ATYR1923

Efzofitimod is a potential first-in-class, disease modifying therapy for patients with severe inflammatory lung diseases with high unmet medical need. Efzofitimod 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. aTyr is initially investigating efzofitimod in pulmonary sarcoidosis, a major form of interstitial lung disease (ILD), a group of immune-mediated disorders that can cause progressive fibrosis of the lung. In response to the COVID-19 pandemic, we also conducted a Phase 2 trial in patients hospitalized with COVID-19 related respiratory complications. Two separate healthy volunteer studies have been completed with efzofitimod. ATYR1923-MOA-C9v2

Efzofitimod is a selective modulator of NRP2 that downregulates innate and adaptive immune responses in uncontrolled inflammatory disease states. Efzofitimod’s mechanism of action targets the cellular pathology observed in many severe inflammatory lung diseases, including pulmonary sarcoidosis, certain other ILDs and other severe inflammatory lung disorders like those seen caused by COVID-19. NRP2 expression is upregulated on target immune cells during inflammation, including in sarcoid granulomas. Efzofitimod prevented inflammation and fibrosis in multiple animal models of ILD and has been shown to mediate T cell responses and prevent granuloma formation in vitro. Clinical proof-of-concept was established for efzofitimod in a Phase 1b/2a study in patients with pulmonary sarcoidosis. We believe that by targeting NRP2 to resolve aberrant immune responses, efzofitimod presents a novel mechanism of action, and could prove an effective therapeutic alternative with less toxicity compared to current standard of care for patients with severe inflammatory diseases where there remains a high unmet medical need.

Target Populations

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% of patients. 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.

Interstitial Lung Disease

Pulmonary sarcoidosis belongs to a group of diseases called interstitial lung disease (ILD). ILD are a group of immune-mediated disorders which can cause progressive fibrosis, or scarring, of the lung. The chronic inflammation and tissue scarring results in stiffness in the lungs which makes it difficult to breathe and get oxygen to the bloodstream. Lung damage from ILDs is often irreversible and gets worse over time. There are over 200 different types of ILD, with four main types comprising roughly 80% of all patients: pulmonary sarcoidosis, chronic hypersensitivity pneumonitis (CHP), connective tissue disease-associated ILD (e.g. systemic sclerosis-associated ILD) (CTD-ILD), and idiopathic pulmonary fibrosis (IPF). Despite diverse disease triggers, ILDs share common characteristics involving the lung tissue being infiltrated by various combinations of inflammatory cells and fibrosis, and all are associated with poor outcomes. Current treatment options are limited and generally focused on controlling inflammation, with targeted anti-fibrotic therapies approved for use in select patients. We estimate there are over 500,000 ILD patients in the United States and upwards of 3 million globally.

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.