BenevolentAI Investor Presentation Deck slide image

BenevolentAI Investor Presentation Deck

We expect BEN-2293 to provide both symptomatic relief and to reverse disease progression in atopic dermatitis • BEN-2293 is highly selective for Trk receptors, with IC50 potencies in the low nM range for TrkA, B, and C • BEN-2293 dose dependently inhibits release of inflammatory Th1 and Th2 cytokines TNFa, IFNY, IL-13, and IL-4 in human peripheral blood mononuclear cells (PBMCs) stimulated with an inflammatory T-cell stimulus (anti-CD3/CD28) • BEN-2293 inhibits the release of Calcitonin Gene-Related Peptide (CGRP), a mediator of itch, sensory nerve hypersensitisation and neurogenic inflammation, in dorsal root ganglion (DRG) isolated from adult rats and stimulated with NGF • BEN-2293 series significantly (p<0.05) reduced mouse ear inflammation following administration of PMA, significantly reducing expression of cytokines IL-1B, IL-4, IL-6, CXCL1, MCP-1, and Tarc • BEN-2293 demonstrates excellent tolerability and safety margins in IND/CTA-enabling toxicology studies Key: Tropomyosin-related kinase (Trk) receptor tyrosine kinase family, namely TrkA, TrkB, and TrkC; Nerve Growth Factor (NGF); Brain Derived Neurotrophic Factor (BDNF); Neurotrophin-3 (NTF-3)/NT3 BEN-2293 Inhibition of human primary T-cell activation Luminescence % Inhibition 25000 20000- 15000- 10000- 5000- 0.1 100- 75- 50- 25- 0- -25- -50- TNFa Inhibition of sensory neuron activation -3 -2 THE M 1000 10000 TIME TIITE 10 100 BEN-2293 nM 10 100 1000 10000 BEN-2293 nM Human PBMCs from 2 donors. Anti-CD3/CD28 stimulus +/- BEN-2293 Hillslope IC50 -1 0 Log BEN-2293 (μm) - Donor 1 Donor 2 2.827 0.03033 1 1500 Net ear thickness (x 0.01 mm) 1000- 500- 15- 0.1 IL-4 Sham- Reduction in mouse ear inflammation H.. Vehicle Crisabarole (Img)- Tacrolimus (0.05mg) -Donor 1 Donor 2 PanTrk (0.5mg)- Dexamethasone (0.1mg)- Benevolent 41
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