RORγt

RORγt

The nuclear receptor RORγt (the thymus or t isoform of the retinoic acid-related orphan receptor gamma) is a key regulator of the TH17 immune pathway, which involves the differentiation of T cells to a pro-inflammatory subtype of T helper cells called TH17. RORγt drives the production of key pro-inflammatory proteins, including interleukin (IL)-17A, IL-17F and the receptor for IL-23. In recent years, several clinical studies have shown the TH17 pathway to be critical in chronic autoimmune-related inflammation, thereby bringing RORγt to the forefront of small-molecule drug discovery.

In 2015, Lead Pharma and Sanofi entered into a license and research collaboration agreement to discover, develop and commercialize small-molecule therapies directed against RORγt. Lead Pharma is eligible to receive milestone payments and is entitled to receive royalty payments on global sales from any resulting products. The Lead Pharma–Sanofi collaboration has culminated in the development of a clinical-stage inverse agonist of RORγt known as SAR441169, which progressed to clinical trials in 2019.

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