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Pharma Update

Fenebrutinib, pivotal trials in RMS and PPMS ongoing The only BTKi in H2H Ph III trial in PPMS vs Ocrevus Fenebrutinib BTKi competitive landscape¹ Tolebrutinib Evobrutinib Remibrutinib Ph III program overview Non-covalent Reversible WB B cell IC 50° 8nM WB Myeloid cell IC 50° 31nM Ph III H₂N H₂N N Covalent Irreversible Covalent Irreversible Indication Trial design Phl Ph II Ph III RMS vs placebo FENopta Jaye NH₂ RMS vs teriflunomide FENhance 1/2 PPMS vs Ocrevus FENtrepid Covalent Irreversible 10 nM 84 nM 18 nM 166 nM 1660 nM 67 nM Positive data readout, primary and secondary endpoints achieved • Potential to be best-in-class given high potency, high selectivity, reversibility, and only H2H study vs Ocrevus Large safety database of >2,500 pts who have been dosed with fenebrutinib* • Ph III Ph III Ph III FDA partial clinical hold FDA partial clinical hold RMS, RMS, SPMS, RMS PPMS (vs Ocrevus) PPMS (vs Placebo) RMS ● Further solidifying commitment to MS franchise Roche 1. Kramer, et al (2023) nature reviews neurology 289-304; Crawford, et al. (2018) J Med Chem 61, 2227-2245; Francesco, et al., ACTRIMS-ECTRIMS (2017) 200644. Haselmayer, et al. (2019) J Immunol 202, 2888-2906; Angst D, et al. (2020) J Med Chem 63, 5102-5118. MS-multiple sclerosis; H2H-head-to-head; RMS-relapsing multiple sclerosis; PPMS-primary progressive MS; BTK-Bruton's tyrosine kinase; nM=nanomolar; WD=whole blood; *As of Sept 2023: including non-MS Ph I/II studies 104

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