Stalaris (efzofitimod) / aTyr Pharma, Kyorin - LARVOL DELTA

Late Breaking Abstract - Evaluating immunogenicity of efzofitimod in patients with pulmonary sarcoidosis (ERS 2026) - "Efzofitimod demonstrated a favorable immunogenicity profile in patients with pulmonary sarcoidosis, with no de novo anti-Jo-1 formation and low ADA incidences that were comparable to placebo."

Clinical • Late-breaking abstract • Immunology • Interstitial Lung Disease • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Sarcoidosis

Second Quarter 2026 and Subsequent Period Highlights (The Manila Times) - "Enrollment completed in the Phase 2 EFZO-CONNECT study to evaluate the efficacy, safety and tolerability of efzofitimod in patients with limited or diffuse SSc-ILD. Topline results are expected in the first quarter of 2027. This proof-of-concept study is a randomized, double-blind, placebo-controlled, 28-week study consisting of three parallel cohorts randomized 2:2:1 to either 270 mg or 450 mg of efzofitimod or placebo administered intravenously monthly for a total of six doses."

P2 data • Interstitial Lung Disease • Systemic Sclerosis

Evaluating efzofitimod in a subset of sarcoidosis with the restrictive phenotype (WASOG 2026) - No abstract available

Immunology • Sarcoidosis

New Therapies for Sarcoidosis: Molecular and Pathophysiological Basis. (PubMed, Int J Mol Sci) - "Advances in deciphering sarcoidosis pathobiology-including aberrant Janus kinase (JAK)- signal transducer and activator of transcription (STAT) signaling, mechanistic target of rapamycin (mTOR)-driven metabolic shifts, Th1/Th17.1 immune skewing, effector T-cell exhaustion, and granuloma-centered cytokine circuits-have revealed several targets for intervention. The treatment options are rapidly changing: the SARCORT trial showed that low-dose prednisolone is non-inferior to higher prednisolone doses; the pivotal PREDMETH trial validated methotrexate as a feasible first-line steroid-sparing option; efzofitimod, a novel immunomodulator targeting neuropilin-2, produced steroid-reducing effects in Phase IIbut not in Phase III trials; and JAK inhibitors are accumulating evidence across cutaneous and systemic presentations. The 2025 World Association for Sarcoidosis and Other Granulomatoses (WASOG) statement supports a move toward earlier steroid-sparing approaches. This review..."

Biomarker • Journal • Review • Immunology • Inflammation • Sarcoidosis • mTOR • NRP2

EFZO-FIT: Efficacy and Safety of Intravenous Efzofitimod in Patients With Pulmonary Sarcoidosis (clinicaltrials.gov) - P3 | N=268 | Completed | Sponsor: aTyr Pharma, Inc. | Active, not recruiting ➔ Completed

Trial completion • Immunology • Sarcoidosis

Sarcoidosis, the mysterious disease (AUTO 2026) - "This strategy consists of using corticosteroids as a first-line treatment, and if there is no response or intolerance, switching to methotrexate, and in more severe/"refractory" cases, using biological therapy, mainly anti-TNF (infliximab being the most commonly used)...There are currently a dozen clinical trials underway, mainly with anti-TNF, JAK inhibitors and with Efzofitimod (phase III), a biological immunomodulator, anti-NRP2 in myeloid cells, and with Namilumab, an anti-GM-CSF (phase II)...doi: 10.1136/thorax-2025-223014. PMID: 40393718; PMCID: PMC12505053."

Cardiovascular • Endocrine Disorders • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Metabolic Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Sarcoidosis • Tuberculosis • CSF2 • HLA-DRB1 • NRP2

On track to complete enrollment in the Phase 2 EFZO-CONNECT study to evaluate the efficacy, safety and tolerability of efzofitimod in patients with limited or diffuse systemic sclerosis (SSc, or scleroderma)-related ILD (SSc-ILD) in the first half of 2026. (GlobeNewswire) - "This proof-of-concept study is a randomized, double-blind, placebo-controlled, 28-week study consisting of three parallel cohorts randomized 2:2:1 to either 270 mg or 450 mg of efzofitimod or placebo administered intravenously monthly for a total of six doses. The study intends to enroll up to 25 patients at multiple centers in the United States."

Enrollment status • Interstitial Lung Disease • Scleroderma • Systemic Sclerosis

Announced plans to continue the development of efzofitimod in pulmonary sarcoidosis following a Type C meeting with the FDA to review the results of the Phase 3 EFZO-FIT study and determine the path forward for efzofitimod in pulmonary sarcoidosis. (GlobeNewswire) - "The Company plans to file an IND in June 2026 for a new Phase 3 study in patients with chronic, symptomatic pulmonary sarcoidosis with restrictive lung disease utilizing FVC as the primary endpoint of the study and the KSQ-Lung score as the key secondary endpoint. The Phase 3 trial is expected to be a global, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of efzofitimod in patients with moderate to severe pulmonary sarcoidosis."

IND • New P3 trial • Sarcoidosis

aTyr Pharma Provides Regulatory and Clinical Update for Efzofitimod in Pulmonary Sarcoidosis Following FDA Type C Meeting (Yahoo Finance) - "Based on feedback from the FDA, the Company plans to continue the development of efzofitimod in pulmonary sarcoidosis in a new Phase 3 study in patients with chronic, symptomatic pulmonary sarcoidosis with restrictive lung disease utilizing forced vital capacity (FVC) as the primary endpoint of the study and the King’s Sarcoidosis Questionnaire (KSQ)-Lung score as the key secondary endpoint...The Company plans to submit an investigational new drug (IND) application for this study in June 2026....The Phase 3 trial is expected to be a global, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of efzofitimod in patients with moderate to severe pulmonary sarcoidosis."

FDA event • IND • New P3 trial • Sarcoidosis

Multidisciplinary strategies and new technologies in the management of sarcoidosis. (PubMed, Eur J Intern Med) - "Steroid-sparing agents such as methotrexate, azathioprine, and leflunomide are widely used, while biologics, particularly anti-TNF agents, and emerging small-molecule inhibitors (e.g., JAK and mTOR inhibitors) offer additional options in refractory disease. New investigational therapies, including efzofitimod, are under evaluation...Artificial intelligence and multi-omics approaches may further enhance diagnostic accuracy, phenotyping, and precision medicine in the near future. In conclusion, sarcoidosis stands as a paradigm of complexity in internal medicine, underscoring the need for holistic care, innovation, and collaboration to improve long-term outcomes."

Journal • Review • Fatigue • Immunology • Pain • Sarcoidosis • IL2

aTyr Pharma Presents Additional Findings from Phase 3 EFZO-FIT Study in Late-Breaking Oral Abstract at the European Respiratory Society (ERS) Congress 2025 (GlobeNewswire) - "Clinical benefit for efzofitimod across multiple disease-related health outcomes reported; Improvement in Fatigue Assessment Scale Total Score at week 48 observed in the 5.0 mg/kg efzofitimod treatment group vs placebo (p=0.0226); Improvement in King’s Sarcoidosis Questionnaire-General Health score at week 48 observed in the 5.0 mg/kg efzofitimod treatment group vs placebo (p=0.0197)....'Despite missing the primary endpoint of the study, efzofitimod has clearly demonstrated the potential to durably improve multiple disease-related health outcomes, including cough, shortness of breath, fatigue and general health.'"

Late-breaking abstract • P3 data • Sarcoidosis

Efzofitimod Fails to Meet Primary End Point in Phase 3 Pulmonary Sarcoidosis Trial (HCPLive) - "Study investigators found that the 5.0 mg/kg efzofitimod group had a mean reduction to 2.79 mg in mean daily OCS dose compared to 3.52 in the placebo group (P = .3313). All further statistical testing is reported as nominal findings as the study’s statistical analysis plan was designed on a hierarchical assessment basis...Investigators did find a clinical improvement in the change from baseline on King’s Sarcoidosis Questionnaire (KSQ)-Lung score at week 48 for 5.0 mg/kg efzofitimod (10.36) compared to placebo (6.19; P = .0479). Furthermore, 46.9% of patients on 5.0 mg/kg of efzofitimod achieved complete steroid withdrawal with stable KSQ-Lung score compared to 35.7% on placebo (P = .1241)."

P3 data • Sarcoidosis

New therapeutic options in sarcoidosis. (PubMed, Curr Opin Pulm Med) - "Despite many challenges, well designed studies are warranted to investigate new therapeutic options in sarcoidosis, particularly in patients with refractory forms or unacceptable side-effects with third-line treatment."

Journal • Fibrosis • Immunology • Sarcoidosis • CSF2 • NLRP3 • NRP2

aTyr Pharma Announces Findings from Interim Analysis of Ongoing Phase 2 EFZO-CONNECT Study of Efzofitimod in Systemic Sclerosis-Related Interstitial Lung Disease (SSc-ILD) (GlobeNewswire) - P2 | N=25 | EFZO-CONNECT (NCT05892614) | Sponsor: aTyr Pharma, Inc. | "Key findings to date for efzofitimod include: Stable or improved mRSS for all patients and an improvement of 4 points or greater for three out of four efzofitimod-treated patients with diffuse SSc-ILD, where the minimal clinically important difference (MCID) is a 4 to 6 point improvement at 12 months; Preliminary signals of improvement for inflammatory biomarkers including interferon gamma (IFN-γ) and monocyte chemoattractant protein-1 (MCP-1) and disease biomarkers Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D); Generally safe and well tolerated at all doses, with no treatment related serious adverse events."

P2 data • Interstitial Lung Disease • Systemic Sclerosis

EFZO-FIT, Largest Placebo-controlled Trial in Pulmonary Sarcoidosis - Trial Design and Patient Characteristics (ATS 2025) - P3 | "Efzofitimod, a novel biologic immunomodulator previously showed a positive exposure response relationship across multiple efficacy endpoints including the ability to taper steroids (PMID 37854715).EFZO-FIT (ATYR1923-C-004) is a global (USA, Europe, Japan, Brazil) phase 3, randomized, double-blind, placebo-controlled study evaluating the steroid sparing effect of efzofitimod (NCT05415137). The study enrolled patients with chronic symptomatic pulmonary sarcoidosis on steroids, a population appropriate for evaluating the primary end point of steroid taper."

Clinical • Immunology • Pulmonary Disease • Sarcoidosis

Systematic review and meta-analysis of the efficacy of biologic and targeted synthetic therapies in sarcoidosis. (PubMed, Thorax) - "Meta-analysis supports infliximab use in pulmonary sarcoidosis, although improvements in lung function are modest. There is limited but promising evidence for the use of adalimumab and tofacitinib in cutaneous disease and efzofitimob in pulmonary disease. Study interpretation is limited by small sample sizes and heterogeneity in study design and population.PROSPERO registration numberCRD42024599560."

Journal • Retrospective data • Immunology • Pulmonary Disease • Respiratory Diseases • Sarcoidosis

aTyr Pharma Announces First Quarter 2025 Results and Provides Corporate Update (GlobeNewswire) - "First Quarter 2025 and Subsequent Period Highlights: (i) On track to announce topline data in the third quarter of 2025 from the global pivotal Phase 3 EFZO-FIT study to evaluate the efficacy and safety of efzofitimod in patients with pulmonary sarcoidosis....The study enrolled 268 patients with pulmonary sarcoidosis at 85 centers in nine countries...; (ii) Enrollment ongoing in the Phase 2 EFZO-CONNECT study to evaluate the efficacy, safety and tolerability of efzofitimod in patients with limited and diffuse systemic sclerosis (SSc, or scleroderma)-related ILD (SSc-ILD)....The study intends to enroll up to 25 patients at multiple centers in the United States. Patients who complete the study are eligible to participate in a 24-week open-label extension. Interim data from the study are expected in the second quarter of 2025 and will focus on skin assessments measured at baseline and week 12 in approximately eight patients, including patients in both the efzofitimod and placebo arms."

Clinical data • Trial status • Interstitial Lung Disease • Sarcoidosis • Systemic Sclerosis

EFZO-CONNECT: Study to Evaluate the Efficacy, Safety, and Tolerability of Efzofitimod in Patients With Systemic Sclerosis (SSc)-Related Interstitial Lung Disease (ILD) (SSc-ILD) (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: aTyr Pharma, Inc. | Trial completion date: Dec 2024 ➔ Apr 2026 | Trial primary completion date: Dec 2024 ➔ Apr 2026

Trial completion date • Trial primary completion date • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

aTyr Pharma Announces Fourth Quarter and Full Year 2024 Results and Provides Corporate Update (GlobeNewswire) - "Held a Type C meeting with the U.S. Food and Drug Administration (FDA) to discuss the statistical analysis plan (SAP) for the Phase 3 EFZO-FIT study. The main objective of the meeting was to finalize the way in which the study endpoints are assessed from a statistical standpoint. Based on FDA feedback, steroid reduction will be measured as the absolute change from baseline to week 48....R&D Expenses: Research and development expenses were $54.4 million for the year ended 2024, which consisted primarily of clinical trial costs for the Phase 3 EFZO-FIT and Phase 2 EFZO-CONNECT studies, manufacturing costs for the efzofitimod program and research and development costs for the efzofitimod and discovery programs."

Commercial • FDA event • Sarcoidosis

A human histidyl-tRNA synthetase splice variant therapeutic targets NRP2 to resolve lung inflammation and fibrosis. (PubMed, Sci Transl Med) - "In animal models of lung injury and ILD, including bleomycin treatment, silicosis, sarcoidosis, chronic hypersensitivity pneumonitis, systemic sclerosis, and rheumatoid arthritis-ILD, HARSWHEP reduced lung inflammation, immune cell infiltration, and fibrosis. In patients with sarcoidosis, efzofitimod treatment resulted in down-regulation of gene expression for inflammatory pathways in peripheral immune cells and stabilization of inflammatory biomarkers in serum after steroid tapering. We demonstrate the immunomodulatory activity of HARSWHEP and present preclinical data supporting ongoing clinical development of the biologic efzofitimod based on HARSWHEP in ILD."

Journal • Fibrosis • Immunology • Inflammation • Inflammatory Arthritis • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Sarcoidosis • Scleroderma • Systemic Sclerosis • NRP2

aTyr Pharma Announces Publication Demonstrating Efzofitimod’s Immunomodulatory Activity in Science Translational Medicine (GlobeNewswire) - "aTyr Pharma...announced a publication demonstrating the mechanism of action for its lead therapeutic candidate, efzofitimod, in the journal Science Translational Medicine....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....This mechanism can subsequently disrupt the cycle of chronic inflammation and fibrosis."

Preclinical • Fibrosis • Inflammation

aTyr Pharma Announces Fourth Positive DSMB Review for Efzofitimod in Phase 3 EFZO-FIT Study in Pulmonary Sarcoidosis (GlobeNewswire) - "aTyr Pharma, Inc...today announced the outcome of a fourth, pre-planned interim safety analysis conducted by an independent data and safety monitoring board (DSMB) for the ongoing Phase 3 EFZO-FIT study of the Company’s lead therapeutic candidate, efzofitimod, in patients with pulmonary sarcoidosis. The DSMB recommended that the study continue without any modifications....We look forward to reporting topline results from EFZO-FIT in the third quarter of this year."

DSMB • P3 data: top line • Sarcoidosis

aTyr Pharma to Present Three Posters for Efzofitimod at the American Thoracic Society (ATS) 2025 International Conference (GlobeNewswire) - "Blinded baseline demographics and disease characteristics for ongoing Phase 3 EFZO-FIT™ study of efzofitimod in pulmonary sarcoidosis; topline data from the study expected in the third quarter of 2025; Current epidemiology and treatment practices for pulmonary sarcoidosis in the U.S. based on real-world evidence."

Clinical protocol • P3 data: top line • Real-world evidence • Respiratory Diseases • Sarcoidosis

Therapeutic doses of efzofitimod demonstrate efficacy in pulmonary sarcoidosis. (PubMed, ERJ Open Res) - "Slopes analysis showed that forced vital capacity increased in the Therapeutic group, but decreased in the Subtherapeutic group, over the course of the trial (p=0.035). Treatment with efzofitimod at therapeutic doses, as compared with a subtherapeutic dose or placebo, was associated with a lower rate of relapse as corticosteroids were tapered."

Journal • Immunology • Sarcoidosis

aTyr Pharma Announces Third Positive DSMB Review for Efzofitimod in Phase 3 EFZO-FIT Study in Pulmonary Sarcoidosis (GlobeNewswire) - "aTyr Pharma, Inc...announced the outcome of a third, pre-planned interim safety analysis conducted by an independent data and safety monitoring board (DSMB) for the ongoing Phase 3 EFZO-FIT study of the Company’s lead therapeutic candidate, efzofitimod, in patients with pulmonary sarcoidosis. The DSMB recommended that the study continue without any modifications."

DSMB • Immunology • Sarcoidosis