Taysha IPO Presentation Deck

GM2 gangliosidosis is a family of severe neurodegenerative disorders GM2 gangliosidosis results from a deficiency in the B-hexosaminidase A (Hex A) enzyme B-hexosaminidase A enzyme is composed of 2 subunits encoded by the HEXA and HEXB gene, respectively Mutations of the HEXA gene cause Tay-Sachs disease (TSD) while mutations of the HEXB gene cause Sandhoff disease (SD) - The estimated prevalence of GM2 is 350 patients (US+EU) GMZA Cytoplasmic membrane GM2 ganglioside Lysosome with normal HexA F. Release of cleavage products of GM2 for further use by cell DOPO Lysosome with mutant HexA Accumulation of unbroken GM2 in lysosome Effects of HexA mutation Accumulation of membrane cytoplasmatic bodies (lysosomes) containing ganglioside A * • Destruction of neurons Proliferation of microglia Accumulation of complex lipids in macrophages . Hypotension . Inability to sit and hold head Eye movement anomalies Dysphagia . Convulsions Hypomyelinization, etc . Ataxia . Dysarthria Development of dysphagia Progression of hypotension and seizures . Gradual reduction of motor, cerebral and spinocerebellar functions 16

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