Imara M&A

ELVN-001 Potentially Affords an Improved Therapeutic Index ● ● Target Coverage at Cmin vs. 1L MMR Fold above PCRKL IC50 at Cmin 2.5 2.0- 1.5- 1.0- 0.5- 0 Nilotinib Bosutinib Imatinib Ponatinib 20 40 60 80 100 MMR (%) at 12 Months Clear correlation between target coverage of the approved agents and major molecular response rate (MMR) at 12 months¹ Phosphorylated CRKL or PCRKL IC50 represents a robust pharmacodynamic marker for BCR-ABL inhibition Fold above pCRKL IC50 at Cmin 13- 12 11 10 ● 32109 BTCF43210 Therapeutic Index vs. NHP Safety Margin Ponatinib Nilotinib ELVN-001 Toxicology studies with other ABL TKIs show that the maximum tolerated drug exposure is similar between non-human primates and humans • Data suggests ELVN-001 has the potential for significantly greater therapeutic index than existing TKIs Human (approved dose) Non human primate (MTD) MMR = Major molecular response. MTD= Maximum tolerated dose. NHP = Non-human primate ¹Dasatinib was excluded from our analysis due to its short half-life in humans (3-5 hours), however early clinical responses correlated with dasatinib concentrations above its pCRKL IC50 for more than 13 hours. *NHP data for ponatinib, nilotinib, and dasatinib were obtained from the data reported for the maximum tolerated dose (MTD) in their respective NDAS (Cmin was estimated). NHP data from 28-day GLP tox study for ELVN-001 at 5 mg/kg, a well-tolerated, no adverse event dose (NOAEL) y-axis: mean Cmin plasma concentration at the human approved dose (or NHP MTD) divided by K562 pCRKL ICso in 100% human serum Reference: Ishida et al. Eur J Clin Pharmacol. 2016;72(2):185-93. 29

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