iTANK: a nuniversal technology to boost the efficacy of CAR T cell therapies by inducing dual mode-of-actio

Informations projet

CD20CARNAPT

N° de convention de subvention: 190129097

DOI

10.3030/190129097

Projet clôturé

Date de signature de la CE 26 Septembre 2022

Date de début 1 Octobre 2022

Date de fin 30 Septembre 2025

Financé au titre de

• The European Innovation Council (EIC)

Coût total

€ 3 604 499,00

Contribution de l’UE

€ 2 499 999,00

Coordonné par

ELICERA THERAPEUTICS AB
Sweden

Periodic Reporting for period 3 - CD20CARNAPT (iTANK: a nuniversal technology to boost the efficacy of CAR T cell therapies by inducing dual mode-of-actio)

Période du rapport: 2024-10-01 au 2025-09-30

Résumé du contexte et des objectifs généraux du projet

CAR T cell therapy has transformed the treatment of relapsed or refractory B-cell malignancies such as leukemia and lymphoma, thanks to the four CD19 CAR T-cell-based therapies available in Europe. Nevertheless, 40–50% of treated patients either fail to respond or relapse after receiving approved CD19 CAR T products. This limited durability is mainly caused by antigen loss, tumour heterogeneity, immunosuppressive tumour microenvironment and functional exhaustion of the infused CAR T cells.
Elicera Therapeutics has developed iTANK, a platform designed to bring CAR T cell efficacy to another level by inducing a dual mechanism of action. iTANK arms CAR T cells with NAP, an immune-activating protein that is only released when CAR T are in close proximity to the tumour. This local release triggers broader immune activation and a bystander effect that addresses key resistance mechanisms of conventional CAR T therapy.
With support from the EIC Accelerator, Elicera has conducted a first-in-human CARMA-01 study with CAR-T cells targeting CD20 and achieved highly encouraging preliminary results from the first two treated cohorts. Among the first six patients treated in the Phase I dose-escalation stage, four achieved complete metabolic response, including one individual previously treated with commercial CD19 CAR T therapy. These responses occurred at only 10 to 30% of the intended maximum dose. No severe or unexpected adverse events were observed. Although Phase II dose confirmation study will continue beyond the project, early findings demonstrate clinical feasibility, early efficacy and safety of iTANK-armed CAR T cells in patients who had exhausted standard treatment options.
Thanks to the EIC funding, the project has validated iTANK as a safe, versatile platform technology. The clinical experience and manufacturing infrastructure developed in this project is likely to be used for Elicera’s second iTANK-based programme, ELC-401 dedicated to incurable brain cancer - glioblastoma, provided sufficient funding is secured. Established in this project, a national clinical network and developed GMP and regulatory frameworks position Elicera as an European leader in advanced next-generation CAR T innovations.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Elicera successfully established a fully automated, GMP-compliant production process for CAR20(NAP)-T cells. Throughout the project, material handling, cell transduction and expansion protocols were optimised, resulting in the drug product fulfilling all predefined release criteria. The technology was transferred and implemented at the GMP facility, where all critical steps were qualified and executed according to GMP standards.
The complete process from patient blood collection to final infusion (vein-to-vein) was finalised in a time period of 17 days per patient. It is significantly shorter than the median 54 days reported for available commercial CAR T products. In parallel, all required QC release assays for the CAR20(NAP)-T drug product were established, validated and shown to perform according to specification.
Furthermore, all assays for analysing patient samples were developed and validated, enabling characterisation of mode-of-action markers in the clinical setting. The Clinical Trial Application was submitted and approved by the Swedish Medical Products Agency (MPA) and the Ethics Committee. The conditional requirement from the MPA to complete the outstanding GMP validation work was fulfilled, enabling CARMA-01 study initiation.
During the reporting period, two dose cohorts were treated in the Phase I dose escalation stage, comprising a total of six patients with relapsed or refractory B cell lymphoma. This provided the first clinical experience with ELC-301 and delivered the initial safety and activity data for the iTANK platform in humans.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The project delivered the first clinical proof of concept for Elicera’s iTANK platform by demonstrating preliminary efficacy and a favourable safety profile in patients with relapsed or refractory B cell lymphoma treated with CAR20(NAP)-T cells. Four complete metabolic responses were observed among the first six patients treated at low dose levels, including in one individual previously treated with commercial CD19 CAR T therapy. These outcomes significantly exceed typical expectations for an initial dose-escalation stage and provide the first clinical validation of iTANK’s dual mechanism of action in humans.
The project also advanced the state of the art by establishing a fully GMP-compliant manufacturing process for iTANK-armed CAR T cells with a vein-to-vein time of 17 days, which is substantially shorter than current commercial benchmarks. The associated release assays, patient sample assays and regulatory documentation now provide an operational and analytical framework that is directly transferable to future iTANK-based therapies.
The results further demonstrate that iTANK is a platform technology with broad applicability. The infrastructure, regulatory know-how and clinical experience generated in this project are already being leveraged for Elicera’s second iTANK-based candidate, ELC-401 for glioblastoma. The project therefore delivers important know-how and data that strengthen the competitive position of iTANK as an enhancer of next-generation CAR T therapies and support continued protection of the platform through Elicera’s intellectual property portfolio.
Overall, the project has advanced CAR T cell therapy beyond the current state of the art by providing the first human evidence of improved immune activation and early therapeutic responses with an iTANK-armed CAR T product, by establishing a fast and scalable GMP process, and by laying the groundwork for broader application of the platform in other hard-to-treat cancers.