89 New Therapeutic Modalities Are Proliferating During the last thirty years, the number of therapeutic modalities with entirely new mechanisms of action has proliferated. Not only have they expanded the number of treatable diseases, but they have also improved efficacy and safety. In 2023, more than 25% of clinical trials were harnessing new therapeutic modalities. Discovery of New Modalities Based On Base/Prime Editors* Investigational New Drug Application Approval TPDs γδ T-cells mRNA Vaccines S CRISPR/Cas9 E iPSCs PI A R TALENS E H CAR-T T N ZFNs O I siRNA/RNAi S I Antibiotics C RNA Aptamers E Small Molecules Penicillin (1928) PR Aspirin (1899) ASOs Antibody-Drug Conjugates Proteins Small Peptides Monoclonal Antibodies Insulin (1921) Oxytocin (1953) TILs Prodrugs 1900 1920 1940 1960 1980 2000 2020 Watson & Crick Recombinant Single Molecule Real *This timeline is not exhaustive. (1953) DNA (1972) Polymerase Sequencing by Time Sequencing (2011) Sanger Sequencing Chain Reaction Synthesis (1996) (1977) (1982) Sources: ARK Investment Management LLC, 2024. This ARK analysis is based on a range of external sources, including Biomedtracker, which may be provided upon request. Forecasts are inherently limited and cannot be relied upon. For informational purposes only and should not be considered investment advice or a recommendation to buy, sell, or hold any particular security. Past performance is not indicative of future results.