Celyad spells out its off-the-shelf ambitions

Over the past few years Celyad has made much of its desire to become a player in off-the shelf CAR-T. But it was only yesterday, during the tail end of an R&D presentation, that it spelled out precisely what it planned to do and how. Three new allogeneic CAR-T projects were presented: CYAD-211 targeting BCMA, CYAD-221 against CD19, and CYAD-231, a bispecific construct versus NKG2D ligands and an undisclosed antigen. These are due to enter clinical trials in mid-2020, late 2020 and early 2021 respectively. All use a short hairpin RNA technology licensed last October from Horizon Discovery to knock out endogenous T-cell receptors – the cause of graft-versus-host disease – without gene editing. Meanwhile, a phase I trial of Celyad’s first allogeneic CAR, CYAD-101, also against NKG2D ligands, is ongoing, but to silence the T-cell receptor this asset uses a different mechanism, namely a “TCR inhibitory molecule”. A resurgence of interest in off-the-shelf CAR-T approaches saw Precision Biosciences outline the terms of its Nasdaq flotation yesterday. Celyad will compete against Precision and more established players, and said it was important to hit validated antigens before looking to novel targets.

Celyad's allogeneic CAR-T assets
Project CYAD-101 CYAD-211 CYAD-221 CYAD-231
Target NKG2D ligands BCMA CD19 NKG2D ligands x undisclosed bispecific
TCR silencing tech TIM* shRNA shRNA shRNA
Clinical trial NCT03692429 mid-2020 Late 2020 Early 2021
Allogeneic competition None ALLO-715 (Cellectis/Allogene) UCART19 (Cellectis/Allogene) None
    PBCAR269A (Precision) ALLO-501 (Allogene)  
    P-BCMA-ALLO1 (Poseida) PBCAR0191 (Precision)  
      CTX101 (Crispr)  
      CD19-CAR (Sangamo/NCI)  
Source: company filings; *TCR inhibitory molecule.

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