ATYR1923 is a potential first-in-class, disease modifying therapy for patients with severe inflammatory lung diseases with high unmet medical need. ATYR1923 works by selectively modulating Neuropilin-2 (NRP2) to downregulate the innate and adaptive immune responses in uncontrolled inflammatory disease states to resolve inflammation and prevent subsequent fibrosis. ATYR1923 is conducting a Phase 1b/2a clinical trial in pulmonary sarcoidosis, a major form of interstitial lung disease (ILD), a group of immune-mediated disorders that cause progressive fibrosis of the lung, and a Phase 2 trial in patients with COVID-19 related respiratory complications.


ATYR1923 is a selective modulator of NRP2 that downregulates the innate and adaptive immune responses in uncontrolled inflammatory disease states. ATYR1923’s effect on immune cells potentially overlaps with the cellular pathology observed in severe inflammatory lung diseases, including pulmonary sarcoidosis, certain other ILDs and severe respiratory complications caused by COVID-19. In preclinical studies, ATYR1923 has been observed to inhibit cytokines and chemokines involved in the regulation of inflammatory and fibrotic responses. Furthermore, ATYR1923 has been observed to significantly reduce inflammation-dependent fibrosis and improve respiratory function in animal models of ILD. NRP2 expression is upregulated on target immune cells during inflammation, including in sarcoid granulomas of the lung and skin as well as in the lungs of patients who have died from COVID-19. ATYR1923 specifically and selectively binds to NRP2 on the cell surface. Accordingly, we believe that by targeting NRP2 to resolve aberrant immune responses, ATYR1923 could prove an effective therapeutic alternative, with a novel mechanism of action, and less toxicity compared to current standard of care for patients with severe inflammatory diseases where there remains a high unmet medical need.

Target Populations

Interstitial Lung Diseases

Interstitial lung diseases are a group of immune-mediated disorders which cause progressive fibrosis of the lung. There are over 200 different types of ILD, of which the four major forms are: pulmonary sarcoidosis, chronic hypersensitivity pneumonitis (CHP), connective tissue disease-associated ILD (e.g., rheumatoid arthritis-associated ILD and systemic sclerosis-associated ILD) (CTD-ILD), and idiopathic pulmonary fibrosis (IPF). We have focused our development efforts on ILDs that result in severe, progressive lung disease and share an immune-pathophysiology that has the potential to be impacted by ATYR1923. These lung conditions are recognized as having a measurable immune component involving both innate and adaptive immune mechanisms that contribute to pathogenesis, and can result in progressive disease leading to fibrosis and death. The first ILD that we are investigating clinically is pulmonary sarcoidosis.

Sarcoidosis is an inflammatory disease of unknown cause, characterized by the formation of granulomas, clumps of inflammatory cells, in one or more organs in the body. Sarcoidosis affects people of all ages, with incidence peaking between 20 and 39 years of age. The disorder usually begins in the lungs, skin or lymph nodes, but can affect almost any organ. Sarcoidosis in the lungs is called pulmonary sarcoidosis and affects over 90% patients. Estimates of prevalence vary, but generally indicate that approximately 200,000 Americans currently live with pulmonary sarcoidosis. The prognosis for patients with pulmonary sarcoidosis ranges from benign and self-limiting to chronic, debilitating disease and death. Current standard of care for patients with sarcoidosis involves treatment with corticosteroids and other immunosuppressive therapies, with limited evidence of efficacy and serious long term toxicity. There remains a need for novel treatment options for sarcoidosis patients with progressive disease.

COVID-19 Related Respiratory Complications

COVID-19 is a novel infectious disease that primarily affects the lungs. Many COVID-19 patients with severe disease experience serious, sometimes fatal, respiratory complications caused by an excessive inflammatory response in the lung, primarily driven by T-cells. The inflammatory lung injury related to COVID-19 may be similar to that of ILDs. We believe that ATYR1923’s mechanism of action has substantial overlap with this disease pathology and presents a compelling opportunity to potentially treat this subset of COVID-19 patients for which there are limited available treatment options.

Clinical Development

ATYR1923 Phase 1b/2a Clinical Trial in Pulmonary Sarcoidosis

aTyr is conducting a Phase 1b/2a clinical trial for ATYR1923 in patients with pulmonary sarcoidosis. This trial is a randomized, double-blind, placebo-controlled multiple-ascending dose, first-in-patient study in 36 patients. The study is being conducted in patients with confirmed active pulmonary sarcoidosis undergoing an oral corticosteroid (OCS) tapering regimen, in three cohorts of 12 patients each, at dose levels of 1.0 mg/kg, 3.0 mg/kg and 5.0 mg/kg IV ATYR1923 or placebo dosed every month for 6 months.

The primary objective of the study is to evaluate the safety and tolerability of multiple ascending doses of ATYR1923. Secondary objectives include assessment of the potential steroid-sparing effects of ATYR1923. In addition, ATYR1923 PK and immunogenicity following multiple dose administration will be evaluated. Other exploratory assessments of ATYR1923 efficacy in pulmonary sarcoidosis include the evaluation of changes over time in: lung imaging; lung function assessed by pulmonary function tests; serum biomarkers of interest; health-related quality of life, and skin lesion assessments (for patients with cutaneous involvement at baseline).

aTyr is collaborating with the Foundation for Sarcoidosis Research (FSR), a leading nonprofit organization dedicated to finding a cure for sarcoidosis and improving care for sarcoidosis patients.

Enrollment in this trial has been completed. For more information, click here

ATYR1923 Phase 2 Clinical Trial in COVID-19 Related Severe Respiratory Complications

aTyr is conducting a Phase 2 clinical trial for ATYR1923 in patients with COVID-19 related severe respiratory complications. The trial is a randomized, double blind, placebo-controlled study designed to investigate the safety and preliminary efficacy of ATYR1923 in 32 confirmed COVID-19 positive patients who are hospitalized and do not require mechanical ventilation. Patients enrolled in the trial are randomized 1:1:1 to receive a single intravenous dose of either 1.0 or 3.0 mg/kg ATYR1923 or placebo.

Enrollment in this trial has been completed. For more information, click here

ATYR1923 Phase 1 Clinical Trial

In June 2018, we announced results of our first-in-human Phase 1 clinical trial of ATYR1923 conducted in Australia. This randomized, double-blind, placebo-controlled study evaluated the safety, tolerability, immunogenicity, and PK of intravenous (IV) ATYR1923 in healthy volunteers. The Phase 1 study enrolled 36 healthy volunteers who were randomized to one of six sequential cohorts and received a single infusion of intravenous ATYR1923 or placebo. Ascending ATYR1923 doses by cohort ranged from 0.03 mg/kg to 5.0 mg/kg. The drug was generally well-tolerated at all dose levels tested, with no significant adverse events or induction of anti-drug antibodies observed following ATYR1923 dosing or throughout the one-month follow-up period. The PK of ATYR1923 following single-dose administration was linear across the evaluated dose range. Higher ATYR1923 doses yielded sustained serum concentrations through the end of the one-month follow-up period that were above the predicted therapeutic threshold, supporting a once-monthly dosing regimen.