Therapeutic Pipeline For Specialty Endocrine Disorders And endocrine related cancers
Somatostatin Links Two Deadly Diseases: Acromegaly And Neuroendocrine Tumors
Acromegaly is caused by pituitary tumors that secrete excess growth hormone, which in turn causes elevated circulating levels of Insulin-like Growth Factor-1 (IGF-1). IGF-1 is a hormone that plays a vital role in childhood growth and adult homeostasis. Left untreated, acromegaly can result in serious illnesses and premature death.
Acromegaly is an orphan disease affecting more than 20,000 individuals in the U.S.
Neuroendocrine tumors found in the intestine are called carcinoids. These tumors often present with a variety of abdominal and respiratory symptoms that can be confused with other more common conditions. The subset of neuroendocrine tumors that express somatostain receptors are treatable with targeted therapies.
The estimated prevalence of neuroendocrine tumors is more than 100,000 individuals in the U.S.
The pituitary neuropeptide somatostatin naturally inhibits growth hormone production, and synthetic somatostatin analogs have been routinely used to treat acromegaly as well as neuroendocrine tumors.
However, these somatostatin analogs are only effective in about half of patients with acromegaly, and patients with neuroendocrine tumors frequently become resistant to this therapy. In addition, somatostatin analogs require frequent doctor’s office visits for painful injections that can often lead to injection site reactions.
To overcome these treatment limitations, Crinetics is developing an orally available small molecule for the treatment of acromegaly and neuroendocrine tumors. Crinetics is designing clinical trials to show that our once-a-day pill will improve treatment efficacy and tolerability in acromegalics.
Kisspeptin Regulates GnRH, A Key Hormone In Women’s Reproductive Health
Polycystic ovary syndrome (PCOS) is the most common hormonal disorder among reproductive age women, affecting up to 30 percent of premenopausal women in the U.S. The hallmarks of this disorder are obesity, irregular or no menstruation, infertility, acne, and unwanted excess hair growth (aka hirsutism). If left untreated, PCOS can lead to serious health problems, including type 2 diabetes and heart disease.
In females, secretion of gonadotropin-releasing hormone (GnRH) occurs in pulses. Changes in GnRH pulses during the menstrual cycle coordinate the release of reproductive hormones. In PCOS, the GnRH pulse generator is defective, resulting in dysregulation of fertility and side effects that result from excess androgens.
GnRH receptor agonists have not been widely used to treat PCOS, as they suppress estrogen so drastically that the patient experiences post-menopausal symptoms, including hot flashes and bone loss.
At Crinetics, we have focused on Kisspeptin, a hormone that functions as the master controller of the hypothalamic–pituitary–gonadal axis (HPG axis). Kisspeptin mediates GnRH pulses but does not affect the baseline secretion of estrogen.
Crinetics is developing an orally available small molecule antagonist to the human kisspeptin receptor (KISS1R), which is designed to alleviate unwanted GnRH surges without completely suppressing estrogen production. Crinetics’ KISS1R antagonist represents the first non-steroidal drug candidate that could treat polycystic ovary syndrome at its source, as well as other debilitating women’s health disorders, such as endometriosis and uterine fibroids.
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