aTyr Pharma Announces Publication Demonstrating Efzofitimod’s Immunomodulatory Activity in Science Translational Medicine
aTyr Pharma has announced a significant publication in Science Translational Medicine validating the mechanism of action of efzofitimod, their lead therapeutic candidate. The research demonstrates efzofitimod's unique anti-inflammatory mechanism targeting macrophages through the neuropilin-2 (NRP2) receptor.
The publication details how efzofitimod, derived from histidyl-tRNA synthetase (HARS), binds specifically to NRP2, which is highly expressed in inflammatory sites. This binding inhibits pro-inflammatory receptors and cytokines, potentially disrupting chronic inflammation and fibrosis cycles.
Currently, efzofitimod is undergoing a global Phase 3 EFZO-FIT™ study for pulmonary sarcoidosis and a Phase 2 EFZO-CONNECT™ study for systemic sclerosis-related ILD. The drug has received orphan drug designation in the U.S., E.U., and Japan for sarcoidosis, and Fast Track designation in the U.S. for both pulmonary sarcoidosis and SSc-ILD.
aTyr Pharma ha annunciato una pubblicazione significativa su Science Translational Medicine che convalida il meccanismo d'azione di efzofitimod, il loro principale candidato terapeutico. La ricerca dimostra il meccanismo anti-infiammatorio unico di efzofitimod, che agisce sui macrofagi attraverso il recettore neuropilina-2 (NRP2).
La pubblicazione dettaglia come efzofitimod, derivato dalla sintetasi dell'istidil-tRNA (HARS), si leghi specificamente a NRP2, che è altamente espresso nei siti infiammatori. Questo legame inibisce i recettori e le citochine pro-infiammatorie, potenzialmente interrompendo i cicli di infiammazione cronica e fibrosi.
Attualmente, efzofitimod è oggetto di uno studio globale di Fase 3 EFZO-FIT™ per la sarcoidosi polmonare e di uno studio di Fase 2 EFZO-CONNECT™ per l'ILD correlata alla sclerosi sistemica. Il farmaco ha ricevuto la designazione di farmaco orfano negli Stati Uniti, nell'Unione Europea e in Giappone per la sarcoidosi, e la designazione Fast Track negli Stati Uniti sia per la sarcoidosi polmonare che per SSc-ILD.
aTyr Pharma ha anunciado una publicación significativa en Science Translational Medicine que valida el mecanismo de acción de efzofitimod, su principal candidato terapéutico. La investigación demuestra el mecanismo antiinflamatorio único de efzofitimod, que se dirige a los macrófagos a través del receptor neuropilina-2 (NRP2).
La publicación detalla cómo efzofitimod, derivado de la histidil-tRNA sintasa (HARS), se une específicamente a NRP2, que está altamente expresado en sitios inflamatorios. Esta unión inhibe los receptores proinflamatorios y las citoquinas, lo que potencialmente interrumpe los ciclos de inflamación crónica y fibrosis.
Actualmente, efzofitimod está en un estudio global de Fase 3 EFZO-FIT™ para la sarcoidosis pulmonar y un estudio de Fase 2 EFZO-CONNECT™ para ILD relacionada con la esclerosis sistémica. El fármaco ha recibido la designación de medicamento huérfano en EE. UU., UE y Japón para la sarcoidosis, y la designación de Fast Track en EE. UU. tanto para la sarcoidosis pulmonar como para SSc-ILD.
aTyr Pharma는 Science Translational Medicine에 efzofitimod의 작용 메커니즘을 검증하는 중요한 발표를 했습니다. 이 연구는 efzofitimod가 신경세포-2(NRP2) 수용체를 통해 대식세포를 표적으로 하는 독특한 항염증 메커니즘을 보여줍니다.
발표는 efzofitimod가 히스티딜-tRNA 합성효소(HARS)에서 유래하여 염증 부위에서 고도로 발현되는 NRP2에 특이적으로 결합하는 방법을 자세히 설명합니다. 이 결합은 염증 유발 수용체와 사이토카인을 억제하여 만성 염증 및 섬유증 주기를 방해할 수 있습니다.
현재 efzofitimod는 폐 사르코이드증에 대한 3상 EFZO-FIT™ 연구와 전신 경화증 관련 ILD에 대한 2상 EFZO-CONNECT™ 연구를 진행 중입니다. 이 약물은 미국, 유럽연합 및 일본에서 사르코이드증에 대한 희귀의약품 지정을 받았으며, 미국에서 폐 사르코이드증 및 SSc-ILD 모두에 대해 신속 심사 지정을 받았습니다.
aTyr Pharma a annoncé une publication significative dans Science Translational Medicine validant le mécanisme d'action de efzofitimod, leur principal candidat thérapeutique. La recherche démontre le mécanisme anti-inflammatoire unique d'efzofitimod ciblant les macrophages via le récepteur neuropiline-2 (NRP2).
La publication détaille comment efzofitimod, dérivé de l'histidyl-tRNA synthétase (HARS), se lie spécifiquement à NRP2, qui est fortement exprimé dans les sites inflammatoires. Cette liaison inhibe les récepteurs pro-inflammatoires et les cytokines, perturbant potentiellement les cycles d'inflammation chronique et de fibrose.
Actuellement, efzofitimod est en cours d'étude dans une étude de Phase 3 EFZO-FIT™ pour la sarcoïdose pulmonaire et une étude de Phase 2 EFZO-CONNECT™ pour l'ILD liée à la sclérose systémique. Le médicament a reçu la désignation de médicament orphelin aux États-Unis, dans l'UE et au Japon pour la sarcoïdose, ainsi que la désignation Fast Track aux États-Unis pour la sarcoïdose pulmonaire et SSc-ILD.
aTyr Pharma hat eine bedeutende Veröffentlichung in Science Translational Medicine angekündigt, die den Wirkmechanismus von efzofitimod, ihrem führenden therapeutischen Kandidaten, validiert. Die Forschung zeigt den einzigartigen entzündungshemmenden Mechanismus von efzofitimod, der Makrophagen über den Neuropilin-2 (NRP2) Rezeptor anspricht.
Die Veröffentlichung beschreibt, wie efzofitimod, das aus der Histidyl-tRNA-Synthetase (HARS) abgeleitet ist, spezifisch an NRP2 bindet, das in entzündlichen Stellen hoch exprimiert wird. Diese Bindung hemmt pro-inflammatorische Rezeptoren und Zytokine und könnte chronische Entzündungs- und Fibrosezyklen stören.
Derzeit befindet sich efzofitimod in einer globalen Phase 3 EFZO-FIT™ Studie für pulmonale Sarkoidose und einer Phase 2 EFZO-CONNECT™ Studie für ILD im Zusammenhang mit systemischer Sklerose. Das Medikament hat in den USA, der EU und Japan die Orphan-Drug-Designation für Sarkoidose erhalten und die Fast-Track-Designation in den USA sowohl für pulmonale Sarkoidose als auch für SSc-ILD.
- Publication in prestigious Science Translational Medicine validates efzofitimod's mechanism of action
- Drug has received multiple regulatory designations across major markets
- Advanced clinical development with ongoing Phase 3 and Phase 2 trials
- Novel first-in-class therapeutic targeting unmet needs in ILD treatment
- Clinical trials still ongoing with no guaranteed success
- As a first-in-class drug, regulatory approval pathway may be complex
Insights
The publication of efzofitimod's mechanism of action in Science Translational Medicine represents a scientific validation for aTyr's lead therapeutic candidate, but falls short of being a major catalyst for investors. The peer-reviewed article demonstrates that efzofitimod binds selectively to the neuropilin-2 (NRP2) receptor on macrophages, inhibiting pro-inflammatory pathways and potentially disrupting the cycle of inflammation and fibrosis seen in interstitial lung disease (ILD).
While this scientific validation strengthens the biological rationale behind aTyr's ongoing clinical programs, including the Phase 3 EFZO-FIT study in pulmonary sarcoidosis and Phase 2 EFZO-CONNECT study in systemic sclerosis-related ILD, it doesn't fundamentally alter the clinical development timeline or probability of success. The publication provides third-party validation of the scientific approach but doesn't introduce new clinical data that would change the investment thesis.
The market typically places greater emphasis on clinical milestones and regulatory progress rather than scientific publications. The regulatory designations already secured (orphan drug designation in three regions and Fast Track designation in the US) remain more significant from an investment perspective. This publication primarily serves to reduce scientific risk in the background while the more impactful clinical trials continue to progress.
Peer-reviewed publication validates efzofitimod’s unique anti-inflammatory mechanism of action on macrophages through neuropilin-2 (NRP2) receptor.
Scientific insights further strengthen the rationale for clinical program for efzofitimod in interstitial lung disease (ILD).
SAN DIEGO, March 12, 2025 (GLOBE NEWSWIRE) -- aTyr Pharma, Inc. (Nasdaq: ATYR) (“aTyr” or the “Company”), a clinical stage biotechnology company engaged in the discovery and development of first-in-class medicines from its proprietary tRNA synthetase platform, today announced a publication demonstrating the mechanism of action for its lead therapeutic candidate, efzofitimod, in the journal Science Translational Medicine. The publication, entitled, “A human histidyl-tRNA synthetase splice variant therapeutic targets NRP2 to resolve lung inflammation and fibrosis,” is available on the journal’s website and at: https://www.science.org/doi/10.1126/scitranslmed.adp4754.
“We are pleased to publish this extensive manuscript detailing the preclinical data supporting the development of efzofitimod, which includes all of the data generated for this novel drug candidate from concept to clinic,” said Leslie A. Nangle, Ph.D., Vice President, Research at aTyr. “This peer-reviewed publication in a highly regarded journal such as Science Translational Medicine validates the immunomodulatory activity and extracellularly mediated mechanism of efzofitimod in reducing inflammation and fibrosis. Furthermore, this validation considerably expands the basis for the application of efzofitimod in chronic inflammatory conditions, as well as encourages the potential development of other tRNA synthetase-based therapeutics for disease intervention.”
The publication presents the foundational science, detailed preclinical studies and discovery work behind efzofitimod, a first-in-class immunomodulator derived from a splice variant of histidyl-tRNA synthetase (HARS), which is enriched in human lung and is upregulated by inflammatory cytokines in lung and immune cells. The article also describes the specific and selective binding for efzofitimod to neuropilin-2 (NRP2), a cellular receptor highly expressed by myeloid cells in active sites of inflammation. Through this binding, efzofitimod inhibits the expression of pro-inflammatory receptor and cytokines, thereby downregulating inflammatory pathways in macrophages. This mechanism can subsequently disrupt the cycle of chronic inflammation and fibrosis.
“This publication is a culmination of our innovative drug discovery process and serves as a testament to the overwhelming amount of preclinical work that provides evidence for the immunomodulatory activity for efzofitimod,” said Sanjay S. Shukla, M.D., M.S., President and Chief Executive Officer of aTyr. “This scientific work along with the compelling clinical proof-of-concept generated for efzofitimod in pulmonary sarcoidosis supports the ongoing clinical development program in interstitial lung disease (ILD) and further strengthens the rationale to target ILD in their inflammatory stages using this novel therapeutic agent.”
Efzofitimod is currently being investigated in the global pivotal Phase 3 EFZO-FIT™ study in pulmonary sarcoidosis, a major form of ILD, and the Phase 2 EFZO-CONNECT™ study in systemic sclerosis (SSc, or scleroderma-related ILD). Efzofitimod has received orphan drug designation in the U.S., E.U. and Japan for sarcoidosis and Fast Track designation in the U.S. for pulmonary sarcoidosis and orphan drug designation in the U.S. and E.U. for SSc and Fast Track designation in the U.S. for SSc-ILD.
About Efzofitimod
Efzofitimod is a first-in-class biologic immunomodulator in clinical development for the treatment of interstitial lung disease (ILD), a group of immune-mediated disorders that can cause inflammation and fibrosis, or scarring, of the lungs. Efzofitimod is a tRNA synthetase derived therapy that selectively modulates activated myeloid cells through neuropilin-2 to resolve inflammation without immune suppression and potentially prevent the progression of fibrosis. aTyr is currently investigating efzofitimod in the global Phase 3 EFZO-FIT™ study in patients with pulmonary sarcoidosis, a major form of ILD, and in the Phase 2 EFZO-CONNECT™ study in patients with systemic sclerosis (SSc, or scleroderma)-related ILD. These forms of ILD have limited therapeutic options and there is a need for safer and more effective, disease-modifying treatments that improve outcomes.
About aTyr
aTyr is a clinical stage biotechnology company leveraging evolutionary intelligence to translate tRNA synthetase biology into new therapies for fibrosis and inflammation. tRNA synthetases are ancient, essential proteins that have evolved novel domains that regulate diverse pathways extracellularly in humans. aTyr’s discovery platform is focused on unlocking hidden therapeutic intervention points by uncovering signaling pathways driven by its proprietary library of domains derived from all 20 tRNA synthetases. aTyr’s lead therapeutic candidate is efzofitimod, a first-in-class biologic immunomodulator in clinical development for the treatment of interstitial lung disease, a group of immune-mediated disorders that can cause inflammation and progressive fibrosis, or scarring, of the lungs. For more information, please visit www.atyrpharma.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are usually identified by the use of words such as "anticipate," “believes,” “designed,” “could,” “can,” “expects,” “intends,” “may,” “plans,” “potential,” “will,” and variations of such words or similar expressions. We intend these forward-looking statements to be covered by such safe harbor provisions for forward-looking statements and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements include, among others, statements regarding the clinical development for efzofitimod, including the immunomodulatory activity and unique anti-inflammatory mechanism of action on macrophages through NRP2, the ability of efzofitimod to resolve lung inflammation and fibrosis, and the potential for the ongoing clinical program for efzofitimod in ILD, including pulmonary sarcoidosis and SSc-ILD. These forward-looking statements also reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects, as reflected in or suggested by these forward-looking statements, are reasonable, we can give no assurance that the plans, intentions, expectations, strategies or prospects will be attained or achieved. All forward-looking statements are based on estimates and assumptions by our management that, although we believe to be reasonable, are inherently uncertain. Furthermore, actual results may differ materially from those described in these forward-looking statements and will be affected by a variety of risks and factors that are beyond our control including, without limitation, uncertainty regarding geopolitical and macroeconomic events, risks associated with the discovery, development and regulation of efzofitimod, the risk that we or our partners may cease or delay preclinical or clinical development activities for efzofitimod for a variety of reasons (including difficulties or delays in patient enrollment in planned clinical trials), the possibility that existing collaborations could be terminated early, and the risk that we may not be able to raise the additional funding required for our business and product development plans, as well as those risks set forth in our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and in our other SEC filings. Except as required by law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.
| Contact: |
| Ashlee Dunston |
| Sr. Director, Investor Relations and Public Affairs |
| adunston@atyrpharma.com |
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