Investor Presentaiton

Neuroscience Anti-MTBR-Tau elF2B Activator BMS-986446 (PRX005): Potential best-in-class antibody to slow or halt the progression of Alzheimer's Disease The propagation of Tau pathology as Alzheimer's Disease (AD) progresses is thought to be mediated by Tau "seeds" containing the MTBR region of tau¹ Tau, not Ab, deposition correlates with age of AD onset, disease duration, and cognitive impairment¹ • A Tau fragment (MTBR-Tau 243) has recently been shown to correlate well with tau accumulation as measured by Tau- PET imaging and cognitive impairment³ BMS-986446 targets MTBR-Tau 243 and binds with high affinity to both the 3R and 4R isoforms of tau4,5 Abnormal A Normal- Normal Severe Biomarkers Mild cognitive impairment Dementia Disease progression - Amyloid-ẞ - Tau-mediated neural injury Clinical symptoms - Quality of life Cognitive impairment Social dependence - Motor abnormalities Figure adapted from Masters et al, Nat Rev Dis Prim 2015 Clinical symptoms Amino-terminal domain Nter 1- Proline-rich region Figure adapted from Colin et al, Acta Neuropathologica 2020 Microtubule-binding domain Cter R1 R2 R3 R4 441 carboxy-terminal tail BMS-986446: Preclinical models showed significant reduction of intraneuronal tau pathology and protection. against behavioral deficit in a tau transgenic mouse model in vivo and complete blockade of neuronal tau internalization in vitro5 Ill Bristol Myers Squibb™ 1. Horie, et al. Brain 2021. 2. Murray, et al. Brain. 2015. 3. Horie, et al. Nat Med. 2023. 4. Data on file: Prothena Press release 7/10/2023. 5. Dolan ADPD 2021 Not for Product Promotional Use 128

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