Immunology Investor Event

sanofi SAR444336/THOR-809: Precisely engineered non-ẞ IL-2 Selectively targeting regulatory T cells to restore immune homeostasis PEG SAR444336 IL-2 IL2RBy Tcon IL2RBY IL2R QIL2Ra Treg IL2RBY Signaling IL2Ra Signaling % Tregs in blood % Suppression 16 Tregs expanded in vivo are highly suppressive 60- 40- Dose-dependent Treg expansion in vivo (preclinical model) Gr1: Vehicle Gr2: 0.0025 mpk Gr3: 0.007 mpk Gr4: 0.022 mpk Gr5: 0.067 mpk Gr6: 0.2 mpk D-7 Pre 8 24 36 72 120 168 192 240 D13 D15 D22 Hours Treg suppression →Vehicle -SAR444336 20- 0-1 Days Increased ear thickness (mm) % Tregs 0.6- 0.4- 0.2- Dose-dependent control of skin inflammation (preclinical model) T T 0.0 Vehicle 0.1 0.3 Cys A SAR444336 (mg/kg) FoxP3 demethlyation 15- 10- 5 R2 0.98 P<0.0001 -20 No 16:1 8:1 4:1 2:1 1:1 Treg T T 0 80000 0 10 20 Tconv:Treg ratio 30 40 50 % demethylated FoxP3 Unique platform leverages synthetic biology technology Engineered for: Site-specific PEGylation affords absent binding to IL-2Rẞ with preserved IL-2Ra engagement Low MHC binding to limit immunogenicity Achieves high Treg selectivity Expansion of highly suppressive Tregs with demethylated FOXP3 gene Controls skin inflammation in vivo in preclinical model 47 Immunology Investor Event Phase 1 in healthy subjects in progress

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