Efzofitimod Shows Promising Early Efficacy in Systemic Sclerosis-Related Interstitial Lung Disease

Efzofitimod has demonstrated early signs of clinical efficacy in people with diffuse and limited systemic sclerosis-related interstitial lung disease (SSc-ILD).1

“We are excited to see early signals emerging across multiple skin assessment measures from this initial interim analysis, and we are particularly encouraged by the stable or improved modified Rodnan Skin Score (mRSS), a measure of skin fibrosis, seen in all patients,” Sanjay S. Shukla, MD, MS, President and Chief Executive Officer of aTyr, said in a statement.1 “Remarkably, even at this early 12-week timepoint, we observed meaningful improvement in three out of four efzofitimod-treated patients with diffuse SSc-ILD, a more severe form of the disease. mRSS is a sensitive clinical outcome measure, particularly for diffuse patients, so we consider this trend quite promising. As we continue enrollment and move toward the 24-week endpoints, including lung function as the primary endpoint to evaluate the ILD component of the disease, we look forward to providing additional updates upon completion of the trial.”

aTyr announced data from an interim analysis of 8 patients in the ongoing Phase 2 EFZO-CONNECT™ study, 5 with diffuse and 3 with limited SSc-ILD. The randomized, double-blind, placebo-controlled, proof-of-concept study is designed to last 28 weeks and will evaluate either 270 mg or 450 mg of efzofitimod or placebo dosed intravenously monthly for a total of 6 doses in 3 parallel cohorts randomized 2:2:1, respectively. The study plans to enroll 25 participants, who would be eligible to participate in a 24-week open-label extension after completion. EFZO-CONNECT is primarily evaluating the efficacy of multiple doses of intravenous efzofitimod on pulmonary, cutaneous and systemic manifestations in patients with SSc-ILD, and is evaluating safety and tolerability as secondary outcomes.

The interim analysis evaluated skin assessments and serum biomarkers at baseline and week 12. The investigators found that all patients had stable or improved modified Rodnan Skin Score (mRSS) and 3 of 4 evaluable, efzofitimod-treated patients with diffuse SSc-ILD had at least a 4-point improvement. Notably, the minimal clinically important difference (MCID) is a 4-to-6 point improvement at 12 months.2

Investigators also observed preliminary signals of improvement for inflammatory biomarkers including interferon gamma (IFN-γ) and monocyte chemoattractant protein-1 (MCP-1) and disease biomarkers Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D). In terms of safety, efzofitimod was found to be generally safe and well tolerated at all dose levels and there were no treatment related serious adverse events.1

Efzofitimod is a first-in-class biologic immunomodulator, specifically a tRNA synthetase derived therapy that selectively modulates activated myeloid cells through neuropilin-2 to resolve inflammation without immune suppression designed to prevent the progression of fibrosis. Efzofitimod is also being evaluated in the global Phase 3 EFZO-FIT study in patients with pulmonary sarcoidosis.

REFERENCES

1. aTyr Pharma Announces Findings from Interim Analysis of Ongoing Phase 2 EFZO-CONNECT™ Study of Efzofitimod in Systemic Sclerosis-Related Interstitial Lung Disease (SSc-ILD). News release. aTyr Pharma. June 4, 2025. https://investors.atyrpharma.com/news-releases/news-release-details/atyr-pharma-announces-findings-interim-analysis-ongoing-phase-2

2. Khanna D, Clements PJ, Volkmann ER, et al. Minimal Clinically Important Differences for the Modified Rodnan Skin Score: Results from the Scleroderma Lung Studies (SLS-I and SLS-II). Arthritis Res Ther. 2019;21(1):23. Published 2019 Jan 16. doi:10.1186/s13075-019-1809-y