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Design

* 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

Baseline characteristics, mean or N or %

Effect on FGF19 targets (N = 19)

C4 = 7a-hydroxyl-4-cholesten-3-one
Lower limit of C4 quantitation = 0.9 ng/ml

Primary endpoint: mean % absolute change in liver fat content at W12 (N = 19)

• 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

Fibrosis markers changes at W12, N = 19

• Subjects with severe disease (ELF = 10.1) decreased ELF score by 0.8 at W12

NAS histological response at W12, N = 19

Fibrosis evolution at W12 (liver biopsy), N = 19

• 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

Mean transaminases (U/L), N = 19

LDL-cholesterol (mg/dL) changes during treatment

• 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

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)

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