aTyr Pharma has advanced its novel therapeutic candidate ATYR0101 to investigational new drug (IND) candidate stage for the treatment of pulmonary fibrosis, the company announced today. The therapy will be showcased at the upcoming American Thoracic Society (ATS) 2025 Respiratory Innovation Summit in San Francisco on May 16-17.
ATYR0101 represents a potentially groundbreaking approach to treating fibrotic diseases through a unique mechanism of action. The therapy is a fusion protein derived from a proprietary extracellular domain of aspartyl-tRNA synthetase (DARS) that binds to latent transforming growth factor beta binding protein 1 (LTBP-1), inducing cell death in myofibroblasts—key cells responsible for driving fibrosis progression.
"Fibrosis is a key driver of morbidity and mortality in many diseases, particularly those affecting the lung, where evasion of myofibroblast cell death is a defining feature," said Leslie A. Nangle, Ph.D., Vice President of Research at aTyr. "The unique effects observed with ATYR0101 in preclinical models of fibrosis suggest it may have the potential to reverse fibrosis, which could represent a meaningful advancement in the approach to treating pulmonary fibrosis, where current treatments only slow disease progression."
Novel Mechanism Targets Fibrosis Reversal
Current treatments for pulmonary fibrosis, such as nintedanib and pirfenidone, primarily aim to slow disease progression rather than reverse existing fibrosis. ATYR0101's mechanism of inducing myofibroblast apoptosis through LTBP-1 interaction presents a differentiated approach that could potentially modify or reverse the disease course.
Preclinical studies have demonstrated anti-fibrotic effects in models of both lung and kidney fibrosis, suggesting broader therapeutic potential across multiple fibrotic conditions. The company will present detailed preclinical data during an oral presentation titled "ATYR0101: A New Approach to Fibrosis" at the ATS Respiratory Innovation Summit.
Building on tRNA Synthetase Platform Success
ATYR0101 emerges from aTyr's proprietary tRNA synthetase platform, which leverages evolutionary biology to develop novel therapeutics. The company's lead candidate from this platform, efzofitimod, has already shown promising clinical results in interstitial lung disease.
"Building on the promising clinical results of our lead tRNA synthetase-derived therapy, efzofitimod, in interstitial lung disease, we're excited to advance ATYR0101 into IND-enabling studies," said Sanjay S. Shukla, M.D., M.S., President and Chief Executive Officer of aTyr. "This next candidate from our pipeline exemplifies the transformative potential of our innovative drug discovery platform and highlights our unwavering commitment to pioneering therapies for inflammatory and fibrotic diseases."
Development Timeline and Next Steps
aTyr is currently conducting IND-enabling studies for ATYR0101 and anticipates filing an IND application with the FDA in the second half of 2026. The upcoming presentation at the ATS Respiratory Innovation Summit will feature Ryan Adams, Ph.D., Senior Director of In Vitro Biology, who will present the therapy during the ILD/Fibrosis showcase session on May 17.
Pulmonary fibrosis represents a significant unmet medical need, characterized by progressive scarring of lung tissue that leads to declining lung function and high mortality rates. The condition affects approximately 3 million people worldwide, with idiopathic pulmonary fibrosis (IPF) being one of the most common and severe forms.
If successful in clinical development, ATYR0101 could offer a new therapeutic option for patients with pulmonary fibrosis who currently face limited treatment choices and poor long-term outcomes. The potential to not only halt but potentially reverse fibrotic changes would represent a significant advancement in the management of this devastating condition.
