Investor Presentaiton
Target
protein
E3 ligase
BMS-986458 is a novel ligand directed degrader (LDD)
targeting BCL6 in lymphoma
Transformational potential
Oral small molecule medicine to treat B cell lymphomas
driven by abnormalities in BCL6 signaling pathway.
Causal human biology
Gain-of-function somatic BCL6 mutations lead to B cell
lymphomas and deletion of BCL6 prevents B cell
maturation.
Naive B cells
Healthy,
Germinal
center
Mature B cells
Matching modality to mechanism
that has exquisite
We created a BCL6 LDD
selectivity relative to the
human proteome
-log10 (nominal p-value)
Only target degraded
BCL6
GSNKAL BCL2CSPTIZE
IKZFZFP91
WEE IVDP 4
CHEK1
IKZF3
-4
-2
0
2
4
Log² fold change (vs/ DMSO)
Path to clinical proof-of-concept
Correlate BCL6 degradation with clinical benefit
BCL6 IHC high expression
High BCL6
Malignant
B cells
(e.g., DLBCL)
Ill Bristol Myers Squibb™
BCL6 LDD drug Conc. (μM)
100
-20
-10
Plasma conc.
-0
10-
10
Tumor conc.
-20
1
30
40
50
0.11
-60
0.01
BCL6 levels
-70
80
98%
98%
95%
90
☐
0.001
-100
-2
Veh
2
4
6
8
10
12
14
16
Sample collection time (h)
% BCL6 Degradation
in -30% DLBCL
Not for Product Promotional Use
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