aTyr Pharma (ATYR) Study update summary

Regulatory and clinical update

• FDA Type C meeting reviewed phase III EFZO-FIT results and provided guidance for a new global Phase 3 trial of efzofitimod in pulmonary sarcoidosis, supporting FVC and KSQ-Lung as clinically meaningful endpoints.

• FDA recommended a new phase III study focusing on restrictive lung disease phenotype, optimizing dosing to every three weeks, and incorporating enhanced safety monitoring, including surveillance for anti-synthetase syndrome and a Data Monitoring Committee.

• FDA acknowledged efforts to validate KSQ-Lung for regulatory use and suggested adding symptom measures like cough severity and wheezing as new anchors.

• IND submission for the new Phase 3 study is planned for June 2026.

• Enhanced safety monitoring and risk mitigation strategies will be incorporated.

Study design and patient population

• The new Phase 3 trial will be a global, randomized, double-blind, placebo-controlled, one-year study enrolling up to 372 patients with moderate to severe progressive pulmonary sarcoidosis with restrictive lung disease.

• Focus on a homogenous population: patients with documented pulmonary sarcoidosis ≥6 months, FVC 50–80%, FEV1/FVC ≥0.7, dyspnea score ≥2, KSQ ≤60, and stable on low-dose corticosteroids and/or immunosuppressants.

• Exclusion criteria include significant or advanced fibrosis, severe diffusion impairment, and recent use of biologics, antifibrotics, or certain immunomodulators.

• Primary endpoint: change from baseline in FVC at week 48; key secondary: change in KSQ-Lung score at week 48.

• Participants will remain on stable background therapy, with no forced steroid taper.

Rationale and expected outcomes

• Restrictive phenotype chosen due to observed 124 mL FVC improvement in EFZO-FIT subgroup and to reduce variability, increasing statistical power.

• FVC is a direct measure of patient function, while KSQ-Lung reflects patient-reported outcomes.

• Anticipated placebo group performance is flat to slightly decreased FVC, based on historical data.

• Expected clinically meaningful FVC difference for approval is around 80 mL, with conservative statistical assumptions.

• No interim or futility analysis is planned for the new trial.