Treatment for Endogenous Cushing's Syndrome

This will be a single period, open-label, dose titration study to assess efficacy, safety,
tolerability, and PK of COR-003 in subjects with CS. The trial design will identify both the
minimally effective and maximally tolerated doses in this CS population. Following an initial
screening period, this study will be conducted in 2 treatment phases as follows:

- Dose titration phase: approximately 2 to 16 weeks to achieve an effective and tolerable
maximum dose (the therapeutic dose)

- Maintenance phase: 6 months of treatment at the therapeutic dose without a prior dose
increase following the establishment of the appropriate dose identified in the titration
phase;

- Extended evaluation phase: 6 months of continued treatment after the maintenance phase
(6 - 12 months); dose adjustments will be allowed as required for treatment

Efficacy will be assessed by measuring UFC concentrations at specified times as described in
the clinical protocol.

Blood samples for the PK determination will be collected at the times indicated in the
clinical protocol.

An independent Data Safety Monitoring Board (DSMB) will review the safety of the drug
throughout the study. The constituents of the DSMB membership and a adjudication committee is
specifically described in the clinical protocol.

Subjects completing the 6-month maintenance phase of the study will remain in the study for
an additional 6 months for extended evaluations.

COR-003 will be provided under a compassionate use protocol for subjects who wish to continue
treatment with COR-003.

Inclusion Criteria:

Subjects eligible for enrollment in the study must meet all the following criteria:

1. Male or female ≥18 years of age

2. Able to provide written informed consent prior to any study procedures being
performed; eligible subjects must be able to understand the informed consent form
prior to inclusion into the study.

3. Confirmed diagnosis of newly diagnosed, persistent or recurrent CD if subjects are not
candidates for surgery or radiotherapy CD is defined according to the criteria in the
Endocrine Society Clinical Practice Guideline for diagnosis of CD (Nieman 2008).
Previous medical records will be collected and used to support the diagnosis of CD.

Specifically, CD is defined as

- Mean 24-hour UFC level of ≥1.5X ULN on repeated determination

- Morning plasma corticotropin (ACTH) level of 5 ng/L (1.1 nmol /L) or more

- Either MRI confirmation of pituitary macroadenoma, or inferior petrosal sinus
gradient >3 after corticotropin-releasing hormone (CRH) stimulation for those
patients with a microadenoma, or for subjects who have had prior pituitary
surgery, histopathology confirming and ACTH-staining adenoma. If inferior
petrosal sampling had been performed without CRH, then a central to peripheral
pre-stimulation gradient >2 is required

4. Confirmed diagnosis of newly diagnosed, persistent or recurrent endogenous CS of other
etiology if subjects are not candidates for surgery or radiotherapy. CS will be
defined according to the criteria in the Endocrine Society Clinical Practice Guideline
for diagnosis of CS (Nieman 2008). Previous medical records will be collected and used
to support the diagnosis, and the differentiation of the cause of CS, specifically

- Mean 24-hour UFC level of ≥1.5X ULN on repeated determination

- Ectopic ACTH secretion, not of pituitary origin

- Ectopic CRH secretion

- Adrenal-dependent CS (adrenal adenoma, adrenal autonomy)

- Etiology unknown

5. Subjects MUST have elevated mean 24-hour UFC levels ≥1.5X ULN of assay based on a
minimum of four measurements from adequately collected urine. Urine may be collected
on sequential days.

6. In addition to elevated mean UFC, presence of abnormal values from one of the
following tests:

- Abnormal DST: Elevated 8 AM serum cortisol ≥1.8 ug/dL (50 nmol/L) after 1 mg
dexamethasone orally at 11 PM the evening prior (if not conducted already in the
diagnostic workup of the subject within the previous 2 months before start of
Screening Phase; in that case previous test results and details of conduct will
need to be available by the Baseline visit)

- Elevated late night salivary cortisol concentrations (at least two measurements)
>ULN NOTE: For subjects with estimated glomerular filtration rate (eGFR as
determined by Modified Diet in Renal Disease MDRD equation) >40 and <60
mL/min/1.73 m2 in addition to meeting the UFC criteria, late night salivary
cortisol test results (≥2 measurements) MUST also demonstrate evidence of CS.

7. Previously irradiated subjects with CD or CS of other etiology will be allowed as long
as the radiation treatment occurred > 4 years ago and subjects have not exhibited
evidence for improvement in their underlying Cushing's disease for 6 months. The total
number of previously irradiated subjects enrolled in this study will not exceed 10.

8. Subjects with CD or CS of other etiology who are not candidates for surgery, refuse
surgery, or in whom surgery will be delayed for >6 months. Subjects may be allowed to
participate in the trial while awaiting surgery, but must agree to complete this study
prior to surgery. For subjects who have already undergone surgery, a minimum of 3
months should have elapsed before the subject can be deemed a surgical failure.

9. Subjects on treatment for CD or endogenous CS of other etiology for whom treatment has
been inadequate or not well tolerated must agree to the following minimum washout
periods prior to the Baseline Visit:

- Inhibitors of steroidogenesis (including ketoconazole): 2 weeks

- Dopamine agonists: bromocriptine (2 weeks), cabergoline (8 weeks)

- Octreotide acetate LAR and lanreotide Autogel®: 12 weeks

- Lanreotide SR/long-acting pasireotide: 8 weeks

- Octreotide acetate (immediate release formulation) or short-acting pasireotide: 1
week

- Mifepristone (RU 486): 4 weeks

10. Subjects on megesterol acetate (medroxyprogesterone acetate) must agree to a washout
period of at least 6 weeks prior to the Baseline Visit

11. A female is eligible to enter and participate in the study if she is of:

Non-child bearing potential (i.e. physiologically incapable of becoming pregnant,
including any female who is post-menopausal or surgically sterile). Surgically sterile
females are defined as those with a documented hysterectomy and/or bilateral
oophorectomy or tubal ligation.

Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with
an appropriate clinical profile, e.g. age > 45 years, in the absence of hormone
replacement therapy. However in questionable cases, a blood sample with FSH > 40MIU/ml
and estradiol < 40pg/ml (<140 pmol/L) is confirmatory.

OR Child bearing potential and agrees to use highly effective methods of birth control
while participating in the study and for 2 weeks after the study is completed.

12. Fertile men must also agree to use a medically acceptable form of birth control while
on study drug and up to 2 weeks after the study is completed.

13. Able to comprehend and comply with procedures.

Exclusion Criteria

Subjects will be excluded from the study if any of the following criteria are met:

1. Subjects with Pseudo-Cushing's syndrome based on assessment of the investigator.

2. Subjects with cyclic Cushing's syndrome based on assessment of the investigator

3. Subjects with a non-endogenous source of hypercortisolism such as exogenous source of
glucocorticoids or therapeutic use of ACTH.

4. Known inherited syndrome as the cause of hypercortisolism, including but not limited
to multiple endocrine neoplasia Type 1, McCune Albright Syndrome and Carney Complex

5. Subjects with adrenal carcinoma

6. History of malignancy, other than thyroid, early stage prostate, squamous cell and
basal cell carcinoma, within 3 years prior to the Screening Phase. Subjects with
history of such allowed carcinoma must have a life expectancy of >1 year and must be
on stable doses of their specific therapies. Subjects with early stage prostate cancer
undergoing no treatment due to low grade potential may be enrolled.

7. Clinical or radiological signs of compression of the optic chiasm.

8. Major surgery within 1 month prior to enrollment (ICF signing)

9. Subjects with clinically significant abnormality in 12-lead ECGs during the Screening
Phase needing medical intervention.

10. Subjects with QTc interval of >470 msec during the Screening Phase.

11. Subjects with a history of Torsades des Pointes, or ventricular tachycardia, or
ventricular fibrillation, or history of prolonged QT syndrome (including family
history), or use of medications resulting in QT/QTc prolongation, or hypokalemia <3.0
meq/L.

12. Preexisting hepatic disease; subjects with mild to moderate hepatic steatosis
consistent with fatty infiltration (non-alcoholic fatty liver disease [NAFLD] are
allowed).

13. Positive for hepatitis B surface antigen (HbsAg) or positive hepatitis C test.

14. History or symptoms of recurrent symptomatic cholelithiasis or pancreatitis.

15. Liver function tests (LFT) must not be above the following cut-offs during the
Screening Phase:

- ALT and/or AST >3 X ULN

- Total bilirubin >2 X ULN If all LFTs are within normal limits (WNL) and total
bilirubin (TBN) is elevated, examination of direct and indirect bilirubin may be
conducted. Subjects with isolated indirect TBN up to 3X ULN are presumed to have
Gilbert's syndrome and may be enrolled if all other LFTs are within normal
levels.

16. History of documented or suspected drug-induced liver injury requiring drug
discontinuation of ketoconazole or any azole antifungals.

17. Pregnant or lactating women

18. HIV-positive.

19. History of persistent uncontrolled hypertension (>180/120 mmHg) despite medical
intervention.

20. Subjects with hypercholesterolemia who are currently treated with atorvastatin,
lovastatin or simvastatin and not willing or unable to change to alternative therapies
with pravastatin, fluvastatin, and rosuvastatin within 2 weeks of start of the
Screening Phase.

21. Body habitus preventing repeated venipuncture as required by protocol.

22. Subject is currently in another study or has received any investigational treatment
(drug, biological agent or device) within 30 days or 5 half-lives of treatment,
whichever is longer.

23. Repeated hospitalization for hyperglycemia or any complication of hyperglycemia and
diabetes during the last 12 months

24. Subjects with decreased renal function as defined by eGFR <40 mL/min/1.73 m2, using
MDRD equation for estimating renal function (eGFR).

25. Any other clinically significant medical condition, as determined by the Investigator
that precludes enrollment and participation in the study through completion, including
conditions that would preclude the subject from being able to follow instructions or
to perform the necessary procedures (for example, psychiatric instability or severe
disability).

26. Abnormal free T4. Subjects with TSH participate in the study.

27. Subjects who have a history of alcohol or drug abuse in the 6 month period prior to
enrollment.

28. Subjects who have been treated with mitotane within 6 months of the Screening Phase.

29. Subjects who are currently taking any H2 receptor antagonists, proton-pump inhibitors,
or sucralfate (all of which inhibit absorption of COR-003). A list of orally
acceptable antacids (for example, Mylanta and Maalox) will be provided, and can only
be taken a minimum of 2 hours after dosing of COR-003.

30. Subjects who receive any prohibited concomitant medication:

- Weight loss medications (prescription or over the counter)

- Acetaminophen >3 g total daily dose (due to increased hepatotoxicity)

- Co-administration of strong inducers or inhibitors of CYP3A4 enzyme system that
may interfere with the metabolism of COR-003 and cannot be discontinued prior to
first dose

- The following herbal medicines are prohibited: St John's Wort, echinacea, gingko,
goldenseal, yohimbe, red rice yeast, danshen, silybum marianum, Asian ginseng,
schissandra sphenanther, shankhapushi, and Asian herb mixture (Xiao chai hu tang
and Salboku-to).

- Topical or inhaled steroids

- Carbamazipine, fenofibrate, carbenoxolone.

- Ingestion of genuine licorice.