aTYR PHARMA INC

aTyr Pharma, Inc. is a clinical-stage biotechnology company focused on translating tRNA synthetase biology into new therapies for fibrosis and inflammation. The company's core business model revolves around the discovery and development of novel biologic immunomodulators derived from tRNA synthetases, aiming to address unmet medical needs in immune-mediated disorders. Revenue generation primarily stems from collaboration and licensing agreements, as the company has not yet commercialized any products. Its primary customer segment for collaboration revenue is Kyorin Pharmaceutical Co., Ltd. in Japan, which holds exclusive rights to develop and commercialize efzofitimod for interstitial lung disease (ILD) in that region. The company operates in a single accounting segment, encompassing all activities related to the discovery and development of its product candidates ¹⁰².

The company's lead therapeutic candidate is efzofitimod, a novel biologic immunomodulator in clinical development for interstitial lung disease (ILD). Efzofitimod selectively modulates activated myeloid cells through neuropilin-2 (NRP2) to resolve aberrant inflammation and potentially prevent fibrosis progression without immune suppression. It has received orphan drug designations from the U.S. Food and Drug Administration (FDA) for sarcoidosis and systemic sclerosis (SSc), and Fast Track designations for pulmonary sarcoidosis and SSc-ILD ⁶⁵. The European Commission has also granted orphan drug designations for sarcoidosis and SSc, and Japan's Pharmaceutical and Medical Devices Agency (PMDA) granted orphan drug designation for sarcoidosis to Kyorin Pharmaceutical Co., Ltd. ⁶⁵.

In September 2025, aTyr Pharma announced top-line data from the global Phase 3 EFZO-FIT study for efzofitimod in pulmonary sarcoidosis, which enrolled 268 patients. The study did not meet its primary endpoint of change from baseline in mean daily oral corticosteroid (OCS) dose at week 48, with the 5.0 mg/kg efzofitimod group showing a reduction to an average of 2.79 mg compared to 3.52 mg for placebo (p=0.3313) ⁶⁵. However, the study demonstrated clinically meaningful improvements in the King's Sarcoidosis Questionnaire (KSQ)-Lung score at week 48 for 5.0 mg/kg efzofitimod compared to placebo (p=0.0479), and in a responder analysis of patients achieving complete steroid withdrawal with an improved KSQ-Lung score (p=0.0196) ⁶⁵. Lung function, as measured by forced vital capacity (FVC), was maintained across all groups, and efzofitimod was generally well-tolerated ⁶⁵. Additional findings presented at the European Respiratory Society (ERS) Congress in late September 2025 showed clinical improvements in the Fatigue Assessment (FAS) Total Score (p=0.0226) and KSQ-General Health score (p=0.0197) for the 5.0 mg/kg dose ⁶⁵.

Beyond efzofitimod, the company is building a pipeline of biologics based on its understanding of extracellular tRNA synthetase biology. This discovery platform aims to identify novel tRNA synthetase domains and their target receptors to uncover signaling pathways relevant to immunology and fibrosis ⁶⁶. Two additional pipeline candidates, ATYR0101 and ATYR0750, are currently in preclinical development ⁶⁶. ATYR0101 is a fusion protein derived from aspartyl-tRNA synthetase (DARS), engineered to selectively eliminate activated myofibroblasts by targeting Latent TGF-β Binding Protein-1 (LTBP-1) within the extracellular matrix (ECM) ⁶⁶. Preclinical data suggest ATYR0101 induces apoptosis of myofibroblasts in a TGFβ-dependent manner, showing potential in pulmonary fibrosis, SSc, liver fibrosis, and kidney fibrosis ⁶⁶. ATYR0750 is a fusion protein derived from alanyl-tRNA synthetase (AARS) and acts as a novel ligand to fibroblast growth factor receptor 4 (FGFR4), which is implicated in inflammation and fibrosis, particularly in the liver ⁶⁶.

For the fiscal year ended December 31, 2025, aTyr Pharma reported total revenues of $0.190 million ¹⁰⁰, a decrease from $0.235 million in 2024 ¹⁰⁰. The company incurred a consolidated net loss of $74.123 million ¹⁰¹, compared to $64.022 million in 2024 ¹⁰¹. Basic and diluted EPS for 2025 was $(0.80) ¹⁰¹, compared to $(0.86) in 2024 ¹⁰¹. Research and development expenses increased to $60.219 million ¹⁰⁰ from $54.372 million in 2024 ¹⁰⁰, while general and administrative expenses rose to $17.598 million ¹⁰⁰ from $13.777 million in 2024 ¹⁰⁰. Cash, cash equivalents, restricted cash, and available-for-sale investments totaled $80.9 million as of December 31, 2025 ⁶⁶. Net cash used in operating activities was $61.986 million ⁹⁹, and net cash provided by financing activities was $66.011 million ⁹⁹. Total assets were $93.003 million ⁹⁸, and total stockholders' equity was $67.288 million ⁹⁸.

Year-over-year, total revenues decreased by $0.045 million ¹⁰⁰, or 19.1%, from $0.235 million in 2024 to $0.190 million in 2025 ¹⁰⁰. This decline was due to a decrease in drug product material sold to Kyorin for the Japan portion of the EFZO-FIT study in 2024, compared to product material sold for analytical method validation in Japan in 2025 ¹⁰⁰. Research and development expenses increased by $5.847 million ¹⁰⁰, or 10.7%, primarily driven by a $3.882 million increase in efzofitimod expenses, mainly due to increased manufacturing costs incurred prior to the EFZO-FIT study top-line data announcement, offset by decreased study expenses as the trial completed ¹⁰⁰. Preclinical development and other shared R&D expenses also increased by $1.494 million ¹⁰⁰, and non-cash R&D expenses rose by $0.471 million ¹⁰⁰. General and administrative expenses increased by $3.821 million ¹⁰⁰, or 27.7%, due to pre-commercialization expenses, higher personnel-related costs, and increased professional fees ¹⁰⁰. Non-cash general and administrative expenses increased by $1.493 million ¹⁰⁰. The consolidated net loss widened from $64.022 million in 2024 to $74.123 million in 2025 ¹⁰¹.

During the reported period, aTyr Pharma announced top-line data from the EFZO-FIT study in September 2025, which did not meet its primary endpoint ⁶⁵. The company also announced additional findings from the EFZO-FIT study at the European Respiratory Society (ERS) Congress in late September 2025, demonstrating clinical improvements in secondary endpoints ⁶⁵. In June 2025, interim data from the EFZO-CONNECT study in SSc-ILD showed clinically important improvement in three out of four efzofitimod-treated diffuse SSc-ILD patients based on the modified Rodnan Skin Score (mRSS) assessment at 12 weeks, with efzofitimod being generally well-tolerated ⁶⁵. Operationally, during the first quarter of 2025, the first upstream batch for process performance qualification of efzofitimod drug substance did not meet specifications and was replaced by the CDMO, with the required three upstream batches subsequently completed ¹⁴. The three required downstream batches were initiated and successfully completed in the third quarter of 2025 ¹⁴. The company was also informed by its CDMO of a relocation of the microbial manufacturing site ¹⁴.

aTyr Pharma has scheduled a Type C meeting with the FDA in mid-April 2026 to review the results of the EFZO-FIT study and determine the path forward for efzofitimod in pulmonary sarcoidosis ⁶⁵. The company believes the trial findings indicate drug activity for efzofitimod, evidenced by improvements across multiple clinically relevant efficacy endpoints ⁶⁵. The outcome of this meeting will be crucial in shaping the regulatory strategy and potential for additional clinical trials for efzofitimod in this indication ⁶⁵.

A key growth area for the company is the continued development of efzofitimod for other interstitial lung diseases (ILDs). The company believes efzofitimod has potential applications in chronic hypersensitivity pneumonitis (CHP) and connective tissue disease related ILD (CTD-ILD), including SSc-ILD and rheumatoid arthritis-associated ILD ⁶⁵. The EFZO-CONNECT study, a Phase 2 proof-of-concept clinical trial in patients with SSc-ILD, is ongoing, with enrollment expected to be completed in the first half of 2026 ⁶⁵. This 28-week study aims to evaluate the efficacy, safety, and tolerability of efzofitimod on pulmonary, cutaneous, and systemic manifestations in up to 25 patients, with a primary endpoint of reduction in FVC ⁶⁵. An open-label extension (OLE) was added in July 2024 for patients completing the study who wish to receive ongoing treatment ⁶⁵.

Another significant growth vector is the expansion of the company's pipeline of biologics product candidates based on its extracellular tRNA synthetase biology discovery platform ⁶. The company intends to continue advancing novel tRNA synthetase domains from concept to product candidates in fibrosis and inflammation ⁶. Two programs, ATYR0101 and ATYR0750, have advanced into preclinical development ⁶. ATYR0101, derived from aspartyl-tRNA synthetase (DARS), is being investigated for broad therapeutic applications in fibrotic diseases such as pulmonary fibrosis, SSc, liver fibrosis, and kidney fibrosis, with preclinical studies demonstrating its ability to induce apoptosis of activated myofibroblasts ⁶⁶. ATYR0750, derived from alanyl-tRNA synthetase (AARS), is a novel ligand to fibroblast growth factor receptor 4 (FGFR4) and is being explored for its role in inflammation and fibrosis, particularly in the liver ⁶⁶. The company plans further mechanistic investigations, including in vitro and in vivo preclinical studies, for these candidates ⁶⁶.

The company intends to transition from a clinical-stage biotech to a commercial pharmaceutical company, having initiated pre-commercialization efforts in the U.S. market ⁶. These efforts are expected to continue with stage-appropriate investment as efzofitimod progresses towards FDA approval ⁶. The company estimates a $2-5 billion global market opportunity in pulmonary sarcoidosis and SSc-ILD, based on analyses from independent consultants and its own modeling ¹⁴.

Regarding manufacturing, the company has successfully completed the required three upstream and three downstream process performance qualification drug substance batches for efzofitimod with a new CDMO, and the drug substance material has been forward processed into drug product ¹⁴. The company believes it has sufficient drug product supply for all planned clinical studies, including a potential additional clinical study for efzofitimod in pulmonary sarcoidosis ¹⁴. However, the CDMO's planned relocation of the microbial manufacturing site could significantly impact commercial supply planning and funding needs, potentially requiring future manufacturing batches at a different site or a transition to a new CDMO for commercial supply ¹⁴.

The company's future funding requirements are difficult to forecast and will depend on factors such as the type, number, scope, progress, expansions, results, costs, and timing of clinical trials and preclinical studies, including potential additional clinical studies for efzofitimod in pulmonary sarcoidosis ³⁴. Costs related to manufacturing, regulatory review, and pre-commercialization efforts will also influence capital needs ³⁴. The company expects to finance its cash needs through a combination of equity offerings, grant funding, collaborations, strategic partnerships, and/or licensing arrangements, and potentially debt financings closer to commercialization ⁶⁸. As of December 31, 2025, the company had cash, cash equivalents, restricted cash, and available-for-sale investments of $80.9 million, which it believes will be sufficient to meet material cash requirements for at least one year from the date of the Annual Report ⁶⁶.

The company faces significant risks, including the absence of an established FDA regulatory pathway for drug approval in pulmonary sarcoidosis, meaning the EFZO-FIT study, which did not meet its primary endpoint, may not be sufficient for FDA approval and could necessitate additional, costly clinical trials ²⁴. Clinical trials are inherently expensive, time-consuming, and uncertain, with potential for substantial delays in patient enrollment, manufacturing, or regulatory consensus on trial design, which could materially harm the business ²⁵. The company is a pre-commercial entity with an accumulated deficit of $606.2 million as of December 31, 2025, and will require substantial additional capital to fund operations, complete clinical trials, obtain regulatory approvals, and commercialize products, with no guarantee of securing such funding on favorable terms or at all ³⁴, ⁶⁶. Reliance on third-party contract development and manufacturing organizations (CDMOs) and contract research organizations (CROs) introduces risks of manufacturing stoppages, quality control issues, and delays, as evidenced by a failed upstream batch in Q1 2025 and the CDMO's planned site relocation, which could impact commercial supply planning and funding ²⁹. The company's product candidates represent novel therapeutic approaches based on newly discovered tRNA synthetase biology, which may lead to significant delays, unexpected side effects, or a lack of commercially viable drugs due to limited regulatory experience with such approaches and potential for adverse immune responses or infusion-related reactions ³², ³³. Furthermore, the company is subject to securities class action complaints filed in October 2025, alleging materially false or misleading statements related to efzofitimod, which could result in substantial costs and diversion of management attention, regardless of merit ⁶⁴.

Management's message to shareholders emphasizes the company's commitment to leveraging evolutionary intelligence to translate tRNA synthetase biology into new therapies for fibrosis and inflammation. Despite the EFZO-FIT study not meeting its primary endpoint, management believes the trial results indicate drug activity for efzofitimod, as evidenced by improvements across multiple clinically relevant efficacy endpoints ⁶⁵. A Type C meeting with the FDA is scheduled for mid-April 2026 to discuss the path forward for efzofitimod in pulmonary sarcoidosis ⁶⁵. The company's strategic priorities include advancing efzofitimod toward regulatory approval in pulmonary sarcoidosis, transitioning into a commercial pharmaceutical company with pre-commercialization efforts in the U.S. market, and developing efzofitimod for other ILDs, such as SSc-ILD, with the EFZO-CONNECT study enrollment expected to be completed in the first half of 2026 ⁶⁵. Additionally, management is focused on building a diverse pipeline of biologics product candidates from its tRNA synthetase biology platform, with ATYR0101 and ATYR0750 in preclinical development ⁶⁶. The company believes its current cash, cash equivalents, restricted cash, and available-for-sale investments of $80.9 million as of December 31, 2025, will be sufficient to meet its material cash requirements for at least one year from the date of the Annual Report ⁶⁶.