Research and Development

Endometriosis

Endometriosis is a benign gynaecological disease characterised by the presence of functional endometrial tissue fragments growing outside the uterus cavity, most frequently on the peritoneum, the ovaries, and the bowel. Like the eutopic endometrium, endometriotic tissue is oestrogen-dependent and proliferates during the menstrual cycle. At each menstruation lesions will bleed internally leading to pain, inflammation and adhesion formation. The major symptoms are chronic pelvic pain, painful menstruations and dyspareunia (painful sexual intercourse). Endometriosis is also a leading cause of infertility, with many patients seeking treatment for infertility being diagnosed with endometriosis.

Endometriosis is a highly prevalent condition in women of reproductive age affecting over 20 million women of reproductive age (EU & USA) with 5 million suffering with chronic pelvic pain. A high proportion of patients are asymptomatic, therefore the treatable patient population visiting OB&GYNs is estimated at 6-7 million. The main reasons for patient visits are pain or the inability to conceive. Among women consulting for infertility the incidence of endometriosis is 30-50%, and the incidence is as high as 70-80% among women consulting for chronic pelvic pain.

Current therapies are inadequate and range from symptom management with oral contraceptives or progestins to more aggressive treatments such as danazol or suppression of ovarian activity using GnRH agonists. The latter leads to a suppression of circulating oestrogens and its usage is restricted due to significant negative side effects.

PGL2001 (Steroid Sulfatase Inhibitor, STS-I)

PGL2001 is an oral, once-a-week steroid sulfatase inhibitor (STS-I) being developed for the management of endometriosis, including the relief of pain associated with the condition. Steroid sulfatases (STS) are enzymes expressed in tissues whose growth is oestrogen dependent. In these tissues, STS converts inactive oestrogens and androgens into their corresponding biologically active forms.

PGL2001 has the potential to be the first of a new class of products for the treatment of mild to moderate endometriosis1 and other benign gynaecological conditions.

Development stage: Phase IIa

PGL5001 (c-Jun-N-Terminal Kinase Inhibitor, JNK-I)

PGL5001 is a novel, first-in-class, oral therapy that reduces endometriotic lesions by targeting the inflammatory pathway of the disease and restores progesterone sensitivity. It has the potential to cause regression of the disease rather than simply alleviating symptoms, while the absence of oestrogen suppression in the drug mechanism avoids menopausal side effects such as the life-long impact on bone integrity. Its benefits include reduction of endometriotic lesions, without significant changes in the normal menstrual cycle.

PGL5001 has the potential to be the first of a new class of products for the treatment of endometriosis with a significant inflammatory improvement.

Development stage: Phase IIa / Proof of Concept (POC)


1 “Inhibition of steroid sulfatase decreases endometriosis in an in vivo murine model”, S. Colette, S. Defrère, J.C. Lousse, A. Van Langendonckt, J.P. Gotteland, E. Loumaye, and J. Donnez, Hum. Reprod. (2011) 26(6): 1362-1370 first published online March 25, 2011 doi:10.1093/humrep/der079