Module 9 2024

03/09/2024

The Three ATMP Classes

Gene Therapies: active substance is recombinant nucleic acid Viral vectors: AAV, lentivirus, adenovirus Genetically-modified cells: CAR-Ts, gene-edited HSCs

Somatic Cell Therapies: active substance is cells Cultured cells with modified biological function (eg in vitro differentiated MSCs) Genetically-modified cells where therapeutic effect not due to recombinant nucleic acid

Tissue-engineered Product Cells cultured in a scaffold for regenerative medicine Chondrocytes in gel for cartilage reconstruction

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What’s Next Gene editing: creation of biallelic site specific double strand breaks or homologous recombination Meganuclease, ZFN, TALENS and CRISPR/Cas9 NHEJ to knock out specific genes via Insertion / Deletion (indels) HDR for gene correction via point mutation, safe harbor gene addition and targeted gene addition. CRISPR/Cas9 Easy adaptable and scalable site-specific RNA DNA base hybridization SCD correction via BCLA-11 knock out, HIV correction via CCR5 Knock out Targeted gene correction for DMD Germline engineering Allo-CAR+T

Off-the shelf CART therapy T cells Genome editing via Β 2M knock out Allogeneic CAR+T-NK and double negative T cells In-vivo gene therapy IPSC

CART for solid tumors

Cost reduction Strimvelis: 600,000 EU / treatment Zalmoxis: 149,000 EU / treatment (4 treatments planned)

Glybera: 1,000,000 $ / treatment Kymriah: ~ 475,000 $ / treatment Zongelsma: $425,000/year over 5 years

Casgevy: $2.2K/pt Lyfgenia: $3.1K/pt

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