Imara M&A
ELVN-002: Opportunity for a Selective Irreversible Pan-Mutant HER2 TKI
Current HER2 TKI Landscape
• The high degree of structural homology between EGFR and
HER2 makes it difficult to design HER2-selective inhibitors
• Most approved and investigational agents are dual EGFR/HER2
inhibitors that are dose-limited by EGFR-driven toxicity
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Tucatinib is the only approved HER2-selective TKI, but lacks
potency against key mutants, including HER2 YVMA, the most
common Exon 20 insertion mutation (E201M) in NSCLC, and
L755, the most common HER2 breast cancer mutation
Current HER2 TKIs do not achieve sufficient CNS free drug
levels to address brain metastases, leading to disease
progression in patients with lung and breast cancer
Our HER2 Candidate: ELVN-002
CNS = Central nervous. IM Insertion mutation. NSCLC = Non-small cell lung caner. TKI = Tyrosine kinase inhibitor. NHP = non-human primate.
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Designed to irreversibly inhibit HER2 and multiple key
HER2 mutations, including HER2 YVMA and L755, and
Selectively inhibit HER2 while sparing EGFR to prevent
EGFR-related toxicities, with the potential for improved
efficacy in NSCLC and other cancers
Demonstrated superior pre-clinical activity in HER2-
amplified subcutaneous and intracranial models, and an
improved safety margin in NHPs compared to tucatinib
We believe that our product candidate, if it achieves the target profile, will be able to achieve an improved therapeutic index compared to
current approved and investigational TKIs as well as provide a meaningful therapeutic option to patients with brain metastases
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