Imara M&A

Poor Selectivity Limits Tolerability & Efficacy of 1st, 2nd & 3rd Gen Agents BCR-ABL Coverage Drug & Administration Requirements Compound Company Imatinib (Gleevec®) Dasatinib (Spyrcel®) Nilotinib (TasignaⓇ) Bosutinib (Bosulif®) Ponatinib (IclusigⓇ) Novartis BMS Novartis Pfizer Takeda T3151 Coverage X X X X Off Target(s) & Treatment-Related AEs Myelosuppression: 20-25% Gr 3+ Fluid Retention/Edema: 68% Myalgia/Arthralgia: 50% Gl-related: 50% C-KIT, CSFR-1, PDGFR SRC family, C-KIT, PDGFR-aß C-KIT, PDGFR, CSFR-1, DDR-1 (hERG Channel) SRC family KDR, FGFR, C-KIT, RET, FLT3, PDGFR Myelosuppression: 10-20% Gr 3+ Edema/Effusions: 15-30% FY = Fiscal year. MMR = Major molecular response. MR4.5 = Deep molecular response. PPI = Proton pump inhibitors MMR and MR 4.5 at 12m; 2020 FY Sales (USD) are approximate figures Myelosuppression: 10-20% Gr 3+ Hypertension: 10% Black Box: QT Prolongation, Sudden Deaths Diarrhea: 82% Nausea: 39% Vomiting: 32% Increased LFTs: 20% Myelosuppression: 50% Gr 3+ Hypertension: 70% Black Box: Arterial Occlusive Events, Heart Failure, VTE, Hepatoxicity N/A ++ ++ +++ 1L Efficacy 28% MMR 3% MR4.5 46% MMR 5% MR4.5 44% MMR 11% MR4.5 41% MMR 7.5% MR4.5 82% MMR* 56% MR4.5 Avoid strong CYP3A inhibitors or inducers Avoid strong CYP3A inhibitors or inducers, PPIs, antacids, and H2 blockers Avoid strong CYP3A inhibitors or inducers and PPIs; avoid food 2 hours before and 1 hour after each dose Avoid strong CYP3A inhibitors or inducers, PPIs, antacids, and H2 blockers Avoid strong CYP3A inhibitors or inducers A selective BCR-ABL inhibitor could yield enhanced target coverage, leading to greater efficacy and better long-term tolerability 2021 FY Sales (USD) $1.0B $2.1B $2.0B $500M $500M *Based on the discontinued Ponatinib's 1L CML study; not an approved line of therapy References: Cortes JE et al. J Clin Oncol, 2012; 30(28):3486-92; Kantarjian H et al. NEJM, 2010; 362(24):2260-70; Saglio G et al. NEJM 2010; 362 (24):2251-9; Jain P et al. Lancet Haematol, 2015; 2(3):e118-28; Cortes JE et al. J Clin Oncol. 2016; 34(20):2333-40; Hochhaus A et al. Leukemia. 2016; 30(5):1044-54; Gleevec® (imatinib) USPI; Ilclusig (ponatinib) USPI; Sprycel® (dasatinib) USPI; Tasigna® (nilotinib) USPI; Bosulife (bosutinib) USPI. 21

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