Zodasiran

ANGPTL3 · RNAi (siRNA)

Phase 2/3 Partnered with Amgen

Target: ANGPTL3

Full NameAngiopoietin-like 3

PathwayLipid metabolism - inhibits LPL and endothelial lipase

See Target Biology →

Mechanism of Action

TypeRNAi (siRNA) via TRiM platform

DescriptionZodasiran silences ANGPTL3 mRNA in hepatocytes, reducing circulating ANGPTL3 protein. This releases inhibition of LPL and endothelial lipase, enabling accelerated clearance of TG-rich and LDL particles.

Indications: Homozygous Familial Hypercholesterolemia (HoFH)Mixed DyslipidemiaASCVD Risk Reduction

Target Biology

ANGPTL3 is a liver-secreted protein that inhibits both lipoprotein lipase (LPL) and endothelial lipase. By silencing ANGPTL3, zodasiran unleashes both enzymes, lowering BOTH triglycerides and LDL-cholesterol.

Human Genetic Evidence: ANGPTL3 LoF mutations associated with lower LDL, lower TGs, reduced CV events (familial combined hypolipidemia)

Clinical Data

Gateway

Phase 2 Active, not recruiting Target n=

Indication: Mixed dyslipidemia

Design:

Population:

Primary Endpoint:

Data Expected:

Zodasiran Phase 3 HoFH

Phase 3 Recruiting Target n=

Indication: Homozygous Familial Hypercholesterolemia

Design:

Population:

Primary Endpoint:

Data Expected: 2026-2027

ARCHES-2

n=?

Design: Randomized, placebo-controlled

Population: Patients with mixed dyslipidemia

Investment Analysis

Satya Bio Analysis — estimates based on public data and analyst judgment, not sourced from company materials

Bull Case

Thesis Point	Supporting Evidence	Confidence
ANGPTL3 is genetically validated	LOF mutations show low LDL, low TGs, reduced CV events	High
Dual LDL-C (65%) and TG (70%) reduction with quarterly dosing	ARCHES-2 Phase 2 data	High
Superior to evinacumab	65% vs 47% LDL-C reduction, quarterly SC vs monthly IV	Medium - Different Patient Populations

Bear Case

Risk	Evidence	Mitigating Factors
Crowded lipid market	Statins and PCSK9 inhibitors already available	Different mechanism, additive benefit for high-risk patients
Evinacumab already approved for HoFH	Regeneron has first-mover advantage	Zodasiran more efficacious, more convenient dosing
Quarterly injection vs daily statin	Convenience advantage over biologics, not oral drugs	For severe patients already on injections, quarterly is improvement

Key Debates

Question	Bull View	Bear View	Resolution Catalyst
Can zodasiran demonstrate CV outcomes benefit?	Genetic validation strong; dual lipid lowering may be superior	CV outcomes trials expensive and long; may not be conducted	Phase 3 HoFH data, potential outcomes study

Market Opportunity

Catalysts & Upcoming Events

Event	Timing	Importance	Key Metrics to Watch	Consensus
Phase 3 HoFH data	2026-2027	Critical	LDL-C reduction vs placebo in HoFH	—
Zodasiran Phase 3 HoFH data	2026-2027	high	—	—

Data sourced exclusively from public filings, corporate presentations, and published clinical data. For informational purposes only. Not investment advice. Satya Bio does not provide recommendations to buy or sell securities. Terms · Privacy