Peer-reviewed publication validates efzofitimod’s unique anti-inflammatory mechanism of action on macrophages through neuropilin-2 (NRP2) receptor.

同行评审的出版物验证了efzofitimod通过神经纤毛蛋白-2（NRP2）受体在巨噬细胞上的独特抗炎作用机制。

Scientific insights further strengthen the rationale for clinical program for efzofitimod in interstitial lung disease (ILD).

科学见解进一步强化了efzofitimod在间质性肺病（ILD）中临床计划的理论依据。

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 .

圣地亚哥，2025年3月12日（环球新闻社）-- aTyr制药公司（纳斯达克股票代码：ATYR）（“aTyr”或“公司”），一家临床阶段的生物技术公司，专注于从其专有的tRNA合成酶平台发现和开发首创药物，今天宣布发表了一篇展示其主要候选治疗药物efzofitimod作用机制的论文，该论文刊登在期刊上。

Science Translational Medicine

科学转化医学

. 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:

标题为《一种人类组氨酰-tRNA合成酶剪接变体治疗靶向NRP2以缓解肺部炎症和纤维化》的出版物可在该期刊的网站上和以下网址找到：

https://www.science.org/doi/10.1126/scitranslmed.adp4754

https://www.science.org/doi/10.1126/scitranslmed.adp4754

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。

“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 .

“我们很高兴发布这份详尽的手稿，其中详细介绍了支持 efzofitimod 开发的临床前数据，包括从概念到临床为这个新型候选药物生成的所有数据，”aTyr 研究副总裁 Leslie A. Nangle 博士表示。“这项经过同行评审的发表在备受推崇的期刊上。

Science Translational Medicine

科学转化医学

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.”.

验证了efzofitimod在减轻炎症和纤维化方面的免疫调节活性及细胞外介导机制。此外，这一验证大大拓宽了efzofitimod在慢性炎症疾病中的应用基础，同时也鼓励了其他基于tRNA合成酶的疾病干预疗法的潜在开发。

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.

该出版物介绍了 efzofitimod 背后的基础科学、详细的临床前研究和发现工作，efzofitimod 是一种首创的免疫调节剂，源自组氨酰-tRNA 合成酶 (HARS) 的剪接变体，在人类肺部中含量丰富，并且在肺部和免疫细胞中被炎性细胞因子上调。

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.

该文章还描述了 efzofitimod 对神经纤毛蛋白-2（NRP2）的特异性和选择性结合，NRP2 是一种在炎症活跃部位由髓样细胞高度表达的细胞受体。通过这种结合，efzofitimod 抑制了促炎性受体和细胞因子的表达，从而下调巨噬细胞中的炎症通路。

This mechanism can subsequently disrupt the cycle of chronic inflammation and fibrosis..

这种机制可以随后破坏慢性炎症和纤维化的循环。

“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.

“这份出版物是我们创新药物发现过程的成果，证明了大量临床前工作为 efzofitimod 的免疫调节活性提供了证据，”aTyr 总裁兼首席执行官 Sanjay S. Shukla 医学博士表示。

“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.”.

“这项科学工作以及在肺结节病中为efzofitimod生成的令人信服的临床概念验证支持了正在进行的间质性肺疾病（ILD）临床开发计划，并进一步加强了在炎症阶段使用这种新型治疗剂靶向ILD的理由。”

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.

Efzofitimod目前正在全球关键的3期EFZO-FIT™研究中针对肺结节病（一种主要的ILD形式）进行研究，并在2期EFZO-CONNECT™研究中针对系统性硬化症（SSc，或与硬皮病相关的ILD）进行研究。Efzofitimod已在美国、欧盟和日本获得针对结节病的孤儿药资格认定，并在美国获得快速通道资格认定。

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..

针对肺结节病和在美国及欧盟获得的系统性硬化症（SSc）孤儿药资格，以及在美国获得的SSc相关间质性肺病（SSc-ILD）快速通道资格。

Abo

abo

ut Efzofitimod

盐酸伊唑莫德

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.

Efzofitimod 是一种首创的生物免疫调节剂，目前正处于治疗间质性肺病（ILD）的临床开发阶段。间质性肺病是一组免疫介导的疾病，可引起肺部炎症和纤维化或瘢痕形成。Efzofitimod 是一种基于 tRNA 合成酶的疗法，通过神经纤毛蛋白-2 选择性调节活化的髓系细胞，从而在不抑制免疫的情况下缓解炎症，并有可能预防纤维化的进展。

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..

aTyr目前正在全球III期EFZO-FIT™研究中针对肺结节病（一种主要的ILD形式）患者以及在II期EFZO-CONNECT™研究中针对系统性硬化症（SSc，或硬皮病）相关ILD患者中研究efzofitimod。这些ILD类型治疗选择有限，亟需更安全、更有效的疾病修饰疗法来改善预后。

About aTyr

关于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是一家临床阶段的生物技术公司，利用进化智能将tRNA合成酶生物学转化为针对纤维化和炎症的新疗法。tRNA合成酶是古老而重要的蛋白质，经过进化已产生新的结构域，在人体内能够从细胞外调节多种途径。

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.

aTyr的发现平台专注于通过揭示由其专有的源自全部20种tRNA合成酶的结构域库驱动的信号通路，来解锁隐藏的治疗干预点。aTyr的主要候选治疗药物是efzofitimod，这是一种首创新型生物免疫调节剂，目前正处在用于治疗间质性肺病的临床开发阶段。间质性肺病是一组免疫介导的疾病，可引起肺部炎症以及进行性纤维化或瘢痕形成。

For more information, please visit .

有关更多信息，请访问 。

www.atyrpharma.com

www.atyrpharma.com

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Forward-Looking Statements

前瞻性声明

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.

本新闻稿包含1995年《私人证券诉讼改革法案》所指的前瞻性陈述。前瞻性陈述通常可以通过使用诸如“预期”、“相信”、“设计”、“可能”、“能够”、“预计”、“打算”、“或许”、“计划”、“潜力”、“将”等词语或类似表达方式来识别。

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.

我们打算使这些前瞻性声明受到此类前瞻性声明的安全港条款的保护，并为遵守这些安全港条款作出本声明。这些前瞻性声明包括但不限于关于 efzofitimod 的临床开发相关的声明，包括其通过 NRP2 对巨噬细胞的免疫调节活性和独特的抗炎作用机制、efzofitimod 解决肺部炎症和纤维化的能力，以及 efzofitimod 在 ILD（包括肺结节病和 SSc-ILD）中正在进行的临床项目的潜力。

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.

这些前瞻性陈述也反映了我们对我们计划、意图、预期、策略和前景的当前看法，这些看法基于我们目前可获得的信息以及我们所做的假设。尽管我们认为，这些前瞻性陈述中反映或暗示的我们的计划、意图、预期、策略和前景是合理的，但我们无法保证这些计划、意图、预期、策略或前景将会实现或达成。

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 w.

所有前瞻性陈述均基于我们的管理层的估计和假设，尽管我们认为这些估计和假设是合理的，但其本质上仍存在不确定性。此外，实际结果可能与这些前瞻性陈述中描述的结果有重大差异。

Contact:

联系人：

Ashlee Dunston

阿什莉·邓斯顿

Sr. Director, Investor Relations and Public Affairs

投资者关系与公共事务高级总监

adunston@atyrpharma.com

adunston@atyrpharma.com