A novel click chemistry-based, universal radiolabelling platform revolutionizing the generation of theranostic radiopharmaceuticals

Informazioni relative al progetto

TETRAKIT

ID dell’accordo di sovvenzione: 101218021

DOI

10.3030/101218021

Data della firma CE 2 Giugno 2025

Data di avvio 1 Luglio 2025

Data di completamento 30 Giugno 2027

Finanziato da

• The European Innovation Council (EIC)

Costo totale

Nessun dato

Contributo UE

€ 2 458 700,30

Coordinato da

TETRAKIT TECHNOLOGIES APS
Denmark

Periodic Reporting for period 1 - TETRAKIT (A novel click chemistry-based, universal radiolabelling platform revolutionizing the generation of theranostic radiopharmaceuticals)

Periodo di rendicontazione: 2025-07-01 al 2026-06-30

Sintesi del contesto e degli obiettivi generali del progetto

TETRAKIT is developing a theranostic radiopharmaceutical platform based on DualFAPi, a bivalent small-molecule ligand of fibroblast activation protein (FAP), a marker over-expressed in the stroma of many solid tumours. The platform pairs the same targeting vector with a diagnostic radionuclide (iodine-123, for SPECT imaging) and a therapeutic radionuclide (iodine-131), joined by a single-step click-chemistry radiolabelling step. The overall objective is to bring the lead therapeutic candidate, 131I-DualFAPi, to Clinical Trial Application (CTA) submission and Phase 1/2 clinical studies in triple-negative breast cancer (TNBC), while initiating first-in-human diagnostic imaging with the companion 123I-DualFAPi to confirm tumour targeting, support patient selection and guide treatment monitoring. Because the diagnostic and the therapeutic share the same vector, the first-in-human imaging read-out de-risks the entire therapeutic programme before committing to GMP scale-up and clinical trials. The work is organised across five work packages: GLP toxicology and first-in-human imaging (WP1), GMP manufacturing (WP2), regulatory strategy (WP3), market preparation and IP (WP4), and project management (WP5).

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

During the first reporting period, GLP-compliant extended single-dose toxicology of the compound was completed (Deliverable D1.1) with no findings that would prevent clinical translation. Technology transfer of the 123I-DualFAPi companion diagnostic to University Hospital Magdeburg was carried out, and the first-in-human documentation package was prepared under the physician-led named-patient route of section 13(2b) of the German Medicines Act, including issued manufacturing, testing and batch-record instructions to a GMP-equivalent standard together with quality-control validation; first-in-human imaging has been initiated. In manufacturing, the 131I-DualFAPi formulation was finalised with 24-hour stability confirmed at the injectable dose, and GMP-grade precursor production is well advanced. On the regulatory side, the Investigator's Brochure and the IMPD are in preparation, a CMC gap analysis was completed, and structured engagement with the EMA (SME scientific advice) was initiated. Market-preparation activities progressed, including a Freedom-to-Operate analysis and refinement of the IP and exploitation strategy. Project-management foundations were established, with the Data Management Plan (D5.1) and the exploitation and dissemination plan (D5.2) submitted. Overall implementation stands at approximately 45%, on track overall, with a small number of critical-path tasks being recovered and formally notified to the Agency.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

The project advances a differentiated approach to radioligand therapy. Unlike agents based on scarce or highly toxic radionuclides such as lutetium-177 or actinium-225, TETRAKIT uses iodine radioisotopes (123I and 131I) delivered through a single, modular click-chemistry labelling step, giving a true theranostic pair from one targeting vector. The lead vector is a FAP dimer, designed for higher tumour affinity and retention than monomeric FAP ligands. The companion-diagnostic strategy allows human tumour targeting and dosimetry to be confirmed before committing to therapeutic scale-up, reducing late-stage clinical risk. Validation of the underlying platform is further supported by a second platform compound (18F-FlutraProst) that has progressed to first-in-human use. Expected results by project end include first-in-human imaging and dosimetry data for 123I-DualFAPi and a CTA-ready dossier for the 131I-DualFAPi therapeutic, opening a path to Phase 1/2 studies and, in the longer term, expansion to further FAP-expressing solid tumours.