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Executive Summary

First therapy addressing root cause of AATD liver disease with 96% Z-AAT reduction

Fazirsiran

AAT · RNAi (siRNA)

Phase 3 Partnered with Takeda

Target: AAT

Full NameAlpha-1 Antitrypsin

PathwayProtein misfolding / Liver toxicity

See Target Biology →

Mechanism of Action

TypeRNAi (siRNA) via TRiM platform

DescriptionFazirsiran silences AAT mRNA in hepatocytes, reducing production of both normal and mutant Z-AAT protein. With reduced production, existing toxic aggregates are cleared, and liver damage halts or reverses.

Indications: Alpha-1 Antitrypsin Deficiency Liver Disease (AATD-LD)

Target Biology

In Alpha-1 Antitrypsin Deficiency, the mutant Z-AAT protein misfolds and aggregates in hepatocytes instead of being secreted. This accumulation causes liver damage. By silencing AAT mRNA, fazirsiran prevents production of the toxic aggregates.

Clinical Data

SEQUOIA Phase 2

Phase 2 Completed Target n=

Indication: AATD-LD

Design:

Population:

Primary Endpoint:

Data Expected:

SEQUOIA Phase 3

Phase 3 Recruiting Target n=

Indication: AATD Liver Disease

Design:

Population:

Primary Endpoint:

Data Expected: 2028

SEQUOIA Extension

Phase 3 Active, not recruiting Target n=

Indication: AATD-LD

Design:

Population:

Primary Endpoint:

Data Expected:

AROAAT-2002

n=?

Design: Open-label

Population: AATD patients with liver disease

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
Addresses root cause of AATD liver disease	96% Z-AAT reduction with histological fibrosis improvement	High
No approved therapy exists	AAT augmentation only treats lung disease, not liver	High - Clear Unmet Need
Takeda partnership provides $1B+ potential milestones	Strong pharma partner with rare disease expertise	High

Bear Case

Risk	Evidence	Mitigating Factors
AATD liver disease is rare	~10-15% of AATD patients develop liver disease	Orphan indication with high unmet need
Regulatory path unclear	May require clinical outcomes (not just Z-AAT reduction) for approval	Histology improvement in Phase 2 suggests pathway
Takeda controls development	Limited ARWR influence on timing and decisions	Milestone payments still meaningful

Key Debates

Question	Bull View	Bear View	Resolution Catalyst
Will Phase 3 SEQUOIA show sufficient fibrosis improvement for FDA approval?	Phase 2 showed histological improvement; mechanism sound	Long timeline (2028), regulatory uncertainty	SEQUOIA Phase 3 data

Market Opportunity

Catalysts & Upcoming Events

Event	Timing	Importance	Key Metrics to Watch	Consensus
SEQUOIA Phase 3 data	2028	Critical	Fibrosis improvement, Z-AAT reduction, safety	—

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