SAN DIEGO, Aug. 04, 2022 (GLOBE NEWSWIRE) — Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) today announced that Peter J. Trainer, M.D., vice president of clinical endocrinology, will review additional analyses from the preclinical and Phase 1 clinical studies of CRN04894 in an oral presentation at the 10th International Congress of Neuroendocrinology (ICN), being held August 7-10, 2022. CRN04894 is an investigational, oral, small molecule adrenocorticotropic hormone (ACTH) antagonist that is being developed by Crinetics for the treatment of Cushing’s disease, congenital adrenal hyperplasia (CAH) and other conditions of excess ACTH.
Data from the first-in-human Phase 1 study demonstrated pharmacologic proof-of-concept for CRN04894, as treatment led to reductions in both serum cortisol levels and 24-hour urine free cortisol excretion in the presence of sustained, disease-like ACTH concentrations. Additional details on the upcoming presentation are shown below.
|Title:||CRN04894 an oral, nonpeptide ACTH receptor antagonist reverses ACTH-stimulated glucocorticoid secretion in rodents and humans|
|Date/Time:||August 10, 2022 at 9:00 – 10:40 a.m. BST|
|Session:||Stress Pathology and Emerging Therapies|
|Conference Location:||Scottish Event Campus, Glasgow, Scotland|
Additional details on the presentation session including the presentation abstract can be accessed here. The presentation will be made available on the Crinetics website in accordance with the congress’ embargo policy.
About the CRN04894 Phase 1 Study
The double-blind, randomized, placebo-controlled first-in-human study enrolled 88 healthy volunteers who were divided into multiple cohorts in the single ascending dose (n=39) and multiple ascending dose (n=49) portions of the study. In both portions of the study, safety and pharmacokinetics were assessed. In addition, pharmacodynamic responses were evaluated before and after challenges with injected synthetic ACTH to assess pharmacologic effects resulting from exposure to CRN04894.
Adrenocorticotropic hormone (ACTH) is synthesized and secreted by the pituitary gland and selectively binds to its receptor melanocortin type 2 receptor (MC2R), which is selectively expressed in the adrenal gland. This interaction of ACTH with MCR2 activates the adrenal and results in production of cortisol, a stress hormone that is involved in the regulation of many physiologic systems. These include the regulation of blood sugar levels, metabolism, inflammation, blood pressure, and memory formulation. Diseases associated with excess of ACTH, therefore, can have significant impact on physical and mental health. Cushing’s disease is characterized by chronically elevated cortisol levels caused by tumors that secrete excess ACTH and do not respond to negative feedback by even elevated glucocorticoid levels, resulting in hypertension, central obesity, neuropsychiatric disorders, and metabolic complications among other troubling symptoms. Congenital adrenal hyperplasia is caused by an enzyme deficiency in the normal cortisol synthesis pathway, resulting in a shunting of precursors to the formation of excess adrenal androgens. Excess adrenal androgen production can result in hirsutism, menstrual dysfunction, infertility in men and women, acne, cardiometabolic comorbidities and insulin resistance. Crinetics’ ACTH antagonist, CRN04894, has exhibited strong binding affinity for MC2R in preclinical models and demonstrated suppression of adrenally derived glucocorticoids and androgens that are under the control of ACTH.
About Crinetics Pharmaceuticals
Crinetics Pharmaceuticals is a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for rare endocrine diseases and endocrine-related tumors. Paltusotine, a somatostatin receptor type 2 (SST2) agonist, is in Phase 3 clinical development for acromegaly and Phase 2 clinical development for carcinoid syndrome associated with neuroendocrine tumors. Crinetics has demonstrated pharmacologic proof-of-concept in Phase 1 clinical studies for CRN04777, a somatostatin receptor type 5 (SST5) agonist for congenital hyperinsulinism, and for CNR04894, an ACTH antagonist for the treatment of Cushing’s disease, congenital adrenal hyperplasia, and other diseases of excess ACTH. All of the company’s drug candidates are orally delivered, small molecule new chemical entities resulting from in-house drug discovery efforts.
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