DOWNLOAD THIS SLIDE KIT

BROWSE SLIDES

Design

* NAS (NAFLD Activity Score): steatosis (0 to 3), lobular inflammation (0 to 3), ballooning (0 to 2)

• NGM282: engineered variant of human FGF19
• Rosuvastatin: started at W2 if LDL-cholesterol rise ≥ 10 mg/dl

Endpoints

• Primary: decrease in absolute liver fat content (MRI-PDFF) ≥ 5% at W12
• Exploratory: change in liver histology at W12

Baseline characteristics, mean (SD)

Mean C4 levels (ng/ml)

Mean total serum bile acids (µmol/L)

Primary endpoint: mean absolute liver fat content at W12, %

• Absolute and relative changes in LFC at W12: -11.2 % and -67% (3 mg) ; -10.9% and -57% (1 mg)
• 100% (3 mg) and 92% (1 mg) of subjects achieved primary endpoint of ≥ 5% absolute LFC reduction
• 100% (3 mg) and 92% (1 mg) had a relative decrease in LFC ≥ 30% at W12
• 63% (3 mg) and 33% (1 mg) of subjects normalized LFC (≤ 5%) by W12

Mean transaminases (IU/L)

Histological parameters, %

Fibrosis at baseline and W12 in the NGM282 1 mg group

• Mean change from baseline in fibrosis stage: - 0.1
• One subject had a 2-stage improvement in fibrosis: F2 to F0

Safety and tolerability

• Favorable safety and tolerability profile consistent with other NGM282 studies: no new safety signals identified
• Mild gastrointestinal symptoms (loose/frequent stools) were 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 AEs
• Gastrointestinal symptoms were largely mitigated with separating the timing of injection around meals and decreasing meal size
• Five severe adverse events, all unrelated to study drug:
  • Pneumonia
  • Pleurisy
  • Chest tightness
  • Cardiac arrest (non myocardial infarction)
  • Renal mass

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