Imara M&A

HER2 Mutant NSCLC Landscape: No Approved Selective TKIs Selectivity vs. EGFRWT HER2mut NSCLC Efficacy Compound Platinum- doublet CURRENT & POTENTIAL FUTURE STANDARD OF CARE Poziotinib Company Trastuzumab deruxtecan Daiichi Sankyo (Enhertu®) INVESTIGATIONAL TKIS Pyrotinib BI-1810631 N/A Spectrum Jiangsu HengRui Medicine Stage Boehringer Ingelheim N/A FDA Approved (2L+) PDUFA Nov 2022 (ODAC 09/22) Phase 3 Phase 1a MoA Chemo HER2-ADC topoisomerase payload Irreversible, EGFR/HER2 Irreversible, EGFR/HER2 Irreversible, HER2 N/A HER2-specific < 1x ≤1x > 100x ORR: ~25-35% mPFS: 4-7m ORR: 58% DOR: 8.7m ORR: ~28% mPFS: 5.5m ORR: 19% mPFS: 5.6m ΝΑ Gr 3+ Neutropenia: 19% Nausea: 52% Constipation, diarrhea, vomiting, cough, dyspnea, decreased appetite (20-30% each) Gr 3+ Neutropenia: 16%; Black Box Warning: 12% ILD/pneumonitis (all grades) All Grade Nausea (61%), Anemia (34%), Fatigue (32%) Dose discontinuation due to AE: 8% Safety / Tolerability Gr 3+: Rash (49%) ; Diarrhea (26%) ; Stomatitis (25%) All Grade Rash (91%); Diarrhea (82%); Stomatitis (69%) ; Paronychia (38%) Dose modifications due to AEs: 91% | Dose discontinuations due to AEs: 13% Gr 3+: Diarrhea (17%) All Grade Diarrhea (86%); Fatigue (58%) ; Anemia (36%); Dizziness (33%); Decreased appetite (32%, Hand-foot syndrome (32%) ; Nausea (32%) Dose modification due to AEs: 8% Phase 1 in progress at 6 sites (US, Japan, China Netherlands) - As of April 2022, 11 pts dosed (QD and BID arm). Additional clinical pharmacology studies underway to bridge to a new formulation and assess food / PPI effect. Poor TKI selectivity of dual inhibitors resulting in EGFR-driven toxicities limits efficacy AE = Adverse event. BID = Twice a day. DOR = Duration of response. ILD = Interstitial lung disease. NSCLC = Non-small cell lung cancer. ORR = Overall response rate. PFS = Progression free survival. PPI = Proton pump inhibitor. TKI = Tyrosine kinase inhibitor References: Enhertu® (fam-trastuxumab deruxtecan) USPI; Le, et al. J. Clin Oncol 2021, 40:710-718; Song et al, BMC Medicine (2022) 20:42; NCT04886804, NCT05380947, ASCO TIP 2022 34

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