Endometriosis is a chronic condition that affects up to 10% of women in reproductive age and causes repeated pain symptoms, infertility and impaired quality of life. Currently available treatments for endometriosis have limitations in efficacy or cause harmful side effects. They often lead to systemic estrogen depletion, with known safety issues on bone mineral density and menopausal symptoms. There is no known cure for the disease. Download a pdf about endometriosis »
Forendo Pharma has developed a potential new treatment for endometriosis based on inhibition of the HSD17B1 enzyme, a novel drug target for tissue specific regulation of hormone activity. Proof of efficacy for this novel mechanism has been demonstrated in primate model of endometriosis. The clinical compound FOR-6219 inhibits the conversion of low potency estrone into highly potent estradiol in endometriotic tissues. The most important expected differentiator of FOR-6219 compared to currently available treatments is its selective activity and the ability to act locally in the target tissues, without impacting systemic hormone levels. This selective activity allows a safe and well tolerated, long term treatment opportunity for endometriosis. FOR-6219 is currently in Phase I clinical development
Polycystic ovary syndrome, or PCOS for short, is an endocrine disorder characterized by signs and symptoms of androgen excess and irregular cycles as well as ovarian dysfunction. It is one of the most common conditions in reproductive aged women leading to metabolic disorders, pregnancy complications and infertility. There are currently only symptomatic but no disease-modifying treatment options available.
The HSD17B5 enzyme has a central role in androgen activation in multiple pathways and is also overexpressed in adipose tissue of PCOS patients. Among the various vicious cycles that exist and worsen PCOS, our therapeutic approach is designed to modulate the intra-adipose tissue testosterone production that directly affects further lipid accumulation and insulin resistance. Inhibition of HSD17B5 is expected to lower both intratissue and systemic testosterone levels in women suffering from PCOS. Forendo’s therapeutic program FOR-7191 is currently in the discovery and lead optimization stage and is expected to progress quickly towards clinical trials commencing in 2022.
Forendo and its academic partners will continue to explore the entire therapeutic potential of the HSD17B enzyme class to feed Forendo’s proprietary pipeline and where appropriate partner specific approaches or indications early with selected, high-quality partners.
Forendo was founded by leading academic endocrinology experts and Finnish drug development pioneers. The translation of intracrinology science into first-in-class therapeutic solutions is at the core of our company. Intracrinology enables us and our partners to address diseases on an unprecedented tissue specific level.
The endocrine pattern of steroid hormones action is based on the fact that hormones are synthesized in the gland and reaches the target organ via the blood circulation. Most therapeutic approaches as a result, have focused on modulating synthesis, activity, and metabolism of hormones on a systemic level.
Recently, a new paradigm has evolved around the concept of “intracrinology”. In the intracrine pattern of steroid hormone action, the ligand concentration available for nuclear receptor binding is regulated also, and more decisively, by the target tissue metabolism itself thus enabling a much more focused and potentially much safer point for therapeutic interventions.
While they are mostly known for catalyzing the reaction between the low active 17-keto steroids and the highly active 17-hydroxy steroids, members of the hydroxysteroid (17β) dehydrogenase superfamily (HSD17B) have been implicated to play a role in a number of disease processes. As of today, 14 different family members of the HSD17B enzyme class have been identified in humans.
Forendo is currently pursuing fully proprietary therapeutic programs targeting two members of this family – an HSD17B1 inhibitor in endometriosis and a HSD17B5 inhibitor in PCOS. In 2019, Forendo signed a first alliance exploring potential therapeutic applications of a HSD17B family member outside the women’s health arena, more specifically in chronic liver diseases with Novartis.
Through our academic network, we have preferred access to some of the leading scientists in the field exploring disease-related biology aspects of the entire enzyme class in a bandwidth of indications. Our academic partners are pioneering the work on in vitro and in vivo models as well as tumor xenografts using clinical samples in the oncology setting.