Pharma Update

Fenebrutinib, potential for a best-in-class BTKi in MS Additional Ph II (FENopta) data to be presented at ECTRIMS Fenebrutinib (BTK inhibitor) Macrophage Periphery B cell Ph II (FENopta) results in RMS Total new T1 Gd+ lesions by week and combined* Week 8 Week 12 BTKi dual MOA: inhibits B-cell and myeloid cell B cells/plasmablast Activation via B-cell receptor CNS activation B cell Microglia Myeloid cell Activation via Fc receptor Adjusted mean number of new T1 Gd+ lesions Week 4 0.4 92% (65% to 98%) 22% 0.3 33 (-92% to 68%) 0.2 0.1 0 90% (52% to 98%) Adjusted rate of new T1 Gd+ lesions 0.4 0.3 0.2 0.1 Roche @ean european academy of neurology IR call on October 30 Combined (Weeks 4, 8 and 12) P=0.0022 0 No. of patients 36 70 • Dual MoA targeting both B cells and myeloid cells • Oral, highly selective and only reversible non- covalent BTK inhibitor in Ph III in MS Excellent selectivity limits off-target effects, potential for better safety outcomes . FENopta biomarker study evaluated early impact of fenebrutinib on MRI outcomes and showed significant reductions in brain lesions in RMS patients, meeting primary and secondary endpoints Patients on fenebrutinib 4x likelier to have no new T1 Gd+ & N/E T2 lesions at weeks 4, 8 and 12 vs placebo Safety profile consistent with previous and ongoing trials CSF concentration data from Ph II (FENopta) trial to be presented at ECTRIMS on Oct 10-13th Hua LH et al., EAN 2023; *Results were estimated from a negative binomial model controlling for baseline T1 Gd+ lesion status (presence or absence) and included log number of scans as an offset. Arrows indicate relative reduction (95% CI) of lesions; MS=multiple sclerosis; BTKi-Bruton's tyrosine kinase inhibitor; MoA-mechanism of action; CSF-cerebrospinal fluid; RMS=relapsing multiple sclerosis; Gd+=gadolinium-enhancing; MRI-Magnetic Resonance Imaging; RMS-Relapsing multiple sclerosis; CNS-Central nervous system 103

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