Eydis Bio, Inc.

Novel Compounds for the Treatment of Systemic Sclerosis-associated Interstitial Lung Disease - Project Summary / Abstract Systemic Sclerosis Interstitial Lung Disease (ssc-ild) Is a Progressive Orphan Disease Highlighted by Pulmonary Fibrosis Leading to a High Mortality Rate. Currently, There Are Only Two Fda Approved Ssc-ild Therapies (ofev and Actemra), Both of Which Have Limited Efficacy and Are Mired With Safety Issues, Warranting the Development of Novel Therapeutic Targets to Treat Ssc-ild. Our Preclinical Work Has Identified Tgfβ-activated Kinase 1 (TAK1) as a Key Signaling Element in Fibroinflammatory Signaling Observed in Pulmonary Fibrosis. TAK1 Plays a Critical Role in Facilitating Activation of Protein Kinase-mediated Signaling Pathways Implicated in the Pathogenesis of Ssc-ild, and as a Result Has Emerged as a Novel Target for Regulating Ssc-ild Mediated Inflammation and Fibrotic Signaling. Our Recent Discovery of the Takinib Scaffold Has Identified a Highly Selective (selectivity Score = 0.037), Potent (IC50 = 2.5NM), and Orally Bioavailable (%F = 98%) Small Molecule Inhibitor of TAK1 (HS-276). Preclinical Studies Have Demonstrated That TAK1 Inhibition Attenuates Critical TGFΒ Fibrotic Signaling in Human-derived Fibroblasts, as Well as Limits Pro-inflammatory Cytokine Signaling in Activated Human Macrophages. Furthermore, HS-276 Significantly Reduced Bleomycin-induced Pulmonary Fibrosis, in Vivo. Here, We Will Build Upon These Foundational Proof of Concept Studies and Further Develop HS-276 for the Treatment of Ssc-ild. in Order to Successfully Further Develop Our Program, This Project Includes the Following Specific Aims: Aim 1: in Vivo Pharmacodynamic Studies With HS-276 in Two Distinct Murine Lung Fibrosis Models: (bleomycin and TSK1/+). Aim 2: HS-276 Safety in Bacterial and Fungal Opportunistic Disease Models. Aim 3: Completion of Key GLP Safety and Toxicology Studies Required for Submission of an Ind. Following Successful Completion of These Aims We Will Be Poised to Advance HS-276 Towards Phase I Clinical Trials for the Treatment of Ssc-ild.