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 that we refer to as Stalaris, 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.
In IND enabling studies, the selected Stalaris molecule showed promising results in a well-established mouse model of lung inflammation and pulmonary fibrosis, induced by a chemotherapeutic agent known as bleomycin. When given in two therapeutic doses over 21 days, Stalaris was comparable to, or outperformed approved drugs with daily dosing in reducing lung inflammation and fibrosis in the bleomycin model.
With the selection of this Stalaris molecule, we are harnessing the Resokine pathway and plan to test its potential role in lung disease and to develop Stalaris as a potential therapeutic for patients with rare pulmonary diseases with an immune component, or RPICs.