BenevolentAI Results Presentation Deck

TrkC Atopic Dermatitis - BEN-2293, pan-Trk inhibition 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 Healthy skin Stratum. Skin microbiota corneum Staphylococcus aureus. Stum granu sum Stratum spinosum Stratum basale Dermis Blood vessel B cell I cell Non-lesional skin IL-18 IL-33 TARC IL-25 MDC TSLP mm ILC2 cell CLA CCR4 Lichenification Barrier dysfunction, innate immune system activation and T2-driven inflammation and/or T.22-driven inflammation Keratinocyte Variable T1 and T, 17 activation IL-13 CCR10 CRTH2 T₁2 cell T,22 cell Allergen IL-4 IL-13 cell Acute lesional stage FCER1 Eosinophil OX40L ↓ H4R T,17 cell IgE IL-4 IL-13 IL-31 Trm cell IL-33 TSLP -Cutaneous sensory neuron BenevolentAl Proprietary Chronic lesional stage mu Langerhans cell Med Dermal dendritic cell IDEC ● TrkA TrkA levels in skin dramatically increase in response to inflammatory stimuli NGF produced by AD keratinocytes, is a major mediator of cutaneous hyperinnervation 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 29

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