---
title: "Efzofitimod | PepTracker Pro"
url: https://peptrackerpro.com/peptides/efzofitimod
description: "A first-in-class, intravenous immunomodulatory fusion peptide derived from histidyl-tRNA synthetase that selectively binds neuropilin-2 (NRP2) to dampen inflammation in the lung; in Phase 3 development for pulmonary sarcoidosis, an interstitial lung disease."
lang: en
---

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# Efzofitimod

Medium Evidence

A first-in-class, intravenous immunomodulatory fusion peptide derived from histidyl-tRNA synthetase that selectively binds neuropilin-2 (NRP2) to dampen inflammation in the lung; in Phase 3 development for pulmonary sarcoidosis, an interstitial lung disease.

Aliases ATYR1923 +3 more

Evidence Medium Evidence

Last Updated 2026-07-03

Reading Time 5 min

## What It Is

Efzofitimod (development code ATYR1923; also called iMod.Fc) is a first-in-class immunomodulator built from a naturally occurring splice variant of human histidyl-tRNA synthetase (HARS). Aminoacyl-tRNA synthetases are best known for their housekeeping role in protein synthesis, but the immunomodulatory (iMod) domain released from HARS in inflamed tissue acts as a signaling molecule. Efzofitimod fuses that iMod domain to the Fc region of a human antibody (IgG1), which both stabilizes the molecule and extends its half-life. The fusion binds with high selectivity to neuropilin-2 (NRP2), a receptor that is strongly upregulated on myeloid immune cells (monocytes, macrophages and dendritic cells) at active sites of inflammation. By engaging NRP2, efzofitimod down-regulates pro-inflammatory receptors and cytokines and promotes resolution of inflammation, rather than broadly suppressing the immune system the way corticosteroids do. Its lead indication is pulmonary sarcoidosis — a form of interstitial lung disease (ILD) in which clusters of inflammatory cells (granulomas) accumulate in the lungs and other organs, and where chronic oral corticosteroids remain the mainstay of treatment despite substantial long-term toxicity. Developer aTyr Pharma advanced efzofitimod through a positive Phase 1b/2a study (published in CHEST) into the global Phase 3 EFZO-FIT trial, which randomized 268 patients across the United States, Europe, Japan and Brazil to intravenous efzofitimod 3 mg/kg, 5 mg/kg or placebo on top of a forced steroid taper. In topline results reported in September 2025, EFZO-FIT did not meet its primary endpoint — the reduction in mean daily oral corticosteroid dose at week 48 (2.79 mg for 5 mg/kg vs 3.52 mg for placebo; p=0.33) — but the 5 mg/kg dose showed consistent, pre-specified benefits on patient-reported outcomes (King's Sarcoidosis Questionnaire lung and general-health scores, Fatigue Assessment Scale), complete steroid withdrawal, and maintenance of lung function (forced vital capacity), with a safety profile in line with earlier studies. Following an FDA Type C meeting, aTyr announced plans to meet with the agency and to file a new investigational new drug (IND) application in 2026 for a further global Phase 3 study. Efzofitimod also holds FDA Fast Track and Orphan Drug designations for pulmonary sarcoidosis. It is an investigational, hospital-administered biologic-class peptide given by IV infusion — not an approved drug and not a self-experimentation 'research peptide.' Because it targets a novel resolution-of-inflammation pathway (NRP2) rather than a single cytokine, it is closely watched as a potential steroid-sparing option across interstitial lung diseases.

Also known as: ATYR1923, ATYR-1923, iMod.Fc, efzofitimod alfa

## Regulatory Status

Investigational — not approved; Phase 3 for pulmonary sarcoidosis; FDA Fast Track and Orphan Drug designations

Efzofitimod (ATYR1923, aTyr Pharma) is an investigational intravenous immunomodulator with no marketing approval anywhere as of 2026. Its global Phase 3 EFZO-FIT study in pulmonary sarcoidosis (268 patients) reported topline results in September 2025: it missed its primary endpoint (reduction in daily oral corticosteroid dose at week 48) but showed benefit for the 5 mg/kg dose across several pre-specified secondary measures. The FDA granted efzofitimod Fast Track designation and Orphan Drug designation for pulmonary sarcoidosis. Following a Type C meeting with the FDA, aTyr Pharma stated it intends to file a new IND in 2026 to support an additional global Phase 3 trial. It is administered by intravenous infusion in a clinical setting and is not available as a compounding-pharmacy 'research peptide.'

Effective: July 2026

View FDA Source (https://investors.atyrpharma.com/news-releases/news-release-details/atyr-pharma-announces-topline-results-phase-3-efzo-fittm-study)

## Why Researchers Study It

Efzofitimod is studied as a first-in-class test of whether a tRNA-synthetase-derived immunomodulator can resolve, rather than merely suppress, tissue inflammation by engaging neuropilin-2 (NRP2) on myeloid cells. In pulmonary sarcoidosis and other interstitial lung diseases, patients depend on long-term oral corticosteroids that carry serious cumulative toxicity, so a targeted, steroid-sparing agent that preserves lung function and reduces symptom burden would fill a major gap. Researchers are also interested in the NRP2 resolution pathway as a platform that could extend to other ILDs and chronic inflammatory conditions, and in what the EFZO-FIT results say about endpoint design (steroid-taper vs patient-reported and lung-function outcomes) in rare inflammatory lung disease.

## Proposed Mechanisms

- Derived from the immunomodulatory (iMod) domain of a human histidyl-tRNA synthetase (HARS) splice variant, fused to an antibody Fc region for stability and extended half-life
- Binds selectively and with high affinity to neuropilin-2 (NRP2), a receptor upregulated on myeloid immune cells at active sites of inflammation
- Down-regulates pro-inflammatory receptors and cytokine production in monocytes, macrophages and dendritic cells
- Promotes active resolution of inflammation rather than broad immunosuppression, distinguishing it from corticosteroids
- In preclinical ILD models (bleomycin, silicosis, sarcoidosis, hypersensitivity pneumonitis, systemic sclerosis and RA-ILD) reduced immune-cell infiltration, inflammation and fibrosis
- In sarcoidosis patients, down-regulated inflammatory gene-expression pathways in peripheral immune cells and stabilized serum inflammatory biomarkers during steroid tapering
- Administered as an intravenous infusion dosed by body weight (3 or 5 mg/kg in Phase 3)

## Evidence Snapshot

Medium Evidence

Low

Medium

High

| Study Type | Model | Outcome | Link |
| --- | --- | --- | --- |
| RCT (human, Phase 3 — EFZO-FIT) | Pulmonary sarcoidosis — 268 adults, IV efzofitimod 3 mg/kg or 5 mg/kg vs placebo on a forced steroid taper, 48 weeks | Missed primary endpoint (mean daily oral corticosteroid dose at week 48: 2.79 mg for 5 mg/kg vs 3.52 mg placebo; p=0.3313); 5 mg/kg showed benefit on KSQ-Lung, KSQ-General Health, Fatigue Assessment Scale, complete steroid withdrawal and preserved FVC. Topline Sept 2025 | Source: https://investors.atyrpharma.com/news-releases/news-release-details/atyr-pharma-announces-topline-results-phase-3-efzo-fittm-study |
| RCT (human, Phase 1b/2a) | Pulmonary sarcoidosis — dose-ranging, IV efzofitimod vs placebo with steroid taper | Positive: dose-dependent trends toward reduced steroid use and improved lung function and symptoms; supported advancement to Phase 3. Published in CHEST | Source: https://pubmed.ncbi.nlm.nih.gov/37059508/ |
| Mechanism / translational (Science Translational Medicine 2025) | HARS splice-variant therapeutic (HARSWHEP / iMod.Fc) targeting NRP2 across multiple lung-inflammation and fibrosis models | Demonstrated selective NRP2 binding and resolution of lung inflammation and fibrosis; clarified first-in-class immunomodulatory mechanism | Source: https://www.science.org/doi/10.1126/scitranslmed.adp4754 |
| Regulatory designations / status | Pulmonary sarcoidosis, adults | FDA Fast Track and Orphan Drug designations; not yet approved. Following a 2026 FDA Type C meeting, aTyr plans a new IND and additional global Phase 3 study | Source: https://investors.atyrpharma.com/news-releases/news-release-details/atyr-pharma-provides-regulatory-and-clinical-update-efzofitimod |

## Commonly Discussed Benefits

Inflammation: https://peptrackerpro.com/benefits/inflammation
Immune Support: https://peptrackerpro.com/benefits/immune-support

Researching Efzofitimod? Track it, set reminders, and keep notes in the free app.

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## Safety & Cautions

- Investigational and not approved for any use — its Phase 3 EFZO-FIT trial missed its primary (steroid-reduction) endpoint, so efficacy is not established
- A hospital/clinic-administered intravenous biologic-class peptide given under specialist supervision — not a self-administered or self-experimentation 'research peptide'
- Any vendor offering 'efzofitimod' or 'ATYR1923' as a research chemical is illegitimate; the molecule is a complex Fc-fusion produced only for clinical trials
- As an immunomodulator, it could in principle affect infection risk; the full long-term safety profile is still being characterized
- Benefit seen so far is on secondary and patient-reported outcomes at the 5 mg/kg dose, which require confirmation in a further Phase 3 trial before any conclusions
- Indicated (investigationally) for pulmonary sarcoidosis specifically — use in other interstitial lung diseases remains exploratory

## Comparisons

See how Efzofitimod compares to related peptides:

Efzofitimod vs Ara-290: https://peptrackerpro.com/compare/efzofitimod-vs-ara-290

Efzofitimod vs Batoclimab: https://peptrackerpro.com/compare/efzofitimod-vs-batoclimab

Efzofitimod vs Efgartigimod: https://peptrackerpro.com/compare/efzofitimod-vs-efgartigimod

Efzofitimod vs KPV: https://peptrackerpro.com/compare/efzofitimod-vs-kpv

Efzofitimod vs Nipocalimab: https://peptrackerpro.com/compare/efzofitimod-vs-nipocalimab

Efzofitimod vs Pegcetacoplan: https://peptrackerpro.com/compare/efzofitimod-vs-pegcetacoplan

Efzofitimod vs Rozanolixizumab: https://peptrackerpro.com/compare/efzofitimod-vs-rozanolixizumab

Efzofitimod vs Thymosin Alpha-1: https://peptrackerpro.com/compare/efzofitimod-vs-thymosin-alpha-1

Efzofitimod vs VIP: https://peptrackerpro.com/compare/efzofitimod-vs-vip

Efzofitimod vs Zilucoplan: https://peptrackerpro.com/compare/efzofitimod-vs-zilucoplan

## Calculator Tools

Use our research tools to explore dosing and reconstitution data:

Reconstitution Calculator: https://peptrackerpro.com/calculators

## Citations

1. [1] aTyr Pharma Announces Topline Results from Phase 3 EFZO-FIT Study of Efzofitimod in Pulmonary Sarcoidosis (Sept 2025) PubMed (https://investors.atyrpharma.com/news-releases/news-release-details/atyr-pharma-announces-topline-results-phase-3-efzo-fittm-study)
2. [2] A human histidyl-tRNA synthetase splice variant therapeutic targets NRP2 to resolve lung inflammation and fibrosis. Science Translational Medicine, 2025 PubMed (https://www.science.org/doi/10.1126/scitranslmed.adp4754)
3. [3] aTyr Pharma Provides Regulatory and Clinical Update for Efzofitimod in Pulmonary Sarcoidosis Following FDA Type C Meeting PubMed (https://investors.atyrpharma.com/news-releases/news-release-details/atyr-pharma-provides-regulatory-and-clinical-update-efzofitimod)
4. [4] Efzofitimod Fails to Meet Primary End Point in Phase 3 Pulmonary Sarcoidosis Trial — HCPLive PubMed (https://www.hcplive.com/view/efzofitimod-fails-to-meet-primary-end-point-in-phase-3-pulmonary-sarcoidosis-trial)
5. [5] Efzofitimod — Pulmonary Fibrosis Foundation pipeline profile PubMed (https://www.pulmonaryfibrosis.org/patients-caregivers/medical-and-support-resources/clinical-trials-education-center/pipeline/drug/other-interstitial-lung-disease/efzofitimod)

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