BenevolentAI Investor Day Presentation Deck

TrkC ● ● Atopic Dermatitis - BEN-2293, PanTrk rationale ● NT3/TrkC potentiates stimulated Th2 T-cell inflammatory responses and synergistically enhances T-cell receptor induced IL-4 production by Th2 cells TrkB ● Mast cells within AD skin lesions express high levels of NT3 compared to normal controls AD skin-resident eosinophils express elevated levels of TrkB (together with TrkA and C) and functionally respond to BDNF BDNF/TrkB inhibit eosinophil apoptosis and increase chemotactic index Source: Weidinger et al. Nat Rev Dis Primers 2018 Healthy skin Stratum Skin microbiota corneum Staphylococcus aureus. Stratum granulosum Stum spino um Stratum basa Dermis Blood vessel B cell T cell Non-lesional skin IL-18 IL-33 TARC IL-25 MDC TSLP w ILC2 cell CLA CCR4 IL-5 IL-13 Lichenification Barrier dysfunction, innate immune system activation and T 2-driven inflammation and/or T, 22-driven inflammation Keratinocyte Variable T1 and T 17 activation CCR10 CRTH2 x T₁2 cell T 22 cell Allergen IL-4 IL-13 T₁1 cell Acute lesional stage FceR1 Eosinophil OX40L H4R T 17 cell IL-4 IL-13. IgE IL-31 Trm cell IL-33 TSLP -Cutaneous sensory neuron Chronic lesional stage Langerhans cell Me Dermal dendritic cell Osums IDEC TrkA ● • NGF produced by AD keratinocytes is a major mediator of cutaneous hyperinnervation ● TrkA levels in skin dramatically increase in response to inflammatory stimuli ● Increased NGF in the skin sensitizes primary afferents contributing to peripheral itch sensitization and chronic pruritus Involved in the inflammatory activation of mast cells and basophils Benevolent 44

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