aTyr Pharma Showcases Efzofitimod’s Potential Mechanism In Lung Inflammation In Science Translational Medicine

aTyr Pharma, Inc., a biotechnology company specialising in first-in-class medicines derived from its proprietary tRNA synthetase platform, has announced the publication of a study in Science Translational Medicine detailing the mechanism of action of its lead therapeutic candidate, efzofitimod. The study, titled “A human histidyl-tRNA synthetase splice variant therapeutic targets NRP2 to resolve lung inflammation and fibrosis,” provides insight into the foundational research and preclinical work behind the drug’s development.

Leslie A. Nangle, PhD, Vice President of Research at aTyr, said in a statement, “We are pleased to publish this extensive manuscript detailing the preclinical data supporting the development of efzofitimod, which includes all of the data generated for this novel drug candidate from concept to clinic. This peer-reviewed publication in a highly regarded journal such as Science Translational Medicine validates the immunomodulatory activity and extracellularly mediated mechanism of efzofitimod in reducing inflammation and fibrosis. Furthermore, this validation considerably expands the basis for the application of efzofitimod in chronic inflammatory conditions and encourages the potential development of other tRNA synthetase-based therapeutics for disease intervention.”

Efzofitimod is an immunomodulator derived from a splice variant of histidyl-tRNA synthetase (HARS), abundant in human lung tissue and upregulated in response to inflammatory cytokines. The research highlights its selective binding to neuropilin-2 (NRP2), a receptor in myeloid cells at inflammation sites. By inhibiting pro-inflammatory receptors and cytokines, efzofitimod helps to regulate macrophage-driven inflammatory pathways, potentially breaking the cycle of chronic inflammation and fibrosis in lung disease.

“This publication is a culmination of our innovative drug discovery process and serves as a testament to the overwhelming amount of preclinical work that provides evidence for the immunomodulatory activity of efzofitimod. This scientific work, along with the compelling clinical proof-of-concept generated for efzofitimod in pulmonary sarcoidosis, supports the ongoing clinical development program in interstitial lung disease (ILD) and further strengthens the rationale to target ILD in their inflammatory stages using this novel therapeutic agent,” said Sanjay S. Shukla, M.D., M.S., President and Chief Executive Officer of aTyr. 

Currently, efzofitimod is being tested in a global Phase 3 EFZO-FIT™ trial for pulmonary sarcoidosis, a prevalent form of interstitial lung disease (ILD), and a Phase 2 EFZO-CONNECT™ study for systemic sclerosis-associated ILD (SSc-ILD). The drug has received orphan drug designation in the U.S., E.U., and Japan for sarcoidosis and Fast Track designation in the U.S. for both pulmonary sarcoidosis and SSc-ILD. These regulatory recognitions highlight the potential of efzofitimod as a breakthrough therapy for chronic lung diseases.