aTYR PHARMA INC (ATYR)

The company is a clinical stage biotechnology company that uses what it calls evolutionary intelligence to translate tRNA synthetase biology into new therapies for fibrosis and inflammation. tRNA synthetases are ancient, essential proteins that have evolved novel domains regulating diverse pathways outside the cell in humans. Its discovery platform draws on a proprietary library of domains derived from all 20 tRNA synthetases to uncover signaling pathways and therapeutic intervention points. The process combines knowledge of tRNA synthetase evolution, protein structure, gene splicing and tissue-specific regulation to identify active domains, then uses screening to find target cells and extracellular receptors.

The lead candidate is efzofitimod, a biologic immunomodulator in development for interstitial lung disease (ILD). It is an Fc fusion protein whose active moiety matches the immunomodulatory domain of histidyl-tRNA synthetase (HARS amino acids 2 to 60). It selectively modulates activated myeloid cells through neuropilin-2 (NRP2) to resolve inflammation without immune suppression and potentially prevent fibrosis. In September 2025, the global Phase 3 EFZO-FIT study in 268 patients with pulmonary sarcoidosis did not meet its primary endpoint of reduction in daily oral corticosteroid dose at week 48. Nominal improvements were reported on several secondary and pre-specified measures, including the King's Sarcoidosis Questionnaire (KSQ)-Lung score at the 5.0 mg/kg dose, and the drug was generally well tolerated. A Type C meeting with the FDA is scheduled for mid-April 2026 to determine the path forward. A Phase 2 proof-of-concept study, EFZO-CONNECT, is testing efzofitimod in systemic sclerosis-associated ILD (SSc-ILD), enrolling up to 25 patients in the U.S., with enrollment expected to complete in the first half of 2026. Two preclinical programs are also in the pipeline: ATYR0101, a DARS-derived Fc fusion protein that targets LTBP-1 to eliminate activated myofibroblasts in fibrotic disease, and ATYR0750, an AARS-derived fusion protein that acts as a novel ligand for FGFR4.

The company targets ILD, a group of immune-mediated disorders that can cause lung inflammation and scarring and for which treatment options are limited. Sarcoidosis and SSc-ILD are the two major forms in focus, and chronic hypersensitivity pneumonitis and other connective tissue disease-related ILDs are potential further uses. Efzofitimod has orphan drug designations from the FDA and the European Commission for sarcoidosis and systemic sclerosis, and FDA Fast Track designations for pulmonary sarcoidosis and SSc-ILD. In Japan, Kyorin Pharmaceutical holds exclusive development and commercialization rights under a January 2020 agreement. Kyorin funds all Japanese activities, and the company supplies the drug product. The agreement has generated $20.0 million in upfront and milestone payments, with up to $155.0 million more in milestones and tiered royalties on Japanese net sales possible. Kyorin has also received a Japanese orphan drug designation for sarcoidosis.

The strategy is to advance efzofitimod toward approval in pulmonary sarcoidosis, expand it into other ILDs, and build a pipeline of biologics from tRNA synthetase domains through internal research and external collaborations. The company has begun pre-commercialization efforts in the U.S. as it aims to move from a clinical stage biotech to a commercial pharmaceutical company.