A robust pipeline of TRuC-T cell therapies for solid and hematologic cancers

We are developing a wide range of cell therapies for solid tumors as well as blood cancers by targeting a number of different surface antigens on cancer cells that have beneficial expression characteristics. We are also supplementing our basic TRuC-T cell format with innovative enhancements to combat the hostile tumor microenvironment in case certain cancer indications prove more resistant.

Our most advanced program, gavo-cel, targets tumors that express the protein mesothelin, including ovarian cancer, non-small cell lung cancer, malignant pleural/peritoneal mesothelioma, and cholangiocarcinoma. Our preclinical programs are a combination of additional novel targets, technological enhancements for autologous therapies, and the expansion of TRuC-T cells into autoimmune diseases. We have also developed an allogeneic (“off-the-shelf”) TRuC-T cell.

  • Pipeline
  • Innovations in Progress
indications
preclinical
phase 1
phase 2
phase 3

Solid Tumors

gavo-cel
Target: Mesothelin
Ovarian cancer, NSCLC, MPM, Cholangiocarcinoma
Indications: Ovarian cancer, NSCLC, MPM, Cholangiocarcinoma
Progress: Phase 1
TC-510
(PD-1 Switch)
Target: Mesothelin
Solid tumors
Indications: Solid tumors
Progress: Preclinical
CD70
Solid Tumors, Hematological Malignancies
Indications: Solid Tumors, Hematological Malignancies
Progress: Preclinical
GPC3
Solid Tumors
Indications: Solid Tumors
Progress: Preclinical
IL-15
Enhancements
Solid Tumors
Indications: Solid Tumors
Progress: Preclinical
Allogeneic
Target: Mesothelin
Solid tumors
Indications: Solid tumors
Progress: Preclinical

Autoimmune Diseases

TRuC Tregs
Autoimmune Diseases
Indications: Autoimmune Diseases
Progress: Preclinical

NSCLC: non-small cell lung cancer; MPM: malignant pleural/peritoneal mesothelioma; aALL: adult acute lymphoblastic leukemia; DLBCL: diffuse large B-cell lymphoma; NHL: other non-Hodgkin lymphoma (NHL) subtypes including follicular lymphoma (FL), mantle cell lymphoma (MCL), primary mediastinal B-cell lymphoma (PMBCL)

Innovations in Progress

We continue to broaden our platform through internal research and collaboration with leading academic laboratories and industry partners. These innovations fall into three broad categories:

Novel Targets

Due to the TRuC platform’s versatility, we have the capability to target many different cancer antigens. We are focused on the discovery and validation of novel targets to broaden the reach of TRuC-T cells in solid tumors and hematologic cancers. Our strategy for determining the right target is based on:

  • Expression profile of the tumor antigen
  • Scientific evidence and validation of the tumor antigen
  • Evaluation of patient population of target indications, market landscape, and competition
  • Clinical path forward

Enhancements

We are developing:

  • TRuC-T cells with switch receptors which will be equipped to turn a suppressive signal from the tumor microenvironment into a positive. Our lead switch receptor is TC-510, a PD-1:CD28 switch receptor, and we are also developing further activating and kill switches based on activating and inhibitory concepts for our TRuCs.
  • Several enhancements to control “off-tumor” activity and counter the immunosuppressive microenvironment of solid tumors. These include mechanisms such as those that block a key cancer defense known as the PD-1/PD-L1 pathway and cells that secrete IL-15 which promotes the formation of memory T cells and triggers survival and differentiation signals in the absence of antigen stimulation.
  • Dual TRuC-T cells, which are designed to target more than one cancer antigen and address tumor heterogeneity and antigen escape. These second-generation TRuC-T cells will also be also enhanced to counter the hostile tumor microenvironment.

Novel Targets

Due to the TRuC platform’s versatility, we have the capability to target many different cancer antigens. We are focused on the discovery and validation of novel targets to broaden the reach of TRuC-T cells in solid tumors and hematologic cancers. Our strategy for determining the right target is based on:

  • Expression profile of the tumor antigen
  • Scientific evidence and validation of the tumor antigen
  • Evaluation of patient population of target indications, market landscape, and competition
  • Clinical path forward

Allogeneic TRuCs

We are focused on developing and evaluating designs for allogeneic, or “off-the-shelf,” TRuC-T cells to allow for a simpler manufacturing process that can deliver product candidates to patients sooner. Our novel allogeneic approach builds off the knowledge of our autologous TRuC-T cell platform and requires the integration of non-alloreactive TCRαβ subunits which reduces Graft versus Host Disease (GvHD) yet maintains the full functionality of the TCR. The approach involves collecting immune cells from healthy donors instead of the patient, enabling a larger patient population to potentially receive the product candidate since some patients may be too ill to provide healthy T cells for the manufacturing process. We inactivate the endogenous TCR alpha gene with a This allogeneic cell therapy approach is also designed to avoid eliciting an immune reaction to the patients’ healthy tissue (i.e., graft versus host disease).