don't get rejected either because now the patient's new blood system is entirely donor-derived cells, and this is a donor-derived product, right? We're engineering the donor's T cells, so there's no risk of rejection of the engineered T cells either, and we haven't seen, you know, any issues with that as well.

Gil, Analyst — Needham

I do want to spend a second on the Ash data. So some responses in the dose level four appear to be less robust than expected. Can you discuss the underlying cause for what we saw in how the company has done about addressing it?

Gavin MacBeath, CEO

Yeah. So if you take a look at our ASH data, one of the figures in that poster shows the chimerism data. So what you'd be looking at is 19 patients and the rows of this figure indicate different time points following their transplant at which we've measured donor chimerism. And what we're looking for is complete donor chimerism. So we've completely eliminated all of the patient's blood cells and replaced them with donor cells. And if you look at that figure, what you'll see is that the first 13 patients in our study had exceptional responses, right? We saw conversion to complete donor chimerism, and they typically maintain that and continue to maintain that to this day. However, there does seem to be a shift in the last six patients that we enrolled on the study, where you see a lot more incomplete chimerism and a couple relapses. And so what happened is it happens to be the point at which we moved to dose level four, but it's also a point at which we started to have some challenges in our manufacturing suite. And we were unable to, we had to push the manufacturing process further in order to get to the target dose level. And so for several of those patients in those last six patients, the manufacturing process was pushed beyond the normal 17 days, and we had to expand the cells more than we had typically been doing in previous manufacturing runs. And so in our ASH data, we also highlighted the fact that, retrospectively, we did an analysis of all the patients on the study that had done really well, so 14 patients, complete donor carmarism, no issues, versus six patients that had either incomplete chimerism or relapse. And what we found is that the patients that did well all had relatively little amount of ex vivo expansion of their T cells during the manufacturing process, whereas the patients that had the relapse or incomplete chimerism, their cells were expanded to a greater degree in the manufacturing process, which typically leads to more T cell exhaustion and a less robust product. We have now corrected this problem because we've developed a new manufacturing process that's shorter, takes 12 days instead of 17 days, and we don't have to expand the cells as much. And so with this new manufacturing process, we actually do even better than those patients that did well in that first cohort. So what we're doing now is we're actually enrolling additional patients all to be treated with that commercial-ready manufacturing process, the new shorter process. And in fact, we recently announced that we've completed enrollment in what we call cohort C of the study, which is over 10 patients now enrolled and treated with product produced with this shorter manufacturing process. So we will be sharing data, early data on those patients in the next couple of months publicly. We want to get comfort that this new manufacturing process is working as well as the original process was, particularly in the early phases of the trial. We want to get those data and present those data publicly before we launch our pivotal trial, which will all happen by mid-year.

Gil, Analyst — Needham

But just spending a second on Covert-C here, the type of data we're going to be looking for, I'm assuming these chimerism data, how much follow-up do you think you're going to have at this club?

Gavin MacBeath, CEO

Yeah, so by the time we present these data, we anticipate having eight patients that will have at least two months follow-up post-dosing. So chimerism data out to two months for eight patients, and then initial chimerism data post-dosing for another, an additional four patients beyond those eight. But one of the things that we showed recently in February at the tandem meetings of ASTCT and CIBMTR is that the chimerism measurement that you see two months post-transplant is actually highly predictive of long-term outcome. So if you have complete donor chimerism at two months, you actually have a very good prognosis, whereas any mixed chimerism at two months, those patients are at much higher risk of relapse. In fact, we saw a hazard ratio of over four when you compared the groups with mixed chimerism versus the patients with complete chimerism at that two-month mark. So we believe that the two-month chimerism data on these eight patients will actually be quite meaningful with their predictive power. We'll also share data on T-cell persistence and activation markers, proliferation markers, what we're seeing in vivo with this product, you know, in patients that have been dosed by that point.

Gil, Analyst — Needham

That would be very helpful. And maybe shifting gears to the Ivitil study, what are you thinking you're going to need to show here to be successful?

Gavin MacBeath, CEO

Yeah, so, you know, based on the data that we've seen so far, we are designing the pivotal study to have a target hazard ratio of 0.52 for relapse-free survival. We've seen that in the phase one. We believe this new manufacturing process will be as good or perhaps better than what we've been seeing so far in the study. So we believe that powering this study to achieve a hazard ratio of 0.52 for RFS is a somewhat conservative approach to ensuring success in this pivotal trial. Now, with those numbers, this is about 140 patients per arm, and based on the enrollment that we saw in cohort C and the amount of enthusiasm we've seen from investigators, we're now projecting that that study will fully enroll and get to a top-line readout 24 months from when we start the study. So mid-2028 is when we anticipate top-line data from the pivotal study.

Gil, Analyst — Needham

You did have one patient that received an additional dose that drove them back into remission, basically. Is this something that you're going to have as an allowed protocol in the pivotal study, or how do you view this?

Gavin MacBeath, CEO

Yeah, so this is a very interesting result we got in one of our patients in the phase one study. So this patient received two infusions, but they had a delayed second infusion due to receiving steroids to treat GVHD. And so that patient had a full-blown relapse. In fact, their chimerism was 20%. We then gave them a relatively small third infusion. We only had 370 million cells left over from our manufacturing, but we administered those cells and the patient immediately within three weeks had complete donor chimerism, and they went into remission and remained in remission for five months. That patient did ultimately relapse, but it was clear proof of mechanism that our cells effectively target cancer cells in the patient. So in our pivotal trial, we have included in the protocol that if a patient has impending relapse, in other words, their chimerism is increasing, and they look like they're at risk of relapsing, that we're allowing a third infusion to, you know, essentially prevent relapse in those patients. So that is being included in the pivotal study.

Gil, Analyst — Needham

Very good. So, you know, we've followed other products in the transplant space in the fast, and there's been one major pushback as it relates to their costs, primarily because, as you well know, a transplant is kind of a homebrew for hospitals. So how are you addressing this? Now, obviously, most things don't have an efficacy label on them. So just wondering how you think about pricing.

Gavin MacBeath, CEO

Yeah, so we've done quite a bit of work with payers to understand what would be acceptable for pricing in this space. And we're hearing that because of the real unmet need here and because of the large economic burden on clinical sites, the burden of relapse, right, if a patient relapses, they're typically readmitted to the hospital, they could end up in ICU, they're having other complications. Because of that, we believe we could support pricing that's in the same range of other cell therapy products. So Ticelra is a TCR T-cell product that was priced at $727,000, and TagV is currently being reimbursed around $565,000. So we're comfortable with the pricing in the range of $650,000 to $700,000 for this product. We also note that this would not be bundled with transplant. This would be considered a separate therapy from transplant. Right now, the DRG code for reimbursement for transplant is DRG014. This would be mapped to DRG018, which is what other cell therapy products would be mapped to, including CAR-T therapy, including TIL therapy, as well as TCRT therapy. They've all been mapped to DRG018.

Gil, Analyst — Needham

So you're also looking at other, you have an additional product looking at other HLA subtypes. Can you remind us what the timeline is on these additional studies?

Gavin MacBeath, CEO

Yeah. So, you know, as I said earlier, TSC-101 targets patients with the HLA type AO2-01, but in order to expand that to other HLA types, we're taking a general approach, and that is to target antigens that are derived from the protein CD45. CD45 is a large protein that's expressed in almost every lineage of heme cell, but not in any non-heme tissue. So it's the same mechanism of action as TSC-101, just targeting antigens derived from CD45 that are present on the patient cells, but not the donor cells. And so all of these products are called TSC-102, but they then have the suffix based on the HLA type. So we have two that have already cleared INDs for HLA-A0301 and HLA-A0101. And then we have another product in development right now in, you know, late stage discovery for an A2402. So our plan is that they would all be in the same phase one clinical trial as an umbrella study so that we can, you know, basically follow the same path that we followed with TSC 101 in a phase one study. So the first two, the INDs have already cleared. So we're looking to launch the phase one in the second half of this year with the first two products and then add in the A2402 when it becomes available. It is an opportunity to explore some other patient populations with this study. So we'd likely add other diseases like NHL into the study, as well as explore the use of our product in combination with myeloablative conditioning, which is what's used exclusively in pediatric transplants. So an opportunity to sort of further expand the addressable market with this program.

Gil, Analyst — Needham

Now, given that like any other cell therapy, manufacturing is a big component here. How scalable is manufacturing of TSC 101? And like if you become commercial, like how much more investment do you think you would need?

Gavin MacBeath, CEO

Yeah, so our strategy for commercial manufacturing is to partner with an external CDMO that has manufacturing capabilities both in the U.S. and ex-U.S. And so, you know, we're currently working with a CDMO that has those capabilities and capacity issues has the capacity to support the type of commercial launch that we're looking to do. We're ultimately targeting several thousand patients a year. And so this CDMO has that capability.

Gil, Analyst — Needham

And how should we think about margins as it relates to manufacturing? I've seen a couple of drug launches in cell therapy space and usually have negative margins.

Gavin MacBeath, CEO

Yeah, so if we're pricing at $675K, we're anticipating that our cost of goods all in, so materials, labor, suite time is in the order of around $250,000, $260,000. So we have significant profit margin there. We also believe we can significantly bring down the cost of goods of manufacturing in the commercial setting. And so we're working on strategies to do that now. But conservatively, we still have a very large profit margin. The other key thing to profit margins is success rate. So if you are making in-spec product 95% of the time, you're going to have a really good profit margin. If you're only making in-spec product 50% of the time, you're in big trouble. So our focus is not just on the profit margin, but also on the success rate for in-spec product. And kind of a last point there, if you have to identify a key bottleneck in manufacturing what would that be um it's really comes down to um the manufacturing suite and you know how many slots you can get per month um so building out the capacity which is not just space but it's people uh as well that's that's really the constraint um but um other than that there's there's no other constraints uh to the system i don't want to spend a few minutes on solid malignancies.

Gil, Analyst — Needham

This is a big part of the story until pretty recently. So maybe just starting with the reasons to deprioritize plexi-T programs.

Gavin MacBeath, CEO

Yeah. So we have been running a phase one study with our solid tumor program, treating patients with initially one and then ultimately more than one TCRT cell product at a time. And so that study has also been going for a couple of years. And what we were finding is, one, it's a very challenging setting to work in. You're engineering product from patients that have late-stage cancer, and so very often while you're manufacturing product, the patient progresses and becomes unable to receive the product. It's also challenging because patients have to undergo lymphodepletion, and that's very challenging for patients that have undergone multiple rounds of chemotherapy. And it's also taking away their T cells, which is what's fighting their cancer, right? And so ultimately, our decision to terminate the Plexi-T trial and pivot to in vivo engineering was driven by two things, right? One, by the challenges of ex vivo manufacturing in the late stage setting and the challenges, you know, the clinical challenges associated with treating those patients. but two, just the really attractive opportunity to develop an in vivo engineering platform for solid tumors. So in vivo engineering, you're essentially genetically engineering the patient's T cells in their body, right? So you administer a lentivirus, a modified lentivirus that delivers the gene for the TCR directly to T cells in the patient's circulation. And so this solves a number of issues. One, the patient doesn't have to undergo lymphodepletion, which is fantastic, right, for the patient. Two, there's no delay in manufacturing. The product's made instantaneously in the patient's blood system, not in a lab. And three, it's much more cost effective, right? It's an off-the-shelf product that can be delivered immediately for a fraction of the cost that ex vivo manufacturing requires. So for all of those reasons, this is a really strong incentive to develop an in vivo engineering platform for solid tumors.

Gil, Analyst — Needham

So why not consider a strategy, and this is a strategy used by one of your private peers, where you basically follow the patients around from relatively early in their disease process and collect the T cells really, really early on and kind of provide the product much later when they need it.

Gavin MacBeath, CEO

Yeah, so you could do that. You know, the challenge is that only a fraction of the patients for which you collect T cells early on are actually going to end up getting the product. There's many clinical reasons why they, you know, may not ultimately receive the product if you collect the cells early. So that's just a big risk and an expense to take. But two, I just think ultimately the attraction of in vivo engineering is just, you know, far outweighs ex vivo engineering, even if you, you know, are collecting T cells early for the patient, you're still with the challenge of an expensive, you know, one at a time process compared to an off the shelf product that you can give a patient right when they need it. So I think just the attraction of in vivo engineering, you know, really suggests for us that that's the future for solid tumors. By the way, this is not an option in our heme program, because, you know, that program is successful because we're treating patients very early on post-transplant when their disease burden is really low, right? So it's an opportunity to completely cure the patient when they have almost no cancer cells. But at that point, they also have almost no T-cells, right? They've just come off a transplant where their whole blood system has been obliterated by conditioning therapy. And so, you know, they just don't have the T-cells to engineer with an in vivo platform at that stage of their post-transplant treatment, that's why it makes much more sense for our heme program to continue with ex vivo manufacturing, collecting the donor's T-cells prior to the transplant so that the product is ready to go when the patient's ready to receive it.

Gil, Analyst — Needham

And how are the discussions with potential in vivo partners going?

Gavin MacBeath, CEO

In vivo partners?

Gil, Analyst — Needham

Yeah.

Gavin MacBeath, CEO

Like for the solid tumor program? So at this point, we have partnered with a service provider that has an in vivo engineering platform. We're working with them to develop the lentivirus. We've done some, you know, exciting preclinical work already with this program. And so when we're ready to reenter the clinic, we will let everyone know. But it is an exciting prospect already underway.

Gil, Analyst — Needham

All right. So kind of a last point, you know, cash position, cash resources, projected runway, and how does this align with company catalyst?

Gavin MacBeath, CEO

Yeah, so we ended last year with 152 million in cash. And so that provides runway through to the second half of 2027. We are planning to launch this pivotal trial this year. So we're currently funded to start that trial, but not funded to complete the trial um so we are um you know planning to round out our cash position uh to completely uh fund the pivotal trial uh with runway uh beyond the the top line readout which would happen again in mid-2028 okay makes sense any last items and kind of maybe message for our listeners or investors? Yeah, I guess I would end by just saying that there's a lot of aspects to this heme program that are perhaps underappreciated in terms of how unique it is among cell therapy programs. So for a start, you know, with manufacturing, we don't have some of the challenges of other cell therapy programs because we're actually engineering the T cells from a healthy donor rather than from a cancer patient, right? So the donor is typically a young, healthy individual with plenty of T-cells, so much more consistent starting material for manufacturing. The second point is that we aren't racing the clock in terms of our manufacturing. We start manufacturing before the patient goes to transplant, so our product is ready before the patient is ready to receive it. So there's no time issue associated with that. And then three, from a commercial standpoint, this is actually a sort of made for a commercial launch type program because these patients, we don't have to go looking for them. They've already been referred to a transplant center in order to get a transplant. So they've been treated by an oncologist in the community setting, referred to a transplant center. there's only 120 transplant centers in the U.S. that do allogeneic transplants for AML and MDS. So very concentrated market. These patients come in, they're HLA-typed automatically in order to get their transplant because you need to know their HLA type as well as the donor's HLA type before they have the transplant. So we don't have to, you know, figure out where the patients are. We know what their HLA type is. We know where they are. And our clinical trial right now, we have 22 clinical sites active with our phase one study. We're actually going to expand that to 25 to 30 sites for the pivotal study. And all the major transplant centers in the U.S. are participating in this study. So they're already going to be familiar with the data. In fact, over 50 percent of all transplants in the United States occur in one of the clinical sites that will be involved in our pivotal trial. So it's sort of pre-marketed already if this program is successful.

Gil, Analyst — Needham

Maybe a last but important point to remind everyone, there are no other therapeutics that have curative intent in the MLMDS.

Gavin MacBeath, CEO

Yeah, absolutely. Yeah. So the only thing that cures a patient right now in this setting is a transplant itself. And that's what we're looking to make fully curative, right, not just for the 60% of patients currently cured, but for all patients. I would add to that that, what was I going to say? Shoot, I have lost my train of thought, but that's a good note to end on, right? We're looking to cure patients. This is the only way to do it. Oh, I know what I was going to say. We actually think the transplant market is going to increase over time. And the reason is because there's a lot of clinical activity, a lot of development activity going on in patients, you know, relapse refractory patients. And any success in that area is actually going to drive more patients to transplant, because in order to qualify for a transplant, you typically need to be in complete remission. And so any success from new agents that are being developed right now will actually increase the number of patients that will go to transplant. So our market is likely to increase significantly over the coming years because more and more patients are going to qualify for and get referred to transplant.

Gil, Analyst — Needham

Great. Thank you as always, Gavin.

Gavin MacBeath, CEO

Yeah, great to talk again.