The results suggest that ATYR2810 reduces metastasis and improves chemosensitivity by down-regulating key genes linked to these processes.
SAN DIEGO, April 11, 2022 (GLOBE NEWSWIRE) — aTyr Pharma, Inc. (Nasdaq: LIFE), a biotherapeutics company committed to the discovery and development of innovative drugs based on novel biological pathways, today announced a poster presentation at American Association for Cancer Research (AACR) 2022 Annual Meeting, which will be held April 8-13, 2022 in New Orleans, LA, and virtually. The poster and corresponding abstract can be viewed on the AACR website until July 13, 2022. The poster is also available on the aTyr website.
The poster presents the results of a preclinical study, conducted in collaboration with Dr. Arthur M. Mercurio and his laboratory at the University of Massachusetts Medical School, characterizing the breast cancer subtypes most sensitive to treatment with ATYR2810, a fully humanized monoclonal antibody that selectively and functionally blocks the interaction between neuropilin-2 (NRP2) and VEGF by binding directly to the site of the VEGF binding pocket. Interrogation of ATYR2810 activity in combination with chemotherapy on a panel of breast cancer cell lines using a in vitro The 3D colony formation assay revealed that highly aggressive and more mesenchymal cell lines associated with metastasis, including triple-negative breast cancer (TNBC), were the most reactive. Data from patient-derived organoid and patient-derived xenograft models of 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 related to the epithelial-mesenchymal transition (EMT) process. Additionally, 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 the prevention of tumor persistence.
“Very aggressive tumors such as TNBC have been shown to have high expression of NPR2 and are usually treated with resection and chemotherapy, although the potential for metastasis and tumor regrowth, which would be strongly linked to the EMT process, is raised. The ability of ATYR2810 to downregulate EMT-associated genes, reduce metastasis, and improve chemosensitivity in these highly aggressive subtypes of breast cancer provides valuable insight into the types of tumors that may benefit of treatment with ATYR2810,” said Leslie A. Nangle, Ph.D., Vice President, Research at aTyr. “These findings suggest that ATYR2810 could serve as a novel therapeutic agent for the treatment of advanced and metastatic cancers. We look forward to advancing ATYR2810 into 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: Cutting-edge research: Experimental and molecular therapeutics 1 / Chemistry
Session date and time: Monday, April 11, 2022 from 1:30 p.m. to 5:00 p.m. ET
Location: New Orleans Convention Center, Exhibit Halls D through H, Poster Section 16
Billboard number: ten
Permanent abstract number: LB085
aTyr is developing ATYR2810 as a potential therapeutic agent for certain aggressive tumors where neuropilin-2 (NRP2) is involved. ATYR2810 is a fully humanized monoclonal antibody designed to specifically and functionally block the interaction between NRP2 and one of its main ligands, VEGF. ATYR2810 is the first Investigational New Drug (IND) candidate from aTyr’s internal research program designing monoclonal antibodies to selectively target the NRP2 receptor and its associated signaling pathways. NRP2 is a cell surface receptor strongly expressed in certain tumours, in the lymphatic system and on key immune cells implicated in cancer progression. Increased expression of NRP2 is associated with poorer outcomes in many cancers. Preclinical data suggest that ATYR2810 may be effective against certain types of solid tumors. ATYR2810 is currently being studied for IND.
aTyr is a biotherapeutic company committed to the discovery and development of innovative drugs based on new biological pathways. aTyr’s research and development efforts focus on a recently discovered area of biology, the extracellular functionality and signaling pathways of tRNA synthetases. aTyr has built a global intellectual property portfolio directed towards a potential pipeline of protein compositions derived from 20 tRNA synthetase genes and their extracellular targets. aTyr is primarily focused on efzofitimod, a clinical-stage product candidate that binds to the neuropilin-2 receptor and is designed to downregulate immune engagement in fibrotic lung disease. For more information, please visit http://www.atyrpharma.com.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are generally identified by the use of words such as “anticipates”, “believes”, “estimates”, “would expects, ‘intends’, ‘may’, ‘plans’, ‘plans’, ‘seeks’, ‘should’, ‘will’ and variations of these words or similar expressions. We intend that these forward-looking statements be covered by these safe harbor provisions for forward-looking statements and make this statement in order to comply with these safe harbor provisions. These forward-looking statements include statements regarding the potential therapeutic benefits and applications of NRP2 antibodies, including ATYR2810; timelines and plans for certain development activities; and some development goals. These forward-looking statements also reflect our current beliefs about our plans, intentions, expectations, strategies and prospects, which are based on information currently available to us and assumptions made by us. Although we believe that our plans, intentions, expectations, strategies and prospects, as reflected or implied by these forward-looking statements, are reasonable, we cannot guarantee that the plans, intentions, expectations or strategies will be achieved or realized. All forward-looking statements are based on our management’s estimates and assumptions which, although we believe to be reasonable, are inherently uncertain. In addition, actual results may differ materially from those described in these forward-looking statements and will be affected by a variety of risks and factors beyond our control, including, without limitation, uncertainty regarding the COVID-19 pandemic. 19, the risks associated with the discovery, development and regulation of our product candidates, the risk that we or our partners stop or delay preclinical or clinical development activities of any of our existing or future product candidates for various reasons (including difficulties or delays in recruiting patients into trials), the possibility that existing collaborations may be terminated prematurely, and the risk that we may not be able to raise additional funds necessary for our business plans and product development, as well as the risks set forth in our most recent annual report on Form 10-K, Rapp quarterly reports on Form 10-Q and in our other filings with the SEC. Except as required by law, we undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise.
Director, Investor Relations and Corporate Communications