BioNTech Investor Day Presentation Deck

How do different types of neoantigens induce T-cell responses and kill tumors? NATURE REVIEWS | DRUG DISCOVERY Identification of neoantigens for individualized therapeutic cancer vaccines Franziska Lang', Barbara Schrörs', Martin Löwer¹, Özlem Türeci² and Ugur Sahin 2,3 T cell count Tumour growth ICB therapy Neoantigen vaccine ផ្ទុ Evolution of neoantigen-specific T cell responses Tumour onset Restrained neoantigen-specific T cells Ignored neoantigen-specific T cells Cross-reactive guarding neoantigen-specific T cells Lang F, et al. Nature Rev Drug Discov 2022; 21:261-282. Level of neoantigen presentation Threshold for effective priming of naive T cells Threshold for effective activation of memory T cells Guarding Restrained Ignored neoantigens neoantigens neoantigens Characteristic feature Guarding neoantigens Supreme neoantigens with strong antigenicity that drive early priming and rapid expansion of neoantigen- specific cytotoxic T cells Neoantigen cross-recognized by preformed memory T cells induced by heterologous immunity Restrained neoantigens Neoantigens that are immunogenic in the immunotherapy-naive host and induce PD1+ memory T cells that proliferate and expand under ICB Ignored neoantigens Neoantigens that do not induce a relevant immune response in the tumor-bearing host but are able to drive tumor immunity once memory effector T cells are induced by vaccination Target discovery Estimated frequency Extremely rare <2% of all mutations <2% of all mutations 15-25% of all mutations BIONTECH 25

View entire presentation