Investor Presentaiton

38 Werner Helicase is Synthetic Lethal with Microsatellite Instability Targeting Development Candidate in H2 2023 Werner Helicase Inhibitors Phenocopy Genetic SL in MSI-High Cancers Nanomolar Potency, Biochemical and Cellular Activity, and Selectivity over other RecQ Helicases Werner Helicase Synthetic Lethality in MSI-High Cancer Cells TATA Normal ATAT WRN resolves TA Repeat 2° Structures to prevent Catastrophic DNA Fragmentation in MMR-deficient Cells Werner GSK Werner Helicase Synthetic Lethal with High-MSI CellPress Werner Syndrome Helicase is Required for the Survival of Cancer Cells with Microsatellite Instability IDEAYA Publication ISW MSS terminal cell count terminal cell count fold change (control) fold change (control) HCT116 LoVo 1.5- 1.0- 0.5- 0.0 0.0 cont WRN cont WRN SW620 SW948 1.5 1.0- 0.5- TATATATATATATATATATATATA MSI-H ATATATATATATATATATATATAT (TA)n repeat TATATA WAVE MMR Expanded (TA)n repeat TATATATATATATATATATAL ᎬᏆᏆᏆᏌᏆᏌᏆᏆᏌᏆᏆᎽᏆᏌ Replication slippage Cruciform formation ATR WRN proficient WRN TATATATA ATATATATA - ⚫ DS DNA breaks MUS81-EME1 WRN SLX4 TATATATATATATATATA TATATATATATATATAL Intact genome Cell Press, iScience, March 2019, Hager et al 0.0 0.0- cont WRN cont WRN Analysis of pan-cancer screen datasets reveals WRN essentiality in MSI-H cancer cell lines CCLE MSI-H CCLE MSS CCLE unannotated - ド DepMap (CRISPRko) WRNi SATATATATATATATATA TATATATATATATATATA Chromosome shattering -2.0 -1.5 -0.5 0.5 -1.0 0.0 WRN Gene Effect (Chronos) CRISPR (DepMap 22Q2 Public+Score) IDEAYA / GSK Data: AACR 2023, M. Fischer et. al. GSK Strategic Partnership: 50/50% US Profit Share and ex-US Royalties, ~$1B Milestones, incl up to $20M Preclinical / Ph1 Clinical; Cost Share 80% (GSK) / 20% (IDEAYA); Potential Combination with GSK's JemperliTM, a PD-1 IO Agent BIOSCIENCES IDEAYA

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