T-knife Therapeutics Presents Preclinical Data at the American Association for Cancer Research (AACR) Annual Meeting Demonstrating a Potential Best-in-Class PRAME Targeted TCR-T Therapy

– TK-6302, a supercharged PRAME targeting TCR-T therapy, demonstrates best-in-class preclinical anti-tumor efficacy as compared to current clinical stage PRAME TCR-T approaches, providing the potential for broad, deep and durable responses in hard-to-treat solid tumor indications

– Submission of a Clinical Trial Application (CTA) for TK-6302 planned for the fourth quarter of 2025 and will be supported by a comprehensive body of data on its potency and safety

/EIN News/ -- SAN FRANCISCO and BERLIN, April 25, 2025 (GLOBE NEWSWIRE) -- T-knife Therapeutics, Inc., a biopharmaceutical company developing T cell receptor (TCR) engineered T cell therapies (TCR-T) to fight cancer, today announced multiple data presentations at the American Association for Cancer Research (AACR) Annual Meeting. Preclinical data demonstrated that TK-6302, T-knife’s supercharged PRAME targeting TCR-T, outperformed other clinical-stage approaches. The company plans to submit a Clinical Trial Application (CTA) for TK-6302 in the fall of 2025 and to initiate a Phase 1 clinical study of TK-6302 in early 2026.

“We embarked on a strategy to engineer our T cells with leading-edge technologies to materially differentiate the depth, breadth and durability of our TCR-T therapies,” stated Peggy Sotiropoulou, Ph.D., Chief Scientific Officer of T-knife. “Multiple preclinical datasets demonstrate greater target affinity, superior cytotoxicity, and increased T-cell fitness and persistence as compared to clinical-stage PRAME targeting TCR-T approaches.”

John Haanen, M.D., Ph.D., Director of the Center for Cellular Therapy at the Netherlands Cancer Institute (NKI) in Amsterdam and Professor of Translational Immunotherapy of Cancer at Leiden University Netherlands, added, “T-knife is establishing a leadership position in next-generation T cell engineering technologies, and is reimagining the suite of tools needed to address the challenges of first-generation TCR-T approaches. TK-6302 employs a high affinity PRAME targeting TCR, a co-stimulatory CD8 coreceptor, a FAS checkpoint converter and non-viral gene editing of a patient’s T cells. These enhancements result in robust preclinical data sets that support the potential of TK-6302 to drive broad, deep and durable responses for patients.”

Data Overview
A poster titled “TK-6302, a supercharged PRAME TCR-T cell therapy containing a high affinity TCR, an activating CD8 coreceptor (costimCD8 CoR) and a FAS-based switch receptor, drives sustained anti-tumor responses” (abstract 3198) detailed data showing best-in-class potential for TK-6302. Through the incorporation of a high-affinity TCR, a chimeric CD8 co-receptor that engages CD4 T cells and provides co-stimulation upon TCR engagement, and a FAS checkpoint converter that boosts T cell fitness in the periphery and prevents apoptosis in the tumor, TK-6302 demonstrated higher in vitro anti-tumor activity compared to known clinical-stage PRAME TCR-T approaches. Additionally, TK-6302 T cells maintained early memory phenotype upon serial killing and were protected from the inhibitory death signals in the tumor microenvironment. They also efficiently eliminated multiple rounds of complex tumor spheroids, while benchmark clinical-stage PRAME TCR-T cells failed to control long term growth of cancer cells.

A poster titled “MyT^TM platform-identified PRAME TCRs for T cell therapy demonstrate superior efficacy and best-in-class potential compared to clinical benchmarks” (abstract 3483) outlined the advantages of TCR discovery through the MyT platform to avoid the challenges of central tolerance when using human donor-derived TCRs. PRAME-directed TCRs were identified using the MyT platform, resulting in T cells with high affinity, high cytokine secretion and high cytotoxicity. Importantly, benchmarking showed that the selected lead TCR candidate displayed higher in vitro efficacy compared to publicly disclosed clinical-stage TCRs, which was retained during multiple rounds of tumor cell restimulation. Furthermore, MyT TCRs showed no off-target recognition.

A poster titled “A FAS-based switch receptor tailored to PRAME positive cancer indications, engineered to boost T cell engraftment, and anti-tumor activity” (abstract 4867) presented an extensive characterization of the tumor microenvironment of PRAME positive indications, and reviewed the effects of a novel FAS (CD95)-based checkpoint converter. T-knife’s proprietary approach increased the fitness of PRAME TCR-T cells, and boosted long-term persistence and anti-tumor activity, indicating the potential of deeper and more durable clinical responses at lower doses.

A poster titled “Optimal activation of TCR-T cells in solid tumors through addition of best-in-class single chain CD8 coreceptors results in CD4 engagement and improved T cell fitness and persistence” (abstract 4868) discussed the superior results of using its proprietary single-chain CD8 co-receptors (CoR) engineered with intracellular costimulatory signaling motifs (co-stimCD8 CoR) versus wild type CoR. PRAME TCR-T cells expressing co-stimCD8 CoR conferred higher functionality to CD4 T cells and had improved T cell fitness, resulting in enhanced functionality in serial killing experiments, including enhanced activity in 3D tumor spheroid models.

A poster titled “Combined targeting of cancer cells and tumor stroma by engineering dual-specific T cells expressing a TCR and a CAR” (abstract 6109) highlighted the advantage of also targeting fibroblast activating protein (FAP), a common cell surface antigen of cancer associated fibroblasts. Dual targeting T cells combining a PRAME-TCR and a FAP-CAR enabled the depletion of cancer associated fibroblasts and disrupted the tumor’s supportive stroma and immune barriers, thereby enhancing TCR-T cell infiltration and tumor eradication.

Copies of the posters and associated videos can be found at: https://www.t-knife.com/technology/scientific-publications.

About T-knife Therapeutics
T-knife is a biopharmaceutical company dedicated to developing T cell receptor (TCR) engineered T cell therapies (TCR-Ts) to deliver broad, deep and durable responses to solid tumor cancer patients. The company’s unique approach leverages its proprietary platforms and synthetic biology capabilities to design the next-generation of supercharged TCR-Ts with best-in-class potential.

The company’s lead program, TK-6302, is a supercharged PRAME targeting TCR-T that includes novel enhancements to improve T cell fitness and persistence, to overcome the immunosuppressive tumor micro-environment, and to improve durability of response. The company plans to submit a Clinical Trial Application (CTA) in the fall of 2025 to initiate a Phase 1 clinical study of TK-6302 in 2026.

T-knife was founded by leading T cell and immunology experts utilizing technology developed at the Max Delbrück Center for Molecular Medicine together with Charité – Universitätsmedizin Berlin, is led by an experienced management team, and is supported by a leading group of international investors, including Andera Partners, EQT Life Sciences, RA Capital Management and Versant Ventures. For additional information, please visit the company’s website at www.t-knife.com.

T-knife Therapeutics, Inc. 
Camille Landis  
Chief Business Officer / Chief Financial Officer 
media@t-knife.com