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 (10-20 times) in fetal blood 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.
Estetrol has been developed by PRB from 2001-2015 for applications in women such as contraception and menopausal hormone therapy. The most important preclinical studies have been reported in a special Supplement of the journal Climateric in 2008. It was found that E4 behaves preclinically and clinically as an estrogen, however remarkably with estrogen-antagonistic effects in breast cancer models.
Between 2009 and 2013 PRB developed E4 in a phase II program for oral contraception in collaboration with the Belgian company Uteron Pharma. Those studies in more than 400 women showed that E4 is effective and safe in a dose of 15-20 mg per day, in combination with a progestin.
In 2015 Pantarhei sold all rights, assets and patents of E4 to the Belgian company Mithra Pharmaceuticals. All rights for oncological and veterinary E4 applications (including breast cancer and prostate cancer) were exclusively licensed back to PRB. Mithra is developing the Women’s Health applications of E4 (i.e. hormonal contraception and menopausal hormone therapy).
For these and other oncological developments PRB created its subsidiary company Pantarhei Oncology (PRO). 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.