22 March 2019 - - Dutch pharmaceutical company Lead Pharma has achieved a fourth milestone under its license and collaboration agreement with French drugmaker Sanofi (NYSE: SNY), triggering an undisclosed milestone payment, the company said.

The milestone payment is linked to Sanofi's dosing of the first human volunteers in a Phase I clinical trial of SAR441169, a novel inverse agonist of the nuclear hormone receptor RORγt.

This Phase I study by Sanofi will assess the tolerability, safety, and pharmacokinetics of single and ascending once daily oral dosing of SAR441169 in healthy adult subjects, and is aimed at gaining early evidence on effectiveness after four weeks of oral treatment in patients with moderate to severe psoriasis.

A range of human diseases are driven by deregulated immune function. These immune-mediated disorders include joint diseases such as rheumatoid arthritis and inflammatory bowel diseases such as ulcerative colitis and Crohn's disease.

Often, these diseases are characterized by inappropriate activation of molecules termed cytokines, which are important mediators of normal immune function.

When inappropriately activated, these powerful molecules can cause severe damage to multiple body systems. Symptoms of immune-mediated diseases range from mild skin rashes to severe organ failure to death.

In addition to the significant suffering of patients, the socioeconomic burden of just rheumatoid arthritis has been estimated at approximately USD 40bn in the US alone.

The nuclear receptor retinoic acid receptor-related orphan receptor gamma, also known as RORγt, is a key regulator of the cytokine immune pathway, which leads to 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 -17A, IL-17F and the receptor for IL-23. In the last years, several clinical studies have validated the critical role of the IL-17 pathway in chronic autoimmune-related inflammation.

Recent findings have demonstrated that the biological function of RORγt can be moderated with small molecules and have advanced this target to the cutting edge of drug discovery.

Lead Pharma is a pharmaceutical company focusing on the discovery and development of innovative medicines for the treatment of autoimmune diseases and cancer.

Lead Pharma's drug discovery engine combines medicinal, structural, and computational chemistry with molecular pharmacology, cell and tissue-based pharmacology.

The company has a pipeline of small molecule drugs in various stages of drug discovery and pre-clinical development.

Lead Pharma is a privately owned company based in Oss, the Netherlands. Shareholders in the company include BOM Brabant Ventures, Oost NL, Biox Biosciences and Waterman ventures.

In February 2015, Lead Pharma and Sanofi entered into a license and research collaboration agreement to discover, develop and commercialise 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.