We established a discovery program to leverage our knowledge of the Resokine pathway to vary exposure and activity of the iMod domain through protein engineering. The goal of the program was to develop a potential therapeutic which would possess only the N-terminal immuno-modulatory and fibro-modulatory activities of Resokine.
Our Fc fusion experiments helped delineate how to enhance the exposure of the iMod domain of Resokine while maintaining activity and provide insights into this domain harboring immuno-modulatory activity. Experiments have indicated that Fc fusion proteins can increase exposure and maintain iMod domain activity. Our efforts in this discovery program have led to the selection of our second product candidate.
Interstitial Lung Diseases (ILDs) and the Role of Immunology
The Resokine pathway may play an important role in maintaining lung health. We believe the Resokine pathway plays a role in the regulation of tissue homeostasis with respect to immune cell invasion and residence, including in lung tissue.
Among the various forms of ILD, we have identified several that result in severe and progressive lung disease and share immune-pathophysiology features that have the potential to be impacted by our demonstrated iMod.Fc activities. Examples of rare pulmonary diseases with an immune component include idiopathic non-specific interstitial pneumonias, idiopathic pulmonary fibrosis, lymphocytic interstitial pneumonia, bleomycin (the chemotherapeutic agent)-induced pulmonary fibrosis, and ILD in the setting of systemic sclerosis, or scleroderma, and sarcoidosis.
Clinical Development Plan
aTyr Pharma plans to commence a Phase 1 clinical program for the iMod.Fc program later this year. This randomized, double-blind, placebo-controlled study will investigate the safety, tolerability, immunogenicity, pharmacokinetics and pharmacodynamics (PD) of intravenous iMod.Fc in healthy volunteers.