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Item 1. Business

2026-03-04 compared with 2025-03-05 · 243 added, 513 removed, 697 unchanged (52% of the section changed)

We are a clinical-stage biotechnology company focused on developing a robust pipeline of T cell receptor (TCR)-engineered T cell, or TCR-T, therapies for the treatment of patients with cancer.

Our approach is based on the central premise that we can learn from patients who are winning their fight against cancer to treat those who are not.

Over the past several years, we have built our ImmunoBank, a repository of therapeutic TCRs that recognize diverse targets and are associated with multiple human leukocyte antigen, or HLA, types.

We then use these TCRs to manufacture enhanced TCR-T therapies to treat a broad population of patients with both hematologic, or heme, and solid tumor malignancies.

Every TCR in our ImmunoBank has come from our proprietary platform technologies, and we are continuing to expand our ImmunoBank.

We are advancing a robust pipeline of TCR-T therapy product candidates for the treatment of patients with heme malignancies and solid tumors.

Our lead product candidates, TSC-100 and TSC-101, are in development for the treatment of patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and acute lymphoblastic leukemia (ALL), who are undergoing allogeneic hematopoietic cell transplantation (HCT).

The products are designed to eliminate residual disease and promote complete donor chimerism, thereby preventing relapse.

TSC-100 and TSC-101 target the antigens HA-1 and HA-2, respectively, which are well-recognized TCR targets that were first identified in patients with exceptional responses to HCT-associated immunotherapy.

We are currently conducting a multi-arm Phase 1 "umbrella" clinical study of TSC-100 and TSC-101, the ALLOHA Phase 1 heme trial, with 15 clinical sites activated, and we plan to open additional sites before the end of 2025.

In addition, we are developing multiple TCR-T therapy product candidates for the treatment of solid tumors.

One of the challenges of treating solid tumors is that they are heterogeneous – not every tumor cell expresses a given target and some tumor cells lose half their HLA genes.

To address this challenge, we are developing what we refer to as multiplex TCR-T therapy, or T-Plex, in which we treat a patient with more than one TCR-T therapy product candidate at a time.

We are designing these multiplex therapies to be a simultaneous administration of up to three highly active TCR-T therapy product candidates, selected from our ImmunoBank, that are customized for each patient based on which targets are expressed in their tumors and which HLA genes are still intact.

We continue to prioritize expanding the ImmunoBank with TCRs for additional targets and multiple HLA types for each target.

We have now advanced seven TCR-T therapy product candidates into Phase 1 development for solid tumors:

TSC-203-A0201 (PRAME, HLA-A*02:01);

TSC-200-A0201 (HPV16, HLA-A*02:01);

TSC-201-B0702 (MAGE-C2, HLA-B*07:02);

TSC-202-A0201 (MAGE-A4, HLA-A*02:01);

TSC-204-A0201 (MAGE-A1, HLA-A*02:01);

TSC-204-C0702 (MAGE-A1, HLA-C*07:02);

and TSC-204-A0101 (MAGE-A1, HLA-A*01:01).

In addition to clearing these seven solid-tumor investigational new drug (IND) applications, the U.S.

Food and Drug Administration (FDA) has cleared our IND application for T-Plex, enabling us to treat patients with multiplex TCR-T therapy.

We plan to further expand the ImmunoBank by filing IND applications for additional TCR-T therapy product candidates.

We have initiated a Phase 1 solid tumor clinical trial, the PLEXI-T trial, with 15 clinical sites activated, and we plan to open additional sites before the end of 2025.

We are a fully integrated clinical-stage biotechnology company focused on developing a robust pipeline of T cell receptor (TCR)-engineered T cell, or TCR-T, therapies for the treatment of patients with cancer.

Our lead product candidate, TSC-101, is in development for the treatment of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who are undergoing allogeneic hematopoietic cell transplantation (HCT).

The product is designed to eliminate residual disease and promote complete donor chimerism, thereby preventing relapse.

TSC-101 targets HA-2, an antigen that is present on all blood cells, malignant or benign, in patients with the HLA type A*02:01.

We are currently conducting a Phase 1 clinical study of TSC-101 (the ALLOHA trial, NCT05473910) and during the fourth quarter of 2025, following a productive End-of-Phase meeting with the U.S.

Food and Drug Administration (FDA), we reached agreement on a registrational path forward for the TSC-101 program as a potential treatment for patients with AML and MDS.

The pivotal study will mirror our ongoing Phase 1 ALLOHA study, using a biologically-assigned (genetically randomized) control arm to support relapse-free survival as the primary endpoint.

We are further expanding our hematologic (heme) malignancies program with the addition of TCRs targeting other HLA types.

TSC-102-A01 and TSC-102-A03 are allogeneic, donor-derived TCR-T therapy candidates targeting epitopes derived from CD45.

Like TSC-101, these candidates are designed to eliminate residual cancer cells and prevent relapse in patients undergoing HCT.

TSC-102-A01 and TSC-102-A03 are designed for patients with HLA types A*01:01 and A*03:01, respectively.

We are also developing multiple TCR-T therapy product candidates for the treatment of solid tumors.

One of the challenges of treating solid tumors is that they are heterogeneous – not every tumor cell expresses a given target.

To address this challenge, we are developing what we refer to as multiplex TCR-T therapy, in which we treat a patient with more than one TCR-T therapy product candidate at a time.

We are designing these multiplex therapies to be a simultaneous administration of up to three highly active TCR-Ts that are customized for each patient based on which targets are expressed in their tumors.

On November 3, 2025, following our alignment with the U.S.

Food and Drug Administration (FDA) on the registrational path forward for the TSC-101 program, we made the strategic decision to prioritize clinical development of our heme program and pause further enrollment in our solid tumor Phase 1 trial (PLEXI-T), while focusing our preclinical efforts on in vivo engineering for solid tumors.

We believe an in vivo approach represents a promising and more cost-efficient way to deliver off-the-shelf, multiplexed TCR-T therapy for solid tumors.

While primarily focused on oncology, we believe our target discovery platform is well suited to identify targets that cause T cell-driven autoimmune disorders.

We have identified a set of indications in which T cells play a key role and are currently identifying targets and developing potential treatment options for these disorders.

Initial indications include ankylosing spondylitis, ulcerative colitis and scleroderma.

In addition, the Company is continuing to discover targets for Crohn's disease in partnership with Amgen.

We have an internal good manufacturing practices, or GMP, facility to manufacture clinical supply for our TCR-T therapy product candidates.

This facility allows us to rapidly, cost-effectively, and consistently manufacture our TCR-Ts.

Our TCR-T therapy product candidates are manufactured using a non-viral transposon/transposase system.

This non-viral platform approach can be rapidly applied to new TCR-T therapy product candidates in a cost-effective manner without the need for extensive process development.

The larger cargo capacity of our non-viral vector delivery system allows us to include additional T cell enhancements in our product candidates.

In both our heme and solid tumor programs, we are introducing the gene for CD8α/β along with the TCR gene, which enables us to engineer both cytotoxic and helper T cells with our TCRs.

To provide an operationally flexible and cost-effective approach for our heme program, we have developed a manufacturing platform to genetically engineer T cells using a transposon/transposase system.

This non-viral platform can be rapidly applied to new TCR-T therapy product candidates without the need for extensive process development.

Our non-viral vector delivery system allows us to include additional T cell enhancements in our product candidates.

In our heme program, we are introducing the gene for CD8α/β along with the TCR gene, which enables us to engineer both cytotoxic and helper T cells.

We believe this enhancement has the potential to improve responses to TCR-T therapy in the clinic compared to engineering cytotoxic T cells alone.

In our solid tumor program, we are also adding a dominant-negative (DN) form of TGFβRII to our T cells, which enables them to proliferate despite the presence of TGFβ in the hostile tumor microenvironment.

This has the potential to enhance T cell persistence.

Our GMP facility has the estimated capacity to manufacture clinical trial materials for up to 250 TCR-T components per year.

To further increase our existing clinical manufacturing capacity and prepare for potential commercialization, we have engaged a global contract development and manufacturing organization, or CDMO, with worldwide commercial capabilities to support both the heme and solid tumor programs.

The CDMO is on track to add capacity and to support additional clinical manufacturing of the heme program in the second half of 2025.

T cells are an essential component of the adaptive immune system and provide protection against cancer, infection, and autoimmune disorders.

Multiple approaches have been and are continuing to be explored to develop effective T cell-based therapies for the treatment of cancer, including checkpoint inhibitor therapy, tumor infiltrating lymphocyte, or TIL, therapy, and chimeric antigen receptor (CAR) T cell, or CAR-T, therapy.

The success of checkpoint inhibitor and TIL therapy depends on the specific T-cells present in the patient.

If their T-cells do not have appropriate anti-cancer specificities, the therapy is unlikely to be effective.

In addition, TIL therapy has, to date, shown limited applicability for the treatment of heme malignancies.

In contrast, CAR-T therapy has proven effective

in certain heme malignancies of lymphoid origin but has shown only limited activity in myeloid malignancies or solid tumors.

To address a broader patient population, we believe additional T cell-based approaches are needed that more closely mimic the way the immune system recognizes and fights cancer.

The successful development of TCR-T therapy product candidates has three key prerequisites:

(i) an effective anti-cancer TCR;

(ii) knowledge of the precise peptide antigen that is recognized by the TCR;

and (iii) confirmation that the TCR does not recognize problematic off-targets.

We believe our approach provides us with the following key advantages:

• Our TCR-T therapy product candidates are based on highly active TCRs that are clinically relevant.

Many other approaches to T cell therapy rely on specifically expanding T cells that are already present in the patient.

Our platform analyzes anti-cancer T cells from a broad set of individuals, including patients responding to immunotherapy as well as healthy donors, to find the most active and clinically relevant TCRs against each target.

We believe that we can develop TCR-T therapy product candidates for a wide range of patients, including those who do not have T cells that efficiently recognize their cancers.

• Our TCR-T therapy product candidates are designed to be used in combination with each other.

We have built the ImmunoBank of TCRs to allow for multiplexed TCR-T therapy, which has the potential to address the heterogeneous nature of solid tumors and address resistance due to target or HLA loss.

We continue to expand the ImmunoBank with TCRs for additional targets as well as multiple common HLA types for each target.

• Our approach is expandable.

The ImmunoBank has the flexibility to be used with new and optimized methods of T cell engineering that we may develop over time.

We are currently employing the validated approach of patient-specific ex vivo engineering, but as the field evolves, our TCRs may be transitioned to "off-the-shelf" methods, including allogeneic T cells or in vivo engineering.

As we expand the ImmunoBank to include TCRs across additional targets and HLA types, we believe we will increase the eligible patient population for our clinical trials, which will allow for rapid and efficient clinical trial enrollment with fewer screen failures.

We are advancing a robust pipeline of TCR-T therapy product candidates for the treatment of patients with heme malignancies and solid tumors.

Our lead product candidates, TSC-100 and TSC-101, are in development for the treatment of patients with heme malignancies to eliminate residual disease and prevent relapse following HCT.

In addition, we are developing multiple TCR-T therapy product candidates for the treatment of various solid tumors.

We have developed and continue to expand the ImmunoBank with the goal of delivering customized multiplex TCR-T therapy to a wide range of patients with cancer.

Our lead product candidate, TSC-101, is a T cell receptor (TCR)-engineered T cell (TCR-T) therapy candidate in development for the treatment of patients with heme malignancies to eliminate residual disease and prevent relapse following allogeneic bone marrow transplantation (hematopoietic cell transplantation or HCT) (the ALLOHA trial, NCT05473910).

We are further expanding this program with TCRs targeting additional antigens across different HLA types, such as TSC-102-A01 and TSC-102-A03.

We are also developing multiplex TCR-T therapy candidates for the treatment of various solid tumors.

We have built a diverse collection of therapeutic TCRs that recognize cancer-specific targets and are associated with multiple human leukocyte antigen (HLA) types, to provide customized multiplex TCR-T treatments for patients with a variety of solid tumors.

We are currently engaged in preclinical development of an in vivo engineering platform to deliver off-the-shelf TCR-T therapy.

In addition, we are using our target discovery platform to identify targets that cause T cell-driven autoimmune disorders.

We have identified a set of indications in which T cells play a key role and are currently identifying targets and developing potential treatment options for these disorders.

Initial indications include ankylosing spondylitis, ulcerative colitis, and scleroderma.

Our current proprietary pipeline is summarized in the figure below.

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We have a collaboration with Amgen Inc., or Amgen, to identify the antigens recognized by T cells in patients with Crohn's disease.

Amgen will evaluate a variety of modalities to create therapeutic candidates based on targets discovered by TScan and will retain all global development and commercial rights.

With our differentiated platform as the foundation, we are building a three-pillar research and development strategy to create transformational TCR-T therapy product candidates for patients.

Our Heme Program.

We are developing TCR-T therapy product candidates to treat patients with heme malignancies, including AML, MDS, and ALL who are undergoing allogeneic HCT.

In the first phase of our clinical development strategy, we are initially focusing on clinically validated cancer targets that have been discovered in patients with exceptional responses to HCT-associated immunotherapy, including HA-1 and HA-2.

Additionally, we are planning to expand our heme program to include additional HLA types.

We have now advanced TSC-102-A0301, which targets an HLA-A*03:01-restricted epitope on CD45, into IND-enabling activities.

We are currently enrolling patients in a multi-arm Phase 1 "umbrella" clinical study with 15 clinical sites activated and additional sites planned to be opened in 2025.

The study protocol allows us to conduct clinical trials of TSC-100 and TSC-101 in parallel, with patients enrolled in treatment arms based on their genotype.

Eligible patients require donors who are negative for either the target antigen or the HLA-A*02:01 allele.

Through the development of our heme malignancies program, we have built a foundation of manufacturing, clinical, and regulatory capabilities, which we are also applying to the development of our broader portfolio of TCR-T therapy product candidates for solid tumors.

Our Solid Tumor Program .

We are developing a portfolio of autologous TCR-T therapy product candidates designed to be used in combination with each other to treat and eliminate solid tumors.

Our solid tumor product candidates are designed to elicit anti-tumor responses in patients by targeting cancer-specific antigens in their tumor cells.

Our TCR-T therapy product candidates include:

(i) well-recognized cancer targets that have demonstrated anti-tumor activity in clinical trials as well as novel targets that were identified by TargetScan from the T cells of patients responding to immunotherapy, and (ii) naturally occurring TCRs specific to a patient’s HLA type that recognize these cancer-specific targets.

Such targets are not only commonly shared among patients with the same cancer type, but also frequently expressed in multiple solid tumor types, enabling clinical development across multiple indications.

Our first seven product candidates address known and novel targets:

E7 of HPV16 for TSC-200-A0201, MAGE-C2 for TSC-201-B0702, MAGE-A4 for TSC-202-A0201, PRAME for TSC-203-A0201, and MAGE-A1 for TSC-204-A0201, TSC-204-C0702, and TSC-204-A0101.

We have built and continue to expand the ImmunoBank to enable customized multiplex TCR-T therapy for a wide range of solid tumor patients.

Our initial solid tumor indications include non-small cell lung cancer, sarcoma, head & neck cancer, cervical cancer, and anal & genital cancer.

For each patient with a solid tumor malignancy, we first analyze the patient's tumor to determine which targets are expressed at high levels and which HLA genes are still intact.

We then access the ImmunoBank and select up to three TCRs that match their HLA type and address the most highly expressed targets in their tumor.

We will use this set of TCRs to genetically reprogram their T cells to recognize these targets, and the resulting T cells will be infused back into the patient as a multiplex TCR-T therapy.

Enabled by the additional cargo capacity of our non-viral vector delivery system, we are also introducing enhancements to our product candidates to deepen tumor responses and prolong duration of response.

By introducing the gene for CD8α/β along with the TCR gene, we are able to engineer both cytotoxic and helper T cells, which we believe has the potential to improve responses to treatment with TCR-T therapy in the clinic compared to engineering cytotoxic T cells alone.

We are also adding DN-TGFβRII to T cells, which allows them to proliferate despite the presence of TGFβ in the hostile tumor microenvironment.

This has the potential to enhance T cell persistence.

Strategic Partnerships and Collaborations.

T cells play a fundamental role in many other therapeutic areas beyond cancer, such as autoimmune disorders and infectious diseases.

We believe that our TargetScan technology is well suited to discover novel antigens for the development of therapeutics, diagnostics, and vaccines in these other therapeutic areas.

We intend to opportunistically pursue collaborations with strategic partners for applications of our platform technologies outside our core focus of oncology.

Our mission is to create life-changing TCR-T therapy product candidates for patients by unleashing the untapped potential of the human immune system.

Our goal is to use our proprietary platform technologies to identify novel tumor-specific antigens and clinically active TCRs to become a leader in the development of engineered T cell therapies for the treatment of heme malignancies and solid tumors.

Amgen will evaluate a variety of modalities to create therapeutic candidates based on targets discovered by us and will retain all global development and commercial rights.

Our mission is to create life-changing T cell therapies for patients with cancer and autoimmune disorders.

Our strategy includes the following key elements:

• Advance our lead product candidates, TSC-100 and TSC-101, through clinical development.

Our two lead programs, TSC-100 and TSC-101, are designed to target HA-1 and HA-2, respectively, both of which are antigens with clinically demonstrated anti-tumor effects in patients who naturally develop T cells specific to these targets.

We are currently enrolling patients in a multi-arm Phase 1 clinical study of TSC-100 and TSC-101 with 15 clinical sites activated and additional sites planned to be added in 2025.

The study protocol allows us to conduct clinical trials of TSC-100 and TSC-101 in parallel, with patients enrolled in treatment arms based on their genotype.

In addition, through our heme malignancies program, we have established a foundation of manufacturing, clinical and regulatory capabilities to support the development of our broad portfolio of TCR-T therapy product candidates.

• Advance our solid tumor program through clinical development.

We are initially developing our solid tumor TCR-T therapy product candidates against five selected target antigens that are frequently expressed across multiple solid tumor types.

Our first seven solid tumor TCR-T therapy product candidates address known and novel targets, including E7 of HPV16 for TSC-200-A0201, MAGE-C2 for TSC-201-B0702, MAGE-A4 for TSC-202-A0201, PRAME for TSC-203-A0201, and MAGE-A1 for TSC-204-A0201, TSC-204-C0702, and TSC-204-A0101.

We believe that the treatment of solid tumors will require a combination of several therapeutic TCRs, which we refer to as 'multiplex therapy'.

We plan to expand the ImmunoBank to broaden the reach of multiplex TCR-T therapy for the treatment of solid tumors.

• Leverage our proprietary platform technologies to expand the ImmunoBank of therapeutic TCRs to treat a wide range of tumor types .

Our TargetScan technology enables us to identify novel antigens that are broadly expressed across multiple types of solid tumors.

To ensure that the antigens identified are clinically relevant, we use TCRs from tumor samples of patients with exceptional responses to immunotherapy.

Our platform allows us to assess the specificity and cytotoxicity of these TCRs to develop a portfolio of TCR-T therapy product candidates with therapeutic potential.

We continue to prioritize expanding the ImmunoBank with TCRs for additional targets as well as multiple common HLA types for each target, thus enabling us to address tumor heterogeneity and resistance that may arise from target loss or HLA loss.

• Advance our lead product candidate, TSC-101, through clinical development.

Our lead program, TSC-101, is designed to target HA-2 and we are currently enrolling patients in a Phase 1 clinical study of TSC-101 with over 20 clinical sites activated.

In addition, through our heme program, we have established a foundation of manufacturing, clinical and regulatory capabilities to support the development of our broad portfolio of TCR-T therapy product candidates.

• Advance our in vivo solid tumor program through pre-clinical development.

We are initially developing our solid tumor TCR-T therapy product candidates against three selected target antigens, HPV16, MAGE-A4, and PRAME, frequently expressed across multiple solid tumor types.

We believe that the treatment of solid tumors will require a combination of therapeutic TCRs, which we refer to as 'multiplex therapy'.

We have built a diverse collection of therapeutic TCRs that recognize cancer-specific targets, and are associated with multiple HLA types, to provide customized multiplex treatments for patients with solid tumor malignancies.

• Advance our autoimmune program through pre-clinical development.

We are leveraging our target discovery platform to identify targets that cause T cell-driven autoimmune disorders.

We have identified a set of indications in which T cells play a key role and are currently identifying targets and developing potential treatment options for these disorders.

Initial indications include ankylosing spondylitis, ulcerative colitis, and scleroderma.

• Maintain manufacturing capabilities.

We believe that in-house manufacturing capabilities substantially facilitate the successful early development of cell therapies.

For our TCR-T therapy product candidates, we have developed a non-viral gene delivery system, which we refer to as T-Integrate, based on transposons that are designed to enable cost-effective and consistent cell manufacturing with short development times.

We have built an internal, fully operational GMP manufacturing facility that we believe provides sufficient capacity to support our clinical programs in both heme malignancies and solid tumors.

Additionally, we have engaged a global CDMO with commercial capabilities to further increase manufacturing capacity for both the heme and solid tumor programs and prepare for potential commercial manufacturing.

The CDMO is on track to support clinical manufacturing of the heme program in the second half of 2025.

The additional cargo capacity of our non-viral vector delivery system allows us to add T cell enhancements to our product candidates.

By introducing the gene for CD8α/β along with the TCR gene, we are able to engineer both cytotoxic and helper T cells, which we believe has the potential to improve responses to TCR-T therapy in the clinic compared to engineering cytotoxic T cells alone.

We are also adding DN-TGFβRII to T cells, which enables them to proliferate despite the presence of TGFβ in the hostile tumor microenvironment.

This has the potential to enhance T cell persistence.

Having treated over 30 patients with six different TCR-T candidates across both heme and solid tumor malignancies, we consider our approach to be validated.

For our heme program, we have developed a non-viral gene delivery system based on transposons that are designed to enable cost-effective and consistent cell manufacturing with short development times.

We have built an internal, fully operational GMP manufacturing facility that we believe provides sufficient capacity

to support our clinical program.

Additionally, we have engaged a global CDMO with commercial capabilities to further increase manufacturing capacity for the heme program and prepare for potential commercial manufacturing.

• Develop next generation T cell engineering capabilities .

Our long-term vision is to develop off-the-shelf products, either through allogeneic T-cell engineering or in vivo engineering, and provide customized multiplex TCR-T therapy to patients with a wide range of malignancies.

Although our initial solid tumor programs are autologous, we are developing T cell engineering technologies and in-house manufacturing capabilities to transition our therapeutic TCRs to alternative modalities.

We are developing off-the-shelf product candidates through in vivo engineering with the goal of providing customized multiplex TCR-T therapy to patients with a wide range of malignancies.

We are in early stages of developing T cell engineering technologies and in-house manufacturing capabilities.

• Opportunistically pursue strategic partnerships and collaborations to maximize the full potential of our platform .

Our platform represents a powerful tool to identify targets and TCRs in therapeutic areas outside of oncology, such as autoimmune disorders and infectious diseases.

Our platform represents a powerful tool to identify targets in therapeutic areas outside of oncology, such as autoimmune disorders.

We intend to seek strategic partners with proven clinical development and commercialization capabilities for certain targets and/or assets that do not overlap with our internal programs or our core focus.

To date, we have a research collaboration and license agreement with Amgen to identify the antigens recognized by T cells in patients with Crohn’s disease.

Under the terms of the agreement, TScan received a $30.0 million upfront payment and is eligible to earn success-based milestone payments of over $500 million, based upon the achievement of certain development and commercial milestones as well as tiered single-digit royalty payments on net sales of products developed

from the collaboration.

Amgen will evaluate a variety of modalities to create therapeutics based on targets discovered by TScan and will retain all global development and commercial rights to such therapeutics.

Under the terms of the agreement, we received a $30.0 million upfront payment and is eligible to earn success-based milestone payments of over $500 million, based upon the achievement of certain development and commercial milestones as well as tiered single-digit royalty payments on net sales of products developed from the collaboration.

Amgen will evaluate a variety of modalities to create therapeutics based on targets discovered by us and will retain all global development and commercial rights to such therapeutics.

We have also expanded our target discovery capabilities to include both CD8+ and CD4+ T-cells by engineering our platform to include class II antigen presentation.

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Building on the Remarkable Success of Immunotherapy

The development of TCR-T therapy product candidates requires three key prerequisites:

(i) an effective anti-cancer TCR;

(ii) knowledge of the precise peptide antigen that is recognized by the TCR;

and (iii) confirmation that the TCR does not recognize problematic off-targets.

Each of these prerequisites is technically challenging.

Historically, targets of anti-cancer T cell clones were identified through a manual and labor-intensive process, and the identification of each target was often a multi-year project.

As a result, only a few dozen targets have been identified to date and most clinical development efforts are focused on a short list of the most promising targets.

Two key shortcomings in the TCR field remain:

low response rates and limited duration of response.

These are in part related to solid tumors being heterogenous, and to poor persistence of engineered T cells in patients.

We believe we can overcome these known issues by adding enhancements to our product candidates, such as the addition of CD8α/β to improve persistence compared to CD8α alone.

We are also co-introducing DN-TGFβRII, which is designed to overcome immunosuppression from TGFβ in the tumor microenvironment.

Our approach is based on the central premise that we can learn from patients who are winning their fight against cancer in order to treat those who are not.

Using our proprietary platform technologies, we are analyzing the T cells of cancer patients with exceptional responses to immunotherapy to discover clinically relevant targets and TCRs.

We have built and are expanding the ImmunoBank with the goal of delivering customized multiplex TCR-T therapy to a wide range of patients with cancers.

Our discovery process enables us to build and expand the ImmunoBank with what we believe represents the most active TCRs isolated from a large group of diverse patients who are responding to immunotherapy.

We are developing TCR-T therapy product candidates that use these clinically relevant TCRs to reprogram the T cells of patients who do not spontaneously generate effective anti-cancer T cells and thus do not respond to immunotherapy.

Such patients will first have their tumors undergo HLA typing and testing for the presence of tumor-specific targets.

Next, to manufacture engineered T cells, white blood cells will be obtained from either the patient or a healthy donor using a procedure called leukapheresis.

We will then transport these white blood cells to our in-house manufacturing facility, where we isolate the T cells and genetically engineer them using TCR sequences from the ImmunoBank.

We believe the continued expansion and diversification of the ImmunoBank will enable us to deliver customized multiplexed TCR-T therapies to more

patients, where each patient’s T cells are engineered with multiple TCRs that are matched to their specific tumor and HLA type.

For example, if a patient’s tumor expresses high levels of a particular cancer target, their T cells will be reprogrammed with a TCR that recognizes that particular cancer target.

The FDA's clearance of our T-Plex IND application for the simultaneous administration of different TCRs, as well as secondary IND applications for the first seven TCRs in our solid tumor program, allows us to rapidly and efficiently expand the ImmunoBank and enables us to work toward our goal of bringing customized, multiplex therapies to patients.

Once the T cells are engineered with a combination of the most relevant TCRs, they will be transported back to the treatment facility and reintroduced into the patient by intravenous infusion.

Following the infusion, the engineered T cells, which are designed to recognize multiple targets expressed by the patient’s tumor, will proliferate in vivo and mount an anti-cancer immune response.

Key Features of Our Approach

We believe there are three key advantages to our approach:

• Our TCR-T therapy product candidates are based on highly active TCRs that are clinically relevant.

Many other approaches to T cell therapy rely on specifically expanding T cells that are already present in the patient.

Our platform analyzes anti-cancer T cells from a wide variety of patients who are responding to immunotherapy in order to find the most active and clinically relevant TCRs against each target.

We believe that we can develop TCR-T therapy product candidates for a wide range of patients, including those who do not have T cells that efficiently recognize their cancers.

• Our TCR-T therapy product candidates are designed to be used in combination with each other.

We have built and are expanding the ImmunoBank of TCRs to allow for multiplex TCR-T therapy, which has the potential to address the heterogeneous nature of solid tumors and address resistance developing due to loss of a single target.

We believe this approach may allow us to overcome the limitations and challenges of TCR-T development to date.

As the ImmunoBank is populated with more TCRs, we expect that patient eligibility will expand, as will our target market opportunities.

• Our approach is expandable.

The ImmunoBank has the flexibility to be used with new and optimized methods of T cell engineering that we may develop over time.

We have built the ImmunoBank to be compatible with both autologous and allogeneic engineering technologies in order to potentially transition to generating off-the-shelf, allogeneic T cells that have been pre-engineered with our TCRs for direct administration to patients.

Our Heme Malignancies Program

We are developing our heme malignancies program to treat patients with AML, MDS, or ALL who are undergoing allogeneic HCT.

In the first phase of our clinical development strategy, we are initially focusing on well-recognized cancer targets that have been discovered in patients with exceptional responses to HCT-associated immunotherapy, including HA-1 and HA-2.

Our program is based on the well-established observation that patients who are mismatched with their donors for minor histocompatibility antigens, or miHAs, such as HA-1 or HA-2, and naturally mount a T cell response against those antigens, show significantly lower relapse rates following HCT.

By developing TSC-100 and TSC-101, TScan aims to recreate this natural graft versus leukemia response to prevent relapse in patients undergoing HCT.

We plan to further expand this program with the addition of TCRs targeting additional antigens across different HLA types.

For example, TSC-102-A0301, a TCR-T therapy product candidate targeting an HLA-A*03:01-restricted epitope on CD45, is currently in IND-enabling activities.

Minor histocompatibility antigens like HA-1 and HA-2, and lineage-specific antigens like CD45, are distinct from other cancer-associated antigens such as WT1 previously targeted by TCR-Ts in heme malignancies.

We are developing our heme program for patients with hematologic malignancies undergoing allogeneic HCT.

In the first phase of our clinical development strategy, we are initially focusing on HA-2, an antigen found on the blood cells of patients who are HLA-A*02:01 positive.

Our program is based on the well-established observation that patients who are mismatched with their donors for patient-specific antigens, such as HA-2, and mount a T cell response against those antigens, show significantly lower relapse rates following HCT.

By developing TSC-101, we aim to recreate this natural graft versus leukemia response to prevent relapse in patients undergoing HCT.

We are further expanding this program with the addition of TCRs targeting additional antigens across different HLA types.

For example, TSC-102-A01 and TSC-102-A03, TCR-T therapy product candidates targeting CD45 in patients who are HLA-A*01:01- and HLA-A*03:01-positive, respectively.

Antigens like HA-2 and CD45 are distinct from other cancer-associated antigens such as WT1 previously targeted by TCR-Ts in heme malignancies.

As shown below, cancer-associated antigens like WT1 have low and heterogenous expression and were previously selected so that normal blood cells in the patient would be spared.

WT1-targeted TCR-Ts proved to have relatively poor efficacy in patients with ALL and AML, potentially due to the rapid emergence of resistant tumor cells that lacked WT1 expression and thus escaped killing by engineered T cells.

HA-1, HA-2, and CD45, in contrast, have high and homogenous expression, making it less likely for tumors cells to escape due to low antigen expression.

Although HA-1, HA-2, and CD45 are also expressed in normal blood cells, treating patients who are positive for these antigens, but have undergone hematopoietic cell transplantation from donors who are negative, ensures that the engineered T cells selectively eliminate all the patient’s blood cells – malignant, pre-malignant, or normal – while sparing donor-derived normal blood cells.

This strategy therefore enables high levels of anti-cancer efficacy with what we believe to be less risk of life-threatening toxicities to normal cells.

We are conducting a Phase 1 clinical trial of our lead TCR-T therapy product candidates, TSC-100 and TSC-101, in parallel, with patients enrolled in treatment arms based on their genotype, as shown below.

Patients who are positive for the target antigen, HA-1 or HA-2, as well as the HLA-A*02:01 allele, which is the HLA type required to display HA-1 and HA-2 on the cell surface for recognition by a T cell, are eligible for enrollment, provided they are paired with donors who are negative for either the target antigen or the HLA-A*02:01 allele.

ALLOHA, a Multi-arm Phase 1 Trial for TSC-100 and TSC-101 in Subjects with AML, ALL, and MDS

HA-2 and CD45, in contrast, have high and homogenous expression, making it less likely for tumors cells to escape due to low antigen expression.

Although HA-2 and CD45 are also expressed in normal blood cells, treating patients who are positive for the HLA types that present these antigens with HCT donors who are negative for those HLA types ensures that the engineered T cells selectively eliminate the patient’s blood cells – malignant, pre-malignant, or normal – while sparing the healthy donor-derived normal blood cells.

This strategy enables high levels of anti-cancer efficacy with potentially less risk of life-threatening toxicities to other cells in the body.

We are conducting a Phase 1 clinical trial of our lead TCR-T therapy product candidate, TSC-101, with patients enrolled in the treatment arm based on their genotype, as shown below.

Patients who are positive for the target antigen, HA-2, as well as the HLA-A*02:01 allele (the HLA type required to display HA-2 on the cell surface for recognition by a T cell) are eligible for enrollment, provided they are paired with a donor who is negative for the HLA-A*02:01 allele.

ALLOHA, a Phase 1 Trial Evaluating TSC-101 in Patients Undergoing Allo-HCT

Background on Heme Malignancies

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This regimen is intended to kill both the patient’s leukemia cells as well as their native blood cells and blood cell precursors, including hematopoietic stem cells in their bone marrow.

The patient then receives hematopoietic stem cells from an HLA-matched donor.

The patient then receives hematopoietic stem cells from an appropriately-matched donor.

The stem cells engraft in their bone marrow and start to repopulate their body with new blood cells, which are now genetically identical to the donor.

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Approximately 5,600 allogeneic HCT procedures are performed yearly in the U.S.

in patients with AML, MDS, or ALL.

As a curative therapy for many heme malignancies, use of HCT has been steadily increasing over the last two decades, with increased use driven largely by increasing donor qualification, an increase in disease prevalence due to aging populations, and improved conditioning regimens permitting broader use in older and frailer patient segments.

in patients with AML and MDS.

As a curative therapy for many heme malignancies, use of HCT has been steadily increasing over the last two decades, with increased use driven largely by increasing donor qualification, an increase in disease prevalence due to aging populations, and alternative conditioning regimens permitting broader use in patients, including older and frailer patient segments.

In addition, newer, more effective leukemia therapies continue to drive an increasing use of HCT in patients who previously failed to achieve proper remission prior to transplant.

While the approval of CAR-T therapies has significantly impacted the treatment of B cell malignancies over the last decade, HCT in non-B cell malignancies is anticipated to remain the standard of care for patients.

An example of the limitations associated with CAR-T therapy is the difficulty differentiating tumor from normal cells as seen with CD19-targeted CAR-T therapies.

CD19 is a target highly expressed on the surface of tumor cells, as well as normal B cells, which are also eliminated by CD19 targeted CAR-T cells.

While loss of B cells does not generally lead to serious complications, toxicity on other normal myeloid blood cell types such as neutrophils would cause a life-threatening complication called febrile neutropenia in which bacterial infections occur due to the loss of neutrophils.

This is one reason why CAR-T therapies cannot be used in non-B cell heme malignancies such as myeloid leukemias and HCT remains the standard of care for those patients.

However, despite the increasing use of HCT and the resulting clinical benefits or cures, approximately 40% of the patients who receive HCT relapse within two years, at which point there are limited treatment options, and the prognosis is very poor.

Clinical observations have shown that if the T cells of the donor recognize certain miHAs in the patient’s leukemia cells, such as proteins that have single amino acid differences between the patient and the donor, the T cells of the donor drive a specific graft vs.

However, despite the increasing use of HCT, there are limited treatment options for patients who relapse post-HCT, and the prognosis is very poor.

Clinical observations have shown that if the T cells of the donor recognize certain antigens in the patient’s leukemia cells, but not the donor's blood cells, the T cells of the donor drive a specific graft vs.

leukemia, or GvL, effect, whereby the engrafted donor T cells detect remaining leukemia as foreign and eliminate the remaining disease.

the patient often experiences a long-term remission from their cancer, or even a complete cure.

If the miHAs are also expressed in non-hematopoietic tissues, the patient may develop graft vs.

host disease, or GvHD, but if the miHAs are only expressed in blood cells, a specific GvL effect is observed without an increase in GvHD.

Our heme malignancies program is focused on targeting miHAs that are exclusively expressed in hematopoietic cells in order to induce the GvL effect while potentially mitigating the risk of GvHD.

TSC-100 is an allogeneic, donor derived TCR-T therapy product candidate directed at eliminating all native blood cells, including residual cancer cells, in HA-1-positive and HLA-A*02:01-positive patients with heme malignancies who undergo HCT using a donor who is either HA-1-negative or HLA-A*02:01-negative.

We selected this product candidate based on its superior affinity, cytotoxic activity, and specificity compared to the other potential candidates.

TSC-100 is designed to elicit an anti-tumor response in patients by targeting HA-1, which is present on malignant and normal blood cells of HA-1-positive patients but not on any of the new, donor-derived blood cells they receive from a donor who is either HA-1-negative or HLA-A*02:01-negative.

We believe that donor T cells specifically engineered to express this TCR will generate an anti-tumor effect in patients, leading to a reduction in relapse rates and an increase in long-term survival.

HA-1 was one of the first miHAs to be discovered in a patient undergoing HCT.

HA-1 is a peptide antigen derived from the protein ARHGAP45, which is an intracellular protein expressed at high levels in all blood cells but not in any other tissue.

ARHGAP45 comes in two forms.

In HA-1-positive individuals, the peptide has the sequence VL H DDLLEA and, if the individual has the HLA type A*02:01, the antigen is efficiently displayed on the surface of blood cells.

In HA-1-negative individuals, the peptide has the sequence VL R DDLLEA, and the HA-1 antigen is not displayed.

Approximately 60% of people have the VL H DDLLEA sequence and approximately 42% of people in the U.S.

have the HLA type A*02:01, which means that approximately 25% of individuals in the U.S.

are HA-1-positive with the specific HLA type required for antigen expression.

Studies of patients receiving HCT have shown that in cases where the T cells of an HA-1-negative donor naturally develop a response to HA-1 in an HA-1-positive patient, the T cells mediate a specific GvL effect, and the patient often experiences a long-term remission.

TSC-100 is based on this clinical observation and is designed to specifically cause this GvL effect in patients receiving HCT.

We are developing TSC-100 as a treatment for patients with cancer who are HA-1-positive and have been deemed eligible for HCT.

For each patient, a healthy donor who is HA-1-negative or HLA-A*02:01-negative will be identified.

Hematopoietic stem cells isolated from that donor will be used as the source of transplant material.

In parallel, T cells isolated from the same donor will be genetically engineered to recognize HA-1.

Once engraftment of donor stem cells is established in the patient, TSC-100 will be infused into the patient with the goal of eliciting a highly specific anti-tumor effect.

The engineered donor T cells are designed to recognize and eliminate all of the patient’s native blood cells, including residual leukemia cells, which are HA-1-positive, thereby preventing relapse and potentially promoting complete cures.

Because the patient’s new healthy blood cells are derived from the donor and are therefore either HA-1-negative or HLA-A*02:01-negative, we believe that TSC-100 should have minimal toxic side effects.

Because people inherit two copies of every chromosome, one from their mother and one from their father, everyone has two copies of the ARHGAP45 gene.

HA-1-positive patients can therefore be either homozygous for HA-1 (+/+), with both genes encoding the HA-1-positive peptide (VL H DDLLEA), or heterozygous for HA-1 (+/-), with one gene encoding the HA-1-positive peptide and the other encoding the HA-1-negative peptide (VL R DDLLEA).

To ensure that TSC-100 can effectively eliminate healthy blood cells and leukemia cells that are either homozygous HA-1-positive (+/+) or heterozygous HA-1-positive (+/-), we assessed the activity of TSC-100 against blood cells derived from a variety of healthy donors and patients with AML and ALL.

Like TSC-100, TSC-101 is an allogeneic, donor derived TCR-T therapy product candidate directed at eliminating residual cancer cells in HA-2-positive and HLA-A*02:01-positive patients with heme malignancies who undergo HCT using a donor who is either HA-2-negative or HLA-A*02:01-negative.

HA-2, which is derived from the protein MYO1G, is another miHA that has been identified to be clinically relevant.

In patients who naturally develop HA-2-specific T cells, a GvL effect has been observed and these patients experience long-term remissions.

We are developing TSC-101 based on a highly active TCR we discovered that recognizes HA-2.

Unlike HA-1, the HA-2 antigen is highly prevalent, with approximately 95% of individuals in the U.S.

As a result, the patient often experiences a long-term remission from their cancer, or even a complete cure.

If the antigens are also expressed in non-hematopoietic tissues, the patient may develop graft vs.

host disease, or GvHD, but if the antigens are only expressed in blood cells, a specific GvL effect is observed without an increase in GvHD.

Our heme malignancies program is focused on targeting patient-specific antigens that are exclusively expressed in hematopoietic cells in order to induce the GvL effect while potentially mitigating the risk of GvHD.

TSC-101 is an allogeneic, donor derived TCR-T therapy product candidate directed at eliminating residual cancer cells in HA-2-positive and HLA-A*02:01-positive patients with heme malignancies who undergo HCT.

The treatment includes selecting a donor who is HLA-A*02:01-negative.

TSC-101 targets HA-2, which is an antigen derived from the protein MYO1G, and was selected as a product candidate based on its superior affinity, cytotoxic activity, and specificity compared to other potential TCR-T cell candidates we discovered.

The HA-2 antigen is highly prevalent, with approximately 95% of individuals in the U.S.

being HA-2-positive.

However, as with HA-1, a specific HLA type, HLA-A*02:01, which is present in approximately 42% of individuals in the U.S., is required to display the HA-2 antigen on the cell surface for recognition by a T cell.

As a result, approximately 40% of HCT patients would be positive for both HA-2 and HLA-A*02:01 and therefore be eligible for treatment with TSC-101 using a donor who is negative for HLA-A*02:01, regardless of whether the donor is HA-2-positive or HA-2-negative.

Such donors are straightforward to identify and should be available to most patients who undergo half-matched, or haploidentical, transplantation using family members as donors, as

patients typically have between two and three potential haploidentical donors.

However, a specific HLA type, HLA-A*02:01, which is present in approximately 42% of individuals in the U.S., is required to display the HA-2 antigen on the cell surface for recognition by a T cell.

As a result, approximately 40% of HCT patients would be positive for both HA-2 and HLA-A*02:01 and therefore be eligible for treatment with TSC-101 using a donor who is negative for HLA-A*02:01.

Such donors are straightforward to identify and should be available to most patients who undergo half-matched (haploidentical) from a family member or mismatched unrelated donors (MMUD) identified through donor registries such as the National Marrow Donor Program (NMDP).

A summary of the treatment paradigm for TSC-101 is shown below.

Patient Journey for TSC-101

TSC-102-A0301

Like TSC-100 and TSC-101, TSC-102-A0301 is an allogeneic, donor derived TCR-T therapy product candidate directed at eliminating residual cancer cells in patients with heme malignancies who are HLA-A*03:01-positive undergoing HCT using a donor who is HLA-A*03:01-negative.

TSC-102-A01 and TSC-102-A03

Like TSC-101, TSC-102-A01 and TSC-102-A03 are allogeneic, donor derived TCR-T therapy product candidates directed at eliminating residual cancer cells in patients with heme malignancies who are HLA-A*01:01- and HLA-A*03:01-positive, respectively, undergoing HCT using a donor who is negative for the HLA type.

CD45, which is derived from the protein PTPRC, is an antigen that has been identified to be clinically relevant.

For example, radiolabeled CD45 is in clinical trials for relapsed AML, and a CAR-T product candidate targeting CD45 with epitope-edited HSCs is in pre-clinical development.

We are developing TSC-102-A0301 based on a highly active TCR we discovered that recognizes a CD45 antigen presented on HLA-A*03:01.

TSC-102-A0301 is currently in IND-enabling activities.

We are developing TSC-102-A01 and TSC-102-A03 based on highly active TCRs we discovered that recognize a CD45 antigen presented on HLA-A*01:01 and HLA-A*03:01, respectively.

The FDA has cleared our IND applications for both TSC-102-A01 and TSC-102-A03, allowing us to initiate study start-up activities.

The CD45 antigen is expressed on all nucleated cells of hematopoietic origin.

As with TSC-100 and TSC-101, a specific HLA type, HLA-A*03:01, which is present in approximately 22% individuals in the U.S.

is required to display the CD45 antigen on the cell surface for recognition by TSC-102-A0301.

HLA-A*03:01 negative donors are straightforward to identify and should be available to most patients who undergo HLA half-matched, or haploidentical, transplantation using family members as donors.

HLA-A*03:01 negative donors can also be mismatched unrelated donors readily identified through donor registries such as the National Marrow Donor Program.

Having such donor options thus enables virtually all HLA-A*03:01 positive patients to potentially qualify for treatment with TSC-102-A0301.

As with TSC-101, a specific HLA type is required to display the CD45 antigen on the cell surface.

Donors who are negative for the HLA type are straightforward to identify and should be available to most patients who undergo HCT with haploidentical family members or MMUD identified through donor registries such as the NMDP.

Clinical Development Plan for Our Heme Malignancies Program

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and worldwide.

The use of haplo greatly expands the donor pool for patients undergoing HCT and provides patients with the optionality to choose donors who are mismatched on specific HLA types, such as A*02:01, as opposed to being mismatched on certain minor antigens, such as HA-1 or HA-2.

We are developing our product candidates with a specific focus on patients undergoing haplo donor transplantation with donors who are negative for either the miHA or the specific HLA type.

We believe the engineered donor T cells will recognize any residual leukemia cells, which are target-positive, in the patient and prevent relapse with the potential to promote complete cures.

Because the patient’s new healthy blood cells are derived from the donor and are therefore either target-negative or not able to express the target, we expect that these product candidates should have minimal toxic side effects.

Another recent advance is the recognition that transplants from 1-2 HLA mismatched unrelated donors (MMUD) have equivalent outcomes as fully HLA-matched MUD transplants when PTCy is used to prevent GvHD.

The increasing use of alternative donors, such as MMUD and haplo donors for allo-transplants has not only greatly expanded donor availability, thereby enabling more patients to undergo transplant, but also makes it straightforward to identify donors negative for the HLA-A*02:01, HLA-A*01:01, or HLA-A*03:01 so that patients with those HLA-types could be treated with TSC-101, TSC-102-A01, or TSC-102-A03, respectively.

Phase 1 Clinical Trial

The clinical studies for TSC-100 and TSC-101 are well underway, within a multi-arm, controlled, Phase 1, "umbrella" design clinical trial to investigate the safety and efficacy of TSC-100 and TSC-101 in patients with AML, MDS, and ALL that are undergoing HCT following RIC.

We are currently treating patients at the third and final dose level.

The clinical study for TSC-101 is well underway, within a Phase 1 clinical trial to investigate the safety and efficacy of TSC-101 in patients with AML, MDS, and ALL that are undergoing HCT following RIC.

We are currently treating patients using a fixed dosing regimen (as compared to weight-based dosing) manufactured using our commercial-ready manufacturing process.

Our Phase 1 clinical trial is designed to include measurements of early surrogate markers of efficacy, such as donor chimerism, or the percentage of blood cells that are donor-derived, and whether patients continue to have detectable residual leukemia, referred to as minimal residual disease, or MRD, in their post-transplant bone marrow biopsy, both of which are predictors of relapse.

As shown in the graphic below, we are also including a control arm, comprising patients who do not meet the HLA or miHA genetic criteria and are treated with standard RIC haplo transplantation alone.

Comparisons of both safety and efficacy outcomes with this control arm will potentially enable all patients treated with TSC-100 or TSC-101 to be included as part of the efficacy analysis for the initial Phase 1 trial prior to transitioning the program into a registrational trial towards a potential future biologics license application, or BLA, filing.

Multi-Arm Phase 1 Clinical Trial Design

We also included a genetically randomized control arm, comprising patients who do not meet the HLA or HA-2 genetic criteria and are treated with standard RIC-HCT alone.

Comparisons of both safety and efficacy outcomes with this control arm will support transitioning the program to include a registrational trial required for a potential future biologics license application, or BLA, filing.

Clinical data

In December 2024 we reported updated results from the ongoing Phase 1 ALLOHA trial, which we presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition.

At that time, 38 patients had been enrolled in the trial and undergone HCT, with 26 in the treatment arm and 12 in the control arm.

In December 2025, we reported updated results, dated as of September 19, 2025, from the ongoing ALLOHA Phase 1 trial, which we presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition.

In that presentation, we reported that 42 patients had been enrolled in the trial and undergone HCT, with 23 in the TSC-101 treatment arm and 19 in the control arm.

The key endpoints in the trial are safety and efficacy, with exploratory endpoints of donor chimerism and MRD.

As shown below, event-free survival favored the treatment arm (HR=0.30;

P=0.04) and early trends suggested a lower probability of relapse (HR=0.28;

As of the latest data cut (December 2, 2024, shown below), 2 of 26 (8%) of treatment-arm patients relapsed compared to 4 of 12 (33%) control-arm patients.

One treatment-arm relapse and subsequent mortality occurred in a very high-risk patient who was taken to transplant without first achieving complete remission, and the other was an extramedullary relapse in the patient's central nervous system with no evidence of systemic relapse.

Median time to relapse was not evaluable in the treatment-arm versus 160 days in the control arm.

Eight of 38 (21%) patients in the study had TP53 mutations, with 6 cases in the treatment-arm and 2 cases in the control arm.

Of the 4 patients in the treatment arm with these mutations who received TCR-T cell infusions, none has relapsed, and one patient has now been relapse-free for 22 months.

Of the two patients in the control arm with mutated TP53, both relapsed within 6 months of transplant and died shortly thereafter.

TSC-100 and TSC-101 infusions were generally well-tolerated at all three dose levels with no dose-limiting toxicities.

As of the September 19, 2025 data cut, we have observed durable responses with 3 of 3 (100%) of patients 2-years post-HCT showing no evidence of disease, versus 1 of 4 (25%) in the control arm.

In the treatment arm, 4 of 19 (21%) evaluable patients relapsed compared to 6 of 18 (33%) evaluable control-arm patients.

Eight of 37 (22%) patients had TP53 mutations, with 6 cases in the treatment arm and 2 cases in the control arm.

Of the 6 patients in the treatment arm, only 1 has relapsed.

Both patients with TP53 mutations in the control arm have relapsed and subsequently succumbed to their disease.

The first patient with a TP53 mutation to receive TSC-101 has now reached two years of follow-up and remains relapse-free.

Relapse-free survival (HR=0.50;

p=0.23) and overall survival (HR=0.61;

p=0.52) favored the treatment arm.

TSC-101 infusions were generally well-tolerated at all three dose levels with no dose-limiting toxicities.

Observed adverse events were similar across the treatment and control arms and were generally consistent with post-HCT adverse events.

TSC-100 and TSC-101 TCR-T cells were detected at all time points in all treated patients, including those who have been on study for over a year, with clear evidence of a dose-persistence relationship (shown below).

Mixed chimerism or relapses following TSC-101 infusions were found to be significantly associated with greater ex vivo expansion of TCR-T cells during the manufacturing process.

A new commercial-ready process reduces the manufacturing time from 17 days to 12 days and has shown promising significant reduction in ex vivo expansion.

Anticipated timeline

We have now successfully manufactured our product candidates and dosed patients in both treatment arms of the Phase 1 clinical trial.

Patients have been enrolled up to the third dose level in both treatment arms with no dose limiting toxicities thus far, suggesting that the third dose level will likely become the recommended Phase 2 dose.

We have opened expansion cohorts at dose level 3 to further characterize safety and evaluate translational and efficacy endpoints.

We plan to continue development of TSC-101 only, as TSC-101 enables treatment of ~98% of patients with the HLA type A*02:01.

We expect to initiate a registrational trial for TSC-101, pending further feedback from regulatory authorities, in the second half of 2025.

We plan to present additional data from the Phase 1 trial by the end of the year, including two-year relapse data on the initial patients.

We also plan to file an IND application for TSC-102-A0301, a TCR-T therapy product candidate targeting an HLA-A*03:01-restricted epitope on CD45, in the second half of 2025.

In our Phase 1 clinical trial, we have now completed enrollment in Cohort C, where at least 10 patients will be treated with our commercial-ready manufacturing process at the highest dose level.

We intend to share early data on these patients and subsequently initiate a registrational trial for TSC-101 using the commercial-ready manufacturing process, pending further feedback from regulatory authorities, in the second quarter of 2026.

To expand our heme program, we recently filed investigational new drug (IND) applications with the U.S.

Food and Drug Administration (FDA) for TSC-102-A01 and TSC-102-A03, TCR-T therapy product candidates targeting CD45 in patients who are HLA-A*01:01- and HLA-A*03:01-positive, respectively.

The FDA has cleared our IND applications for TSC-102-A01 and TSC-102-A03, allowing us to initiate study start-up activities.

We plan to initiate a Phase 1 study for both TSC-102 candidates in the second half of 2026.

Future market expansion opportunities

If TSC-100 and TSC-101 demonstrate the ability to significantly reduce relapse rates after HCT, there could potentially be new opportunities to expand the curative potential of HCT combined with TSC products to greater numbers of patients.

Currently, only about 7,350 patients with AML, MDS, or ALL undergo HCT per year in the U.S.

If TSC-101 demonstrates the ability to significantly reduce relapse rates after HCT, there could potentially be new opportunities to expand the curative potential of HCT combined with TSC products to greater numbers of patients.

Currently, only about 5,600 patients with AML and MDS undergo allogeneic HCT per year in the U.S.

out of approximately 35,000 patients diagnosed each year.

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First, only patients who achieve a clinical complete remission (CR) are referred for HCT since the relapse rates of patients not in CR are considered too high to effectively use HCT.

If HCT, combined with either TSC-100 or TSC-101, markedly reduces relapse rates, patients who do not achieve CR could possibly undergo HCT and benefit from its curative potential.

If HCT, combined with TSC-101, markedly reduces relapse rates, patients who do not achieve CR could possibly undergo HCT and benefit from its curative potential.

This market expansion would require a separate clinical trial.

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This is because the conditioning regimen of HCT is considered the primary modality for eliminating residual leukemia cells and reducing doses further would result in greater relapse rates.

If the relapse rates could be reduced by treatment with either TSC-100 or TSC-101 post HCT, however, a clinical trial could test the use of minimal intensity conditioning prior to HCT.

If successful, this would further expand the curative potential of HCT combined with TSC-100 or TSC-101 therapy to older, frailer patients.

We could also expand the addressable market through the addition of TCRs for other HLA types, of which TSC-102-A0301 is an example of this approach.

A final market expansion opportunity could occur from the use of either TSC-100 or TSC-101 as a chemotherapy and radiation-free conditioning regimen for non-malignant diseases such as sickle cell anemia which are currently treated with HCT.

Since chemotherapy and radiation are associated with the risk of long-term toxicities such as cancer, heart damage, lung damage and infertility, cellular therapies such as TSC-100 or TSC-101 could reduce those risks and increase the numbers of patients willing to undergo HCT for non-malignant diseases.

Solid Tumor Program

We are developing a portfolio of autologous TCR-T therapy product candidates designed to be used in combination with each other to treat and eliminate solid tumors.

If the relapse rates could be reduced by treatment with TSC-101 post HCT, however, a clinical trial could test the use of minimal intensity conditioning prior to HCT.

If successful, this would further expand the curative potential of HCT combined with TSC-101 therapy to older, frailer patients.

We could also expand the addressable market through the addition of TCRs for other HLA types, of which TSC-102-A01 and TSC-102-A03 are examples of this approach.

A final market expansion opportunity could occur from the use of TSC-101 as a chemotherapy and radiation-free conditioning regimen for non-malignant diseases such as sickle cell anemia which are currently treated with HCT.

Since chemotherapy and radiation are associated with the risk of long-term toxicities such as cancer, heart damage, lung damage and infertility, cellular therapies such as TSC-101 could reduce those risks and increase the numbers of patients willing to undergo HCT for non-malignant diseases.

Our Solid Tumor Program

We are developing a portfolio of TCR-T therapy product candidates designed to be used in combination with each other to treat and eliminate solid tumors.

Our solid tumor product candidates are designed to elicit an anti-tumor response in patients by targeting cancer-specific antigens in their tumor cells.

Our TCR-T therapy product candidates include:

(i) well-recognized cancer targets that have demonstrated anti-tumor activity in clinical trials as well as novel targets that were identified by TargetScan from the T cells of patients responding to immunotherapy and (ii) naturally occurring TCRs specific to a patient’s HLA type that recognize these cancer-specific targets.

(i) well-recognized cancer targets that have demonstrated anti-tumor activity in clinical trials as well as novel targets that were identified by our target discovery platform from the T cells of patients responding to immunotherapy and (ii) naturally occurring TCRs specific to a patient’s HLA type that recognize these cancer-specific targets.

Our seven solid tumor TCR-T therapy product candidates address known and novel targets, including HPV16 for TSC-200-A0201, MAGE-C2 for TSC-201-B0702, MAGE-A4 for TSC-202-A0201, PRAME for TSC-203-A0201, and MAGE-A1 for TSC-204-A0201, TSC-204-C0702, and TSC-204-A0101.

To date, we have received FDA clearance for eight INDs for the treatment of solid tumors.

These include a primary IND for the entire solid tumor program, which we refer to as T-Plex, which supports the simultaneous use of multiple TCRs to create customized multiplex TCR-T therapy product candidates based on target and HLA expression.

The FDA has also cleared INDs for TSC-203-A0201 (PRAME, HLA-A*02:01);

TSC-200-A0201 (HPV16, HLA-A*02:01);

TSC-201-B0702 (MAGE-C2, HLA-B*07:02);

TSC-202-A0201 (MAGE-A4, HLA-A*02:01);

TSC-204-A0201 (MAGE-A1, HLA-A*02:01);

TSC-204-C0702 (MAGE-A1, HLA-C*07:02);

and TSC-204-A0101 (MAGE-A1, HLA-A*01:01).

We plan to further expand the ImmunoBank by filing INDs for additional TCRs.

We have built the ImmunoBank, a repository of highly active TCRs, to enable multiplex TCR-T therapy.

We are expanding the ImmunoBank with additional TCRs that recognize diverse targets and are associated with multiple HLA types to provide a broad array of therapeutic options for patients with various types of solid tumors.

For patients with a solid tumor malignancy, we analyze their tumor to determine which targets are expressed at high levels in their cancer.

We then access the ImmunoBank and select up to three TCRs that match their HLA type and address the most highly expressed targets in their tumor.

We use this set of TCRs to genetically reprogram their T cells to recognize these targets and the resulting engineered T cells are infused back into the patient simultaneously as a multiplex TCR-T therapy.

We Are Building the ImmunoBank of TCRs to Enable Multiplex TCR-T Therapy

Initial targets of interest include HPV16, MAGE-A4, and PRAME.

We have built a diverse collection of therapeutic TCRs that recognize cancer-specific targets to enable multiplex TCR-T therapy for patients with various types of solid tumors.

We are currently engaged in preclinical development of an in vivo engineering platform to deliver off-the-shelf TCR-T therapy.

TCR-T Therapy Product Candidates for the Treatment of Solid Tumors

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Despite their efficacy in only a subset of patients, checkpoint inhibitors have annual sales of about $34 billion in the U.S.

One reason why patients do not respond to current immunotherapy treatments is that they lack T cells with highly active TCRs that recognize cancer-specific antigens in their tumors.

By reprogramming the patient’s own T cells to recognize these targets, we believe that we can expand the dramatic responses observed with checkpoint inhibitor therapy to the patients for whom these therapies are ineffective.

Our solid tumor program is designed to overcome key solid tumor resistance mechanisms of target loss and HLA loss.

Solid tumors are notoriously heterogeneous, with a solid tumor often expressing more than one target antigen.

We believe that by targeting multiple antigens expressed on in-tact HLAs, we will be able to drive deep and durable responses.

We continue to prioritize expanding the ImmunoBank with TCRs across different targets and HLA types to potentially enable customized multiplex TCR-T therapy.

Our Solid Tumor Product Candidates

Our seven clinical-stage solid tumor TCR-T therapy product candidates address known and novel targets, including E7 of HPV16 for TSC-200-A0201, MAGE-C2 for TSC-201-B0702, MAGE-A4 for TSC-202-A0201, PRAME for TSC-203-A0201, and MAGE-A1 for TSC-204-A0201, TSC-204-C0702, and TSC-204-A0101.

All of these targets are frequently expressed in the solid tumors of interest to us, including NSCLC, sarcoma, head and neck cancer, cervical cancer, and anal and genital cancer.

In 2024, it is estimated that in the U.S., approximately 190,000 patients were diagnosed with NSCLC, 14,000 with sarcoma, 58,000 with head and neck cancer, 14,000 with cervical cancer, and 28,000 with anal and genital cancer.

We have advanced a combination of known and novel targets into clinical development, which is allowing us to use the product candidates targeting known antigens as backbones for our initial clinical trials evaluating multiplex TCR-T therapy.

For example, we plan to evaluate TSC-203-A0201, which targets PRAME, a well-known and clinically validated tumor-specific protein, in combination with TSC-201-B0702 targeting MAGE-C2.

TSC-200 (HPV16)

We are developing the TSC-200 series of product candidates as TCR-Ts targeting human papilloma virus, or HPV.

Over 25% of head and neck cancers are caused by HPV infection, including up to 70% of oropharangeal cancers.

HPV antigens are a particularly compelling set of targets as HPV proteins drive tumorigenesis in these cancers, which means that these proteins are (1) present in every tumor cell in an HPV-positive tumor and (2) essential to the survival of the tumor cell.

In addition to head and neck cancers, HPV is found in more than 90% of cervical, anal and genital cancers.

Phase 1 clinical data from the National Cancer Institute showed tumor regression with objective clinical responses in 50% of patients with metastatic HPV-positive cancers who were treated with a TCR-T therapy candidate targeting E7 of HPV16, which we believe provides clinical support for the inclusion of an HPV16-targeting TCR-T, TSC-200-A0201, in our multiplex TCR-T treatment strategy.

We have advanced TSC-200-A0201 (HPV16, HLA-A*02:01) into Phase 1 development.

We also intend to extend our discovery efforts to include additional HPV16-derived antigens presented on other HLA types as the program advances, such as TSC-200-C0702 (HPV16, HLA-C*07:02), currently in discovery.

TSC-201 (MAGE-C2)

We are developing the TSC-201 series of TCR-T therapy product candidates as TCR-Ts targeting melanoma-associated antigen C2, or MAGE-C2.

We initially identified MAGE-C2 as the target of T cells from a melanoma patient responding to TIL therapy.

MAGE-C2 is a cancer testis antigen, or CTA, that is exclusively expressed in testis and is not expressed in normal adult tissues.

The testis is an immune-privileged tissue and, as a result, we believe that targeting MAGE-C2 should not pose a significant safety concern.

In addition, MAGE-C2, which contributes to tumorigenesis by suppressing the cellular mechanisms responsible for controlling cell division, is selectively expressed across multiple different types of tumors, including approximately 25% of head and neck cancers, and approximately 50% of non-small cell lung cancers.

Tumors expressing MAGE-C2 have been shown to be associated with metastasis and poor patient survival.

We are currently advancing three MAGE-C2 TCRs:

TSC-201-B0702 (MAGE-C2, HLA-B*07:02), currently in Phase 1 development;

TSC-201-A0201 (MAGE-C2, HLA-A*02:01), currently in discovery;

and TSC-201-A2402 (MAGE-C2, HLA-A*24:02), currently in discovery.

We are also using ReceptorScan to identify additional TCRs for MAGE-C2 epitopes presented on other HLA alleles to further expand the ImmunoBank and increase the addressable patient population.

TSC-202 (MAGE-A4)

We are developing the TSC-202 series of TCR-T therapy product candidates as TCR-Ts targeting melanoma-associated antigen 4, or MAGE-A4.

MAGE-A4 is a clinically established CTA that contributes to tumorigenesis by interfering with cell cycle arrest.

MAGE-A4 is expressed in 33% of cervical cancers enabling multiplexing with TSC-200, and MAGE-A4 is expressed in 50% of non-small cell lung cancers, 40% of head and neck cancers, and 20-70% of sarcomas depending on sub-type.

We have advanced one MAGE-A4 TCR-T therapy product candidate, TSC-202-A0201, into Phase 1 development.

TSC-203 (PRAME)

We are developing the TSC-203 series of TCR-T therapy product candidates as TCR-Ts targeting Preferentially Expressed Antigen in Melanoma, or PRAME.

Like MAGE-C2, PRAME contributes to tumorigenesis by suppressing cellular signals that control cell division, and higher expression levels of PRAME in tumors correlate with increased metastasis and poor patient outcomes.

PRAME is a CTA that, like MAGE-C2 and MAGE-A4, is absent in adult tissues except in the ovaries and testis.

Approximately 50% of NSCLCs, approximately 25% of cervical cancers, approximately 90% of head and neck cancers, and approximately 10-90% of sarcomas (depending on sub-type) express PRAME.

Notably, sarcoma subtypes that highly express PRAME also highly express MAGE-A4, making this an attractive indication for multiplex therapy.

We are currently advancing three PRAME TCR-T therapy product candidates:

TSC-203-A0201 (PRAME, HLA-A*02:01), currently in Phase 1 development;

TSC-203-B0702 (PRAME, HLA-B*07:02), currently in lead optimization;

and TSC-203-A2402 (PRAME, HLA-A*24:02) currently in discovery.

TSC-204 (MAGE-A1)

We are developing the TSC-204 series of TCR-T therapy product candidates as TCR-Ts targeting melanoma-associated antigen 1, or MAGE-A1.

MAGE-A1 is a cancer/testis gene frequently overexpressed in a wide variety of solid tumors, including approximately 45% of head and neck cancers, 50% of cervical cancers and 50% of NSCLC.

Using our TargetScan platform, we initially identified MAGE-A1 as one of the targets of expanded T cells from a head and neck cancer patient responding to checkpoint inhibitor therapy.

Multiple different TCRs from this patient recognize a novel HLA-C*07:02-restricted epitope of MAGE-A1, and one of these TCRs is the basis of TSC-204-C0702 (MAGE-A1, HLA-C*07:02), currently in Phase 1 development.

In addition to this TCR-T therapy product candidate, we further expanded the TSC-204 series by using ReceptorScan to identify additional TCRs for MAGE-A1 epitopes presented on several other common HLA alleles to further expand the addressable patient population.

We are currently advancing five MAGE-A1 TCR-T therapy product candidates:

TSC-204-A0201 (MAGE-A1, HLA-A*02:01), currently in Phase 1 development;

TSC-204-C0702 (MAGE-A1, HLA-C*07:02), currently in Phase 1 development;

TSC-204-A0101 (MAGE-A1, HLA-A*01:01) currently in Phase 1 development;

TSC-204-A0301 (MAGE-A1, HLA-A*03:01) currently in discovery;

and TSC-204-B0702 (MAGE-A1, HLA-B*07:02) currently in discovery.

We are continuing to leverage our platform technologies to expand patient eligibility for multiplex TCR-T therapy.

We plan to expand the ImmunoBank to address different HLA types to enable customized multiplex TCR-T therapy product candidates while also addressing the potential issue of HLA loss leading to resistance for a wide range of solid tumor patients.

Clinical Development Plan for Our Solid Tumor Program

For the initial first-in-human studies for our solid tumor TCR-T therapy product candidates, we are evaluating multiple TCRs in parallel to determine the safety and preliminary efficacy of multiplex TCR-T therapy.

The FDA has cleared our IND application for T-Plex, which serves as the primary IND application for our solid tumor program, enabling customized simultaneous administration of TCR-T therapy product candidates to be administered to patients based on the targets and HLAs expressed in their tumors.

Specific TCRs for each patient are chosen from the ImmunoBank consisting of high affinity, naturally occurring TCRs that recognize a variety of prevalent cancer-specific targets and are associated with common HLA types.

Each unique TCR-T therapy product candidate has been or will be filed as a secondary IND application and will reference the primary T-Plex IND application.

In addition to the T-Plex IND application, the FDA has cleared secondary IND applications for seven TCR-T therapy product candidates:

TSC-203-A0201 (PRAME, HLA-A*02:01);

TSC-200-A0201 (HPV16, HLA-A*02:01);

TSC-201-B0702 (MAGE-C2, HLA-B*07:02);

TSC-202-A0201 (MAGE-A4, HLA-A*02:01);

TSC-204-A0201 (MAGE-A1, HLA-A*02:01);

TSC-204-C0702 (MAGE-A1, HLA-C*07:02);

and TSC-204-A0101 (MAGE-A1, HLA-A*01:01).

We have initiated a multicenter Phase 1 clinical trial to evaluate the safety, preliminary efficacy, and feasibility of repeat dosing of multiplex TCR-T therapy.

We are enrolling patients with NSCLC, sarcoma, head and neck cancer, cervical cancer, and anal and genital cancer.

We expect that many of the clinical trial sites enrolling patients in our heme malignancies program are planning to join our solid tumor Phase 1 study.

We are currently enrolling and treating patients in this study.

After establishing single agent safety for each of our initial solid tumor TCR-T therapy product candidates in a multi-arm Phase 1 clinical trial, we plan to test our solid tumor TCR-T therapy product candidates in combination with other TCR-T therapy product candidates in the ImmunoBank in patients who are positive for the respective targets of these therapies.

We will explore up to three-TCR simultaneous administrations in patients who are positive for the respective targets.

A summary of our planned Phase 1 clinical strategy is shown below.

Dose Escalation Scheme Provides a Rapid Path to Multiplex TCR-T Therapy in Phase 1

Anticipated timeline

As we advance our solid tumor program, we anticipate submitting IND filings for additional TCRs.

We believe this trial will serve as the first step towards our long-term goal of expanding the ImmunoBank to provide customized multiplex TCR-T therapy product candidates for virtually any patient with a solid tumor malignancy.

We have successfully manufactured product candidates and infused patients with singleplex therapy and expect to dose our first multiplex patient in the first half of 2025.

We plan to report safety and response data for multiplex therapy in the second half of 2025.

ImmunoBank – Flexible Content for Diverse Platforms

Our current clinical development strategy is based on autologous T cell engineering.

As the field of T cell engineering evolves, a wide variety of additional manufacturing platforms are being developed that may further improve TCR-T products.

For example, companies such as Lyell Immunopharma, Inc.

are developing methods to enhance autologous T cell engineering to provide improved duration of efficacy, while companies such as Allogene Therapeutics, Inc.

are developing ways to engineer allogeneic T cells and companies such as Umoja Biopharma, Inc.

are developing ways to engineer T cells in vivo .

All of these engineering platforms require validated “content” – TCRs that recognize tumor-specific antigens on cancer cells without recognizing problematic off-targets.

As we advance the ImmunoBank of TCRs through clinical development, we intend to continue to optimize our own manufacturing platform, in preparation for potential commercial manufacturing.

Ultimately, we aspire to build the largest collection of validated TCR “content” that can be used with a variety of T cell engineering platforms.

Expansion Opportunities Beyond Oncology

One reason why patients may not respond to current immunotherapy treatment options is that they lack T cells with highly active TCRs that recognize the cancer-specific antigens in their tumors.

By reprogramming the patient’s own T cells to recognize these target antigens, we believe that we can expand the dramatic responses observed with checkpoint inhibitor therapy to the patients for whom these therapies have historically been ineffective.

In addition, solid tumors are notoriously heterogeneous:

not every cancer cell in a tumor expresses a given antigen.

We believe that by targeting multiple antigens in a patient's tumor, we will be able to drive deep and durable responses.

We have built a diverse collection of therapeutic TCRs to enable customized multiplex TCR-T therapy.

We are currently engaged in preclinical development of an in vivo engineering platform to deliver off-the-shelf TCR-T therapy.

Development Plan for Our Solid Tumor Program

On November 3, 2025, following our alignment with the U.S.

We treated seven patients at dose level 3 or higher with singleplex therapy and two patients with multiplex therapy in the PLEXI-T study.

No dose-limiting toxicities were observed in these cohorts.

Six of the seven patients treated with singleplex therapy received at least 6 billion cells over two infusions, administered 28 days apart.

Of these patients, one (treated with the PRAME TCR) achieved a confirmed partial response, three achieved stable disease with varying degrees of tumor shrinkage (two with the PRAME TCR and one with the HPV-16 TCR), and the remaining two had progressive disease.

Additionally, of the two patients that were treated with multiplexed therapy (HPV/PRAME and HPV/MAGE-A4), neither patient received the target dose of 4 billion cells of each TCR-T over two infusions, and both patients had evidence of disease progression.

The inability to provide the target dose, coupled with the challenges associated with lymphodepletion and extended vein-to-vein times in the late-line disease setting, further reinforce our decision to focus on an in vivo engineering approach.

We have now partnered with a third party specializing in the development of a lentiviral-based platform for in vivo engineering of T cells and believe this approach represents a promising, cost-efficient, and clinically tractable way to deliver off-the-shelf, multiplexed TCR-T therapies for solid tumors.

Our Autoimmune Program

Our primary focus is on the development of T cell therapies to treat cancer.

However, T cells play a fundamental role in many other disease areas, such as infectious disease and autoimmune disorders.

We believe that our TargetScan technology is well suited to discover novel antigens for the development of therapeutics, diagnostics, and vaccines in these other areas.

We intend to build additional corporate value by opportunistically pursuing collaborations with strategic partners for applications of our platform technologies outside our core focus.

Other Diseases

TargetScan can also be used for novel target discovery in additional infectious diseases and autoimmune disorders.

For example, infections such as tuberculosis, influenza, and HIV have been shown to be T cell-mediated and are associated with high mortality rates.

In addition, many autoimmune disorders such as rheumatoid arthritis, psoriasis, and scleroderma are largely T cell-mediated, but with poorly defined instigating self-antigens.

Our TargetScan technology, which provides an unbiased, genome-wide method to discover the natural targets of disease-relevant T cells, is well positioned to identify these self-antigens.

We believe the discovery of these targets could enable the development of novel, more targeted therapeutic approaches to treat these diseases.

Our proprietary platform is designed to:

(i) discover anti-cancer TCRs from patients with exceptional responses to immunotherapy;

(ii) determine novel targets of clinically relevant TCRs;

(iii) discover novel TCRs that recognize clinically validated targets;

(iv) identify off-target interactions of TCRs to eliminate candidates that could potentially pose a safety risk;

and (v) manufacture TCR-T therapy product candidates efficiently and consistently without the use of viral vectors using our T-Integrate technology.

The central elements of our platform that we believe differentiate us from other cell therapy companies are TargetScan, ReceptorScan, SafetyScan, the ImmunoBank, and T-Integrate.

At the core of our proprietary platform is TargetScan, which enables us to identify natural targets of TCRs using an unbiased, genome-wide, high-throughput screen.

We have developed this technology to be extremely versatile and applicable across multiple therapeutic areas, including cancer, autoimmune disorders, and infectious diseases.

It can be applied to virtually any TCR that plays a role in the cause or prevention of disease.

Using TargetScan, we have identified approximately 200 novel antigens as targets of tumor infiltrating T cells from patients who are actively responding to immunotherapy.

We believe this provides us with a competitive advantage, because not only are we among the first to identify these targets as tumor-specific antigens, but we have also already identified highly active TCRs that recognize these targets.

Two of our pipeline programs emerged from TargetScan:

TSC-201-B0702 (MAGE-C2, HLA-B*07:02) and TSC-204-C0702 (MAGE-A1, HLA-C*07:02), the latter of which was featured in the peer-reviewed journal Cell in 2022.

ReceptorScan.

To further expand our ability to discover and develop therapeutic TCRs, we have developed our proprietary ReceptorScan technology to enable us to identify and clone highly active TCRs that recognize known or clinically validated targets.

We co-culture hundreds of millions of CD8+ T cells from either healthy donors or cancer patients with dendritic cells, also referred to as antigen-presenting cells, that display the target antigen of interest to the T cells.

T cells that recognize the target of interest proliferate

and are subsequently isolated based on their ability to recognize a fluorescently labeled version of the target.

We then use single cell sequencing to identify the specific TCR sequences that recognize the target.

Our novel technologies allow us to gene-synthesize hundreds of TCRs simultaneously and to rapidly sort through hundreds of target-specific TCRs in a single high-throughput screen to identify the most active clones.

Using ReceptorScan, we have identified our two lead TCR-T therapy product candidates, TSC-100 targeting HA-1 and TSC-101 targeting HA-2, as well as several other pipeline programs, including TSC-203-A0201 (PRAME, HLA-A*02:01), TSC-200-A0201 (HPV16, HLA-A*02:01), TSC-204-A0201 (MAGE-A1, HLA-A*02:01), TSC-204-A0101 (MAGE-A1, HLA-A*01:01), and TSC-202-A0201 (MAGE-A4, HLA-A*02:01).

SafetyScan is designed to identify potential off-target interactions of a given TCR and eliminate those TCR candidates that cross-react with proteins expressed at high levels in normal tissue.

We believe this will allow us to reduce the risk and enhance the potential safety profile of our TCR-T therapy product candidates early in development before we initiate clinical trials.

We are expanding the ImmunoBank, our diverse repository of therapeutic TCRs, to allow for multiplex TCR-T therapy, which has the potential to address the heterogeneous nature of solid tumors and address resistance developing due to loss of a single HLA haplotype.

We believe this approach may allow us to overcome the limitations and challenges of TCR-T development to date.

We continue to prioritize expanding the ImmunoBank with TCRs for additional targets as well as multiple HLA types for each target, thus helping us overcome the key solid tumor resistance mechanisms of target loss and HLA loss.

Finally, we are expanding the ImmunoBank to have the flexibility to be used with new and optimized methods of T cell engineering that we may develop over time.

We have built the ImmunoBank to be compatible with autologous, allogeneic, and in vivo engineering technologies in order to potentially transition to generating off-the-shelf products for direct, customized administration to patients.

Manufacturing cell therapies is highly complex, and associated challenges have led to significant delays or failures in the development of many cell therapies.

To enable the rapid, cost-effective, and consistent manufacturing of TCR-T therapy product candidates, we have developed a non-viral vector delivery system that we refer to as T-Integrate.

Our TCR-T therapy product candidates are manufactured using a transposon/transposase system, in which the DNA encoding the TCR is manufactured as a Nanoplasmid, a non-viral vector.

The Nanoplasmid, together with an mRNA sequence encoding a transposase enzyme, is introduced into the T cell by electroporation.

After the T cell translates the mRNA into protein, the transposase enzyme inserts the TCR sequence from the Nanoplasmid, as well as any enhancements such as CD8 a / b and DN-TGF b RII, into the genome of the T cell.

This system is highly reproducible, as the only required components are a Nanoplasmid, which is different for each TCR product, and an mRNA, which is constant for all TCR products.

Unlike lentivirus, both components are routinely manufactured in a cost-effective manner without the need for extensive process development.

We have a 51,100 square-foot GMP manufacturing facility (consisting of GMP clean room suites, laboratories, warehouse and office space) to manufacture clinical supply for our TCR-T therapy product candidates.

Our manufacturing platform has enabled us to efficiently develop and manufacture many different TCR-T therapy product candidates, allowing us to deliver customized multiplex therapy to patients with cancer.

We have successfully manufactured product candidates and have dosed patients in both our heme malignancies and solid tumor Phase 1 programs.

The FDA has cleared eight IND applications for our solid tumor program, including our primary IND application T-Plex, which supports the use of multiple TCR-T therapy product candidates to create customized multiplex TCR-T therapy, as well as IND applications for TSC-200-A0201 (HPV16, HLA-A*02:01), TSC-201-B0702 (MAGE-C2, HLA-B*07:02), TSC-202 (MAGE-A4, HLA-A*02:01), TSC-203-A0201 (PRAME, HLA-A*02:01), TSC-204-A0201 (MAGE-A1, HLA-A*02:01), TSC-204-C0702 (MAGE-A1, HLA-C*07:02), and TSC-204-A0101 (MAGE-A1, HLA-A*01:01), demonstrating our manufacturing capabilities.

To further increase our clinical manufacturing capacity and prepare for potential commercialization, we have engaged a global contract development and manufacturing organization, or CDMO, with worldwide commercial capabilities to support both the heme and solid tumor programs.

The CDMO is on track to support clinical manufacturing of the heme program in the second half of 2025.

However, T cells play a fundamental role in other disease areas.

Many autoimmune disorders such as ankylosing spondylitis, ulcerative colitis and scleroderma are largely T cell-mediated, but with poorly defined instigating self-antigens.

We believe our target discovery platform is well suited to identify self-antigens that cause T cell-driven autoimmune disorders.

We are currently in early stages of identifying targets and developing potential treatment options for these disorders.

We intend to build additional corporate value by opportunistically pursuing collaborations with strategic partners for applications of our platform outside our core focus areas.

License and Collaboration Agreements

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On May 8, 2023, we entered into a Research Collaboration and License Agreement with Amgen Inc.

(Amgen), or the Amgen Agreement, to identify antigens recognized by T cells in patients with Crohn’s disease utilizing our proprietary target discovery platform, or TargetScan.

Under the terms of the Amgen Agreement, Amgen will then evaluate a variety of modalities to create therapeutics based on targets discovered by TScan and will retain all global development and commercialization rights.

(Amgen), or the Amgen Agreement, to identify antigens recognized by T cells in patients with Crohn’s disease utilizing our proprietary target discovery platform.

Under the terms of the Amgen Agreement, Amgen will then evaluate a variety of modalities to create therapeutics based on targets discovered by us and will retain all global development and commercialization rights.

Amgen made an upfront payment of $30.0 million to us, and we are eligible to earn success-based milestone payments of over $500 million based upon the achievement of certain development and commercial milestones, as well as tiered single-digit royalty payments on net sales of products developed from the collaboration, subject to reductions set forth in the Amgen Agreement.

Exclusive Patent License Agreement with BWH

On December 5, 2018, we entered into an Exclusive Patent License Agreement with The Brigham and Women’s Hospital, Inc., or BWH, as amended on July 26, 2019 and further amended and restated on April 20, 2021, or, collectively, the BWH Agreement, pursuant to which we obtained an exclusive, sublicensable, worldwide license to practice under certain of BWH’s patent rights for identifying T cell epitopes, which are relevant to our TargetScan technology for identifying potential therapeutic products.

On December 5, 2018, we entered into an Exclusive Patent License Agreement with The Brigham and Women’s Hospital, Inc., or BWH, as amended on July 26, 2019 and further amended and restated on April 20, 2021, or, collectively, the BWH Agreement, pursuant to which we obtained an exclusive, sublicensable, worldwide license to practice under certain of BWH’s patent rights for identifying T cell epitopes, which are relevant to our target discovery platform for identifying potential therapeutic products.

The original 2018 BWH Agreement granted us the right to practice BWH’s patent rights in a certain field of use, MHC Class I License Field.

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We also have the right to terminate the BWH Agreement in its entirety or on a country-by-country basis, for any reason upon 90 days’ prior written notice to BWH.

BWH may terminate the BWH Agreement:

BWH may terminate the BWH

(i) without notice if we fail to maintain insurance required by the BWH Agreement;

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Primary human blood cells are the source of T cells, along with a vector that delivers the desired genetic elements into these T cells.

As a more operationally flexible and cost-efficient alternative to lentivirus, we have developed a manufacturing platform to genetically engineer T cells using a transposon/transposase system, which we refer to as T-Integrate.

We have designed our programs to use a transposon vector and corresponding transposase enzyme, which is derived from sfR fall armyworm, to deliver our TCRs into the genome of T cells.

Our transposon/transposase system effectively inserts our TCRs and other exogenous genes, such as CD8, at random locations in the genome.

We have designed our heme program to use a transposon vector and corresponding transposase enzyme, which is derived from sfR fall armyworm, to deliver our TCRs into the genome of T cells.

Our transposon/transposase system effectively inserts our TCRs and exogenous genes, such as CD8, at random locations in the genome.

The transposon is delivered as a Nanoplasmid and has no antibiotic selection element, reducing the risk of inadvertent transmission of antibiotic resistance into T cells.

The transposase is delivered as mRNA.

The transposase is

delivered as mRNA.

mRNA is transiently expressed in the cell, reducing exposure of cells to prolonged transposase activity, which could result in multiple transposition events where the transposon would be moved around the genome.

We have developed a manufacturing process currently producing product for clinical studies, using industry standard equipment and instrumentation.

We have developed a manufacturing process currently producing product for our clinical program, using industry standard equipment and instrumentation.

The equipment and instrumentation used in our manufacturing facility allows for functionally closed processes in a small footprint.

For clinical product manufacturing, we use single-use bag and tubing kits, supplies, and process reagents that are available from well-established vendors who specialize in supplying clinical grade reagents for the cell and gene therapy industry.

For clinical product manufacturing, we use single-use consumables as well as process reagents that are available from well-established vendors who specialize in supplying clinical grade reagents for the cell and gene therapy industry.

Our TCR-T therapy product candidates are released and characterized using well-developed analytical methods.

The final product used in clinical studies is cryopreserved, simplifying logistics and reducing risk of delivery failures to support patient dosing.

The final product used in clinical studies is cryopreserved, simplifying logistics to support patient dosing.

We have controls and safeguards throughout the entire process to ensure product identity, integrity, sterility, and chain of custody.

A clearly defined and documented manufacturing process, performed by trained operators using specialized instrumentation in an appropriately designed, commissioned, and operated manufacturing facility is critical for the manufacturing of safe, effective, and well-characterized cell therapies.

Our cell product manufacturing facility in Waltham, MA has been designed and built to support multiple programs through Phase 1 and Phase 2 clinical development, with a projected capacity to support up to 250 TCR-T components per year.

A clearly defined and documented manufacturing process, performed by trained operators in an appropriately designed, commissioned, and operated manufacturing facility is critical for the manufacturing of safe, effective, and well-characterized cell therapies.

Our cell product manufacturing facility in Waltham, MA has been designed and built to support multiple programs through Phase 1 and Phase 2 clinical development.

We believe internalizing our manufacturing process and product testing enables us to better control this key aspect of clinical development and reduces the risk of program delay due to third-party reliance.

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We have engaged a CDMO with global capabilities to support increased capacity and potential commercial manufacturing.

The CDMO is on track to support clinical manufacturing of the heme program in the second half of 2025.

We believe our novel and proprietary platform technologies, TargetScan, SafetyScan, and ReceptorScan, and our in-house cell therapy expertise constitute a meaningful competitive advantage in successfully developing novel and highly safe and effective treatments for cancer.

We believe our diverse collection of therapeutic TCRs and our in-house cell therapy expertise constitute a meaningful competitive advantage in successfully developing novel and highly safe and effective treatments for cancer.

However, the biopharmaceutical industry in general, and the cell therapy field in particular, is characterized by rapidly advancing and changing technologies, intense competition, and a strong emphasis on intellectual property.

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We face competition from segments of the pharmaceutical, biotechnology and other related markets that pursue the development of TCR-based or cell-based therapies for the treatment of cancer.

We expect to compete with a number of other TCR-based companies, utilizing both cell therapy and other therapeutic modalities, such as Immatics N.V., Adaptimmune Therapeutics, Plc., Affini-T Therapeutics, Inc., Medigene AG, T-Knife GmbH, Enara Bio Ltd., Immunocore Holdings, Plc., and 3T Biosciences Inc.

We may also face competition from companies focused on other T cell therapies (e.g., TIL, CAR-T, gammadelta T cells) such as Iovance Biotherapeutics, Inc., Instil Bio, Inc., Achilles Therapeutics plc, Kite Pharma, Inc., a subsidiary of Gilead, Inc.

(including Yescarta, which is approved for the treatment for large B cell lymphoma or follicular lymphoma, two types of non-Hodgkin lymphoma), Juno Therapeutics, Inc., a subsidiary of Bristol-Myers Squibb, Inc., Regeneron Pharmaceuticals, Inc., through their acquisition of 2seventy Bio, Inc.’s research pipeline, AstraZeneca plc, through their acquisition of Gracell Biotechnologies, Inc., Legend Biotech Corporation, Autolus Therapeutics plc, Sana Biotechnology, Inc., Lyell Immunopharma, Inc., Allogene Therapeutics, Inc., Century Therapeutics, Inc., and Adicet Bio, Inc.

We expect to compete with a number of other TCR-based companies, utilizing both cell therapy and other therapeutic modalities, such as Immatics N.V., Adaptimmune Therapeutics, Plc.

(who sold their cell therapy assets to US WorldMeds, LLC in July 2025), Affini-T Therapeutics, Inc., Medigene AG (who initiated insolvency proceedings in April 2025), T-Knife GmbH, Immunocore Holdings, Plc., and 3T Biosciences Inc.

We may also face competition from companies focused on other T cell therapies (e.g., TIL, CAR-T, gammadelta T cells) such as Iovance Biotherapeutics, Inc., Instil Bio, Inc., Kite Pharma, Inc., a subsidiary of Gilead, Inc.

There are also companies utilizing other cell-based approaches that may be competitive to our product candidates.

For example, companies such as Takeda Pharmaceutical Company, Ltd., Celyad, S.A., ImmunityBio, Inc., Celularity, Inc., Fate Therapeutics, Inc., and Nkarta, Inc.

For example, companies such as Takeda Pharmaceutical Company, Ltd.

(who announced the discontinuation of all cell therapy initiatives in October 2025), Celyad, S.A., ImmunityBio, Inc., Celularity, Inc., Fate Therapeutics, Inc., and Nkarta, Inc.

are developing therapies that target and/or engineer natural killer, or NK, cells.

In addition, for our lead programs, TSC-100 and TSC-101, we may face competition from BlueSphere Bio, VOR Biopharma, Inc., IN8bio, Inc., Orca Biosystems, Inc., and Marker Therapeutics, Inc., who are also developing cell therapies in the post-HCT setting.

In addition, for our lead program, TSC-101, we may face competition from BlueSphere Bio, IN8bio, Inc., Orca Biosystems, Inc., Fred Hutchinson Cancer Center partnered with Promicell Therapeutics Inc., and Marker Therapeutics, Inc., who are also developing cell therapies in the post-HCT setting.

The named companies are not fully inclusive of all possible competitive threats.

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As a result, obtaining market acceptance of, and gaining a significant share of the market for, and commanding a certain price for any of our TCR-T therapy product candidates that we successfully introduce to the market may pose challenges.

In addition, many companies are developing new oncology therapeutics, and we cannot predict what the standard of care will be as our product candidates progress through clinical development.

In addition, many companies are developing new oncology therapeutics, and we cannot predict what the standard of care will be as our product candidates progress through preclinical and clinical development.

We could see a reduction or elimination in our commercial opportunity if our competitors develop and commercialize drugs that are safer, more effective, have fewer or less severe side effects, are more convenient to administer, are less expensive, are more accessible, or receive a more favorable label than our TCR-T therapy product candidates.

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We also seek to protect our proprietary rights by entering into confidentiality agreements and proprietary information agreements with suppliers, employees, consultants and others who may have access to our proprietary information.

The steps we have taken to protect our trade secrets, trademarks, patent applications and other intellectual property and proprietary rights may not be adequate, and third parties could infringe, misappropriate

or misuse our intellectual property.

If this were to occur, it could harm our reputation and adversely affect our business, competitive position, financial condition or results of operations.

As of the date hereof, our patent portfolio includes a patent family exclusively licensed from BWH, including a granted U.S.

patent, a pending U.S.

As of the date hereof, our patent portfolio includes a patent family exclusively licensed from BWH, including 2 granted U.S.

patents, a pending U.S.

non-provisional patent application, and multiple foreign granted patents and non-provisional patent applications, relating to methods and compositions for identifying target antigens specific to T cells.

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provisional patent applications, multiple granted foreign patents, and more than 200 pending international and foreign patent applications.

The claims of these patent applications are directed toward various aspects of our therapy candidates and research programs, including compositions of matter and uses thereof directed to SARS-CoV-2 immunodominant antigens, anti-SARS-CoV-2 TCRs, anti-SARS-CoV-2 vaccines, anti-HA-1 TCRs (including the TSC-100 TCR-T therapy product candidate), anti-HA-2 TCRs (including the TSC-101 TCR-T therapy product candidate), anti-HPV TCRs (including the TSC-200 TCR-T therapy product candidate), anti-MAGE-C2 TCRs (including the TSC-201 TCR-T therapy product candidate), anti-MAGE-A4 TCRs (including the TSC-202 TCR-T therapy product candidate), anti-PRAME TCRs (including the TSC-203 TCR-T therapy product candidate), and anti-MAGE-A1 TCRs (including the TSC-204 TCR-T therapy product candidate), as well as platform technologies including a phospholipid scrambling reporter-based T cell antigen screening platform and certain screening methods thereof, and a TCR multiplexing platform and certain therapeutic methods thereof.

The claims of these patent applications are directed toward various aspects of our therapy candidates and research programs, including compositions of matter and uses thereof directed to SARS-CoV-2 immunodominant antigens, anti-SARS-CoV-2 TCRs, anti-SARS-CoV-2 vaccines, anti-HA-2 TCRs (including the TSC-101 TCR-T therapy product candidate), anti-CD45 TCRs (including the TSC-102 TCR-T therapy product candidate), anti-HPV TCRs (including the TSC-200 TCR-T therapy product candidate), anti-MAGE-C2 TCRs (including the TSC-201 TCR-T therapy product candidate), anti-MAGE-A4 TCRs (including the TSC-202 TCR-T therapy product candidate), anti-PRAME TCRs (including the TSC-203 TCR-T therapy product candidate), and anti-MAGE-A1 TCRs (including the TSC-204 TCR-T therapy product candidate), as well as platform technologies including a phospholipid scrambling reporter-based T cell antigen screening platform and certain screening methods thereof, and a TCR multiplexing platform and certain therapeutic methods thereof.

These patent applications, if issued, are expected to expire on various dates from 2038 through 2046, in each case without taking into account any possible patent term adjustments or extensions and assuming that appropriate maintenance and governmental fees are paid.

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We have filed multiple patent families encompassing pending U.S.

and foreign patent applications covering aspects of our heme malignancies programs including claims to the composition-of-matter and uses thereof of TSC-100, TSC-101, and other anti-HA-1 and anti-HA-2 TCRs and related T cell therapies.

and foreign patent applications covering aspects of our heme malignancies programs including claims to the composition-of-matter and uses thereof of TSC-101, and other anti-HA-2 TCRs, anti-CD45 TCRs, and related T cell therapies.

We expect the issued Australian and Singaporean patents, as well as any additional patents within these families, if issued, to expire no earlier than 2041 (without taking into account any possible patent term adjustments or extensions and assuming that appropriate maintenance and governmental fees are paid).

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For certain aspects of our business, we rely on certain technology and intellectual property rights that we in-license from third parties.

We have an exclusive patent license from BWH to a patent family directed to aspects of a granzyme B (GzB)-based antigen screening technology platform, as well as compositions-of-matter and certain screening methods thereof (consisting of one granted U.S.

patent, one pending U.S.

patent application, a granted patent in each of Australia, France, Germany, Great Britain, Japan, Netherlands, Switzerland, and six foreign patent applications pending in Australia, Canada, China, Europe, Hong Kong, and Japan).

patents, one pending U.S.

patent application, a granted patent in each of Australia, France, Germany, Great Britain, Netherlands, Switzerland, two granted patents in Japan, and six foreign patent applications pending in Australia, Canada, China, Europe, Hong Kong, and Japan).

Any patents issuing from the U.S.

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These sanctions could include, among other things, the imposition by the FDA of a clinical hold on trials, the FDA’s refusal to approve pending applications or related supplements, withdrawal of an approval, untitled or warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, restitution, disgorgement, civil penalties, or criminal prosecution.

Such actions by government agencies could also require us to expend a large amount of resources to respond to the actions.

actions by government agencies could also require us to expend a large amount of resources to respond to the actions.

Any agency or judicial enforcement action could have a material adverse effect on us.

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or (iii) molecules that result from the replication of those described in (i) or (ii).

Specifically, under the NIH Guidelines, supervision of human gene transfer trials includes

evaluation and assessment by an Institutional Biosafety Committee (IBC), a local institutional committee that reviews and oversees research utilizing recombinant or synthetic nucleic acid molecules at that institution.

Specifically, under the NIH Guidelines, supervision of human gene transfer trials includes evaluation and assessment by an Institutional Biosafety Committee (IBC), a local institutional committee that reviews and oversees research utilizing recombinant or synthetic nucleic acid molecules at that institution.

The IBC assesses the safety of the research and identifies any potential risk to public health or the environment, and such review may result in some delay before initiation of a clinical trial.

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This group provides authorization as to whether or not a trial may move forward at designated check points based on access to certain data from the trial and may recommend halting the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.

Human clinical trials for BLA approval typically involve a three-phase process, although some phases may overlap or be combined.

Phase 1, the initial clinical evaluations, consists of administering the drug and testing for safety and tolerated dosages and in some indications, such as rare disease, as preliminary evidence of efficacy in humans.

Phase 2 involves a study to evaluate the effectiveness of the drug for a particular indication and to determine optimal dosage and dose interval and to identify possible adverse side effects and risks in a larger patient group.

When a product is found safe, and initial efficacy is established in Phase 2, it is then evaluated in Phase 3 clinical trials.

Phase 3 trials consist of expanded multi-location testing for efficacy and safety to evaluate the overall benefit-to-risk index of the investigational drug in relationship to the disease treated.

Human clinical trials for BLA approval typically involve a three-phase process, although some phases may overlap, be combined, or in some cases, be deemed unnecessary to establish safety and efficacy.

Phase 1, the initial clinical evaluation, generally involves of administering the drug and testing for safety and tolerated dosages, and in some indications, such as rare disease, generates preliminary evidence of efficacy in humans.

Phase 2 generally involves a study to evaluate the effectiveness of the drug for a particular indication and to determine optimal dosage and dose interval and to identify possible adverse side effects and risks in a larger patient group.

Phase 3 clinical trials generally consist of expanded multi-location testing for efficacy and safety to evaluate the overall benefit-to-risk index of the investigational drug in relationship to the disease treated.

In March 2022, the FDA released a final guidance, “Expansion Cohorts:

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The results of preclinical and human clinical testing are submitted to the FDA in the form of a BLA for approval to commence commercial sales.

Our clinical trials may not be completed successfully within any specified period, or at all.

Our clinical trials may not be completed

successfully within any specified period, or at all.

Government regulation may delay or prevent marketing of product candidates or new drugs for a considerable period of time and impose costly procedures upon our activities.

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For a gene therapy product, the FDA also will not approve the product if the manufacturer is not in compliance with current Good Tissue Practice, or cGTP.

These are FDA regulations that govern the methods used in, and the facilities and controls used for, the manufacture of human cells, tissues, and cellular and tissue-based products, or HCT/Ps, which are human cells or tissue intended for implantation, transplant, infusion, or transfer into a human recipient.

These are FDA regulations that govern

the methods used in, and the facilities and controls used for, the manufacture of human cells, tissues, and cellular and tissue-based products, or HCT/Ps, which are human cells or tissue intended for implantation, transplant, infusion, or transfer into a human recipient.

The primary intent of the cGTP requirements is to ensure that cell and tissue-based products are manufactured in a manner designed to prevent the introduction, transmission and spread of communicable disease.

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Market Exclusivity

The Patient Protection and Affordable Care Act, as amended by the Health Care Education and Reconciliation Act, or, collectively, the ACA, signed into law on March 23, 2010, includes a subtitle called the Biologics Price Competition and Innovation Act of 2009, or the BPCIA, which created an abbreviated approval pathway for biological products shown to be similar to, or interchangeable with, an FDA-approved reference biological product.

The Biologics Price Competition and Innovation Act of 2009, or the BPCIA, which created an abbreviated approval pathway for biological products shown to be similar to, or interchangeable with, an FDA-approved reference biological product.

Bio-similarity, which requires that there be no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency, can be shown through analytical studies, animal studies, and a clinical trial or trials.

Interchangeability requires that a product is biosimilar to the reference product, and the product must demonstrate that it can be expected to produce the same clinical results as the reference product and, for products administered multiple times, the biologic and the reference biologic may be switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic.

However, complexities associated with the larger, and often more complex, structure of biological products, as well as the process by which such products are manufactured, pose significant hurdles to implementation that are still being worked out by the FDA.

Interchangeability requires that a product be biosimilar to the reference product, and the product must demonstrate that it can be expected to produce the same clinical results as the reference product and, for products administered multiple times, the biologic and the reference biologic may be switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic.

A reference biological product is granted four- and 12-year exclusivity periods from the time of first licensure of the product.

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“First licensure” typically means the initial date the particular product at issue was approved in the U.S.

new indication, route of administration, dosing schedule, dosage form, delivery system, delivery device or strength, or for a modification to the structure of the biological product that does not result in a change in safety, purity, or potency.

Date of first licensure does not include the date of licensure of (and a new period of exclusivity is not available for) a biological product if the licensure is for a supplement for the biological product or for a subsequent application by the same sponsor or manufacturer of the biological product (or licensor, predecessor in interest, or other related entity) for a change (not including a modification to the structure of the biological product) that results in a new indication, route of administration, dosing schedule, dosage form, delivery system, delivery device or strength, or for a modification to the structure of the biological product that does not result in a change in safety, purity, or potency.

Therefore, one must determine whether a new product includes a modification to the structure of a previously approved product that results in a change in safety, purity, or potency to assess whether the licensure of the new product is a first licensure that triggers its own period of exclusivity.

Whether a subsequent application, if approved, warrants exclusivity as the “first licensure” of a biological product is determined on a case-by-case basis with data submitted by the sponsor.

In addition, under the Orphan Drug Act, the FDA may designate a biologic product as an “orphan drug” if it is intended to treat a rare disease or condition (generally meaning that it affects fewer than 200,000 individuals in the U.S., or more in cases in which there is no reasonable expectation that the cost of developing and making a biologic product available in the U.S.

In addition, under the Orphan Drug Act, the FDA may designate a biological product as an “orphan drug” if it is intended to treat a rare disease or condition (generally meaning that it affects fewer than 200,000 individuals in the U.S., or more in cases in which there is no reasonable expectation that the cost of developing and making a biologic product available in the U.S.

for treatment of the disease or condition will be recovered from sales of the product).

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A rare pediatric disease designation does not guarantee that a sponsor will receive a PRV upon approval of its BLA.

Moreover, a sponsor who chooses not to submit a rare pediatric disease designation request may nonetheless receive a PRV upon approval of their marketing application if they request such a voucher in their original marketing application and meet all of the eligibility criteria.

Moreover, a sponsor who chooses not to submit a rare pediatric disease designation request may nonetheless receive a PRV

upon approval of their marketing application if they request such a voucher in their original marketing application and meet all of the eligibility criteria.

If a PRV is received, it may be sold or transferred an unlimited number of times.

Under current statutory sunset provisions, the FDA may award a PRV for an approved rare pediatric disease product application only if the sponsor has received rare pediatric disease designation for the drug by December 20, 2024, and after September 30, 2026, the FDA may not award any rare pediatric disease PRVs.

Congress may vote to reauthorize this program, but its future remains unknown at this time.

Under current statutory provisions, the FDA may not award a PRV for an approved rare pediatric disease product application after September 30, 2029, although the FDA’s authority to do so could be extended by Congress in the future.

Expedited Development and Review Programs

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Additionally, under FDORA, a platform technology incorporated within or utilized by a biological product is eligible for designation as a designated platform technology if (1) the platform technology is incorporated in, or utilized by, a biological product approved under a BLA;

(2) preliminary evidence submitted by the sponsor of the licensed biological product, or a sponsor that has been granted a right of reference to data submitted in the application for such biological product, demonstrates that the platform technology has the potential to be incorporated in, or utilized by, more than one biological product without an adverse effect on quality, manufacturing, or safety;

manufacturing, or safety;

and (3) data or information submitted by the applicable person indicates that incorporation or utilization of the platform technology has a reasonable likelihood to bring significant efficiencies to the biological product development or manufacturing process and to the review process.

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Post-Marketing Requirements

Following approval of a new product, a pharmaceutical company and the approved product are subject to continuing regulation by the FDA, including, among other things, monitoring and recordkeeping activities, reporting to the applicable regulatory authorities of adverse experiences with the product, providing the regulatory authorities with updated safety and efficacy information, product sampling and distribution requirements, and complying with promotion and advertising requirements, which include, among others, standards for direct-to-consumer advertising, restrictions on promoting drugs for uses or in patient populations that are not described in

the drug’s approved labeling, or off-label use, limitations on industry-sponsored scientific and educational activities and requirements for promotional activities involving the internet.

Although physicians may, in their independent professional medical judgment, prescribe legally available drugs for off-label uses, manufacturers typically may not market or promote such off-label uses.

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Moreover, a third-party payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved.

Adequate third-party reimbursement may not be available to

enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development.

Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development.

Additionally, coverage and reimbursement for drug products can differ significantly from payor to payor.

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Department of Health and Human Services (HHS) (e.g., the Office of Inspector General), the Drug Enforcement Administration, the Consumer Product Safety Commission, the Federal Trade Commission, the Occupational Safety & Health Administration, the Environmental Protection Agency, state Attorneys General and other state and local government agencies.

Our current and future business activities, including for example, sales, marketing, and scientific/educational grant programs must comply with healthcare regulatory laws, as applicable, which may include the Federal Anti-Kickback Statute, the Federal False Claims Act, as amended, the privacy and security regulations promulgated under the Health Insurance Portability and Accountability Act, or HIPAA, as amended, physician payment transparency laws, and similar state laws.

Anti-Kickback Statute, the Federal False Claims Act, as amended, the privacy and security regulations promulgated under the Health Insurance Portability and Accountability Act, or HIPAA, as amended, physician payment transparency laws, and similar state laws.

Pricing and rebate programs must comply with the Medicaid Drug Rebate Program requirements of the Omnibus Budget Reconciliation Act of 1990, as amended, and the Veterans Health Care Act of 1992, as amended.

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In addition, private individuals have the ability to bring actions under the Federal Civil False Claims Act and certain states have enacted laws modeled after the Federal False Claims Act.

Additionally, HIPAA created additional federal criminal statutes that prohibit, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-party payors and knowingly and willfully falsifying, concealing, or covering up a material fact or making any materially false, fictitious, or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.

Additionally, HIPAA created additional federal criminal statutes that prohibit, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-party payors and knowingly and willfully falsifying, concealing, or covering up a material fact or making any material false, fictitious, or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.

Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.

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however legislation has been introduced in the U.S.

Congress that would, if enacted, reverse these payment reductions.

that would, if enacted, reverse these payment reductions.

In addition to provider payment cuts under Medicare, the American Rescue Plan Act of 2021 also eliminated the statutory Medicaid drug rebate cap, previously set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024.

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Further, under the IRA, orphan drugs are exempted from the Medicare drug price negotiation program, but only if they have one orphan designation and for which the only approved indication is for that disease or condition.

If a product receives multiple orphan designations or has multiple approved indications, it may not qualify for the orphan drug exemption.

The implementation of the IRA is currently subject to ongoing litigation challenging the constitutionality of the IRA’s Medicare drug price negotiation program.

Under the One Big Beautiful Bill Act of 2025, this restriction was eliminated;

and effective for the 2028 initial price applicability year, all orphan drugs, regardless of the number of orphan drug designations or indications, are exempt from the Medicare drug price negotiation program The implementation of the IRA is currently subject to ongoing litigation challenging the constitutionality of the IRA’s Medicare drug price negotiation program.

The outcome of these challenges on the IRA, and the effects of the IRA on our business and the healthcare industry in general are not yet known.

On April 15, 2025, the Trump administration published Executive Order 14273, “Lowering Drug Prices by Once Again Putting Americans First,” which generally directs the federal government to take measures to reduce drug prices, including eliminating the so-called “pill penalty” under the Inflation Reduction Act that creates a distinction between small molecule and large molecule products for purposes of determining when a drug may be eligible for drug price negotiation.

On May 12, 2025, the Trump administration published Executive Order 14297, “Delivering Most-Favored-Nation Prescription Drug Pricing to American Patients,” which generally, among other things, directs the federal government to establish and communicate most-favored-nation (MFN) price targets to pharmaceutical manufacturers to bring prices for American patients in line with comparably developed nations.

Further, the Executive Order directs the federal government to support regulatory paths to allow direct-to-patient sales for companies that meet these targets.

It also states that the Administration will take additional aggressive action (for example, examining whether marketing approvals should be modified or rescinded or opening the door for individual drug importation waivers) should manufacturers fail to offer American consumers the MFN lowest price.

It also directs the Secretary of Commerce and the U.S.

Trade Representative to “take all necessary and appropriate action to ensure foreign countries are not engaged in any act, policy, or practice that may be unreasonable or

discriminatory or that may impair United States national security .

including by suppressing the price of pharmaceutical products below fair market value in foreign countries.” Notably, a similar “Most Favored Nation” pricing rule enacted under the first Trump administration was subject to an injunction resulting from judicial challenges to the rule, which was formally rescinded by the former Biden Administration in August 2021.

On December 19, 2025, CMS released two proposed rules that would incorporate MFN pricing principles into federal reimbursement for prescription drugs.

The first proposal, the Global Benchmark for Efficient Drug Pricing Model (GLOBE) for Medicare Part B, would require manufacturers of specified single source drugs and sole source biologics to pay incremental rebates based on international benchmark prices, with participation triggered for products meeting CMS’s spending and eligibility criteria.

The second proposal, the Guarding U.S.

Medicare Against Rising Drug Costs (GUARD) model for Medicare Part D, would similarly mandate manufacturer rebates for qualifying sole source drugs where the Medicare net price exceeds an MFN benchmark derived from international reference pricing methodologies.

As proposed, GLOBE would begin a five year performance period on October 1, 2026 and GUARD would begin its performance period in 2027.

These proposals will likely be subject to legal challenges that could delay their implementation or modify their impact on manufacturer pricing and revenue.

Additionally, in November 2025, CMS introduced the GENErating cost Reductions fOr U.S.

Medicaid (GENEROUS) Model, a voluntary MFN framework for manufacturers participating in the Medicaid Drug Rebate Program.

Although it is voluntary, the GENEROUS Model could also impact the drug pricing landscape for manufacturers.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

Certain states are also pursuing cost containment efforts through Prescription Drug Affordability Boards (PDABs) and similar entities.

While many PDABs have been granted authority to promote drug price transparency and reporting, some states have granted PDABs more expansive authority, including to set Upper Payment Limits (UPLs) on select, high price drugs.

The adoption and implementation of UPLs may put downward pressure on drug prices and impact our company’s future revenues.

We expect that the healthcare reform measures that have been adopted and may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that we receive for any approved product and could seriously harm our future revenues.

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(i) it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition;

(ii) either (a) such condition affects no more than five in 10,000 persons in the EU when the application is made, or (b) the product, without the benefits derived from orphan status, would not generate sufficient return in the EU to justify the necessary investment in its development;

(ii) either (a) such condition affects no more than five in 10,000 persons in the EU when the application is made, or (b) the product, without the benefits derived from orphan

status, would not generate sufficient return in the EU to justify the necessary investment in its development;

and (iii) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the EU, or if such a method exists, the product will be of significant benefit to those affected by the condition, as defined in Regulation (EC) 847/2000.

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Many benefits accrue to sponsors of product candidates with PRIME designation, including but not limited to, early and proactive regulatory dialogue with the EMA, frequent discussions on clinical trial designs and other development program elements, and accelerated marketing authorization application assessment once a dossier has been submitted.

Importantly, a dedicated contact and rapporteur from the EMA’s CHMP or Committee for Advanced Therapies are appointed early in PRIME scheme facilitating increased

understanding of the product at the EMA’s committee level.

Importantly, a dedicated contact and rapporteur from the EMA’s CHMP or Committee for Advanced Therapies are appointed early in PRIME scheme facilitating increased understanding of the product at the EMA’s committee level.

A kick-off meeting initiates these relationships and includes a team of multidisciplinary experts at the EMA to provide guidance on the overall development and regulatory strategies.

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Once the European Commission’s legislative proposals are approved (with or without amendment), they will be adopted into EU law.

Brexit and the Regulatory Framework in the United Kingdom

The UK formally left the EU on January 31, 2020, and the EU and the UK have concluded a trade and cooperation agreement, or TCA, which was provisionally applicable since January 1, 2021 and has been formally applicable since May 1, 2021.

The TCA includes specific provisions concerning pharmaceuticals, which include the mutual recognition of GMP, inspections of manufacturing facilities for medicinal products and GMP documents issued but does not provide for wholesale mutual recognition of UK and EU pharmaceutical regulations.

Regulatory Framework in the United Kingdom

At present, the UK has implemented EU legislation on the marketing, promotion and sale of medicinal products through the Human Medicines Regulations 2012 (as amended).

The regulatory regime in the UK therefore largely aligns with current EU regulations, however it is possible that these regimes will diverge in the future now that the UK’s regulatory system is independent from the EU and the TCA does not provide for mutual recognition of UK and EU pharmaceutical legislation.

For example, the EU Clinical Trials Regulation does not apply in the UK and the current UK clinical trials legislation is based on the now repealed Clinical Trials Directive 2001/20/EC.

For example, the EU Clinical Trials

Regulation does not apply in the UK and the current UK clinical trials legislation is based on the now repealed Clinical Trials Directive 2001/20/EC.

However, on December 12, 2024, the UK government introduced a legislative proposal – the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2024 – that, if implemented, will replace the current regulatory framework for clinical trials in the UK.

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Human Capital

As of February 28, 2025, we had 194 full-time employees and 1 part-time employee, 41 of whom have Ph.D.

As of February 27, 2026, we had 142 full-time employees and 0 part-time employees, 29 of whom have Ph.D.

Of these full-time employees, 112 employees are engaged in research and development activities and 30 are engaged in finance, business development and other general and administrative functions.

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We recognize that attracting, motivating and retaining talent at all levels is vital to our continued success.

Our employees are a significant asset, and we aim to create an equitable, inclusive and empowering environment in which our employees can grow and advance their careers, with the overall goal of developing, expanding and retaining our workforce to support our current pipeline and future business goals.

future business goals.

By focusing on employee retention and engagement, we also improve our ability to support our clinical trials, our pipeline, our platform technologies, business and operations, and also protect the long-term interests of our securityholders.

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In addition, we routinely post on the “Investors and Media” page of our website investor and scientific presentations, SEC filings, press releases, public conference calls and webcasts and other statements about our business and results of operations, some of which may contain information that may be deemed material to investors.

Accordingly, investors should monitor these portions of our website, in addition to following our press releases, SEC filings, public conference calls and webcasts, as well as our social media channels (our Twitter and LinkedIn).

This list of channels may be updated from time to time on our investor relations website and may include other social media channels than the ones described above.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business