Our Science

Unleashing Potential in a High-profile Drug Target Superfamily


We see the unseen: additional therapeutic potential in nuclear receptors, a drug target superfamily, and are exploring this unknown territory. Nuclear receptors are well-known in the scientific community. Oral drugs based on the nuclear receptors have successfully treated breast and prostate cancer, type 2 diabetes, non-alcoholic steatohepatitis (NASH), and inflammatory disease. Nuclear receptors are unique among transcription factors since they have well-defined pockets that allow regulation by highly potent and selective small molecule ligands.

Discovery Strategy

We combine imagination, scientific rigor, and broad-based technologies in our focused research strategy. To begin, we developed high-throughput assays for several unexplored or orphan nuclear receptors and screened these against diverse compound libraries to identify selective chemical probes. Next, by implementing orthogonal assays, we confirmed the direct binding of these chemical probes to the receptor ligand-binding domain. In several cases, we identified both agonist and antagonist probe compounds that were used to support target validation.

Lead compounds were optimized by iterative medicinal chemistry to improve drug-like properties. Subsequently, by tapping into the scientific literature, publicly available databases, and our internal exploratory pharmacology, our scientific team developed therapeutic hypotheses and identified potential addressable patient populations. This strategy yielded three significant Orphagen pipeline programs.

Partnerships and Collaborations

Orphagen believes strongly in partnerships and collaborations to accelerate our path to discovery, clinical development and commercialization. We have attracted significant partners and continue to be open to a wide range of collaborators. As we approach a pivotal company milestone of moving into clinical development with OR-449, we will continue to evaluate collaboration and business development opportunities for both this lead candidate and other programs.

Our legacy of successful partnerships began in 2008 with a strategic partnership for development of small molecule antagonists to the orphan nuclear receptor RORγ for autoimmune diseases such as psoriasis. This was the first of many competitive development programs for oral RORγ antagonists that swept the industry, including major pharmaceutical companies such as Merck, Pfizer, Amgen, J&J, AbbVie, GSK, and Takeda. Orphagen has engaged in additional pharmaceutical research collaborations based on its internally developed technology.