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

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

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

Efzofitimod Is an Immunomodulator of Myeloid Cell Function and Novel Therapeutic Candidate for Interstitial Lung Diseases (ATS 2024) - "Conclusions These results demonstrate that efzofitimod acts on myeloid cells to alter their differentiation and promote macrophages with diminished inflammatory potential. Given the central role of myeloid cells in the pathology of numerous ILDs and other chronic inflammatory and fibrotic diseases, efzofitimod may have broad therapeutic potential in ILD and beyond."

Immunomodulating • Fibrosis • Immunology • Inflammation • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Sarcoidosis • NRP2

aTyr Pharma to Present Poster Describing Efzofitimod’s Mechanism of Action at the American Thoracic Society 2024 International Conference (GlobeNewswire) - "aTyr Pharma, Inc...announced that the company will present data for its lead therapeutic candidate, efzofitimod, at the American Thoracic Society (ATS) 2024 International Conference, which is scheduled to take place May 17 – 22 in San Diego, CA....Additionally, the data further validates the discovery of NRP2 as an important new immune target, with higher expression of NRP2 detected on circulating monocytes from ILD patients compared to healthy donors and on macrophages within pulmonary sarcoidosis granulomas and other tissues from chronic inflammatory diseases. These findings suggest that efzofitimod may have broad therapeutic potential in diseases where myeloid cells play a central role in pathology, including ILD."

Clinical data • Immunology • Interstitial Lung Disease • Sarcoidosis

aTyr Pharma Announces Second Positive DSMB Review for Efzofitimod in Phase 3 EFZO-FIT Study in Pulmonary Sarcoidosis (GlobeNewswire) - "aTyr Pharma, Inc...announced that an independent data and safety monitoring board (DSMB) recommended that the ongoing Phase 3 EFZO-FIT study of its lead therapeutic candidate, efzofitimod, in patients with pulmonary sarcoidosis could continue without any modifications after a second pre-planned, interim analysis....EFZO-FIT is a global Phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of efzofitimod in patients with pulmonary sarcoidosis."

DSMB • Immunology • Sarcoidosis

aTyr Pharma Announces First 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 SSc-ILD....R&D Expenses: Research and development expenses were $13.4 million for the first quarter 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 • Enrollment status • Immunology • Interstitial Lung Disease • Sarcoidosis • Systemic Sclerosis

Developmental drugs for sarcoidosis. (PubMed, J Autoimmun) - "Prednisone the currently recommended first line therapy is associated with significant toxicity however none of the other guideline recommended steroid sparing therapy is approved by regulatory agencies for use in sarcoidosis, and data in support of their use is weak...Our paper provides an update on developmental drugs in sarcoidosis and outlines several novel pathways that may be targeted for future drug development. Currently available trials are highlighted and ongoing challenges to drug development and clinical trial design are briefly discussed."

Journal • Fibrosis • Immunology • Inflammation • Inflammatory Bowel Disease • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Sarcoidosis

aTyr Pharma Announces Fourth Quarter and Full Year 2023 Results and Provides Corporate Update (GlobeNewswire) - "Phase 3 EFZO-FIT study of efzofitimod in pulmonary sarcoidosis anticipated to complete enrollment in the second quarter of 2024....Continued enrollment in the Phase 2 EFZO-CONNECT study to evaluate the efficacy, safety and tolerability of efzofitimod in patients with SSc-ILD....R&D Expenses: Research and development expenses were $42.3 million for the year ended 2023, 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 • Enrollment status • Immunology • Interstitial Lung Disease • Sarcoidosis • Systemic Sclerosis

aTyr Pharma Announces Expanded Access Program (EAP) for EFZO-FIT Clinical Trial Participants (GlobeNewswire) - "aTyr Pharma, Inc...announced plans to initiate an Individual Patient Expanded Access Program (EAP) for its lead therapeutic candidate, efzofitimod, for patients with pulmonary sarcoidosis. The Individual Patient EAP is intended to allow access for patients who complete the Phase 3 EFZO-FIT study and wish to receive treatment with efzofitimod outside of the clinical trial."

Trial status • Immunology • Pulmonary Disease • Sarcoidosis

Anti-inflammatory Therapy for Sarcoidosis. (PubMed, Clin Chest Med) - "The last decade has seen an explosion of studies and trials evaluating novel therapeutic agents and treatment strategies. Currently available anti-inflammatory therapies and several novel therapies are discussed here."

Journal • Review • Immunology • Sarcoidosis