About TRYNGOLZA

TRYNGOLZA is a GalNAc-conjugated antisense oligonucleotide inhibitor of apolipoprotein C-III (apoC-III) production1

GalNAc enables targeted delivery to the liver, where apoC-III mRNA is generated1,20

ApoC-III acts on the4:

  • LPL-independent pathways by inhibiting hepatic clearance of triglyceride-rich lipoproteins, which play an important role in patients with FCS because of the substantial deficit in LPL activity4
  • LPL-dependent pathway by inhibiting lipoprotein lipase (LPL) activity, the primary mechanism by which plasma triglycerides are hydrolyzed4

Normal triglyceride metabolism

TRYNGOLZA Mechanism Of Action Graphic, Adapted from Gaudet 2014 TRYNGOLZA Mechanism Of Action Graphic, Adapted from Gaudet 2014

Adapted from Gaudet 2014.4

Due to their absent or severely impaired LPL function, people with FCS can only rely on the LPL-independent pathway to break down triglycerides in the blood.4

FCS=familial chylomicronemia syndrome; GalNAc=N-acetylgalactosamine; mRNA=messenger ribonucleic acid; TG=triglyceride; TRL=triglyceride-rich lipoproteins; VLDL=very-low-density lipoprotein.

TRYNGOLZA is designed to work by1:

Illustration of TRYNGOLZA MOA Stage 1: Targeting Hepatocytes

1

Targeting hepatocytes

Illustration of TRYNGOLZA MOA Stage 2: Selectively Binding to apoC-III mRNA

2

Selectively binding to apoC-III mRNA

Illustration of TRYNGOLZA MOA Stage 3: Degrading apoC-III mRNA

3

Degrading apoC-III mRNA

 
 
Illustration of TRYNGOLZA MOA Stage 1: Targeting Hepatocytes

1

Targeting hepatocytes

Illustration of TRYNGOLZA MOA Stage 2: Selectively Binding to apoC-III mRNA

2

Selectively binding to apoC-III mRNA

Illustration of TRYNGOLZA MOA Stage 3: Degrading apoC-III mRNA

3

Degrading apoC-III mRNA

This process results in reduced serum apoC-III protein and reduced triglyceride levels.1

TRYNGOLZA reduces apoC-III, which is a key regulator of triglyceride metabolism in both LPL-dependent and LPL-independent pathways.1,4

Pharmacodynamics: sustained reductions observed in fasting apoC-III from baseline over 1 year1

ApoC-III is a regulator of triglyceride metabolism.4

Fasting apoC-III placebo-corrected mean percent change from baseline1
Month 1 Month 3 Month 6 Month 12
-57% -69% -72% -80%
Fasting apoC-III placebo-corrected mean percent change from baseline1
Month 1 -57%
Month 3 -69%
Month 6 -72%
Month 12 -80%
TRYNGOLZA & apoC-III mRNA Binding TRYNGOLZA & apoC-III mRNA Binding DNA Structure DNA Structure 2

Chylomicrons