Estetrol (E4) is an estrogen, produced by the human fetal liver during pregnancy. It is 
present in high concentrations in the blood of pregnant women and at even higher levels in fetal blood (10-20 times) at parturition. This high exposure of the vulnerable developing fetus implies that E4 might be a safe estrogenic steroid for human use. Estetrol was identified by Egon Diczfalusy at the Karolinska Institute in Stockholm in 1965. It has been discovered as a potential drug for human use by Herjan Coelingh Bennink at Pantarhei Bioscience (PRB) in 2001. Since then PRB has performed several pre-clinical and clinical studies with E4.
In 2015 Pantarhei sold all rights, assets, and patents of E4 to the Belgian company Mithra Pharmaceuticals. All rights for the oncological and veterinary E4 applications (including breast cancer and prostate cancer) were exclusively licensed back to Pantarhei. Mithra is developing the Women’s Health applications of E4 (i.e. hormonal contraception and menopausal hormone therapy).
Proof-of-concept clinical studies (phase I/II) are ongoing with E4 in patients with advanced hormone sensitive (ER+) breast and advanced prostate cancer. The first results are promising. Pantarhei is potentially interested in pharmaceutical partners for the further oncological development of E4.