The board of directors of Immunotech Biopharm Ltd. announced that the Company has obtained the clinical approval for the Denocabtagene Ciloleucel Injection from the National Medical Products Administration. Denocabtagene Ciloleucel Injection, originally known as CAR-T-19-D2, CAR-T-19-DNR and RC19D2, targets CD19 antigens and an antagonist of proteins in the downstream signaling of TGF-ß, it is an injection for the treatment of patients with relapsed and refractory diffuse large B-cell lymphoma ("DLBCL"). The injection has the goal of overcoming chimeric antigen receptor T cells' ("CAR-T cells") pain points in terms of the lack of persistence, the lack of efficacy in the treatment of solid tumours, and in the prevention of tumour recurrence. Based on the current progress, the Company expects to conduct the clinical trial of Denocabtagene Ciloleucel Injection in 2023. CAR-T cells are T cells that have been genetically engineered to produce an artificial T-cell receptor and chimeric antigen receptors that have been engineered to give T cells the new ability to target a specific protein on the surfaces of cells. CAR-T cells are remarkably
effective in the treatment of patients with relapsed and refractory lymphoma. Despite this, CAR-T cells' therapeutic effect on a certain proportion of patients is still very poor partly because of mechanisms in lymphomas to evade attack by the immune system, as is the case of most other malignant solid tumours. The functional components of the Denocabtagene Ciloleucel Injection are T cells that are genetically modified to express an anti-CD19 chimeric antigen receptor and an antagonist of proteins in the downstream signaling of TGF-ß. CD19 is widely expressed on the surface of B cells during all phases of B cell development. Furthermore, the vast majority of tumour cells from diseases caused by the mutation of B cells and their precursor cells such as B cell lymphoma and acute B lymphocytic leukaemia also express CD19, making CD19 one of the targets for the treatment of these tumours. By linking the anti-CD19 single-chain antibody, protein transmembrane domain, and co-stimulatory molecular domain, the technology may avoid issues such as the failure of autoimmune cells to recognise human CD19 protein, the inhibition of tumour cells on immune cells and the insufficient second messenger signalling pathway. This may enable the modified T cells to directly recognise the CD19 molecule and kill the cells carrying the target, thereby achieving the purpose of treating the tumour. In addition, the synchronisation of transcription and translation of the antagonist of proteins in the downstream signaling of TGF-ß within the cells has the potential to inhibit the immunosuppressive effect caused by TGF-ß in the tumour microenvironment and prevent the weakening and depletion of CAR-T cells' immune killing ability, thereby further improving
the therapeutic effect.