T-knife Therapeutics Announces Dosing of First Patient with TK-8001 in the IMAG1NE Phase 1/2 Clinical Trial

The IMAG1NE Phase 1/2 trial is an accelerated dose-titration, open-label, multi-center Phase 1/2 trial to evaluate TK-8001 in patients with MAGE-A1 positive solid tumors

TK-8001 targets a MAGE-A1 epitope presented on HLA-A*02:01

IMAG1NE utilizes biomarker-guided patient selection criteria to enroll those patients that have the highest potential for safe, deep, and durable responses

MAGE-A1 is an attractive therapeutic target that is highly cancer specific and demonstrates significant consistency of expression between primary tumor and metastases


San Francisco, CA and Berlin, Germany – October 20, 2022 - T-knife Therapeutics, Inc., a clinical-stage biopharmaceutical company dedicated to developing T cell receptor-based immunotherapies that deliver transformational benefits to cancer patients, today announced it has dosed the first patient in the IMAG1NE Phase 1/2 clinical trial. The IMAG1NE trial is designed to evaluate the safety and preliminary efficacy of TK-8001, a T cell receptor (TCR) engineered T cell therapy (TCR-T) specific for the Melanoma-associated Antigen Gene-A1 (MAGE-A1), in patients with solid tumors.

“We believe our MyT Platform is distinct in its ability to identify TCRs that have been naturally optimized for affinity, specificity and sustaining long-term T cell function, making TK-8001 a promising new therapy to target MAGE-A1 positive solid tumors,” stated Eugen Leo, M.D., Ph.D., Chief Medical Officer of T-knife. “Our IMAG1NE trial combines a TCR with best-in-class potential, manufacturing designed to select the most potent T cells, and biomarker-guided patient selection criteria that seeks to enroll those patients that we believe have the highest likelihood of safe, deep and durable responses to TK-8001.”

“We are excited to bring our first MyT Platform derived product candidate into the clinic,” added Thomas M. Soloway, Chief Executive Officer of T-knife. “This is a significant milestone representing the rapid progress at T-knife, and we are thankful for the support and trust we have received from our many collaborators, investigators and the patient community as we pursue our goal to build a global company focused on bringing the power of TCR-based therapies to cancer patients.”  

In preclinical studies, the MAGE-A1-directed TCR incorporated in TK-8001 exhibited high binding affinity and specificity to a MAGE-A1 epitope presented on HLA-A*02:01. Importantly, T cells incorporating the MyT Platform derived TK-8001 TCR demonstrated in vitro serial killing activity and enhanced in vivo anti-tumor activity compared to T cells engineered with TCRs derived from human donors. 

The IMAG1NE Phase 1/2 trial is an accelerated dose-titration, open-label, multi-center Phase 1/2 trial designed to evaluate the safety and preliminary efficacy of TK-8001 in patients with MAGE-A1 positive solid tumors. The Phase 1 part of the study is focused on the selection of a dose to advance into the Phase 2 part of the study. The Phase 1 dose escalation part is designed to enroll approximately 6 to 18 patients to assess the safety and tolerability of TK-8001 at various doses. Once the recommended Phase 2 dose has been identified, TK-8001 will then be evaluated in an expansion part of the trial.   

About TK-8001 TCR-T Targeting MAGE-A1 Positive Solid Tumors

TK-8001 is a TCR-T specific for the Melanoma-associated Antigen Gene-A1, or MAGE-A1. MAGE-A1 is associated with hallmarks of aggressive cancers and poor clinical prognosis, and there is an emerging body of evidence indicating its involvement as a potential driver of tumorigenesis. MAGE-A1 represents an attractive therapeutic target given the high unmet need in MAGE-A1 expressing cancers, no reported protein expression in healthy tissues other than testis (an immune privileged site where HLA is not expressed and antigen is not presented), and significant consistency of expression between the primary tumor and metastases. As high affinity TCRs specific for MAGE-A1 in humans are eliminated through central immunological tolerance, T-knife believes its MyT Platform is a differentiated means to discover and select MAGE-A1 specific TCRs with an optimal affinity and specificity profile. 

About the T-knife MyT™ Platform

Genetic engineering of T cells with T-cell receptors (TCRs) recognizing antigens aberrantly or over-expressed in cancers can redirect these T cells to the tumor, potentially offering curative responses to cancer patients. However, the ability to identify potent cancer-specific TCRs has been limiting for the field of TCR-T. In the case of self-antigens, T cells bearing those TCRs are eliminated during T cell development to avoid recognition and attack of healthy tissues. For non-self tumor antigens, such as those derived from mutations or viral sequences, the very low T cell frequency in the blood has limited TCR discovery efforts.

To overcome these challenges, T-knife has developed transgenic mice carrying the human TCRαβ gene loci and expressing single or multiple human HLAs. Immunizing these mice with human tumor antigens, for which mice are not tolerant, allows for the identification of both CD4+ and CD8+ T cells with TCRs that have optimized affinity / specificity profiles capable of mediating significant anti-tumor activity. The TCRs from these mice are of higher affinity for tumor self-antigens than TCRs isolated from human donors and are naturally optimized to maintain a high specificity profile, making MyT mice a powerful high-throughput platform for rapidly generating TCRs with best-in-class potential.

About T-knife Therapeutics

T-knife is a clinical-stage biopharmaceutical company dedicated to developing T cell receptor-based immunotherapies that deliver transformational benefits to cancer patients, initially focused on T cell receptor (TCR) engineered T cell therapies (TCR-Ts), a modality that holds the potential to generate transformational responses in patients with solid tumors. The Company’s unique approach leverages its proprietary MyT Platform, a next-generation T cell receptor and epitope discovery engine that produces fully human, tumor-specific TCRs, naturally selected in vivo for optimal affinity and specificity.

T-knife is advancing a portfolio of TCR-T product candidates against targets with high unmet medical need, including cancer testis antigens and commonly shared tumor-driving neoantigens. T-knife was founded by leading T cell and immunology experts utilizing technology developed at the Max Delbrück Center for Molecular Medicine together with the Charité – Universitätsmedizin Berlin. For additional information, please visit the Company’s website at www.t-knife.com.