aTyr Pharma Announces Publication of Two Abstracts in American Journal of Respiratory and Critical Care Medicine
Abstracts originally accepted for presentation at the 2020
Findings confirm that aTyr’s lead clinical candidate, ATYR1923, selectively binds to Neuropilin-2 (NRP2), a unique target expressed on key immune cells in inflammatory conditions
“We are very pleased to have these abstracts, which were originally accepted for presentation at the
Details of the abstracts are as follows:
P1173 - ATYR1923 Specifically Binds to Neuropilin-2, a Novel Therapeutic Target for the Treatment of Immune-Mediated Diseases
Neuropilin-2 (NRP2) is a pleiotropic cell surface receptor known to be expressed on a number of different immune cell types that plays a key role in regulating inflammatory responses. aTyr Pharma’s lead clinical candidate, ATYR1923, is a fusion protein combining a novel immunomodulatory domain from histidyl-tRNA synthetase (HARS) and a human IgG1 Fc. ATYR1923 has previously demonstrated potent immunomodulatory activity in vitro and in vivo. ATYR1923 specifically and selectively binds to NRP2 on the cell surface, which was discovered by cell microarray screening and confirmed by surface plasmon resonance (SPR) and also by flow cytometry analysis of HEK293 cells over-expressing NRP2. Furthermore, ATYR1923 was also found to bind to cells that endogenously express NRP2 on the surface (such as THP-1 polarized M1 macrophages). These findings indicate that modulation of the NRP2 signaling pathway could be a novel therapeutic approach to immune-mediated diseases. ATYR1923 is currently being evaluated in a Phase 1b/2a study in patients with pulmonary sarcoidosis, an inflammatory disease which can result in lung fibrosis.
P983 - Neuropilin-2, the Specific Binding Partner to ATYR1923, Is Expressed in Sarcoid Granulomas and Key Immune Cells
aTyr reports for the first time that NRP2 is expressed in samples obtained from lung and skin of sarcoidosis patients. More specifically, NRP2 expression was readily detectable within the granulomas in both skin and lung samples. In this abstract, the company demonstrates that NRP2 expression can be detected on key immune cells known to play an important role in inflammation and granuloma formation. These findings highlight the potential of ATYR1923 to exert its effect on various immune cells directly related to the pathology of the target patient population.
aTyr is developing ATYR1923 as a potential therapeutic for patients with interstitial lung diseases. ATYR1923, a fusion protein comprised of the immuno-modulatory domain of histidyl tRNA synthetase fused to the FC region of a human antibody, is a selective modulator of neuropilin-2 that downregulates the innate and adaptive immune response in inflammatory disease states. aTyr is currently enrolling a proof-of-concept Phase 1b/2a trial evaluating ATYR1923 in patients with pulmonary sarcoidosis. This Phase 1b/2a study is a multi-ascending dose, placebo-controlled, first-in-patient study of ATYR1923 that has been designed to evaluate the safety, tolerability, steroid sparing effect, immunogenicity and pharmacokinetics profile of multiple doses of ATYR1923.
Neuropilin-2 (NRP2) is a cell surface receptor that plays a key role in lymphatic development and in regulating inflammatory responses. In many forms of cancer, high NRP2 expression is associated with worse outcomes. NRP2 can interact with multiple ligands and co-receptors through distinct domains to influence their functional roles, making it a potential drug target with multiple distinct therapeutic applications. NRP2 interacts with type 3 semaphorins and plexins to impact inflammation and with forms of vascular endothelial growth factor (VEGF) and their receptors, to impact lymphangiogenesis. In addition,
aTyr is a biotherapeutics company engaged in the discovery and development of innovative medicines based on novel immunological pathways. aTyr’s research and development efforts are concentrated on a newly discovered area of biology, the extracellular functionality and signaling pathways of tRNA synthetases. aTyr has built a global intellectual property estate directed to a potential pipeline of protein compositions derived from 20 tRNA synthetase genes and their extracellular targets. aTyr’s primary focus is ATYR1923, a clinical-stage product candidate which binds to the neuropilin-2 receptor and is designed to down-regulate immune engagement in interstitial lung diseases. For more information, please visit http://www.atyrpharma.com.
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Source: aTyr Pharma, Inc.