Treating Endometriosis

ADVERTISEMENT FEATURE Forendo Pharma forendo.com Treating endometriosis By using a tissue-specific hormone inhibitor to rebalance local estrogen metabolism, Forendo Pharma could provide long-term treatment to millions of women suffering from endometriosis. With its expertise in tissue-specific hormone O OH therapies, the Finnish company Forendo Pharma HSD17B1 is tackling endometriosis, a condition that affects 10% of women of childbearing age. “Endometriosis is a difficult condition to treat, mainly because the estrogen-deficiency symptoms generated by HSD17B2 the currently used drugs prevent long-term use. HO HO profile Unlike these therapies, our strategy uses novel Estrone (E1) Estradiol (E2) 17-β-hydroxysteroid dehydrogenase (HSD17B) * Low activity * Highly active inhibitors which act locally, without impacting the Figure 1: Forendo’s FOR-6219. The basic concept behind the HSD17B1 inhibitor involves blockage of the systemic estrogen level,” said company CEO Risto conversion of estrone to estradiol. Lammintausta. The company was founded in 2013 by Finnish estrogen action, by converting non-active estrone cannot be controlled with hormonal therapies or drug development pioneers to exploit the find- into active estradiol within endometrial cells. When even surgery. “Whilst more efficient tools for diagno- ings of leading endocrinology researchers Matti this pathway is blocked, the build-up of high levels sis also need to be developed in order to provide an Poutanen and Antti Perheentupa, from the University of the estrogenic hormone estradiol is prevented, opportunity to treat women at an earlier stage and of Turku and Turku University Hospital, Finland. Led which will limit the ability of endometrial cells to form prevent these problems, HSD17B1 inhibitors offer a by Lammintausta, who has over 30 years of experi- endometriotic lesions. treatment option that could be offered before reach- ence in pharmaceutical R&D, and with substantial “Using HSD17B1 inhibitors we have shown that we ing these stages,” said Perheentupa. international investment from funds including Novo can inhibit estradiol production inside human endo- “Effective therapies for relief of endometriosis- Seeds, Karolinska Development, Novartis Venture metriosis samples ex vivo,” explained Lammintausta. associated pain that have minimal side effects com- Fund, Merck Ventures and Innovestor, the company Forendo’s potent and selective lead compounds prise the ‘holy grail’ of endometriosis management as is growing and expects its first endometriosis drug to have also demonstrated in vivo proof of efficacy in a stand-alone approaches or adjunctively with surgery. enter clinical development in 2018. primate disease model of endometriosis. Novel inhibition of HSD17B1 offers great promise in Endometriosis occurs when endometrial tissue, this field, which has significant morbidity and unmet normally formed in the lining of the uterus, starts to clinical needs in those affected,” said Linda Giudice, grow outside the uterine cavity, creating endome- Novel inhibition of professor of obstetrics, gynecology and reproductive triotic lesions. This can lead to painful periods and HSD17B1 offers sciences at the University of California, San Francisco, ovulation, pain during or after sexual intercourse, and chair of Forendo’s Advisory Board. abnormal bleeding, chronic pelvic pain, fatigue and great promise in this field, Forendo Pharma’s HSD17B1-inhibitor drug can- infertility. There is no known cure for the condition, which has significant didate, FOR-6219, is now progressing into clinical which is estimated to affect 170 million women and development. The company plans to take the drug teen girls. morbidity and unmet through clinical proof of concept before partnering “Efficient drug treatments are currently based on clinical“ needs for further development stages. Forendo’s pipeline suppression of ovarian estrogen synthesis or antago- also includes fispemifene, a selective estrogen- nizing estrogen action,” explained Poutanen. “These receptor modulator that is a phase 2 asset for the systemic therapies lead to estrogen deprivation Linda Giudice, professor of obstetrics, treatment of male urological conditions. The com- but often offer only modest efficacy. They also have gynecology and reproductive sciences, pany is open to opportunities to use its expertise harmful safety profiles, and can cause loss of bone University of California in tissue-specific hormone mechanisms for other density and several menopause-like side effects that applications and in 2018 will seek series B funding preclude long-term use.” There are potentially multiple benefits to this to broaden its women’s health pipeline. “With our inhibition, including reduced endometrial cell prolif- tissue-specific hormone therapeutics approach, Endometriosis development candidate eration and diminished inflammation, but one of the Forendo is well placed to make a real difference to Forendo Pharma has developed a novel clinical biggest advantages will be the reduction in off-target women’s health in the near future, and we look for- candidate compound that blocks the formation of effects. “Selectivity is a critical feature, and inhibiting ward to working with partners to make this happen,” high levels of the potent estrogen estradiol, which the local estradiol production with HSD17B1 inhibi- said Lammintausta. is responsible for the proliferation of endometriotic tors is likely to have long-term tolerability, providing lesions and contributes to pain. Most important, a long-term treatment option for the often young it does this without affecting ovarian hormone and active women who suffer from the condition,” Maarit Merla, Head of production. The concept, developed together with Lammintausta added. Business Development the University of Turku scientists, is based on the pre- Part of the problem with the disease has been Forendo Pharma viously unexploited drug target HSD17B1. the delay in diagnosis and treatment, which leads Turku, Finland contact The endometriotic tissue of women with endo- to further complications and often means that the Tel: +358 40 3108023 metriosis shows high estrogen levels. The enzyme disease has progressed. In such cases the patient may Email: [email protected] HSD17B1 is part of the mechanism that regulates present with infertility symptoms or chronic pain that ADVERTISER RETAINS SOLE RESPONSIBILITY FOR CONTENT biopharmadealmakers.nature.com | September 2017 | B25 ©2017 Mac millan Publishers Li mited. 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