MF101, an ER beta-selective agonist, is designed for the treatment of vasomotor symptoms such as hot flashes and night sweats in menopausal women.
In animal studies the compound has been shown to prevent tumour formation in the breast or uterus, suggesting that MF101 will not increase the risk of either breast or uterine cancer.
In Phase 1 clinical testing of MF101, the drug was found to be safe, well tolerated and taken with high compliance. A multicentre Phase 2 double blind, placebo-controlled, randomised clinical trial of MF101 is expected to begin in early 2006.
The data, which were presented at the American Society for Reproductive Medicine's 61st Annual Meeting in Montreal, demonstrated the oestrogen receptor beta (ER beta)-selectivity of MF101 and isolated analogues.
The data also showed that MF101 did not stimulate oestrogen dependent tumour formation or uterine proliferation and therefore may be a safer alternative to currently marketed hormone therapy (HT).
The theory been put forward by the Bionovo researchers, who hypothesise that ER beta-selective oestrogens may be safer for menopausal symptoms because they do not cause proliferation of breast cancer or uterine cells like oestrogens used in current HT regimens.
HRT has been widely used in post-menopausal women because many doctors believe the treatment eases hot flashes and other acute symptoms of menopause, as well as increases bone density, protects against heart disease and stroke, and delays the onset of dementia.
However, latest evidence has shown that HRT increased the risk of breast cancer while providing no benefit against heart disease and stroke.
"After the Women's Health Initiative determined that the risks of traditional HT likely outweigh the benefits, there is a clear need for novel, safe compounds to treat or prevent a range of conditions associated with menopause," commented Jennifer Jackson, lead author of the study.
"We found that the active estrogenic compound in MF101 represents a possible novel class of oestrogen receptor-subtype selective modulators that may be safer than the current estrogens used in HT that are known to increase the risk of breast and uterine cancer."
While the two oestrogen receptors, oestrogen receptor alpha (ER alpha) and ER beta, share common structural domains and have similar affinity for oestradiol, a wide variety of structurally different compounds bind to the oestrogen receptors with different affinities, acting as selective agonists or antagonists in various tissues.
Previous studies have shown that ER alpha mediates the proliferative effects of oestrogens in MCF-7 breast cancer cells, whereas ER beta inhibits cell proliferation and tumour formation in a mouse xenograft model.
"Based on the data from our preclinical and clinical study of MF101, we are excited to take this candidate into Phase 2 trials," said Isaac Cohen, Bionovo's president and chief executive officer.
"The symptoms of menopause are a condition that is under-treated because of the high risk of life-threatening side effects," he added.