Pharma Update

Englumafusp alfa (CD19-4-1BBL) in r/r NHL First-in-class B cell-targeted costimulatory T cell agonist Englumafusp alfa + Columvi Pharmacodynamic biomarker data support novel MoA Signal 2 (costimulation) CD19-4-1BBL T cell Tumor cell lysis CD3- CD20 Signal 1 (T cell activation) Glofitamab CD19 CD20 Effector function ↑ Tumor cell killingt Duration of responset Tumor cell (malignant B cell) Modified from Johannes Sam, Roche PRED CD8 T-cell Expansion Change from baseline (C2D8 pre-dose) 8.000- 2.000 0.500 0.125 Pre-dose C2D8 post-dose C2D9 C3D1 pre-dose C3D1 post-dose C3D2 C3D8* C4D1 pre-dose C5D1 pre-dose* RG6076 dose group • Low • Medium • High Glofitamab RG6076 • • Signal 1: NK or T cell activation delivered by Columvi Signal 2: CD19-4-1BBL leads to enhanced NK and T cell activation and promotes a durable immune response First-in-class 4-1BB agonist with B cell targeted co- stimulation of T cells • A dose relationship with reversal of PD1+ terminally differentiated CD8 T-cell expansion in blood is emerging at the C3D8, C4D1, and C5D1 timepoints • Data indicate that CD19-4-1BBL costimulation may lead to a more durable response to Columvi and potentially prevent disease escape Ph I studies for Columvi + CD19-4-1BBL or costimulatory bispecific CD19 x CD28 in r/r NHL ongoing Hutchings et al. ASH 2022; TCB-T cell bispecific; NK-natural killer; R/R=relapsed refractory; NHL-non-Hodgkin's lymphoma; MoA-Mode of action 93 Roche

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