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Pharma Update

Enspryng in neurological disorders gMG, AIE, and MOG-AD First-in-class anti-IL-6R mAb with best-in-disease potential in AcHR+ gMG Enspryng (Anti-IL-6 receptor mAb) gMG: Autoantibodies at the NMJ1 Ph III (LUMINESCE) trial design Neutral pH (7.4) FcRn Anti-AChR Anti-MuSK Nerve terminal Anti-LRP4 MG patients (N=186) MGFA class II-IV, ≥12 yrs • MG-ADL ≥5 Enspryng + SOC 24 weeks Mechanism of anti-MuSKs AChR+, MUSK+, LRP4+ R Mechanism autoantibody positive 1:1 Agrin of anti-AChRs LRP4 ACh Blocked ACh-AChR binding Patients on stable baseline therapy Reduced density Complement of AChR No requirement on previous Acidic pH (6.0) AChE and/or ColQ Cell treatment failure/s AChR- MuSKO Rapsyn. MAC MAC formation and damage of the postsynaptic membrane Placebo + SOC Increased AChR internalization Primary endpoint: and degradation IL-6 receptor gets internalized and degraded Roche • . Recycling mAb with high-affinity to soluble and membrane-bound IL-6R Engineered to enable maximal inhibition of IL-6 signaling • Convenient SC Q4W home administration Mean change from baseline MG-ADL score at week 24 in the AChR+ population • IL-6 blockade has the potential to reduce autoantibody-mediated NMJ damage in gMG . High unmet need: ~10-30% of patients fail SOC therapies with only up to 40% of patients on approved biologics achieve minimal symptom expression² ⚫ Ph III (LUMINESCE) results in gMg expected in 2024 Additional Ph III studies in 2 other autoantibody mediated rare neurological diseases ongoing with first-in- disease potential: Ph III (CIELO) in AIE and Ph III (METEOROID) in MOG-AD 1.Gilhus N.E. et al., Nat Rev Dis Primers. 2019; 2. Howard JF Jr, et al. Lancet Neurol. 2021 IL-6R-interleukin 6 receptor; MG=myasthenia gravis; gMG= generalized myasthenia gravis; AcHR-acetylcholine receptor; NMJ-neuromuscular junction; SC=subcutaneous; Q4W=every 4 weeks; MOG-AD=myelin oligodendrocyte glycoprotein antibody-associated disease; LPI=last patient in; AIE-autoimmune encephalitis; SOC=Standard of care; MGFA-Myasthenia Gravis Foundation of America; MG-ADL-Myasthenia Gravis Activities of Daily Living 105
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