In vitro activity: LYC-55716, a novel immune modulatory medicine developed by Lycera, is a synthetic and orally available small molecule agonist of RAR-related orphan receptor γ (RORγ). It combines multiple anti-tumor mechanisms into a single therapeutic by modulating gene expression to reprogram immune cells for improved function, as well as decrease immunosuppressive mechanisms. In January 2018, Lycera announced the initiation of a multi-center Phase 1B combination study in patients with advanced, relapsed, or refractory solid tumors such as metastatic Non-Small Cell Lung Cancer in combination with pembrolizumab.

Kinase Assay: LYC-55716, a novel immune modulatory medicine developed by Lycera, is a synthetic and orally available small molecule agonist of RAR-related orphan receptor γ (RORγ). It combines multiple anti-tumor mechanisms into a single therapeutic by modulating gene expression to reprogram immune cells for improved function, as well as decrease immunosuppressive mechanisms.

Cell Assay: LYC-55716 selectively binds to the nuclear receptor transcription factor RORγ, forming a receptor complex that translocates to the nucleus, and binds to ROR response elements (ROREs), enhancing the function, proliferation and survival of type 17 T cells, including Th17 (helper T cells) and Tc17 (cytotoxic T cells), which may increase the expression of co-stimulatory molecules and decrease the expression of co-inhibitory molecules on T cells leading to increased production of cytokines and chemokines by T cells, decreases proliferation of regulatory T cells (Tregs), and abrogation of tumor-induced immunosuppression. This ultimately induces a T-cell-mediated immune response against cancer cells and leads to a reduction in tumor cell growth. RORγ, the nuclear receptor transcription factor that is involved in Th17/Tc17 differentiation, plays a key role in immune activation. LYC-55716 is orally bioavailable, while the new generation of immuno-oncology drugs-ncluding PD-1/PD-L1 inhibitors are delivered by injection.