TScan Therapeutics, Inc. Common Stock Study update

Please go ahead. Thank you everyone for joining us this morning.

This morning I'll be providing a major strategic update to the company that we announced this morning. Just as a reminder, we are a publicly traded company, so I will make forward-looking statements during this presentation. As many of you recall, in the history of TScan, one of our core objectives has been to deliver TCR-engineered T-cell therapies to patients with cancers, and in fact, cancers with both heme and solid tumor malignancies. Last October, in October of 2025, we announced that we were pausing the solid tumor program in order to develop an in vivo engineering platform for solid tumors. I'm exciting today to announce that this program has actually made tremendous progress over the last year. In fact, we have now, as of today, advanced two product candidates in this program into IND-enabling activities.

We've developed an in vivo lentiviral platform that efficiently delivers the genes for these TCRs into T cells in vivo. Those T cells get engineered and are able to clear target cancer cells in mouse models. Our strategy moving forward is to focus this program on our two most active TCRs from our previous clinical trial, a TCR directed at the antigen PRAME, and a TCR directed at the antigen MAGE-A4. We'll be moving both of those products forward into IND-enabling activities. Over the coming two years, this program is going to create significant value inflection points. For example, we will be presenting preclinical data on our final constructs that we've moved into IND-enabling activities, as well as regulatory updates in Q1 of 2027.

We are planning to file our first IND in Q4 of 2027, and then finally to launch a Phase 1 trial in Q4 of 2027. Sorry, file the first IND in Q3, and launch the pivotal trial in Q4. I'm also pleased this morning to update on data in our heme program. We actually have very strong clinical data with our now commercial-ready manufacturing process, in which we enrolled patients and treated them with this process, a cohort of patients that we refer to as Cohort C. As we previously disclosed, we've reached agreement with the FDA on a Phase 3 study, and in fact, launched that study, and we've in fact enrolled our first seven patients on this study. However, unfortunately, we have not been able to secure sufficient funding to complete that clinical trial.

It is obviously a large study and requires a significant amount of capital to complete the trial. We made the very difficult strategic decision to pause the phase III study and allow the data in these 21 patients to mature, to get longer-term follow-up on these patients. At the same time, we remain committed to establishing our manufacturing process at an external CDMO that has the capabilities of providing product in a commercial setting. For this program, we are now actively seeking strategic partnerships. The key value inflection points for this program moving forward is that we remain committed to presenting 6-month data on these 14 patients in Cohort C in Q4 of this year at a major medical meeting.

We will present updated data on all 21 patients, the patients in Cohort C, plus the 7 patients that we have already enrolled in the pivotal trial. We will present data on those patients in Q2 of next year. At that point, all of the patients in the study will have had over 1 year of follow-up. Finally, again, key strategic inflection point for us is to secure a strategic partnership that can fund this program moving forward. Finally, for our autoimmune program, we have previously disclosed that we have discovered targets in HLA-B*27-driven autoimmune diseases, such as ankylosing spondylitis. We are, with the strategic reorganization, halting further development of this program, pending partnerships. Obviously a value inflection point for us would be to secure a strategic partnership in autoimmunity.

With that as background, our updated pipeline slide now really focuses on the solid tumor effort. As I said, we will be moving 2 products into IND-enabling activities, one directed at PRAME, the other directed at MAGE-A4. We in fact have other TCRs in late stage discovery that continue to build out on these targets. For example, we have a product that has now reached the end of discovery that recognizes PRAME presented on a different HLA, the HLA-A*24:02. We continue to build out our products to provide better HLA coverage in these well-validated targets of PRAME and MAGE-A4. As you can see on the bottom of the pipeline slide, we are pausing further development in the heme program as well as autoimmunity and are actively seeking partnerships for these programs.

We believe that this strategy is the best strategy to move our products forward and bring the most value both to patients and to shareholders with this new reorganized company. Just want to spend a few moments walking through the solid tumor program and what we are trying to accomplish with this program. Just by way of introduction, really needs no introduction, but solid tumors represents an incredibly large unmet medical need. Over half a million patients every year in the U.S. die from solid tumor indications. In fact, just looking at melanoma alone, over 8,500 patients die from melanoma, despite the fact that there are about 20 approved therapies in this space. About 125,000 patients die annually from non-small cell lung cancer, despite there being over 50 approved therapies in this space.

There's still a very keen need for effective therapies that address these deadly diseases. We are developing TCR-engineered T cell therapies for very prevalent cancer-specific antigens that are uniquely addressed by TCR-engineered T cell therapies. PRAME, as many of you know, is expressed in over 90% of melanomas. MAGE-A4 is actually quite prevalently expressed in a variety of different cancers, including non-small cell lung cancer, head and neck cancer, and ovarian cancer. These are the primary targets for the two products that we are moving into IND-enabling activities. Just by way of introduction to in vivo engineered technology. In vivo engineering really solves some of the key challenges of autologous TCR T cell therapy. For a start, traditional autologous therapy requires manufacturing product for patients one at a time, and often is plagued by out-of-spec issues, significant cost of goods.

In vivo program, that completely eliminates those issues. The lentivirus is made as a large batch, and that same product is essentially an off-the-shelf product that can be delivered to patients without delay. There's no vein-to-vein time issues for treating patients, and there's no need for lymphodepletion prior to administering the product. So far, T cell-targeted lentiviruses are clearly the way to go for this type of in vivo therapy. We believe that the lentiviral approach is particularly appropriate for oncology because it enables permanent genetic integration of the gene of interest, the TCR, into the T cells of the patient, which means that these cells can now continue to propagate in the patient. They can form memory cells, driving long-term immune surveillance.

With this method, you actually see higher levels of engineered T cells in patients based on other studies that are being performed, as well as greater expansion of these engineered T cells than you typically see with an ex vivo engineered product. In fact, this last year has seen an incredible explosion in the area of in vivo engineered CAR T programs. For example, just highlighting three companies here that have had really remarkable results. Kelonia, Eesa Biotech, and Legend. All three of those companies have delivered engineered CAR T therapy using lentivirus into patients. In all three cases, we've seen 100% response rates in patients, albeit relatively small number of patients treated so far, but really remarkable results with this approach. As a company, we've asked how can we build on this type of work but really bring these therapies to solid tumors?

TCR-engineered T cell therapies really provide the mechanism for delivering engineered T cell therapy to solid tumors. Traditionally, it's been very challenging to treat solid tumors with CAR T therapy, and we've seen much better results in the clinic with TCR-engineered T cell therapies. What I'm showing you here on the left is an example of a tumor sample that we collected as part of our previous Plexity study. You can see very robust expression of PRAME in this cutaneous melanoma sample, showing essentially all the tumor cells expressing PRAME at a very high level. PRAME is an intracellular protein, so not addressable by a CAR T therapy.

A T cell can recognize this target PRAME because the tumor cell is presenting an antigen derived from PRAME, shown in the figure on the right here in pink, an antigen derived from PRAME displayed on a class I HLA molecule. In this case, the most common HLA-A*02:01, which represents about 42% of the U.S. population. The T cell is able to recognize this target and mount an anticancer immune response, kill that tumor cell, and so ultimately shrink tumors and the goal, obviously, to completely cure the patient. We have previously disclosed in our corporate deck that we've got some early data. This is not with our current construct. This is with an earlier version of our construct, in which what we showed is that mice that have been engrafted with human PBMCs and then treated with our lentivirus are able to control tumor growth.