Imara M&A
ELVN-002 Potently Inhibited HER2 & HER2 Mutants While Sparing EGFR
BT474 HER2WT pHER2 IC50
Beas2b HER2S310F PHER2 IC50
Beas2b HER2¹755S pHER2 IC50
Beas2b HER2YVMA PHER2 IC50
Beas2b HER2YVMA PHER2 IC50
in 100% human serum (fold shift)
BT474 (HER2wt) cytotox IC50
NCI-N87 (HER2wt) cytotox IC50
Ba/F3 HER2YVMA Cytotox IC50
H2073 (EGFRwt) pEGFR IC50
A431 (EGFRwt) pEGFR IC50
A431 (EGFRwt) cytotox IC50
Human Hepatocyte stability, extraction ratio
GSH in human liver cytosol,
(% remaining @ 1h)
Kinetic Solubility pH 7.4 (UM)
Poziotinib
3.5
1.9
4
2.1
69
(33x)
0.9
0.4
1.5
1.4
1.3
0.6
68
80%
5.6
Pyrotinib
13
2
3.5
324
(65x)
2.3
2.6
3.2
6.4
10
75
74
34%
< 0.1
Tucatinib
12
16
99
127
>1000
(~10x)
22
44
119
>10000
>10000
>10000
76
9.3
ELVN-002
13
2.8
4.7
4.2
33
(8x)
3.9
3.3
5.1
2160
2290
3530
22
70%
260
In contrast to tucatinib,
potent pharmacodynamic
activity for HER2 YVMA (71%
of E20IM NSCLC) & HER2
L755 (22% HERmut BRC)
In contrast to dual inhibitors,
our candidates spare EGFR
ELVN-002 has exceptional
drug like properties and PK
profile for a covalent TKI
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