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STAT3 Degradation Elicits an IFNy Gene Signature in TME and
Sensitizes Solid Tumor Mouse Models to PD-1 Inhibition
IFNY mRNA Signature Predictive
of Clinical Responses to
Anti-PD-1 (Pembrolizumab)
Expression Score
IFNY, and Expanded
Immune Gene Signature
2.8
2.6
2.4
2.2
2.0
1.8
1.6
1.4
1.2
1.0
0.8
IFN-Y
ID01
CXCL10
CXCL9
HLA-DRA
STAT1
IFNG
IFNY Signature
Nonresponder Responder
Ayers et. al. JCI 2017 (Merck)
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IFNy mRNA Signature in TME
Elicited by STAT3 Degradation in
Preclinical Model
Tumor Column (mm³)
Log(Count)
Log(Count)
3000
2000
1000-
200-
70
3000-
1000
300
Vehicle •-KTX-201 q2d
Stat 1
5
vehicle
Cxc19
vehicle
GEP
10
Days
15
KTX-201
KTX-201
20
Log(Count)
Log(Count)
Log(Count)
100-
50-
2000-
1000-
500-
50-
30-
Ifny
Vehicle KTX-201
Cxcl10
vehicle
Ido1
KTX-201
vehicle KTX-201
On treatment Day 11; n-6/grp
STAT3 Degrader Sensitizes CT-26
Model to Anti-PD-1 via Activation
of Anti-tumor Immunity
Tumor Volume (mm³)
4000
3000
2000
1000
Lead-in aPD1
Day -2
0
04
Tx
start
CT-26
Vehicle (PBS + Isotype Ab)
KTX-201 5 mg/kg Q2d IP + Isotype Ab
Anti-PD1 10 mg/kg BIW IP + PBS
Combination
Rechallenged age-matched naïve control
20
Tx
end
40
Tx Days
end
CT-26
rechallenge
60
80
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