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A new approach to treating endometriosis

The risk of endometriosis recurring after surgery is high, while therapy often leads to menopausal-like side-effects. The need for new approaches with equal or better efficacy and fewer or milder sideeffects is therefore clear. Hormos Medical is responding by developing a novel disease-specific drug.
Hormos Medical Ltd.

Endometriosis is characterised by ectopic growth of endometrial tissue outside the uterine cavity, and is a leading cause of disability in women of reproductive age and responsible for chronic pelvic pain, pain during intercourse, and infertility.

Hormos Medical’s lead product for postmenopausal estrogen deficiency, ospemifene, is approaching filings for market authorisation; while its second product, fispemifene, is in clinical studies for treating androgen deficiency symptoms in men.

Estrogen has long been recognised as the most important factor stimulating the growth of endometriosis, and treatment designed to suppress ovarian estrogen synthesis or inhibit estrogen action has proved useful. No one protocol appears to be superior in terms of efficacy, however, and all current therapies are hampered by severe side-effects.

Endometrial biology and the aetiological study of endometriosis in recent years have shown that the local synthesis of estrogen plays an important role in the disease. Together with its academic partners, Hormos Medical has been in the front line of this work, which has resulted in the discovery of a number of novel drug targets for the treatment of steroid-dependent diseases such as endometriosis. These targets include 17β-hydroxysteroid dehydrogenases (17HSDs), the key enzymes that regulate the local synthesis of sex steroids in normal and diseased tissue.

An exciting family of enzymes

The role of 17HSDs in the formation of sex steroids in peripheral tissue has been the subject of extensive study, and over 10 closely related isoforms have been isolated. These enzymes offer novel mechanisms for regulating sex steroid effects, such as how estrogen behaves, in a tissue-specific way. Designing drugs that inhibit 17HSD isoenzymes selectively represents a very interesting way forward.

17HSD Type 1 enzyme enhances the estrogen response in breast and endometrial tissue, for example, by converting low-bioactive estrone to highbioactive estradiol. Selective inhibitors of the enzyme offer a highly selective therapeutic approach for diseases such as endometriosis, uterine fibroids, and breast cancer.

The potent and highly selective 17HSD Type 1 inhibitors discovered by Hormos Medical have demonstrated proof of concept in a primate endometriosis disease model, dissolving endometriosis plaques without interfering with circulating hormones. These products are now progressing to the clinical study phase.

As the 17HSD enzyme family offers multiple novel drug targets and opportunities for tissue-specific hormonal therapies, Hormos Medical is working on inhibitors for other 17HSD subtypes and evaluating their efficacy in relation to breast and prostate cancer in particular.

> Risto Lammintausta
(Published in HighTech Finland 2009)