Sanofi has entered into a definitive agreement to acquire Principia Biopharma Inc., a late-stage biopharma company focused on immune-mediated diseases, in a transaction valued at approximately $3.36 billion.

Principia’s Bruton tyrosine kinase (BTK) inhibitors add to Sanofi’s efforts to accelerate a portfolio of next gen transformative treatments for autoimmune diseases. BTK is present in the signaling pathways of key innate and adaptive cell types of the immune system. Being able to block or disrupt these signaling processes can help stop inflammation and tissue destruction related to autoimmune diseases and target some of the underlying pathophysiology.

BTK inhibitor ‘168: In a Phase 2b study in patients with multiple sclerosis, ‘168 reduced Gd-enhancing T1 hyperintense lesions by 85% compared to placebo. In June, Sanofi initiated the Phase 3 program for the BTK inhibitor, comprising four clinical trials across the disease spectrum. The Principia acquisition will provide an opportunity to expand the development program to evaluate indications beyond central nervous system diseases.

Rilzabrutinib, an oral BTK inhibitor is currently in a Phase 3 program in moderate to severe pemphigus, a rare, debilitating autoimmune disease that causes blistering of the skin and mucous membranes. A Phase 3 program for immune thrombocytopenia, a disease that causes high risk for bleeding events, is expected to be begin by the end of 2020. Also, there’s an ongoing Phase 2 program for IgG4-related diseases, which is driven by chronic inflammation, immune cell infiltration, and fibrosis within organs that can lead to severe morbidity.

PRN473, a topical agent is currently in Phase 1 trials and is being developed for immune-mediated diseases that could benefit from localized application to the skin.

The Principia BTK inhibitor franchise is based on its Tailored Covalency platform that allows the design of both reversible covalent and irreversible covalent small molecule inhibitors that are more selective with less off-target effects. The optimized target residence time has potential to deliver a desired efficacy with a stronger safety profile.