aTyr Pharma (ATYR) investor relations material

Key clinical insights and trial results

• Efzofitimod demonstrated significant quality-of-life improvements and functional benefits in pulmonary sarcoidosis, with a large treatment effect on forced vital capacity (FVC) in restrictive patients, exceeding typical clinical expectations.

• The EFZO-FIT trial, the largest interventional pulmonary sarcoidosis study to date, showed that patients could be managed with substantially less steroid use, prompting anticipated updates to treatment guidelines.

• Consistent, durable improvements were observed in patient-reported outcomes, including cough, shortness of breath, fatigue, and general health, with benefits emerging early and persisting through week 48.

• Safety profile was favorable, with most adverse events mild or moderate and low immunogenicity, positioning efzofitimod as a safer alternative to current therapies.

• The drug’s mechanism targets neuropilin-2, modulating pro-inflammatory macrophages, and is supported by landmark preclinical research.

Regulatory and development strategy

• Recent FDA meetings provided a clear pathway for approval, requiring a new phase III trial with FVC as the primary endpoint and King's Sarcoidosis Questionnaire (KSQ) as a key secondary endpoint.

• The next trial will focus on a restrictive lung phenotype, enrolling approximately 372 patients, with stable background immunomodulator use and minimal steroid tapering to avoid confounding results.

• Dosing will shift to a Q3 regimen, increasing drug exposure by about 30% without raising safety concerns, aiming for 17 doses over one year.

• The trial is designed to detect a clinically meaningful FVC improvement of 80 mL, with statistical power to demonstrate significance even at lower effect sizes.

• Protocol submission to the FDA is planned within the month, with trial initiation targeted for later this year.

Market opportunity and strategic outlook

• Efzofitimod addresses a large unmet need in sarcoidosis, especially among restrictive patients, estimated at 40,000 in the U.S., who have exhausted standard therapies.

• Pricing estimates are being revised upward, with expectations now at the higher end of the $150,000–$200,000 range due to the severity of the target population.

• The drug’s mechanism is effective across phenotypes when matched to the appropriate functional endpoint, supporting potential expansion beyond restrictive patients.

• The company’s pipeline includes a proof-of-concept trial in systemic sclerosis and plans to advance the ATYR0101 anti-fibrotic program into the clinic next year.

• Financial position supports ongoing development, with a focus on capital efficiency as the new phase III trial is launched.