Medigene Presents Latest Data on UniTope and TraCR Technology at PEGS and SITC 2024

Medigene AG, an oncology platform company focused on the research and development of T cell receptor (TCR)-guided therapies for the treatment of cancer, presented latest updates on its End-to-End (E2E) Platform technology – the UniTope and TraCR technology, a universal detection system for tagging and tracking recombinant TCRs (rTCRs), at the Protein and Antibody Engineering Summit (PEGS) in Barcelona from November 5-7, 2024, and the Society of Immunotherapy of Cancer (SITC) 2024 conference in Houston, TX, USA from November 6-10, 2024.

“Precise tracking of T cells engineered to express rTCRs is essential for thoroughly vetting rTCR candidates to identify optimal 3S (specific, sensitive and safe) lead candidates, assess specific rTCR sequences during drug product development, and provide consistent monitoring of TCR-T cells throughout Good Manufacturing Practice production.

At Medigene, we are constantly aiming to expand our End-to-End (E2E) Platform by integrating new proprietary technologies such as the UniTope and TraCR system to optimize our discovery process for selection of 3S rTCRs. With UniTope and TraCR, rTCR sequences of any specificity can also be precisely identified during drug product manufacture through accurate assessment of rTCR expression and frequency of rTCR-T cells.

During the clinical phases of development, these technologies support robust quality control processes for drug product release, facilitates precise dosing calculations for therapeutic administration and provides a simple methodology for assessing the pharmacokinetics and pharmacodynamics of TCR-T cells post-infusion in patients, all of which contribute to optimizing patient safety,” – said Dolores Schendel, CSO of Medigene AG.

The data presented at both conferences showcased Medigene’s novel UniTope and TraCR System for universal identification of rTCRs in TCR-T therapies. This system enables standardized tagging, enrichment and tracking of rTCRs by use of simple flow cytometry-based technologies with a single detection reagent.

Bioinformatic studies were used to identify a unique, six-amino-acid peptide, designated as UniTope, with predicted low immunogenicity. This sequence is absent in all natural TCR chains, enabling rTCRs to be earmarked with a unique identifier through seamless integration of UniTope directly in the rTCR sequence of either chain of any TCR heterodimer. A corresponding antibody, designated TraCR, was developed that specifically binds to UniTope-modified rTCRs, but not to any natural TCR sequence, enabling precise identification of tagged rTCRs.

Comprehensive studies compared UniTope-modified rTCRs with unmodified rTCRs for 3S attributes of specificity, sensitivity and safety.

In vitro tests showed that integrating UniTope in rTCRs expressed by TCR-T cells targeting the neoantigen mKRAS G12V or the cancer-testis antigens NY-ESO-1 and PRAME preserved TCR expression as well as function, confirming that UniTope-modification had no impact on the rTCRs structural and functional attributes.

Safety assessments further validated TCR-T cells with UniTope-modified rTCRs maintained a high safety profile with no signals for unintended recognition of cells originating from primary healthy tissues.

Overall, equivalent specificity, safety, and functionality of UniTope-modified rTCRs, compared with unmodified rTCRs, demonstrates the versatility of the UniTope & TraCR System as a high precision technology that facilitates optimized development of TCR-T therapies.

About Medigene AG

Medigene AG (FSE: MDG1) is an immuno-oncology platform company dedicated to developing T cell receptor (TCR)-guided therapies to effectively eliminate cancer. Its End-to-End Platform generates optimal 3S (sensitive, specific and safe) T cell receptors with unique and distinctive attributes that are utilized in multiple therapeutic modalities, such as T cell receptor engineered T cell (TCR-T) therapies, TCR-guided T cell engager therapies and TCR-natural killer cell therapies for both its in-house product pipeline and partnering.

Medigene’s lead TCR-T program MDG1015 is a potential best-in-class, TCR-T therapy to treat multiple solid tumor indications. The End-to-End Platform technologies enable armoring and enhancing of these T cells to overcome the immunosuppressive tumor microenvironment (TME) and ensure the T cell drug product composition maximizes safety, efficacy and durability of response. Medigene’s MDG1015 received IND approval in Q3 2024 and is filing for CTA in Q4 2024.

About Medigene’s End-to-End Platform

Medigene’s approach to immunotherapy harnesses the immense power of natural T cell receptors. By combining these TCRs with different components of the immune system such as T cells, natural killer (NK) cells or a CD3 complex (TCE, T cell engager), highly specific, sensitive and safe modalities are formed to either complement and/or activate the body’s defense systems against cancer.

Medigene’s comprehensive End-to-End (E2E) Platform is built on a foundation of proprietary and cutting-edge technologies, driving the development of highly specific TCR-guided therapies, including the latest advancements in TCR-T, TCR-NK and TCR-TCE drug products. The E2E Platform incorporates sophisticated TCR generation and optimization techniques, such as Allogeneic-HLA TCR Priming, and integrates advanced product armoring and enhancement features like PD1-41BB and CD40L-CD28 Costimulatory Switch Proteins, and iM-TCR.

In addition, the E2E Platform offers solutions to developing optimal cell therapy drug products for improved safety, efficacy and durability. Collaborations with partners like BioNTech, Regeneron and WuXi Biologics further underscore the platform’s capabilities and its potential to revolutionize cancer treatment.

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