SAN DIEGO—aTyr Pharma Inc. announced today that the company has initiated two new discovery programs from its tRNA synthetase platform. These programs will investigate the functionality of selected fragments of alanyl-tRNA synthetase (AARS) and aspartyl-tRNA synthetase (DARS) in immunology, fibrosis, and cancer.
This announcement comes after the company published a poster at the 2021 Society for Laboratory Automation and Screening digital conference, in January. The poster demonstrated that these extracellular tRNA synthetase fragments bind to innate and adaptive immune cells — including natural killer (NK) cells.
“We are pleased to initiate these discovery programs, which build on our proprietary biology platform and add to our developing pipeline in immunology, fibrosis and oncology,” stated Dr. Sanjay S. Shukla, president and CEO of aTyr. “We continue to leverage our broad intellectual property portfolio covering tRNA synthetases and their related signaling pathways to translate this underexplored area of biology into potential first-in-class therapies for diseases with high unmet need.”
The poster described a mass spectrometry proteomics-based approach to identify target receptors for two distinct extracellular tRNA synthetase fragments. The utilization of this workflow — which included recombinant protein expression, flow cytometry, and receptor screening in living cells using the ligand-receptor capture TriCEPS technology — resulted in the identification of receptor targets for fragments of the tRNA synthetases AARS and DARS, as well as insights into their potential biological activity in immunology, cancer, and fibrosis. The approach can also be applied more broadly to identify receptor targets of extracellular proteins and other ligands, like peptides, antibodies, or viruses.
The initial research will primarily focus on further understanding the effects of these fragments on NK cell biology in cancer. The discovery programs will use the company’s novel approach to identifying target receptors for tRNA synthetase fragments in order to help characterize the mechanism of action of these proteins.
“These transformative findings, which received an enthusiastic response at SLAS in our poster presentation, highlight the important pathways that extracellular tRNA synthetase fragments interact with, including NK cells. The research approach was similar to the process by which we identified Neuropilin-2 (NRP2) as the target receptor for the HARS fragment that forms the active component of our lead tRNA synthetase derived drug candidate, ATYR1923,” Shukla explained. “This finding has led to advances in our understanding of ATYR1923 and to the development of our panel of selective anti-NRP2 antibodies, including ATYR2810. We look forward to further characterizing AARS and DARS binding targets to help support and guide future drug development.”