Figure 1

AI-augmented Pipeline for Target Discovery

Figure 2

Figure 3

Figure 2 data

Figure 2D cell images

Figure 2 WB raw images

Figure 2 RNASeq raw data

Extended Figure 6

A549 TNIK KD; hippo pathway

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Architectural superposition of TNIK inhibitor structures
with the predicted INS018_055 binding mode and effects
on TGF-β-induced EMT/FMT cellular programs

In vivo effects of INS018_055 treatment in mouse models
of lung diseases

Figure 3 data

Figure 3C pathology

Figure 4

In vivo effects of INS018_055 treatment by inhalation in rat models of lung fibrosis

Figure 4 data

Figure 4 inhalation study_pathology (HE)

Figure 4 inhalation study_pathology (MT)

Figure 5

In-vitro and in vivo studies on the effect of INS018_055 on kidney cells or mouse model of kidney fibrosis

Figure 5 data

Figure 5A WB raw images

Figure 6

Pharmacokinetic analysis in clinical phase I trials

Figure 6 data

Extended Data Figure 1

Supplementary figure describing Target ID approach

Figure 5B and 5D UUO pathology images

Extended Data Figure 2

PandaOmics scores transparency and in-silico validation of TNIK

IPF donor fibroblast and epithelial cell imaging for FMT and EMT assays

Extended Data Figure 4

Extended Data Figure 3

SPR assays and cell viability assays

Extended Data Figure 3

Extended Data Figure 5

Effect of IN18_055 on TGF-β-induced, or combination of TGF-β and TNF-α induced EMT/FMT cellular programs

Extended Data Figure 5B

Extended Data Figure 5A_raw cell images

Extended Data Figure 5B_WB raw images

Extended Data Figure 6

Effect of TNIK deletion on TGF-β signaling in A549 cells

Extended Data Figure 6D

Extended Data Figure 6B_A549_shTNIK1_Western
raw image

Extended Data Figure 6A_shTNIK-1
raw images of cells

Extended Data Figure 7

Extended Data Figure 7_pathology (HE)

Extended Data Figure 7

INS018_055 inhibits inflammation in a bleomycin-induced lung (BLM) fibrosis mouse model

Extended Data Figure 8_pathology

Extended Data Figure 8

Extended Data Figure 8

In vivo study on the effect of combination therapy of INS018_055 and sub-optimal dose Pirfenidone on mouse model of bleomycin induced lung fibrosis

Extended Data Figure 9

In vivo effects of INS018_055 treatment in combination with maximum therapeutic dose of Pirfenidone in mouse models of lung fibrosis

Extended Data Figure 9

Extended Data Figure 10

in vitro and in vivo study of INS018_055 on skin fibrosis

Extended Data Figure 10

Figure 3 INS018_055 concentrations in plasma and lung

Figure 4 INS018_055 concentrations in plasma and lung

Figure 5 INS018_055 concentrations in plasma and kidney

Extended Data Figure 8 INS018_055 and pirfenidone concentrations in plasma and lung