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Pharma Update

Satralizumab in thyroid eye disease Potential disease-modifying treatment option with a well-established safety profile Thyroid eye disease Disease process of TED usually follows the trajectory of Rundle's curve* IL-6 as a potential target for treating TED Roche IL-6 in TED² Ph III (SatraGo-1/SatraGo-2) trial design Orbital volume (CT) in TED patients with or without detectable IL-6 mRNA expression in OF (RT-PCR) W24 W48 W72 D1 W2 W4-Q4W until W20 W24 W26 W28-Q4W until W44 Clinical Manifestations Inflammation Fibrosis Active Phase 1-3 Years Inactive Phase 3+ Years Complex orbital inflammatory autoimmune disease¹ Retroorbital volume (mm²) 2500 P<0.05 P<0.05 P<0.05 2000 1500 1000 500 TU 0 IL-4 + IL-6 + IL-10 Cytokine gene expression in orbital fat tissue R satralizumab n=60 1:1 placebo n=60 Primary endpoint Final in Final person phone visit call satralizumab placebo satralizumab / placebo phone call follow-up • • Most common orbital disease in adults, with symptoms such as redness, dry eye, double vision, protrusion of the eye with periorbital swelling and vision loss¹ Treatment options limited; faster and durable disease modification needed to prevent downstream fibrosis • . IL-6 is a pleiotropic cytokine produced by orbital fibroblasts, macrophages and adipocytes of TED patients, mediating inflammation and fibrosis Satra binds to the IL-6R, preventing IL-6 from binding, inhibiting inflammatory signalling pathways3,4 Two identical Ph III studies investigating Satra in TED (SatraGo-1/SatraGo-2) initiated Q3 2023 * Rundle's curve depicts schematically the typical course of thyroid eye disease severity with time; 1. https://eandv.biomedcentral.com/counter/pdf/10.1186/s40662-014-0009-8.pdf; 2. Hiromatsu et al. J Clin Endocrinol Metab. 2000 Mar;85(3):1194-9; 3. Traboulsee A, et al. Lancet Neurol 2020;19:402–412; 4. Yamamura T, et al. N Engl J Med 2019;381:2114-2124; TED-Thyroid eye disease; CT-Computed tomography; OF-Orbital fat; IL-6=interleukin-6; IL-6R-Interleukin-6 receptor; RT-PCR-Reverse transcriptase polymerase chain reaction; Satra-Satralizumab; W=week; IL-4(10)=Interleukin 4(10) 127
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