On April 11, 2022 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 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which is being held April 8 – 13, 2022, in New Orleans, LA, and virtually (Press release, aTyr Pharma, APR 11, 2022, View Source [SID1234611983]). The poster and corresponding abstract are available for browsing on the AACR (Free AACR Whitepaper) website through July 13, 2022. The poster is also available on the aTyr website.
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The poster presents findings from a preclinical study, conducted in collaboration with Dr. Arthur M. Mercurio and his lab at the University of Massachusetts Medical School, characterizing the subtypes of breast cancer that are most responsive to treatment with ATYR2810, a fully humanized monoclonal antibody that selectively and functionally blocks the interaction between neuropilin-2 (NRP2) and VEGF by directly binding at the site of the VEGF binding pocket. Interrogation of ATYR2810 activity in combination with chemotherapy across a panel of breast cancer cells lines using an in vitro 3D colony formation assay revealed that highly aggressive and more mesenchymal cell lines associated with metastasis, including triple negative breast cancer (TNBC), were most responsive. Data from both patient derived organoid and patient derived xenograft models from TNBC where ATYR2810 demonstrated anti-tumor activity showed downregulation of key genes known to promote metastasis and drug resistance, including CXCR4 and a set of genes linked to the process of epithelial-mesenchymal transition (EMT). Furthermore, ATYR2810 monotherapy inhibited spontaneous lung metastasis in an experimental model of TNBC, demonstrating the potential therapeutic effects of blocking the NRP2/VEGF signaling axis on preventing tumor persistence.
"Highly aggressive tumors such as TNBC have been shown to have elevated NPR2 expression and are typically treated with resection and chemotherapy, though the potential for metastasis and tumor regrowth, which is thought to be strongly linked to the process of EMT, is high. The ability of ATYR2810 to downregulate genes associated with EMT, reduce metastasis and enhance chemosensitivity in these highly aggressive subtypes of breast cancer provides valuable insight regarding the types of tumors that may benefit from treatment with ATYR2810," said Leslie A. Nangle, Ph.D., Vice President, Research at aTyr. "These findings suggests that ATYR2810 may serve as a novel therapeutic agent for the treatment of advanced and metastatic cancers. We look forward to advancing ATYR2810 to a Phase 1 study in cancer patients in the second half of the year."
Details of the poster and corresponding abstract are as follows:
Title: ATYR2810, a fully humanized monoclonal antibody targeting the VEGF-NRP2 pathway sensitizes highly aggressive and chemoresistant TNBC subtypes to chemotherapy
Authors: Zhiwen Xu, Alison G. Barber, Christoph Burkart, Hira Lal Goel, Justin Rahman, Kristina Hamel, Zachary Fogassy, Lisa Eide, Clara Polizzi, Jasmine Stamps, Luke Burman, Kaitlyn Rauch, Ann Menefee, Yanyan Geng, Sofia Klopp Savino, Yeeting E. Chong, Darin Lee, Suzanne Paz, Arthur M. Mercurio, Leslie A. Nangle. aTyr Pharma, University of Massachusetts Chan Medical School, Pangu BioPharma, IAS HKUST – Scripps R&D, Hong Kong University of Science and Technology.
Abstract Control Number: 7998
Session Title: Late-Breaking Research: Experimental and Molecular Therapeutics 1 / Chemistry
Session Date and Time: Monday, April 11, 2022 from 1:30PM – 5:00PM ET
Location: New Orleans Convention Center, Exhibit Halls D – H, Poster Section 16
Poster Board Number: 10
Permanent Abstract Number: LB085
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.