Imara M&A

Review of Asciminib (Scemblix®), 4th Generation Allosteric TKI Observations ● • ~30% discontinued due to lack of efficacy/AE by 48 wk • ~50% discontinued by 96 wk, but only 1.2% due to PD/death T3151 dosed 5x higher resulting in more dose reductions, enhanced pancreatic toxicity (25%) & elevated liver enzymes Drug-drug interactions: CYP3A4, CYP2C9 Potential off-target resistance liabilities: PgP & BCRP Requires fasting 2 hours before and 1 hour after each dose ● ● . Approved in US based on 3L+ ASCEMBL Trial Strong launch & blockbuster sales projections in 3L+ alone demonstrate the size of the market (1L Ph3 readout 2024) ● PD Progressive disease. TKI = Tyrosine kinase inhibitor References: Hochhaus et al. ASH 2020; Cortes et al. ASH 2020; ASH 2021; Novartis Q2 2021 IR; Scemblix (Asciminib) USPI; ASCO 2022; Eadie et al Oncotarget 2018 Emerging BCR-ABL mutations upon discontinuation due to lack of efficacy or progressive disease No mutations ATP Binding Site Myristol Binding Pocket Asciminib (n=39) 22 (56%) M244V (n=3), E355G, F359V, T3151 ATP Binding Site A337T (n=3), P465 Mutations at baseline & end of treatment F359C/V (n=3), F317L (n=2), Y253H Bosutinib (n=30) 20 (67%) T3151, V299L None M244V (n=2), E255V, F317L, Q252H 22

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