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

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

aTyr Pharma Announces Third Quarter 2024 Results and Provides Corporate Update (GlobeNewswire) - "Continued enrollment in the Phase 2 EFZO-CONNECT study to evaluate the efficacy, safety and tolerability of efzofitimod in patients with systemic sclerosis (SSc, or scleroderma)-related interstitial lung disease (SSc-ILD)....Interim data from the study are expected in the second quarter of 2025."

P2 data • Immunology • Interstitial Lung Disease • Systemic Sclerosis

COMPARATIVE EFFICACY OF MEDICAL TREATMENT EFFECTS ON PULMONARY-RELATED OUTCOMES IN PATIENTS WITH SARCOIDOSIS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS (CHEST 2024) - "For improvement in FVC, transdermal nicotine had the highest SUCRA value with a 46% probability of having the first or second rank; nicotine, chloroquine, and roflumilast had a 16%,11%, and 26% chance of being ranked first, respectively, while riociguat and bosentan were found to perform worse, even than placebo...For functional exercise capacity, as measured by 6MWT improvement, riociguat had the highest SUCRA value with a 79% probability of having the first or second rank; riociguat, infliximab 3mg/kg, and ARA 290 have a 65%, 11%, and 8% chance of being ranked best, respectively, while ustekinumab and bosentan performed worse. For chronic fatigue, as measured by FAS, melatonin had the highest SUCRA value with an 87% probability of having the first or second rank; melatonin and nicotine have a 66% and 18% of being ranked first, respectively, while methylphenidate and N-acetyl cysteine (NAC) performed worse... Transdermal nicotine (tobacco was associated with reduced..."

Retrospective data • Review • Fatigue • Immunology • Inflammation • Inflammatory Bowel Disease • Sarcoidosis

Contemporary Concise Review 2023: Interstitial lung disease. (PubMed, Respirology) - "A novel modality for monitoring of disease included the 4-min gait speed. New treatment modalities include inhaled pirfenidone, efzofitimod, for sarcoidosis, and earlier use of immunosuppression in connective tissue disease-ILD."

Journal • Review • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Rheumatology • Sarcoidosis

Efzofitimod for the Treatment of Pulmonary Sarcoidosis (CHEST 2024) - No abstract available

Immunology • Sarcoidosis

2251: Best of CHEST Journals, Presented by CHEST, CHEST Critical Care, and CHEST Pulmonary (CHEST 2024) - "Describe the tolerability, safety, and effect on outcomes of efzofitimod in pulmonary sarcoidosis...3. Recognize distinct patterns of exercise limitation in patients with post-acute sequelae of COVID-19."

Critical care • Immunology • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Sarcoidosis

aTyr Pharma’s Lead Therapeutic Candidate Efzofitimod for Pulmonary Sarcoidosis to be Featured in Best of CHEST Journals at CHEST 2024 Annual Meeting (GlobeNewswire) - "The presentation will review data supporting the efficacy of efzofitimod in pulmonary sarcoidosis, including findings from a Phase 1b/2a study for key efficacy endpoints including measures of steroid reduction, lung function, sarcoidosis symptoms and inflammatory biomarkers that were published in CHEST and a post hoc analysis of the Phase 1b/2a study that evaluated time-to-first-relapse and relapse rate for steroid use that was published in the European Respiratory Journal. Efzofitimod is currently being investigated in the global pivotal Phase 3 EFZO-FIT study in 268 patients with pulmonary sarcoidosis. Topline data from the study are expected in the third quarter of 2025."

P1/2 data • P3 data: top line • Immunology • Sarcoidosis • Systemic Sclerosis

aTyr Pharma Announces Second Quarter 2024 Results and Provides Corporate Update (GlobeNewswire) - "Continued enrollment in the Phase 2 EFZO-CONNECT study to evaluate the efficacy, safety and tolerability of efzofitimod in patients with systemic sclerosis (SSc, or scleroderma)-related ILD (SSc-ILD)...the Company expects to report interim data from the study in the second quarter of 2025....R&D Expenses: Research and development expenses were $14.0 million for the second quarter 2024, which consisted primarily of clinical trial costs for the...Phase 2 EFZO-CONNECT studies..."

Commercial • Enrollment status • P2 data • Immunology • Interstitial Lung Disease • Sarcoidosis • Scleroderma • Systemic Sclerosis

Efficacy and Safety of Intravenous Efzofitimod in Patients With Pulmonary Sarcoidosis (clinicaltrials.gov) - P3 | N=268 | Active, not recruiting | Sponsor: aTyr Pharma, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2025 ➔ Sep 2025 | Trial primary completion date: Dec 2024 ➔ Jul 2025

Enrollment closed • Trial completion date • Trial primary completion date • Immunology • Sarcoidosis

EFFICACY OF BIOLOGIC AND TARGETED SYNTHETIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS IN THE TREATMENT OF SARCOIDOSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS (EULAR 2024) - "We found relatively abundant yet inconsistent support for infliximab; potential efficacy of tofacitinib, limited yet consistent support for adalimumab, rituximab and anakinra; inefficacy of golimumab, ustekinumab, and efzofitimod; and inconclusive results for sarilumab. b/tsDMARDs studies in sarcoidosis have demonstrated potential efficacy of infliximab, adalimumab, anakinra, rituximab, and tofacitinib. Meta-analyses of b/tsDMARDs placebo controlled trial data suggests an overall inefficacy in meeting studies primary outcomes, whilst pooled data from placebo controlled and single arm studies examining lung function has demonstrated a small and clinically non-significant increase in FVC%. Limited studies warrant caution in interpreting these findings."

Retrospective data • Review • Immunology • Inflammation • Rheumatoid Arthritis • Sarcoidosis