1. NGM282 in NASH: 3 mg QD (phase 2)
Design W2
W12
Liver biopsy with NASH
NAS * ≥ 4 with a score ≥ 1 for each component
Stage 1-3 of fibrosis
Liver fat content ≥ 8%
(MRI-PDFF)
N = 19
NGM282 3 mg
NGM282 3 mg
+ rosuvastatin (if needed)
Assessments
Screening W6
W12
W18
Liver Biopsy X -
MDRI-PDFF
LiverMultiScan
* NAFLD Activity Score:
steatosis (0 to 3),
lobular inflammation (0 to 3),
ballooning (0 to 2)
NGM282: engineered variant of human FGF19, administered subcutaneously qd
Rosuvastatin: started at W2 if LDL-cholesterol rise of 10 mg/dl observed
Endpoints
Primary: decrease in absolute liver fat content ≥ 5% at W12
Exploratory: change in liver histology at W12
NGM282-Phase 2
Harrison SA, EASL 2018, Abs. GS-014 1

2. NGM282 in NASH: 3 mg QD (phase 2)
Baseline characteristics, mean or N or %
NGM282 3 mg
N = 19
Age, years (SD)
51.4 (12.6)
Male / Female, N
4/15
Diabetes mellitus, N
7/12
Liver fat content, MRI-PDFF
(proton density fat fraction), % (SD)
17.1% (5.6)
AST, U/l (SD)
65 (32)
ALT, U/l (SD)
82 (39)
Fibrosis stage (SD)
2.5 (0.8)
NAFLD activity score (SD)
5.7 (1.5)
Liver-Inflammation-Fibrosis (LIF) score (SD)
2.80 (0.43)
LDL cholesterol, mg/dL (SD)
97 (27)
Statin naïve/experienced
13/6
7α-hydroxyl-4-cholesten-3-one (C4), ng/ml (SD)
35.1 (24.2)
NGM282-Phase 2
Harrison SA, EASL 2018, Abs. GS-014 2

3. NGM282 in NASH: 3 mg QD (phase 2)
Effect on FGF19 targets (N = 19)
Mean C4 levels, ng/mL
Mean Total serum bile acids, µmol/L 40 35 30 25 20 15 10 5
Baseline W6
W12
p <
Δ at W12
Mean (SD)
Absolute
-33.2 (24.4)
Relative
-93% (10) 6 5 4 3 2 1
Baseline W6
W12
p <
Δ at W12
Mean (SD)
Absolute
-3.5 (2.5)
Relative
-64% (41)
C4 = 7α-hydroxyl-4-cholesten-3-one
Lower limit of C4 quantitation = 0.9 ng/ml
NGM282-Phase 2
Harrison SA, EASL 2018, Abs. GS-014

4. NGM282 in NASH: 3 mg QD (phase 2)
Primary endpoint: mean % absolute change in liver fat content at W12 (N = 19) 20 15 10 5
Baseline W6
W12
p <
Δ at W12
Mean (SD)
Absolute
-11.2% (4.2)
Relative
-67% (17)
100% of subjects achieved primary endpoint of ≥ 5% absolute liver fat content reduction and a decreased of relative liver fat content ≥ 30% at W12
12 (63%) subjects normalized liver fat content (≤ 5%) by W12
NGM282-Phase 2
Harrison SA, EASL 2018, Abs. GS-014

5. NGM282 in NASH: 3 mg QD (phase 2)
Fibrosis markers changes at W12, N = 19
Mean PRO-C3 levels (ng/mL)
ELF Score and components 6 5 4 3 2 1
Baseline W6
W12
p < 0.01
p < 0.05
Δ at W12
Mean (SD)
Absolute
-11.1 (18.4)
Relative
-33% (47)
Mean (SD)
Baseline W6
W12
ELF score
10.1 (1.0)
9.6* (0.8)
9.5* (1.0)
Hyaluronic acid
91.4 (79.7)
67.3 (60.2)
72.1 (90.3)
PIIINP
13.4 (4.6)
9.7* (3.5)
10.3* (3.4)
TIMP-1
270.8 (67.7)
233.6* (51.4)
232.0* (62.5)
*p < 0.01
Subjects with severe disease (ELF ≥ 10.1) decreased ELF score by 0.8 at W12
NGM282-Phase 2
Harrison SA, EASL 2018, Abs. GS-014

6. NGM282 in NASH: 3 mg QD (phase 2)
NAS histological response at W12, N = 19 %
100 90 80 70 60 50 40 30 20 10
-2.3 (1.8)
-1.1 (0.9)
-0.5 (0.8)
-0.7 (0.9)
NAS
Steatosis
Inflammation
Ballooning
Mean change at W12 (SD)
84%
74%
42%
53%
11%
26% 5% 0%
Worsened
Improved
No change
NGM282-Phase 2
Harrison SA, EASL 2018, Abs. GS-014

7. NGM282 in NASH: 3 mg QD (phase 2)
Fibrosis evolution at W12 (liver biopsy), N = 19
42%
47%
11%
Worsened
Improved
No change
Mean change from baseline in fibrosis stage: - 0.5
3 subjects had a 2-stage improvement in fibrosis: all F3 changed for F1
Mean decrease in NAS in subjects with improved fibrosis: -3.5
NGM282-Phase 2
Harrison SA, EASL 2018, Abs. GS-014

8. Mean transaminases (U/L), N = 19
NGM282 in NASH: 3 mg QD (phase 2)
Mean transaminases (U/L), N = 19
Δ at W12
ALT
AST
Absolute
-53*
-37*
Relative
-60%*
-52%*
100 90 80 70 60 40 20 10 30 50
Baseline W2 W4 W6 W8
W10
W12
*p <
NGM282-Phase 2
Harrison SA, EASL 2018, Abs. GS-014

9. LDL-cholesterol (mg/dL) changes during treatment
NGM282 in NASH: 3 mg QD (phase 2)
LDL-cholesterol (mg/dL) changes during treatment
200
150
100 50
Baseline W2 W4 W6 W8
W10
W12
LDL-C levels return to baseline and/or target of < 100 mg/dL with statin treatment
NGM282 3 mg
NGM282 3 mg Rosuvastatin (if needed)
Decreased C4 and increased LDL-cholesterol reflect potent CYP7A1 inhibition
Lipid particle change primarily driven by increase in large LDL particles
Significant reductions in serum triglycerides (56%) and no change in HDL
NGM282-Phase 2
Harrison SA, EASL 2018, Abs. GS-014

10. Safety and tolerability
NGM282 in NASH: 3 mg QD (phase 2)
Safety and tolerability
Favorable safety and tolerability profile consistent with other NGM282 studies (no new safety signals identified)
Mild gastrointestinal symptoms (loose/frequent stools) remain the most common treatment emergent adverse events
Majority were mild and resolved during treatment phase
No subject withdrew from treatment due to any drug-related adverse events
Gastrointestinal symptoms were largely mitigated with separating the timing of injection around meals and decreasing meal size
Three severe adverse events, all unrelated to study drug:
Pleurisy
Chest tightness
Cardiac arrest (non myocardial infarction)
NGM282-Phase 2
Harrison SA, EASL 2018, Abs. GS-014

11. NGM282 in NASH: 3 mg QD (phase 2)
Summary
Potent C4 and bile acid suppression consistent with FGF19 hormone activity
Significant and clinically meaningful reductions across non-invasive markers of NASH-related disease
Large percentage of patients demonstrated histological improvement at W12
Statin co-administration rapidly mitigates LDL-cholesterol elevations
Treatment was safe and well tolerated
NGM282-Phase 2
Harrison SA, EASL 2018, Abs. GS-014