Investor Presentaiton
Research framework provides confidence in new programs:
novel CNS penetrant TYK2 inhibitor for Multiple Sclerosis (MS)
Transformational potential
First-in-class, oral, CNS penetrant TYK2 inhibitor with direct
anti-inflammatory effects in the CNS to treat neuroinflammatory
neurodegenerative disorders.
Causal human biology
Mechanism is supported by human genetics (P1104A loss-of-
function variant), human pathology, clinical fluid biomarkers.
Microglia
Astrocytes
Lymphocytes
Mean clinical score
Matching modality to mechanism
▲ Wild Type
■Heterozygous
▼ Homozygous
BMS TYK2i-CNS Phenocopies
P1104A LoF in EAE
No EAE control
P1104A LOF TYK2 Variant
Protects in EAE Model of MS
4.01
3.5
EAE vehicle control
3.0 EAE CNS-TYK2i #1
2.5
2.0
1.5
1.0
0.5
INS vs.
PO tr. started on day -3
score of
0.0
0 2 4 6 8 10 12 14 16
Days after Immunisation
@
2
4
6 8 10 12 14 16 18 20 22
Days after Immunisation
adapted from Dendrou, 2016
Mean Clinical Score (SEM)
EAE CNS-TYK2i #2
phenocopies
P1104A
pSTAT3
pSTAT3, an indicator of TYK2 activation, is increased in key
inflammatory cells of the brain in multiple sclerosis#.
Path to clinical proof-of-concept
Achieve CNS drug exposure to inhibit CNS TYK2 by at least
70% consistent with pre-clinical data in the EAE mouse
model (above) and quantitative systems pharmacology
modeling of SOTYKTU in psoriasis and SLE.
Sci Transl Med 2016 Nov; 8(363): 363ra149
Ill Bristol Myers Squibb™
# Lu et al, J Neuropathol Exp Neurol 72:1135 (2013);
Dendrou et al:Sci Transl Med 2016 Nov 2;8(363):363ra149. doi: 10.1126/scitranslmed.aag1974
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