On November 9, 2021 aTyr Pharma, Inc. (Nasdaq: LIFE), a biotherapeutics company engaged in the discovery and development of innovative medicines based on novel biological pathways, reported a poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, which is being held November 10 – 14, 2021 in Washington, DC, and virtually (Press release, aTyr Pharma, NOV 9, 2021, View Source [SID1234594984]). The full text of the corresponding abstract is available on the SITC (Free SITC Whitepaper) website. The poster will be available for browsing on the SITC (Free SITC Whitepaper) website starting Friday, November 12 at 7:00 a.m. ET through Sunday, November 14 at 5:00 p.m. ET.
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The poster presents preclinical findings for ATYR2810, providing key insights into its mechanism of action that will help support the clinical development of ATYR2810, including a Phase 1 study in cancer next year. ATYR2810, an anti-Neuropilin-2 (NRP2) monoclonal antibody that blocks NRP2’s VEGF-induced signaling axis, was developed from aTyr’s research platform focused on targeting human disease pathways associated with extracellular tRNA synthetases. This work details the effects of ATYR2810 on tumor associated macrophages (TAMs) differentiated from human triple-negative breast cancer tumor cells. Treatment with ATYR2810 was shown to decrease the suppressive capabilities of TAMs against T cells compared to untreated TAMs. Furthermore, TAMs treated with ATYR2810 showed a decrease in ZEB1 gene expression, which is a master transcription factor regulating epithelial-mesenchymal transition (EMT), a process that is of great importance in regulating tumor growth, progression and metastatic cascade as well as being implicated in tumor evasion of the immune system. These results suggest that ATYR2810 may be able to treat cancer by targeting tumor immune avoidance mechanisms as well as regulating EMT.
Details of the poster and corresponding abstract are as follows:
Title: ATYR2810, an anti-NRP2 monoclonal antibody, targets tumor associated macrophages
Authors: Samantha Tyler, Michaela Ferrer, Erik Escobedo, Kaitlyn Rauch, Sofia Klopp-Savino, Justin Rahman, Zhiwen Xu, Esther Chong, Suzanne Paz, Leslie Nangle. aTyr Pharma, San Diego, CA.
Abstract Number: 699
Date and Time: November 12 – 14, 2021 from 7:00AM – 5:00PM ET
"We are pleased to demonstrate, for the first time, modulation of key cells associated with suppressing T cell-mediated anti-tumor responses in the tumor microenvironment as a result of treatment with ATYR2810, aTyr’s IND candidate in preclinical development for aggressive solid tumors where NRP2 is implicated," said Leslie Nangle, Ph.D., Vice President, Research at aTyr. "It is well known that TAMs suppress T cell activity and play an important role in the induction of EMT, contributing to therapy resistance and metastasis. As we and others have shown, these highly suppressive TAMs express high levels of NRP2. The ability of ATYR2810 to regulate EMT-related genes like ZEB1 in human TAMs and reduce their suppressive nature provides insight into the role of NRP2/VEGF signaling in TAMs. These findings advance our understanding of ATYR2810’s mechanism of action and the process by which it may inhibit tumor progression and disrupt immune evasion."
About ATYR2810
aTyr is developing ATYR2810 as a potential therapeutic for certain aggressive tumors where Neuropilin-2 (NRP2) is implicated. ATYR2810 is a fully humanized monoclonal antibody that is designed to specifically and functionally block the interaction between NRP2 and one of its primary ligands, VEGF. ATYR2810 is the first Investigational New Drug (IND) candidate to arise from aTyr’s in-house research program designing monoclonal antibodies to selectively target the NRP2 receptor and its associated signaling pathways. NRP2 is a cell surface receptor that is highly expressed in certain tumors, in the lymphatic system and on key immune cells implicated in cancer progression. Increased NRP2 expression is associated with worse outcomes in many cancers. Preclinical data suggest that ATYR2810 could be effective against certain types of solid tumors. ATYR2810 is currently undergoing IND-enabling studies.