Corcept Therapeutics, Inc. (CORT)

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Corcept Therapeutics Initiates a Phase 1 Study of Its Lead Selective Cortisol Receptor (GR-II) Antagonist -- CORT 108297

Press Release Source: Corcept Therapeutics On Tuesday February 23, 2010, 9:05 am
MENLO PARK, CA--(Marketwire - 02/23/10) - Corcept Therapeutics Incorporated (NASDAQ:CORT - News), a pharmaceutical company engaged in the discovery and development of drugs for the treatment of severe metabolic and psychiatric disorders, has begun dosing in the Phase 1 study of its next-generation selective cortisol receptor (GR-II) antagonist, CORT 108297.

"The initiation of the Phase 1 study of our lead selective cortisol receptor antagonist, CORT 108297, marks the achievement of the first of Corcept's four key milestones for 2010, which were announced last month," said Joseph K. Belanoff, M.D., Chief Executive Officer of Corcept. "CORT 108297 is the first compound from our three proprietary series of selective cortisol receptor antagonists to reach the clinic."

Dr. Belanoff continued, "We have reported previously that CORLUX?, our first generation cortisol receptor antagonist, proved to be a potent blocker of both Zyprexa and Risperdal induced weight gain and metabolic perturbations in human proof of concept studies. While CORLUX, currently in Phase 3 studies for the treatment of Cushing's Syndrome and psychotic depression, is a potent blocker of both the cortisol (GR-II) and progesterone (PR) receptors, our new compounds may prove to be a significant advance because they block only the cortisol receptor. We anticipate that CORT 108297 and other selective cortisol receptor antagonists may be studied in highly prevalent conditions including the weight gain and metabolic problems caused by the use of antipsychotic medications, diabetes, obesity, hypertension, osteoporosis, Alzheimer's disease and other neurodegenerative diseases, all conditions in which abnormal cortisol activity may play a role."

DOSING INITIATED IN PHASE 1 STUDY OF CORT 108297

We have begun dosing in the Phase 1 single ascending dose safety and tolerability study of CORT 108297 in healthy volunteers. The goal of this study is to establish the tolerability of a single dose of CORT 108297 given at escalating doses to healthy volunteers. We expect to complete this study during the first half of 2010, enabling the initiation of a Phase 1b, multi-dose, dose safety and tolerability study of CORT 108297 later this year. A Phase 2 trial of CORT 108297 for the mitigation of antipsychotic induced weight gain, that might provide initial evidence of effectiveness as well as additional safety data, is planned to begin in 2011.

CORT 108297 is the lead compound from our three series of proprietary selective GR-II antagonists and is a fused-ring azadecalin. This series of compounds has demonstrated a greater than 1000-fold difference in binding affinity for the GR-II receptor compared to the PR receptor.

A microdosing study of CORT 108297 in healthy humans was completed in March 2008, and demonstrated that the compound is well absorbed, has good bioavailability and has a half-life that appears compatible with once-a-day oral dosing. In 2009 we announced results from preclinical studies of CORT 108297 which demonstrated a statistically significant impact on multiple metabolic markers. Specifically, studies of CORT 108297 combined with olanzapine, the active ingredient in Eli Lilly's antipsychotic medication Zyprexa, administered to rats over a 3-week period demonstrated a dose dependent mitigation of weight gain across doses ranging from 2 to 120mg/kg. CORT 108297 also showed statistically significant benefit in preventing weight gain in a preclinical obesity model in which mice were given a high fat diet and a high sucrose drink ("fast food" diet) for four weeks, as well as in a model of modulation of insulin sensitivity.

We have composition of matter and use patents related to CORT 108297 that have issued or are pending and extend into and beyond 2025. Corcept owns worldwide rights to CORT 108297.

PROMISING PRECLINICAL DATA WITH ADDITIONAL SELECTIVE CORTISOL RECEPTOR (GR-II) ANTAGONISTS

We have identified three proprietary series of selective cortisol receptor (GR-II) antagonists: the pyrimidinediones, the azadecalins, and the fused-ring azadecalins. Along with CORT 108297, we have identified and begun testing two additional compounds from the fused-ring azadecalin series, CORT 112716 and CORT 113083. Initial preclinical studies of CORT 112716 and CORT 113083 demonstrated benefit in animal models of olanzapine induced weight gain, and modulation of insulin sensitivity. We plan to conduct additional preclinical studies during 2010 to further define the specific qualities of each compound.

About Weight Gain Caused by Antipsychotic Medications

The group of medications known as second-generation antipsychotics, including olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel) and clozapine (Clozaril), are widely used to treat schizophrenia and bipolar disorder. All medications in this group are associated with treatment emergent weight gain of varying degrees and also carry warning labels relating to treatment emergent hyperglycemia and diabetes mellitus. Weight gain and alterations in metabolic efficiency have been observed for many years in patients with abnormally high circulating cortisol. There is no FDA-approved treatment for the weight gain associated with the use of antipsychotic medications.

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