aTyr Pharma (ATYR) Study update summary

Regulatory and clinical update

• Recent Type C FDA meeting provided feedback guiding the next Phase III study design for efzofitimod in pulmonary sarcoidosis.

• The new global, randomized, double-blind, placebo-controlled, 1-year study will enroll up to 372 patients with moderate to severe progressive sarcoidosis and restrictive lung disease.

• FDA recommended a focus on restrictive lung disease phenotype and optimized dosing, with dosing frequency increased to once every three weeks to enhance drug exposure while maintaining safety.

• Protocol for the new study will be submitted next month, with IND submission planned for June 2026, aiming for rapid enrollment leveraging a global network.

• All background treatments, including corticosteroids and immunosuppressants, will remain stable during the study.

Study design and endpoints

• Primary endpoint is change from baseline in forced vital capacity (FVC) at week 48; KSQ-Lung score is a key secondary endpoint, both recognized by FDA as clinically meaningful.

• The restrictive phenotype is defined by FVC % predicted between 50 and 80 and FEV1/FVC ratio ≥0.7.

• Inclusion criteria ensure a homogeneous, symptomatic, non-fibrotic restrictive population.

• Enhanced safety monitoring, especially for anti-synthetase syndrome, will be included per FDA guidance.

• All background treatments will remain stable during the study.

Rationale and clinical findings

• EFZO-FIT missed its primary endpoint of steroid reduction but showed durable benefits on quality of life measures and a clinically meaningful 124 mL FVC improvement in restrictive patients treated with efzofitimod versus placebo.

• Modeling supports a 3-week dosing interval to increase drug exposure without compromising safety.

• Placebo group in prior studies showed flat to slightly decreased FVC when steroids were stable.

• The new study aims for a conservative, statistically robust FVC difference, likely targeting an 80 mL delta.

• The new trial will focus on a defined patient population with demonstrated benefit from efzofitimod.