aTyr Pharma, Inc. announced the publication in the journal CHEST of positive results from a Phase 1b/2a randomized, double-blind, placebo-controlled clinical trial of its lead therapeutic candidate, efzofitimod, in patients with pulmonary sarcoidosis, a major form of interstitial lung disease. The study demonstrated that efzofitimod was safe and well-tolerated at all doses and exhibited a consistent dose response on key efficacy endpoints and improvements compared to placebo, including measures of steroid reduction, lung function, sarcoidosis symptom measures and inflammatory biomarkers. Efzofitimod is a first-in-class immunomodulator that downregulates innate and adaptive immune responses in uncontrolled inflammatory diseases states via selective modulation of neuropilin-2 (NRP2).

Efzofitimod is currently being investigated in a global pivotal Phase 3 study in patients with pulmonary sarcoidosis known as EFZO-FIT™, which is supported by safety and efficacy data from the Phase 1b/2a study. Efzofitimod has been granted FDA orphan drug and Fast Track designations for sarcoidosis. Phase 1b/2a Clinical Trial in Patients with Pulmonary Sarcoidosis The Phase 1b/2a study was a randomized, double-blind, placebo-controlled, multiple-ascending dose clinical trial in 37 patients with pulmonary sarcoidosis.

The trial consisted of three cohorts testing doses of 1.0 mg/kg, 3.0 mg/kg and 5.0 mg/kg of efzofitimod or placebo, dosed intravenously every month for six months. The primary objective of the study was to evaluate the safety, tolerability, immunogenicity and pharmacokinetic profile of multiple doses of efzofitimod compared to placebo. Secondary objectives included the potential steroid-sparing effects of efzofitimod, in addition to other exploratory assessments of efficacy, such as lung function.

Sarcoidosis is an immune-mediated disease characterized by the formulation of granulomas, clumps of inflammatory cells, in one or more organs of the body, predominantly in the lungs. Almost 200,000 Americans live with pulmonary sarcoidosis and the prognosis ranges from benign and self-limiting to chronic, debilitating disease, with 1 in 5 cases resulting in fibrosis, or scarring, of the lungs, which causes permanent loss of lung function and in many cases death. Current treatment options include corticosteroids and other immunosuppressive therapies, which have limited efficacy and are associated with serious side effects that many patients cannot tolerate long-term.

aTyr is developing efzofitimod as a potential therapeutic for patients with fibrotic lung disease. Efzofitimod, a fusion protein comprised of the immuno-modulatory domain of histidyl-tRNA synthetase fused to the FC region of a human antibody, is a selective modulator of neuropilin-2 that downregulates innate and adaptive immune response in inflammatory disease states. aTyr's lead indication for efzofitimod is pulmonary sarcoidosis, a major form of interstitial lung disease.

Clinical proof-of-concept for efzofitimod was recently established in a Phase 1b/2a multiple-ascending dose, placebo-controlled study of efzofitimod in patients with pulmonary sarcoidosis, which demonstrated safety and a consistent dose response and trends of benefit of efzofitimod compared to placebo on key efficacy endpoints, including steroid reduction, lung function, clinical symptoms and inflammatory biomarkers. aTyr is currently conducting EFZO-FIT™, a Phase 3 study of efzofitimod in pulmonary sarcoidosis patients.