With that, I would like to turn the call over to Gavin MacBeath, PhD, Chief Executive Officer. Mr. MacBeath, you may begin.
Thank you, and thank you, everyone, for joining us this morning. We're excited to be here to present our updated data that we presented at the American Society of Hematology conference over the weekend, as well as some insight into the market opportunity for TSC-101. I do want to remind people that we are a publicly traded company, and so we will be making forward-looking statements during this talk. I'm joined today by Dr. Ran Reshef, who is the Director of Translational Research and the Director of the Blood and Marrow Transplantation Program at Columbia University Irving Medical Center. I'm also joined by our Senior Vice President of Market Access, Stephen Camiolo, as well as our Chief Medical Officer, Dr. Chrystal Louis , who will join us for the Q&A session at the end.
I'm going to start by giving you a brief overview of the heme program and then turn it over to Dr. Ran Reshef to go through the recently updated data. Just as a general introduction to TScan, we're a fully integrated next-generation TCR-T cell therapy company, and our lead program is in heme malignancies. This is the program we're discussing this morning, where we have really promising data in the area of transplantation, where we're working to treat residual disease and prevent relapse in patients undergoing allogeneic transplantation. Based on these exciting data, we intend to launch a pivotal study of TSC-101 in the second quarter of next year. In addition to that, we have a preclinical program in solid tumors. We've had a clinical program developing various TCR-T cell therapies for solid tumors.
We're now moving that program back to preclinical in order to develop an in vivo engineering platform to deliver multiplex TCR-T cell therapy in solid tumors. And then finally, one of the core strengths of TScan is our target discovery platform. And so we continue to use that platform to discover novel autoantigen targets in autoimmunity. So with that, I'm going to turn to the heme malignancies program and really start by just outlining what it is that we're doing and the key unmet need. So as many of you know, for patients with AML and MDS, really the only curative therapy for these patients is to get an allogeneic hematopoietic cell transplant. In fact, this is a very effective therapy. Many patients are cured by this treatment. However, unfortunately, the leading cause of death in transplantation is relapse.
For patients undergoing transplant with reduced intensity conditioning, approximately 40% of patients will relapse within the first two years. If they do relapse, the prognosis is very poor. Unfortunately, about 80% of those patients will pass away within two years of relapse. Our approach is to use a cell therapy product to target any residual cancer in these patients and so prevent relapse following hematopoietic cell transplantation. The way we're doing this is we identify a patient who would qualify for our therapy. In this case, to qualify for TSC- 101, you need to have the HLA type A*02:01 . We would pair that patient with a donor who is HLA A02 negative. In that setting, all of the cells in the patient, all their blood cells would express the antigen HA-2, whereas the donor cells would not express HA-2.
They would be HA-2 negative. The first step is that this patient undergoes a regular, standard of care hematopoietic cell transplantation. They receive stem cells from the donor after conditioning therapy. Following the transplant, all their new blood cells are donor-derived and are HA-2 negative. The way we treat any residual cancer in this patient is we take T cells from the donor and we genetically engineer them to express a T cell receptor that recognizes the antigen HA-2. Then while the patient's still in the hospital, as they've recovered from the transplant, we then give them their first infusion of engineered T cells. At that point, those engineered T cells will target any residual patient-derived blood cells, including the cancer cells, but not touch any of their new healthy donor-derived cells, which are all HA-2 negative.
It's a very clean way to target residual disease to prevent relapse in these patients. We've, for the last several years, had an ongoing phase I study called the ALLOHA study, in which we've been treating subjects with AML, ALL, and MDS with this therapy. This study has included two arms, a treatment arm as well as a control arm. In the control arm, patients are undergoing regular standard of care hematopoietic cell transplant with reduced intensity conditioning, whereas in the treatment arm, the patients, in addition, receive two infusions of engineered T cells. The first infusion, typically about 21 days post-transplant, and the second infusion, approximately 40 days after their first infusion. Obviously, the primary endpoint in this study is to assess safety, but we've also been able to assess preliminary efficacy in this study.
And so we're excited to present updated data at ASH over the weekend. And this includes data on patients that have been on study now for over two years. And so with that, I'm going to turn it over to Dr. Reshef, who will take you through the recent updated data.
Thank you, Gavin. I'm delighted to be here and present the data that was shown over this weekend, which is updated as of September 2025. As you can see here, we've enrolled 23 patients on the TSC-101 arm, and as you already know, there is a control arm on this phase I study, which allows us to compare both the efficacy and the safety of this approach. You could see that we are, in fact, approaching three years from the first patient treated. As you could see, the median time from transplant is now 13 months on the TSC-101 arm, median age of 65, which is very typical for reduced intensity transplants. And what's important to point out is that the majority of these patients, as is typical for this age range, are very high risk, so two-thirds of the patients had AML.
We have about a third of the patients on the TSC-101 arm with a TP53 mutation, which carries a very dismal prognosis, even in the setting of an allogeneic transplant with the curative intent. Two-thirds of the patients had some form of adverse risk, either by molecular mutations or by cytogenetic risks. There are very specific tables and guidelines to designate what's considered adverse risk in AML and MDS. And what's very important is that two-thirds of the patients had MRD positive disease prior to going to transplant. So this together puts us at about 79% of the patients in the TSC-101 arm having very high-risk disease. And in fact, more than half of the patients were also beyond first remission, which is another high-risk category.
As you could see, the arms here are relatively balanced, but if anything, the TSC-101 arm is slightly more enriched for high-risk patients. Next slide, please. Toxicity has been extremely benign. The TSC-101 infusion, compared to other types of cellular immunotherapies, is extremely well tolerated. There were no dose-limiting toxicities reported. There was no increase in incidence of chronic graft-versus-host disease. There were some cases of acute graft-versus-host disease, which is as expected in patients undergoing a transplant. CRS, just to avoid any confusion where it says any CRS, that contains cases of cytokine release syndrome occurring even prior to administration of the cells, because in the type of transplant platform that we used, using post-transplant cyclophosphamide, cytokine release syndrome is an essential part of the transplant itself. It has nothing to do with the cells.
Where you see treatment-emergent CRS, those are truly the cases that occurred after TSC-101 infusion. You could see only three cases that were grade one or two and resolved quite quickly. There was one case of ICANS grade two with changes in mental status after the second infusion in a patient who had relapsing disease, which was treated and resolved within less than 24 hours. So the toxicity profile is very benign for a cell therapy. So this is, of course, a very busy slide at this point with that many patients enrolled on both arms. But what I would like to point out is maybe two things. First of all, the red squares and the blue squares indicate patients who are MRD positive and MRD negative.
And as you could see on the TSC-101 arm, there were plenty of patients who were MRD positive prior to transplant and some patients even MRD positive after transplant who converted to MRD negativity after the first or second infusion of TSC-101. So that gives us more direct evidence for the potency of these cells in eradicating minimal residual disease. And of course, if we look at long-term follow-up, those patients who are more than two years out, we have three out of three in TSC-101 arm that are relapse-free at two years. And in the control arm of the four patients who are potentially two years out, there's only one who's alive and without relapse at this point.
As you can also see, the hazard ratios remain very strong when comparing the probability of relapse with a hazard ratio of 0.46, relapse-free survival at 0.5, and overall survival at 0.61. Next slide. So this is, again, a very busy slide, but just to explain what these checkmarks are showing, this is a measurement of mixed chimerism. So this is another way for us to look at minimal residual disease, at any residual recipient cells that remain in the patient after the transplant. We use here a very high-sensitivity chimerism assay, which is called AlloHeme, which has a sensitivity of 0.2%, which is far better than the standard testing that is currently clinically available. Hopefully, AlloHeme will also become clinically available in the future.
But this gives us a very high sensitivity to detect what we call mixed chimerism, so any residual patient cells that remain in the body after the transplant. So you can see on the control arm a very typical picture for reduced intensity transplant. It very frequently fails to eradicate all of the recipient cells, as you could see by the multiple Xs that are there, many of which ultimately translate into disease relapse. And as you can see on the TSC-101 arm, there is almost universal, apart from a couple of cases, eradication of any residual disease and achievement of complete donor chimerism. I would point out, if you click one more time, there's one patient there that you will probably notice that is going in and out of mixed chimerism.
Those of you with sharp vision would see that this patient received a third infusion of TSC-101. I'm going to talk about that patient in the next couple of slides. This is, in fact, the kind of more detailed description of what this patient underwent. This is a 74-year-old male patient with high-risk AML in first remission, treated by me at Columbia, who received two infusions of TSC-101 at dose level three. He did have a delay in the second infusion because he had experienced acute graft versus host disease, which was not severe, but we decided to delay the second infusion to prevent any safety issues, which turned out to be a non-issue ultimately, but that was the decision at the time. Then the patient ultimately relapsed.
As you could see, the recipient chimerism climbs up all the way to nearly 20%. That reflects that the amount of recipient cells in the marrow or in the blood at that time point is nearly a fifth of the cells, which indicates basically disease relapse. At that point, what we decided to do was to administer a third infusion of TSC-101 at 370 million cells. This was administered without lymphodepletion, without any additional anti-leukemic therapy. As you could see, very rapidly and without any toxicity, in fact, much more rapidly than I anticipated, within a couple of weeks, the patient's chimerism recovered to full donor chimerism, and any evidence of relapse, which was clearly detectable by cytogenetics, had disappeared. There was no evidence of disease at their next evaluations, and this patient remained in complete remission for five months after this third infusion.
So this is the most direct evidence for how potent these cells are, being able to eradicate relapse, not just to prevent relapse in a setting that does not seem to require lymphodepletion and is not associated with any significant toxicity, and I think that was my last slide, Gavin.
Yes, thank you. So at this point, I want to turn our discussion a little bit to the manufacturing of TSC-101. And for those that were also looking at the chimerism slide and had a keen eye, they would note that, as Dr. Reshef said, many of the patients on the TSC-101 arm achieved complete donor chimerism very quickly within weeks of receiving their first infusion of engineered T cells. However, we do note that if you focus on the last six patients, that there seems to have been a shift in this trend, that in fact, four out of these six patients had incomplete chimerism or relapse at various stages. And we note that this is also when we went to a new dosing level, so dose level four, in which we introduced a fixed dosing regimen for TSC-101.
And so that also accompanied a slight increase in the total number of T cells used in the product. But as this is phase I, this provides us a real opportunity to learn as we go, not only about the clinical treatment of these patients, but also about our manufacturing process. And so looking at the patients in the study, not just these four patients, but also previous patients that had incomplete chimerism, such as the patient that Dr. Reshef just highlighted, we wanted to understand whether there were any features in the manufacturing process that would allow us to understand which patients achieve complete donor chimerism and which do not.
What we found is that using our manufacturing process that we call our phase I process, it's the process we've been using throughout the study, that the patients that achieve complete donor chimerism, as shown on the right here, they all had a manufacturing process in which there was a relatively low number of doublings of the T cells in the manufacturing process. The amount of T cell expansion that occurred during the manufacturing process was generally lower for the patients that achieved complete donor chimerism as opposed to the patients that did not achieve complete donor chimerism. This really emphasizes the need to have a short manufacturing process in which you don't lead to this excessive expansion of T cells ex vivo.
Just to provide a little more detail on our phase I process, the way this works is that on day one, we isolate PBMCs that include both CD4 and CD8 T cells. We electroporate them with the transgene. And then on day two, activate the T cells to enable that genetic integration. We then expand the T cells, and on day nine, enrich the T cells for the engineered T cells, so essentially purify out the engineered T cells from non-engineered T cells. We then further expand the cells and freeze the cells on day 17. However, unfortunately, this enrichment process that occurs on day nine, it's magnetic bead-based selection. It's actually a relatively inefficient process. And although we purify the cells very well, it also results in an over 90% loss of the engineered T cells at this step.
So we realized that to enter the commercial setting, we really needed to have an improved manufacturing process that doesn't have this intrinsic inefficiency in the process. And so we have now introduced a new manufacturing process we call our commercial-ready process. It's what we'll be using in the pivotal trial. And this is a much more efficient process. In fact, it's actually got a much lower cost of goods and only takes 12 days. So we basically cut five days off of the manufacturing process. But what you can see is, although the process starts the same, on day six, we both expand and enrich the T cells, but not using magnetic beads now, using a drug selection process. And this is much more efficient. It results in very minimal loss of engineered T cells, and so now only requires 12 days to manufacture the product.
We have now introduced that process into the ALLOHA study. We filed an IND amendment showing comparability of the product with the phase I process. It's gone through that regulatory process, and we've now manufactured product for two patients in the study. As you can see on the right, this new process requires much less ex vivo expansion of the engineered T cells, in fact, only about four to five-fold expansion relative to, on average, 13-fold expansion using the phase I process. We're very excited about this new manufacturing process. We've also initiated and completed initial tech transfer of this process to our external CDMO that will be manufacturing product during the pivotal trial and then ultimately in the commercial setting. Based on all these results, we have met with the FDA.
We had a recent end of phase I meeting with the FDA and reached agreement on a pivotal trial design, which we'll be using starting in Q2 of next year. So in the pivotal trial, we will actually be using a very similar design to what we used in the phase one study. Patients will be assigned to the investigational arm of the study if they have the HLA type A*02:01 and have an available donor that is A2 negative, so exactly the same as what we've been doing in the phase I study. And the control arm in this study will be an internal control arm in which basically patients that don't qualify for TSC-101 will be assigned to the control arm.
This includes patients that don't have the HLA type A*02:01 or are A*02:01 positive, but we were unable to find an A2 negative donor for that patient. Essentially, biological assignment to either the investigational arm or the control arm. We'll be including patients with AML and MDS in the study that are undergoing their first allotransplant and are eligible for reduced intensity conditioning. We anticipate the primary endpoint for the study is relapse-free survival with a key secondary endpoint of overall survival. We are still finalizing the statistical analysis plan and sizing of the study, but we anticipate that the study will be very similar to what we communicated last year, and that is targeting a hazard ratio of around 0.5 - 0.6 for relapse-free survival and anticipate that the study will include approximately 140 treatment arm subjects and a similar number of control arm subjects.
Based on that, we anticipate being able to enroll the study and get to a top-line readout in about two and a half years. Just as a quick word on enrollment, so we have 20 centers involved in the phase I study right now. We intend to expand that to an additional 5-10 clinical sites for the pivotal trial and anticipate being able to enroll the study very rapidly. There's a lot of investigator enthusiasm for this study, and we've now streamlined the process of identifying appropriate donors. We anticipate being able to stay on track with an enrollment schedule that would get us to a top-line readout, as I said, in about two and a half years. With that, I want to turn the microphone over to Stephen Camiolo.
So for those not familiar with Stephen, Stephen joined us earlier this year as head of market access and is actually fairly unique in this world in that he has previously launched three different cell therapy products. So he launched both Yescarta and Tecartus at Kite, and then more recently launched Amtagvi at Iovance. So we're very fortunate to have Stephen now as head of market access. And Stephen, I'm going to turn it over to you to take us through the commercial opportunity for the heme program.
Thank you, Gavin. Today, I'll walk us through the unmet need we're addressing, the highly concentrated market that we're serving, and the significant expansion opportunities ahead, each of which will underscore the commercial potential of our heme portfolio. Let me begin with one of the most important things that we all work with is the patient and the patient experience. One of the strengths of TSC- 101 is how seamlessly it fits into the existing transplant journey. The referral pathways for allogeneic transplant are already well established, and patients receiving TSC- 101 follow the same process they would for standard of care allogeneic transplant. Patients undergo reduced intensity conditioning transplant, recover in the hospital, and around day 21 receive their first infusion of TSC- 101.
They're monitored, discharged, and return roughly 40 days after their first infusion to receive their second infusion, which can be administered in the inpatient or outpatient setting, and that's at the physician's discretion. From a workflow perspective, this integrates directly into the current practice without adding operational complexity. Donor involvement is similarly straightforward. Donors undergo standard HLA testing, and the only incremental step is for one additional peripheral blood apheresis to collect the T cells for manufacturing, which is typically about a two-hour procedure. They then proceed through the usual G-CSF mobilization and apheresis to collect stem cells for the transplant. This process has worked smoothly across our ongoing ALLOHA phase I study, and we do not expect donor logistics to present any barrier in the commercial setting. A critical advantage of TSC-101, and you can go to the next slide, Gavin.
A critical advantage of TSC-101 is the allogeneic product. Being an allogeneic product, this enables us a far more consistent and reliable manufacturing process than autologous therapies, which rely on T cells from heavily pretreated patients. We avoid the traditional vein-to-vein challenges of autologous cell therapy entirely. TSC-101 is manufactured while the patient is undergoing transplant and is ready well before the patient is eligible to receive it. We have partnered with a global CDMO for commercial production and have completed the initial tech transfer. For the pivotal study, we plan to manufacture at two sites, our own GMP facility and at the CDMO, ensuring redundancy, scalability, and robust supply. On the commercial side, our market access planning is well underway. Excuse me, preliminary pricing work indicates a favorable range aligned with recent cell therapy approvals, and we are actively mapping reimbursement pathways with payers.
Because TSC-101 fits directly into established transplant workflows, identification and testing of patients and donors can occur entirely within the existing infrastructure of the transplant centers, supporting rapid adoption. Next slide. So at launch, we expect approximately 6,200 AML and MDS patients in the U.S. will be undergoing allogeneic transplant annually. Of these, 2,600 are HLA-A*02:01 positive, and roughly 2,100 will be matched with an A02 negative donor, the population eligible for TSC-101. To receive TSC-101, these patients will have to undergo transplant with reduced intensity conditioning and will be paired with either a haploidentical or a mismatched unrelated donor. Our phase I ALLOHA study has already shown clear signs of physician enthusiasm.
Transplant physicians are already selecting haploidentical donors over matched unrelated donors to provide access to TSC-101, and in some cases, shifting patients from myeloablative conditioning to reduced intensity conditioning specifically to enable treatment. These early behavior changes are strong indicators that physicians are excited about this product, and these preferences are likely to become more routine as experience with TSC-101 grows. Based on pricing assumptions consistent with existing cell therapies and projected uptake within the eligible population, we estimate peak annual U.S. revenues of more than $1.4 billion. Another major strength of this program is the highly concentrated treatment landscape. Allogeneic transplants for AML and MDS currently occur at approximately 120 centers across the U.S. Our phase I ALLOHA trial is currently being conducted at 20 of the top centers and includes some of the largest transplant centers across the U.S.
For the pivotal study, as Gavin mentioned, we plan to add up to 10 additional sites, and we anticipate launching TSC-101 with about 40 transplant centers across the U.S. These 40 transplant centers collectively treat more than two-thirds of all eligible patients each year. This concentration allows us to reach more of the market with a focused commercial footprint, supporting rapid penetration and a cost-efficient launch model. Excuse me. Next slide. As we've outlined, the TSC-101 addresses the HLA type A*02:01, which is the most common HLA type in the U.S. and Europe. This will allow us to address close to 8,000 patients a year. As we previously disclosed, we're expanding the heme program to address other common HLA types by developing TCR-Ts that target epitopes derived from CD45.
We expect to file INDs next quarter for our first two TSC-102 candidates, targeting HLA-A*03:01 and HLA-A*01:01. In addition, we have a late-stage discovery program targeting HLA-A*24:02, which many, as you know, is the most common HLA type across APAC. Together, these programs will meaningfully expand our global reach. So across the four products, we expect to address approximately 80% of patients in the U.S. and Europe and roughly 50% of patients in APAC, establishing a broad and scalable franchise. To summarize the global opportunity, I want to bring you back to TSC-101 for a moment where we expect to address close to 8,000 patients worldwide. As we advance our CD45-based TSC-102 products, we anticipate doubling that number to around 15,000 patients. And through additional lifecycle management strategies, we believe that we can ultimately reach approximately 20,000 patients globally.
As you can see, we're excited about the potential of this platform and the meaningful benefit we hope to bring to patients in need of relapse prevention. With that, I'll hand the call back to Gavin to provide a summary of where we are and our next steps as a company.
Great. Thank you, Stephen. So yes, in summary, as I mentioned earlier, we've now reached agreement with the FDA on a pivotal trial design. We've transferred our commercial-ready manufacturing process to our external CDMO. And as you just saw, we've now shown that this product produces durable responses with data from patients that are now on study for well over two years. And so moving forward, as Stephen just mentioned, we intend to file INDs for our first two CD45-related products in Q1 of next year and then launch the pivotal study in Q2 of next year.
In preparation for launching the study, as I mentioned in a call that we had several weeks ago, part of our discussions with the FDA is that we are looking to enroll five additional patients at the high end of our anticipated dose range for that study prior to launching the pivotal study. So we're right now actively enrolling patients and treating them with TSC-101. And because we've moved to that commercial-ready process, all five of those patients will be treated with product using the commercial-ready process, the shorter manufacturing process. But we intend to actually enroll beyond those five, so approximately 10 patients over the next two months and treat them with that commercial-ready process so that we can get experience treating patients with that process and so that we can evaluate that early chimerism readout.
And so we intend to share those data with the street prior to launching the pivotal study in Q2 of next year. So with that, happy to turn the call over to the Q&A session and happy to take any questions.
Thank you. At this time, if you would like to ask a question, please click on the raise hand button, which can be found on the black bar at the bottom of your screen. When it is your turn, you will receive a message on your screen from the host allowing you to talk, and then you will hear your name called. Please accept, unmute your audio, and ask your question. Our first question comes from Gaurav Maini with LifeSci Capital. Please unmute your audio and ask your question.
Hi, congrats on the data update. This is Gaurav Maini on for Sam Slutsky from LifeSci Capital. Just a couple of questions from us. So firstly, as it relates to TSC-101 retreatment, are you allowed to retreat in the phase III protocol? And if so, maybe any color on how those patients would be counted towards RFS? And then just a follow-up, if you don't mind.
Yeah, actually, I'll turn that question over to Dr. Chrystal Louis , our CMO.
So thank you for the question. At this particular point in time, we are including the option for retreatment into the phase III protocol. Our intent is ultimately, we don't think we'd have to use it that often, but we do want to have it potentially available. When thinking about how those patients would ultimately be assessed, the administration of a third infusion would be counted as an event that would be specific towards event-free survival or ultimately what's going to be one of our secondary endpoints. And then we would have to determine whether or not it was an event with regards to RFS with either relapse or death. Hopefully, death is not the issue here, but that would be really based on what their clinical outcome would be. So out of the gate, it would be an event with regards to EFS in thinking about the secondary endpoint.
Actually, just to build on that, so I mean, we're excited about the fact that our commercial-ready process is now routinely providing us with enough cells to have that third infusion available for patients. As Chrystal said, we don't anticipate that that would be a common event, but it's nice to have that as an option for patients.
Yep, makes sense. Thank you. And just one more, if you don't mind. So it looks like there's a baseline imbalance favoring the control arm on both TP53 status and pre-HCT MRD status. Maybe can you discuss the historical impact of those baselines on patient outcomes, what this means as it relates to the magnitude of difference we are seeing in the ALLOHA trial, and then what you plan to do in phase III to perhaps better ensure that baselines between the treatment and control are aligned?
The one caveat I would say is that there is an enrichment on the treatment arm with regards to TP53 status and increased complexity of those patients, but not the control arm. That does highlight some plans that we would have to take. Overarchingly, if you actually think about it, it sort of disadvantages the treatment arm because we would have more complex sicker patients on the treatment arm. I think for us in the phase I setting, one of the things that we've actually really been impressed with is that even though we have got what is technically a more complex patient population on the treatment arm, that our efficacy rates and our safety profile has been as good as it has. As regards to the rest of it, I'll leave that to Dr.
Reshef to kind of address, but I did just want to clarify that ultimately, currently, the way that it's structured in the phase one setting, that disadvantage is actually for the treatment arm.
Yeah, thanks, Chrystal. And I think that's exactly the point. If anything, this slight imbalance was disadvantageous to the treatment arm. And despite that, we were able to show a significant advantage to relapse rates and relapse-free survival. I think the numbers are a bit too small, so I don't actually think these differences are statistically significant. And I would suspect that in a registrational trial, now that the signal of efficacy is pretty clear, that people will enroll patients on this trial regardless of risk status. And we would get with larger numbers and more liberal enrollment, we would just get a better balance.
Yes. And then just one final point on that. So as Dr. Reshef said, I mean, we anticipate having a better balance and a larger pivotal study. But in addition to that, we did discuss with the FDA how we would account for any potential imbalance in our final analysis. And so what we presented is that we'll be using Cox proportional hazards models, one for MDS and one for AML, and in those models, then be able to account for any differences in prognostic factors, including risk factors and including TP53 status. So that will be built into the analysis plan so that we can correct for any imbalance in that analysis. And then the final statistical significance would be a weighted average of those two Cox proportional hazard models.
Great. Thank you.
Our next question comes from Selena Zhang with Morgan Stanley. Please go ahead with your question. Selena, please unmute your line using the black bar at the bottom of your Zoom screen.
Hi, this is Selena on for Max. Thank you for taking our question. On the commercial-ready process, did the two patients have product manufactured at dose level four? And if the patients were dosed, are there any observations you can share thus far? Thank you.
Yes. So take that. Yes. So moving forward, both of those products produced cells that were sufficient for dose level four. So one of those was actually a reproduction for a patient that had received their first infusion with the phase I process. But the second patient is receiving the full intended dose level four. And we anticipate that all patients moving forward would also receive the full dose level four. So in both of those manufacturing runs, we were able to generate close to 10 billion cells for each patient. Dose level four requires a total of 2.4 billion cells. So essentially 800 million at the first infusion and 1.6 billion at the second infusion. So as you can see, we are generating more than enough cells now with this commercial-ready process to support dose level four as well as potential additional backup doses.
With regards to the next question, the only thing we could remark on is acute safety after the initial infusion and patients tolerated their infusions well.
Great. Thank you.
Our next question will come from David Nierengarten with Wedbush Securities. David, please go ahead with your question.
Thanks. Just maybe this is an obvious question, but why not just use the manufacturing process that you're used to and maybe split the dose or stay with dose level three in the phase III study? Thanks.
Yeah. So actually, the commercial-ready process has a number of advantages in it. So when you start a phase I program with a cell therapy product, often your initial process is a phase-appropriate process, but you're going to learn as you go and improve on it. And so the commercial-ready process is just so much more efficient. It's so much easier to perform, operationally simpler, fewer steps in the manufacturing suite, but an enormous reduction in cost of goods. So the magnetic bead-based step is actually relatively expensive. Eliminating that actually makes us a much more commercially viable product. So our intention all along was to move to a more commercially viable process. And so this also addresses the production issues that we were experiencing most recently with the phase I process. So I think it makes total sense to move forward with this.
As I said, we've done split runs to demonstrate comparability between the phase I and commercial-ready process. We've presented that to the FDA in an IND amendment. So that regulatory work is already completed, and we're moving forward with the commercial-ready process.
The last piece that I'll add to Gavin's comment is ultimately the difference between dose level three and dose level four. While dose level four is slightly higher, it actually streamlined our processes because we went from weight-based dosing to actual fixed dosing. So the assessment of dose level four with the fixed dosing actually becomes hugely important. And then that all leads into all of the associated commentary that Gavin just made with being able to generate that now well over and above what those associated fixed doses would be.
And if I could add one additional point, Gavin, so something critical to the commercial success is also we were able to reduce timing by five days. So it helps us streamline the process and speed up the manufacturing process.
Our last question will come from Tara Bancroft with TD Cowen. Please go ahead with your question.
Thanks very much. This is Nick on for Tara. Just one from us. What is your level of confidence in replicating these results in the pivotal trial, the RFS rate being successful and supporting approval, and the 21% relapse rate being sufficiently supportive? Thanks.
So, what's our confidence that we're going to continue to see great results that we've seen already? So, I mean, speaking as a CEO, which is always an optimistic person, but I'm very confident in this product. So, the reality is that particularly with this new commercial-ready process with shorter manufacturing and what we've seen in the field of engineered T-cell therapies consistently from other companies, including with Novartis's T-Charge program and others, that shorter manufacturing just results in better T-cell persistence, better in vivo expansion in the patient. And so we anticipate seeing as good or if not better results as we move into the pivotal setting. So, I have a high degree of confidence for what that's worth.
I would think clinically we also have a high degree of confidence in outside of what we're actually seeing, not only from the associated results. What we saw from the actual anti-tumor activity in Dr. Reshef's patient who received the cells without getting lymphodepletion or ultimately having any additional cancer therapy and that associated response gives us incredible encouragement that we are moving forward doing the right thing for a patient population that's still got a huge unmet medical need. But I would have to say as a clinician, the other piece that I'm excited about is that my fellow clinicians are excited about participating. I think you always have to sort of consider and wonder if it's going to take a lot of effort, if it takes a lot of push to get sites and investigators super excited about your trial.
This is one where ultimately not only are our ongoing investigators, and I can also let Dr. Reshef speak to that, excited about what's happening. Our outreach to sites both in the U.S. and ex-U.S. has actually been incredible. But we've also been approached by sites wanting to participate on the trial, not us going out having to find them. And I think all of those things kind of put together that we are truly excited about being able to bring something to a patient population that still has a very significant unmet medical need.
Yeah, I can vouch for the enthusiasm among my colleagues, not just in my institution, but in other institutions as well. There's a high level of interest in this. And I think the story of our patient going into remission with these cells upon overt relapse is a very good proof of concept supporting the potency of these cells. And in terms of the clinical results, I do think that once you cross the first 20 patients, then your results are no longer anecdotal or sporadic. You've shown the proof of concept that this actually works. And when you think about use of control arms in phase one studies, that's generally non-conventional. But we have plenty of benchmarks outside the control arm for how patients with TP53 mutations and complex cytogenetics and beyond first remission. There are plenty of benchmarks. The world of transplant is registry-based and extremely data-driven.
We can compare these results also to these external benchmarks and see that TSC-101 outperforms those significantly.
Thank you very much.
That concludes the question and answer portion of today's call. I will now hand the call back to Gavin MacBeath for closing remarks.
Great. Thank you. So I want to thank everyone for joining us on the call this morning. As it's clearly evident from the call, we're very excited about this product. And so I look forward to sharing additional data from these patients that we're now treating with our commercial-ready process sometime in the first half of next year, and then look forward to launching our pivotal study in Q2. So thank you again for joining us. And with that, we will conclude the call.