aTyr Pharma (ATYR) investor relations material

Study design and methodology

• Phase 3 EFZO-FIT global trial evaluated efzofitimod at 3.0 mg/kg and 5.0 mg/kg versus placebo in 268 patients with moderate to severe pulmonary sarcoidosis across the US, Europe, Japan, and Brazil over 48 or 52 weeks.

• Patients were randomized 1:1:1 to receive 5 mg/kg, 3 mg/kg efzofitimod, or placebo intravenously once a month for 12 doses, with all participants on stable oral corticosteroids for at least 6 months.

• The primary endpoint was change from baseline in mean daily oral corticosteroid (OCS) dose at week 48, with secondary endpoints including King's Sarcoidosis Questionnaire (KSQ) Lung Score, forced vital capacity (FVC), and complete steroid withdrawal.

• Steroid tapering was protocol-guided, using patient and investigator assessments, including Patient Global Assessment every two weeks.

• Baseline demographics and disease characteristics were balanced across treatment groups.

Efficacy results

• The primary endpoint was not met due to a higher than expected placebo response in steroid reduction; mean daily OCS dose reduced to 2.79 mg for 5.0 mg/kg efzofitimod vs 3.52 mg for placebo (p=0.3313).

• 52.6% of patients on 5 mg/kg efzofitimod achieved complete steroid withdrawal at week 48, versus 40.2% on placebo (p=0.0919).

• KSQ Lung Score improved by 10.36 points for 5 mg/kg efzofitimod, 7.33 for 3 mg/kg, and 6.19 for placebo (p=0.0479 for 5 mg/kg vs placebo).

• 29.5% of patients on 5 mg/kg efzofitimod were both steroid-free and had ≥8-point KSQ improvement, compared to 14.4% for placebo (p=0.0199).

• Lung function (FVC) was maintained across all groups at week 48.

Safety and tolerability

• Efzofitimod was well tolerated at both 3.0 mg/kg and 5.0 mg/kg doses, with a safety profile consistent with previous studies.

• Adverse events were mostly mild to moderate and balanced or generally unrelated to the study drug across groups.

• Serious adverse events and discontinuations were limited and similar between groups.

• Incidence of antidrug antibodies was small and similar across groups.

• The drug demonstrated a favorable safety profile compared to current standard treatments like prednisone and methotrexate.