Importantly, STK-009 induced the expression of cytotoxic machinery, pro-survival, and proliferative genes in tumor-infiltrating SYNCAR-002 (figure 3). Conclusions These findings validate that the orthogonal IL-2 platform has the potential to improve the efficacy and durability of CAR T therapy for solid tumor targets such as GPC3 by selectively expanding CAR-T cells in vivo and activating CAR-T cells in a hostile tumor microenvironment.

8 months ago

Preclinical • CAR T-Cell Therapy • IO biomarker

CD19 (CD19 Molecule) • GPC3 (Glypican 3) • IL2 (Interleukin 2)

CD19 expression • GPC3 expression

STK-009/SYNCAR-001

1year

A Phase 1 study to evaluate the safety and tolerability of a combination autologous CD19 CAR T cell therapy (SYNCAR-001) and orthogonal IL-2 (STK-009) in subjects with relapsed or refractory CD19 expressing hematologic malignancies (NCT05665062) (AACR 2023)

Secondary endpoints include assessments of response, pharmacokinetics, and immunogenicity. Exploratory endpoints include assessment of immune cell populations, and relevant gene/protein expression, as well as persistence, phenotype, and functionality of SYNCAR-001 in the peripheral blood and/or bone marrow in response to STK-009.

1 year ago

Clinical • P1 data • CAR T-Cell Therapy

CD19 (CD19 Molecule) • IL2 (Interleukin 2)

CD19 expression

STK-009/SYNCAR-001

over1year

Autologous CD19 CAR-T Cell Therapy (SYNCAR-001) + Orthogonal IL-2 (STK-009) in Subjects With CD19+ Hematologic Malignancies (clinicaltrials.gov)

P1, N=36, Recruiting, Synthekine

over 1 year ago

New P1 trial • CAR T-Cell Therapy

CD19 (CD19 Molecule)

CD19 expression

cyclophosphamide • fludarabine IV • STK-009/SYNCAR-001

2years

Engineered human IL-2/IL-2Rb orthogonal pairs selectively enhance anti-GPC3 CAR T cells to drive complete responses in solid epithelial tumor models (AACR 2022)

STK-009 treatment resulted in significant expansion of SYNCAR-002 and drove infiltration of SYNCAR-002 into tumors. STK-009 treatment also induced intratumoral granzyme B+ and IFN-γ+ production by SYNCAR-002 indicating activation of effector T cell function.These findings validate that the orthogonal IL-2 platform has the potential to improve the efficacy and durability of CAR T therapy for solid tumor targets such as GPC3 by selectively expanding CAR-T cells in vivo, driving CAR-T cells into the tumor, and activating CAR-T cells in the tumor microenvironment.

2 years ago

Preclinical • CAR T-Cell Therapy • IO biomarker

CD19 (CD19 Molecule) • IFNG (Interferon, gamma) • IL2 (Interleukin 2) • GZMB (Granzyme B)

CD19 expression • GPC3 expression • GPC3 overexpression

STK-009/SYNCAR-001

3years

[VIRTUAL] OrthoCARs: Engineered human IL-2/IL-2Rb orthogonal pairs selectively enhance CAR T cell antitumor efficacy by driving T cell expansion and fitness (AACR 2021)

Pharmacokinetic analysis of STK-009 shows stable exposure with minimal clearance, demonstrating the selectivity of STK-009.These findings validate an orthogonal platform that selectively drives potent T cell effector functions of engineered cells without the toxicities mediated by NK cells or non-tumor specific T cells associated with high dose IL-2 therapy. These results demonstrate the ability of this orthogonal platform to improve the efficacy and durability of CARs.

3 years ago

Clinical • CAR T-Cell Therapy • PD(L)-1 Biomarker • IO biomarker

CD19 (CD19 Molecule) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • IL2 (Interleukin 2)

CD19 expression

STK-009/SYNCAR-001