Good afternoon, everyone, and thank you for joining us at the 3rd day of the Needham Healthcare Conference. It is my pleasure to have with me today Gavin MacBeath, CEO of TScan Therapeutics. 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. Maybe just to set the stage with everyone, maybe a brief introduction, discuss TScan Therapeutics's core technology platform, and how do you view this strategy as different when compared to, let's say, CAR T's?
Great. Thank you Gil, for having me on. I appreciate the invitation. Yeah. TScan Therapeutics is a fully integrated clinical stage T cell therapy company focused on bringing TCR-engineered T cell therapies to patients with cancer.
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. 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.
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. 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 2 years of their relapse.
The key unmet need here is can we make transplant more effective? Can we fully cure patients that are undergoing transplant therapy? 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.
When you get a transplant, you completely replace the patient's blood cells with donor blood cells. The relapse occurs if there are any residual cancer cells that are present following the transplant. 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. Immediately following the transplant, we infuse the patient with these engineered T cells, and that targets any residual cancer in the patient. 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.
That's really the key difference between the approach we're taking and approaches like CAR T therapy that are really designed to completely obliterate an entire subset of cells in the patient.
Thank you for that introduction, Gavin. TScan Therapeutics has already shown some pretty impressive clinical data. Could you walk us through some of the earlier results?
Yeah. We've been running a phase I trial with our lead program, TSC-101, for about 3 years now. It's called the ALLOHA™ Study. The most recent update from that study we presented at ASH in December of last year, December 2025. At that update, we showed data from 19 patients treated with our product. Those patients all received an allogeneic transplant and then got 1 or 2 infusions of our engineered T cells.
We also included a control arm in our phase I study. Those were very similar patients, but receiving transplant alone without our cell therapy product. What we showed is that we are reducing relapses in these patients by more than 50%. 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 engineered T cells are still detectable in their blood out past 2 years now. Even a patient that's now out past 3 years, we can still detect the engineered T cells in those patients. Those responses are long-lived. The 3 patients in our study that are out at 2 years, all 3 of those patients are still on study and completely disease-free. That compares to only 1 out of 4 patients in the control arm that made it to that 2-year mark. What we're showing is robust reduction of relapses as well as long-lived responses in these patients.
Maybe it's worth reminding the audience also, what is the total addressable market here given the HLA restrictions?
Yeah. We're about to launch a phase III study with this program, which we intend to launch by the middle of this year. Plan is that it'll be a 2-year study, so that should read out in mid-2028, with the commercial launch in mid-2029. 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's 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. Let's say conservatively 6,200 patients a year get transplanted.
To qualify for our therapy, you need to have the HLA type A0201, which is about 42% of the U.S. population. Then you also need to be paired with a donor that's A2 negative. Our experience has shown that we can find an appropriate donor for each patient about 80% of the time. 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 launch this product in 2029.
Just to spend a 2nd on the requirements for transplant here. I'm assuming you're restricted to one type of transplant as it relates to matching. Can that be expanded at all, or this is just going to be what it is?
Yeah. Just to sort of clarify what Gil's getting at here. In order to qualify for our therapy, the donor has to be A0201 negative. 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. 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 HLA. 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.
9 out of 10 HLAs match, but they're mismatched on just that one HLA, A0201. Right now, our phase I study includes both types of donors, both haploidentical and mismatched unrelated donors. That's the plan for the pivotal trial as well. 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, completely matched on HLAs.
There's very similar outcomes in terms of relapse rates, irrespective of the donor type. Really, the choice of donor really comes down to other factors for the transplant center.
If we are successful, if we can reduce relapse rates by 50%, that makes this a much more compelling transplant to undergo, because you would have a much lower chance of relapsing and ultimately dying from your cancer. 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.
Maybe a bit of a silly question, but doesn't this engineering improve the chances of preventing host rejection or graft rejection?
Graft rejection really has to do with the transplant itself. If you're getting a standard allogeneic transplant, the risk of graft rejection is actually very low. 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 TSC-100, which is a product that we're no longer moving forward.
Over 30 patients, we've never seen graft rejection. In terms of the engineered T cells, when we administer 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.
We haven't seen any issues with that as well.
I do want to spend a second on the ASH data. Some responses in that dose level four appear to be less robust than expected. Can you discuss the underlying cause for what we saw and how the company has gone about addressing it?
Yeah. If you take a look at our ASH data, one of the figures in that poster shows the chimerism data. 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. 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.
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 maintained 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.
What happened is it happens to be the point at which we moved to dose level 4, but it's also a point at which we started to have some challenges in our manufacturing suite. We had to push the manufacturing process further in order to get to the target dose level. For several of those patients in those last 6 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. 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. 14 patients, complete donor chimerism, no issues, versus 6 patients that had either incomplete chimerism or relapse.
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. with this new manufacturing process, we actually do even better than those patients that did well in that 1st cohort. 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.
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. 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.
Just spending a second on Cohort C here, the type of data we're going to be looking for, I'm assuming, is chimerism data. How much follow-up do you think you're going to have at this club?
Yeah. By the time we present these data, we anticipate having 8 patients that will have at least 2 months follow-up post-dosing. Chimerism data out to 2 months for 8 patients, and then initial chimerism data post-dosing for an additional 4 patients beyond those 8. 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 2 months post-transplant is actually highly predictive of long-term outcome.
If you have complete donor chimerism at 2 months, you actually have a very good prognosis, whereas any mixed chimerism at 2 months, those patients are at much higher risk of relapse. In fact, we saw a hazard ratio of over 4, when you compared the groups with mixed chimerism versus the patients with complete chimerism at that 2-month mark.
We believe that the 2-month chimerism data on these 8 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, in patients that have been dosed by that point.
This is very helpful. Maybe shifting gears to the pivotal study, what are you thinking you're going to need to show here to be successful?
Yeah. 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 I. We believe this new manufacturing process will be as good or perhaps better than what we've been seeing so far in the study. We believe that powering the study to achieve a hazard ratio of 0.52 for RFS is a somewhat conservative approach to ensuring success in this pivotal trial. With those numbers, this is about 140 patients per arm.
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.
Mid-2028 is when we anticipate top-line data from the pivotal study.
You did have 1 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?
Yeah. This is a very interesting result we got in 1 of our patients, in the phase I study. This patient received 2 infusions, but they had a delayed 2nd infusion due to receiving steroids to treat GVHD. 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.
We administered those cells, and the patient immediately, within 3 weeks, had complete donor chimerism, and they went into remission and remained in remission for 5 months. That patient did ultimately relapse, but it was clear proof of mechanism that our cells effectively target cells, cancer cells in the patient.
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 3rd infusion to essentially prevent relapse in those patients. That is being included in the pivotal study.
Very good. We've followed other products in the transplant space in the past, and there's been 1 major pushback as it relates to their costs, primarily because, as we well know, a transplant's kind of a home brew for hospitals.
Mm-hmm.
How are you addressing this now? Obviously, most things don't have an efficacy label on them. Just wondering how you think about pricing.
Yeah. We've done quite a bit of work with payers to understand what would be acceptable for pricing in this space. 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.
TECELRA is a TCR T-cell product that was priced at $727,000, and Tagvya is currently being reimbursed around $565,000. We're comfortable with the pricing in the range of $650,000-$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 DRG 014. This would be mapped to DRG 018, which is what other cell therapy products would be mapped to, including CAR T therapy, including TIL therapy, as well as TCR T therapy. They've all been mapped to DRG 018.
You have an additional product looking at other HLA subtypes. Can you remind us what the timeline is on these additional studies?
Yeah. As said earlier, TSC-101 targets patients with the HLA type A0201, 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. 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.
All of these products are called TSC-102, but they then have the suffix based on the HLA type. We have 2 that have already cleared INDs, for HLA-A0301 and HLA-A0101. We have another product in development right now, in late stage discovery for an A2402.
Our plan is that they would all be in the same phase I clinical trial as an umbrella study, so that we can basically follow the same path that we followed with TSC-101 in a phase I study. The first 2, the INDs have already cleared, so we're looking to launch the phase I in the H2 of this year with the first 2 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. An opportunity to sort of further expand the addressable market with this program.
Now, given that like any other cell therapy, manufacturing is a big component here, how scalable is manufacturing of TSC-101? If you become commercial, how much more investment do you think you would need?
Yeah. 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. We're currently working with a CDMO that has those capabilities and capacity. It 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.
How should we think about margins as it relates to manufacturing? I've seen a couple of drug launches in cell therapy space, and they usually have negative margins.
Yeah. If we're pricing at $675,000, 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. We have significant profit margin there. We also believe we can significantly bring down the cost of goods of manufacturing in the commercial setting. We're working on strategies to do that now. Conservatively, we still have a very large profit margin. The other key thing to profit margins is success rate, right?
Yeah.
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, right? Our focus is not just on the profit margin, but also on the success rate for in-spec product.
Kind of a last point there, if you had to identify a key bottleneck in manufacturing, what would that be?
It really comes down to the manufacturing suite and how many slots you can get per month. Building out the capacity, which is not just space, but it's people as well, that's really the constraint. Other than that, there's no other constraints to the system.
I do want to spend a few minutes on solid malignancies, as this is a big part of the story until pretty recently. Maybe just starting with the reasons to deprioritize T-Plex programs.
Yeah. We have been running a phase I study with our solid tumor program, treating patients with, initially 1, and then ultimately more than 1 TCR T-cell product at a time. That study has also been going for a couple of years. What we were finding is, 1, it's a very challenging setting to work in. You're engineering product from patients that have late-stage cancer. 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. It's also taking away their T cells, which is what's fighting their cancer. Right? Ultimately, our decision to terminate the T-Plex trial and pivot to in vivo engineering was driven by 2 things, right?
1, by the challenges of ex vivo manufacturing in the late-stage setting and the clinical challenges associated with treating those patients. 2, just the really attractive opportunity to develop an in vivo engineering platform for solid tumors. With in vivo engineering, you're essentially genetically engineering the patient's T cells in their body, right? You administer a lentivirus, a modified lentivirus, that delivers the gene for the TCR directly to T cells in the patient's circulation. This solves a number of issues. 1, the patient doesn't have to undergo lymphodepletion, which is fantastic, right, for the patient. 2, there's no delay in manufacturing.
The product's made instantaneously in the patient's blood system, not in a lab. 3, 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.
For all of those reasons, there's just a really strong incentive to develop an in vivo engineering platform for solid tumors.
Why not consider a strategy, and this is a strategy used by 1 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?
Yeah. You could do that. 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 may not ultimately receive the product if you collect the cells early. That's just a big risk and an expense to take. 2, I just think ultimately the attraction of in vivo engineering is just far outweighs ex vivo engineering. Even if you are collecting T cells early for the patient, you're still with the challenge of an expensive one-at-a-time process compared to an off-the-shelf product that you can give a patient right when they need it. I think just the attraction of in vivo engineering 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 that program is successful because we're treating patients very early on post-transplant when their disease burden is really low, right? It's an opportunity to completely cure the patient, when they have almost no cancer cells. At that point, they also have almost no T cells, right? They've just come off a transplant, where their whole blood system is being obliterated by conditioning therapy. 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.
How are the discussions with potential in vivo partners going?
In vivo partners?
Yeah.
Like for the solid tumor program?
Yeah.
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 exciting preclinical work already with this program. When we're ready to reenter the clinic, we will let everyone know. It is an exciting prospect already underway.
Great. Kind of a last point, cash position, cash resources, projected runway, and how does this align with company catalyst?
Yeah. We ended last year with $152 million in cash. That provides runway through to the second half of 2027. We are planning to launch this pivotal trial this year. We're currently funded to start that trial, but not funded to complete the trial. We are planning to round out our cash position, to completely fund the pivotal trial, with runway beyond 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 in general?
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. For a start, 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. The donor is typically a young, healthy individual with plenty of T cells, so much more consistent starting material for manufacturing.
The 2nd 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. There's no time issue associated with that.
3, 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. 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.
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. We don't have to figure out where the patients are. We know what their HLA type is. We know where they are.
Our clinical trial right now, we have 22 clinical sites active with our phase I study. We're actually going to expand that to 25-30 sites for the pivotal study. All the major transplant centers in the U.S. are participating in this study. They're already going to be familiar with the data. In fact, over 50% of all transplants in the United States occur in one of the clinical sites that will be involved in our pivotal trial. It's sort of pre-marketed already if this program is successful.
Maybe a last but important point to remind everyone, there are no other therapeutics that have curative intent in AML and MDS, full stop.
Yeah, absolutely. 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. Not just for the 60% of patients currently cured, but for all patients. I would add to that, What was I going to say? Shoot. I have lost my train of thought. That's a good note to end on, right?
That's a good note to end on.
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, relapsed refractory patients. 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.
Any success from new agents that are being developed right now will actually increase the number of patients that will go to transplant. 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.
Great. Thank you as always, Gavin.
Yeah, great to talk again. Thank you.