aTyr Pharma to Present Preclinical Research Demonstrating Anti-Fibrotic Effects of ATYR0101 in Lung and Kidney Fibrosis at Keystone Symposia on Fibrosis
aTyr Pharma announced the presentation of two posters about their tRNA synthetase candidate ATYR0101 at the Keystone Symposia on Fibrosis. The research demonstrates that ATYR0101, a fusion protein derived from aspartyl-tRNA synthetase, binds to LTBP-1 to induce myofibroblast apoptosis, showing significant anti-fibrotic effects in lung and kidney fibrosis models.
The preclinical studies revealed that ATYR0101 reduced key fibrosis measures, including Ashcroft score and collagen content in the bleomycin model of lung fibrosis and the ureteral obstruction model of kidney fibrosis. The compound's mechanism of action differs from current standard treatments, suggesting potential as a novel therapeutic approach for advanced fibrotic conditions.
aTyr Pharma ha annunciato la presentazione di due poster riguardanti il loro candidato alla tRNA sintetasi ATYR0101 presso i Keystone Symposia sulla Fibrosi. La ricerca dimostra che ATYR0101, una proteina fusion derivata dalla sintetasi dell'aspartil-tRNA, si lega a LTBP-1 inducendo l'apoptosi dei miofibroblasti, mostrando significativi effetti anti-fibrotici in modelli di fibrosi polmonare e renale.
Gli studi preclinici hanno rivelato che ATYR0101 ha ridotto importanti misure di fibrosi, inclusi il punteggio di Ashcroft e il contenuto di collagene nel modello di fibrosi polmonare da bleomicina e nel modello di fibrosi renale da ostruzione ureterale. Il meccanismo d'azione del composto è diverso dai trattamenti standard attuali, suggerendo un potenziale come nuova opzione terapeutica per condizioni fibrotiche avanzate.
aTyr Pharma anunció la presentación de dos carteles sobre su candidato a la sintetasa de tRNA ATYR0101 en los Keystone Symposia sobre Fibrosis. La investigación demuestra que ATYR0101, una proteína de fusión derivada de la sintetasa de aspartil-tRNA, se une a LTBP-1 para inducir la apoptosis de los miofibroblastos, mostrando efectos anti-fibróticos significativos en modelos de fibrosis pulmonar y renal.
Los estudios preclínicos revelaron que ATYR0101 redujo medidas clave de fibrosis, incluidos el puntaje de Ashcroft y el contenido de colágeno en el modelo de fibrosis pulmonar por bleomicina y en el modelo de fibrosis renal por obstrucción ureteral. El mecanismo de acción del compuesto es diferente a los tratamientos estándar actuales, lo que sugiere un potencial como un enfoque terapéutico novedoso para condiciones fibróticas avanzadas.
aTyr Pharma는 Keystone Symposia에서 그들의 tRNA 합성효소 후보 ATYR0101에 대한 두 개의 포스터를 발표했다고 발표했습니다. 연구 결과 ATYR0101은 아스파르티닐-tRNA 합성효소에서 유래한 퓨전 단백질로, LTBP-1에 결합하여 myofibroblast의 세포사를 유도하며, 폐 및 신장 섬유증 모델에서 상당한 항섬유화 효과를 보여줍니다.
전임상 연구에서는 ATYR0101이 폐 섬유증의 블레오마이신 모델과 신장 섬유증의 요관 차단 모델에서 Ashcroft 점수와 콜라겐 함량을 포함한 주요 섬유증 지표를 감소시켰음을 밝혀냈습니다. 이 화합물의 작용 기전은 현재의 표준 치료와 다르며, 이는 진행된 섬유증 상태에 대한 새로운 치료 접근법으로서의 가능성을 나타냅니다.
aTyr Pharma a annoncé la présentation de deux affiches concernant son candidat à la tRNA synthétase ATYR0101 lors des Keystone Symposia sur la Fibrose. La recherche montre que l'ATYR0101, une protéine de fusion dérivée de la synthétase de l'aspartyl-tRNA, se lie à LTBP-1 pour induire l'apoptose des myofibroblastes, montrant des effets anti-fibrotiques significatifs dans des modèles de fibrose pulmonaire et rénale.
Les études précliniques ont révélé que l'ATYR0101 a réduit des mesures clés de fibrose, y compris le score d'Ashcroft et la teneur en collagène dans le modèle de fibrose pulmonaire induite par la bléomycine et le modèle d'obstruction urétérale de la fibrose rénale. Le mécanisme d'action du composé diffère des traitements standards actuels, suggérant un potentiel en tant qu'approche thérapeutique novatrice pour les conditions fibrotiques avancées.
aTyr Pharma gab die Präsentation von zwei Postern über ihren tRNA-Synthetase-Kandidaten ATYR0101 bei den Keystone Symposia zur Fibrose bekannt. Die Forschung zeigt, dass ATYR0101, ein Fusionsprotein, das von der Aspartyl-tRNA-Synthetase stammt, an LTBP-1 bindet, um die Apoptose von Myofibroblasten zu induzieren und signifikante antifibrotische Effekte in Modellen für Lungen- und Nierenfibrose zu zeigen.
Die präklinischen Studien zeigten, dass ATYR0101 wichtige Fibrsemaße reduzierte, einschließlich des Ashcroft-Scores und des Kollagengehalts im Bleomycin-Modell der Lungenfibrose und im Ureterobstruktionsmodell der Nierenfibrose. Der Wirkmechanismus des Verbindungen unterscheidet sich von den derzeitigen Standardbehandlungen, was auf ein Potenzial als neuartige therapeutische Strategie für fortgeschrittene fibrotische Erkrankungen hinweist.
- ATYR0101 demonstrated significant reduction in fibrosis markers in preclinical models
- The compound showed effectiveness in both lung and kidney fibrosis models
- Novel mechanism of action different from current standard treatments
- Selective targeting of disease-related myofibroblasts while sparing healthy cells
- Research still in preclinical stage, requiring further clinical validation
- Efficacy in human subjects yet to be demonstrated
Insights
The preclinical data for ATYR0101 demonstrates significant potential in treating both lung and kidney fibrosis through a novel mechanism of action. The compound's ability to bind to LTBP-1 and induce selective apoptosis in myofibroblasts while sparing normal fibroblasts is particularly noteworthy, as this targeted approach could potentially reduce side effects compared to current treatments.
The data from both the bleomycin lung model and ureteral obstruction kidney model shows meaningful reductions in key fibrosis markers. Most importantly, the significant decrease in Ashcroft score and collagen content in the lung model, coupled with reduced fibrosis in the kidney model, suggests broad therapeutic potential across multiple organ systems.
While these results are promising, investors should note this is still preclinical research. The next critical milestone will be translating these findings into human clinical trials to validate the mechanism and efficacy in patients.
The research reveals a differentiated mechanism of action that could position ATYR0101 as a potential breakthrough in fibrosis treatment. The compound's selective targeting of TGFβ-activated myofibroblasts through LTBP-1 binding represents a novel approach that differs from current standard of care treatments.
From a market perspective, this could be significant as the global fibrosis treatment market represents a substantial opportunity. The ability to treat both lung and kidney fibrosis with a single compound could expand the drug's commercial potential. The differentiated mechanism could also support premium pricing if the safety profile proves superior to existing treatments.
However, with aTyr's
ATYR0101 interacts with LTBP-1 to induce myofibroblast apoptosis through a novel anti-fibrotic mechanism to reduce fibrosis and fibrotic markers in models of lung and kidney fibrosis.
SAN DIEGO, Dec. 09, 2024 (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 that the Company will present two posters related to its tRNA synthetase candidate ATYR0101 at the Keystone Symposia on Fibrosis: Inflammation, Drivers, and Therapeutic Resolution, which is scheduled to take place December 8 – 11, 2024, in Whistler, British Columbia, Canada.
ATYR0101 is a fusion protein derived from a proprietary extracellular domain of aspartyl-tRNA synthetase (DARS) that binds to latent transforming growth factor beta binding protein 1 (LTBP-1) to induce myofibroblast apoptosis.
“We are excited by these findings that further demonstrate the way in which ATYR0101 binds a known fibrosis target with pronounced effects in preclinical models of lung and renal fibrosis,” said Sanjay S. Shukla, M.D., M.S., President and Chief Executive Officer of aTyr. “These findings suggest that ATYR0101 has the potential to be a next generation anti-fibrotic for lung and kidney fibrosis with a differentiated mechanism of action compared to current standard of care that could potentially treat advanced fibrotic conditions.”
Details of the presentations appear below. The posters will be available on the aTyr website once presented.
Title: A Newly Evolved Domain of Asp-tRNA Synthetase Interacts with Latent Transforming Growth Factor Beta Binding Protein 1 (LTBP-1) to Induce Myofibroblast Apoptosis
Authors: Ying-Ting Wang, Kristina Hamel, Andrew Imfeld, Yeeting E. Chong, Kaitlyn Rauch, Wayne Liu, Zhiwen Xu, Ryan A. Adams, Leslie Nangle. aTyr Pharma, San Diego, CA.
Poster Number: 1046
Session: Poster Session #1
Date and Time: Monday, December 9, 2024, at 7:30 p.m. PST
The poster presents findings demonstrating that ATYR0101 binds directly to LTBP-1 resulting in caspase-3/7 mediated apoptosis in transforming growth factor beta (TGFβ)-1-differentiated myofibroblasts while having no effect on undifferentiated fibroblasts, which was observed in multiple cell types demonstrating potential in several organ systems. The ATYR0101-induced myofibroblast apoptosis activity was confirmed to be dependent upon LTBP-1, TGFβ activation and downstream gene expression changes. These findings suggest that ATYR0101 has promise as a novel and transformative anti-fibrotic therapeutic with a unique mechanism of action.
Title: Anti-Fibrotic Activity Observed Across Preclinical Models of Pulmonary and Renal Fibrosis for a Potential Therapeutic Based on Asp-tRNA Synthetase
Authors: Alison Barber, Clara Polizzi, Jasmine Stamps, Max Pastenes, Yeeting E. Chong, Andrew Imfeld, Chun Po Fung, Honglei Tian, Zhenguo Wu, Ryan A. Adams, Christoph Burkart, Leslie Nangle. aTyr Pharma, San Diego, CA, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Poster Number: 1045
Session: Poster Session #1
Date and Time: Monday, December 9, 2024, at 7:30 p.m. PST
The poster presents findings investigating ATYR0101 in the bleomycin (BLM) model of lung fibrosis and ureteral obstruction (UUO) model of kidney fibrosis to examine the pharmacological activity of ATYR0101 in experimental models of fibrotic disease. In the lung BLM model, ATYR0101 treatment resulted in a significant reduction in Ashcroft score and collagen content, key measures of fibrosis, in addition to a pronounced reduction of myofibroblasts. In the UUO model, treatment with ATYR0101 resulted in reduced collagen content with a significant reduction of fibrosis. Importantly, ATYR0101 achieves these effects in a differentiated way compared to current standard of care. These findings suggest that ATYR0101 has the potential to be a novel anti-fibrotic therapeutic agent for lung and renal fibrosis with a differentiated profile compared to current standard of care.
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,” “can,” “expects,” “intends,” “may,” “plans,” “potential,” suggest,” “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 research and development activities related to and the potential therapeutic benefits and applications of our current and future product candidates, including ATYR0101 as a transformative, next generation anti-fibrotic differentiated from the current standard of care. 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 our product candidates (including the risk that future findings do not support the findings described in the posters), the risk that we or our partners may cease or delay preclinical or clinical development activities for any of our existing or future product candidates 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
Director, Investor Relations and Public Affairs
adunston@atyrpharma.com
FAQ
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