Korlym (mifepristone) / Corcept Therap - LARVOL DELTA

Molecular Profiling of the Selective Glucocorticoid Receptor Modulators CORT118335 (Miricorilant) and CORT125385 With Lipid-Lowering Properties in the Liver (ENDO 2025) - "Mice were subsequently treated with vehicle, the GR agonist corticosterone (3 mg/kg/day), the GR antagonist mifepristone, CORT118335 or CORT125385 (all 60 mg/kg/day) for three days...GO-term analysis on gene subsets after applying molecular filters suggested that the lipid-lowering effects of SGRMs likely involve corticosterone-like upregulation and SGRM-specific downregulation of genes. We tentatively conclude that CORT118335- and CORT125385-induced GR modulation results in a unique transcriptional profile, thereby lowering hepatic lipid levels."

Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Molecular Profiling of the Selective Glucocorticoid Receptor Modulators CORT118335 (Miricorilant) and CORT125385 With Lipid-Lowering Properties in the Liver (ENDO 2025) - "Mice were subsequently treated with vehicle, the GR agonist corticosterone (3 mg/kg/day), the GR antagonist mifepristone, CORT118335 or CORT125385 (all 60 mg/kg/day) for three days...GO-term analysis on gene subsets after applying molecular filters suggested that the lipid-lowering effects of SGRMs likely involve corticosterone-like upregulation and SGRM-specific downregulation of genes. We tentatively conclude that CORT118335- and CORT125385-induced GR modulation results in a unique transcriptional profile, thereby lowering hepatic lipid levels."

Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

CORCEPT THERAPEUTICS ANNOUNCES FIRST QUARTER FINANCIAL RESULTS AND PROVIDES CORPORATE UPDATE (Businesswire) - "Clinical Development:...Hypercortisolism (Cushing’s Syndrome) - (i) GRACE - Pivotal Phase 3 trial of relacorilant in 152 patients with all etiologies of hypercortisolism - Results presented at Endocrine Society (ENDO) annual meeting and Heart in Diabetes (HiD) conference in June 2024; (ii) GRADIENT - Randomized, double-blind, placebo-controlled, Phase 3 trial of relacorilant in 137 patients with hypercortisolism caused by adrenal gland pathology – Results will be presented at American Association of Clinical Endocrinology (AACE) annual meeting in May 2025...; (iii) CATALYST Part 2 - Randomized, double-blind, placebo-controlled study of Korlym in 136 patients with hypercortisolism - Results to be presented at the American Diabetes Association’s 85th Scientific Sessions (ADA) in June 2025; (iv) MOMENTUM - Enrollment continues in 1,000-patient trial examining the prevalence of hypercortisolism in patients with resistant hypertension - Results expected by year-end."

Clinical data • Cushing’s Disease

Study to Determine the Prevalence of Hypercortisolism in Patients With Type 2 Diabetes and Treatment With Korlym® (Mifepristone) (CATALYST) (clinicaltrials.gov) - P4 | N=1113 | Completed | Sponsor: Corcept Therapeutics | Recruiting ➔ Completed | Trial completion date: Jul 2024 ➔ Dec 2024 | Trial primary completion date: May 2024 ➔ Nov 2024

Trial completion • Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

A RARE CRANIOSYNOSTOSIS RESEMBLING CROUZON SYNDROME WITH VARIANTS INVOLVING THE INTERLEUKIN 11 RECEPTOR. (WRMC 2025) - "Genetic testing showed bi-allelic pathogenic variants in IL11RA (c.82C>T, p.Gln28*; c.1073-1G>C, splice acceptor). CS is one of the most common congenital craniofacial malformations with more genetic heterogeneity than previously thought. IL11RA-related CRSDA should be considered in patients with a Crouzon-like phenotype with or without CS. IL11RA is thought to play a role in restricting premature fusion of sutures by mediating osteoblast-osteoclast differentiation postnatally."

FGFR2 • FGFR3 • IL1R1 • STAT1 • TCF12 • TWIST1

Abraxane® With or Without Mifepristone for Advanced, Glucocorticoid Receptor-Positive, Triple-Negative Breast Cancer (clinicaltrials.gov) - P2 | N=29 | Active, not recruiting | Sponsor: University of Chicago | Trial completion date: Aug 2024 ➔ Aug 2026

Metastases • Trial completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

RESET-medication Glucocorticoid Receptor (GR) Blockade As Disease Modifying Treatment for Depression with Childhood Trauma (clinicaltrials.gov) - P2 | N=158 | Completed | Sponsor: Amsterdam UMC, location VUmc | Recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Nov 2024 | Trial primary completion date: Dec 2023 ➔ Aug 2024

Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • CRP • IL6 • TNFA

REVERSE: Improving Treatment-resistant Post Traumatic Stress Disorder (PTSD) with Glucocorticoid Receptor (GR) Antagonism (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Christiaan Vinkers

New P2 trial • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

PSEN2 Mutations May Mimic Frontotemporal Dementia: Two New Case Reports and a Review. (PubMed, Biomedicines) - "Prominent behavioral and language dysfunction suggesting frontotemporal dementia (FTD) may be underestimated in the literature as a clinical picture in PSEN2 mutations. Thus, it may be reasonable to include PSEN2 in genetic panels when suspecting FTDL. PSEN2 mutations may cause striking WMH, arguably related to myelin disruption induced by amyloid accumulation."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration

Study protocol for a prospective, multicentre study of hypercortisolism in patients with difficult-to-control type 2 diabetes (CATALYST): prevalence and treatment with mifepristone. (PubMed, BMJ Open) - P4 | "In part 1, approximately 1000 participants with difficult-to-control T2D (haemoglobin A1c (HbA1c) 7.5%-11.5% despite multiple therapies) are screened with a 1 mg dexamethasone suppression test (DST)...Those requiring evaluation for elevated ACTH are referred for care outside the study; those with ACTH and DHEAS in the range may advance to part 2, a randomised, double-blind, placebo-controlled trial to evaluate the impact of treating hypercortisolism with the competitive glucocorticoid receptor antagonist mifepristone (Korlym®)...Findings will be presented at scientific meetings and published in peer-reviewed journals. NCT05772169."

Clinical protocol • Journal • Diabetes • Endocrine Cancer • Endocrine Disorders • Metabolic Disorders • Nephrology • Oncology • Type 2 Diabetes Mellitus

Rapid Clinical Improvements in a Patient with Difficult-to-Control Type 2 Diabetes by Addressing Underlying Hypercortisolism with Mifepristone (AACE 2024) - "Case(s) Description A 71-year-old man with long-standing (40+ years) difficult-to-control T2D (continuous glucose monitoring [CGM] time-in-range [TIR] 41%, HbA1c 8%, average glucose 196 mg/dL) despite receiving multiple antihyperglycemic drugs (including U500 insulin, metformin, and GLP1 agonists) also had multiple comorbidities, including resistant hypertension (on 7 antihypertensive medications) and morbid obesity (post gastric sleeve). His biochemical evaluation confirmed hypercortisolism with elevated serum cortisol (2.3 and 2.4 μg/dL) post-1-mg dexamethasone suppression test, and computed tomography imaging revealed a stable sub-centimeter adrenal adenoma...This case emphasizes the vital importance of promptly identifying and addressing hypercortisolism in patients with challenging metabolic derangements. Failure to do so resulted in a worsening clinical picture for this patient, which was ameliorated with the administration of mifepristone to address the underlying..."

Clinical • Cardiovascular • Diabetes • Genetic Disorders • Hypertension • Hypotension • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

INIA Stress and Chronic Alcohol Interactions: Glucocorticoid Antagonists in Heavy Drinkers (clinicaltrials.gov) - P1/2 | N=65 | Completed | Sponsor: Johns Hopkins University | Phase classification: P=N/A ➔ P1/2

Phase classification • Addiction (Opioid and Alcohol)

Rapid Clinical Improvements in a Patient with Difficult-to-Control Type 2 Diabetes by Addressing Underlying Hypercortisolism with Mifepristone (ENDO 2024) - "CASE PRESENTATION: A 71-year-old man with long-standing (40+ years) difficult-to-control T2D (continuous glucose monitoring [CGM] time-in-range [TIR] 41%, HbA1c 8%, average glucose 196 mg/dL) despite receiving multiple antihyperglycemic drugs (including U500 insulin, metformin, and GLP1 agonists) also had multiple comorbidities, including resistant hypertension (on 7 antihypertensive medications) and morbid obesity (post gastric sleeve). His biochemical evaluation confirmed hypercortisolism with elevated serum cortisol (2.3 and 2.4 μg/dL) post-1-mg dexamethasone suppression test, and computed tomography imaging revealed a stable sub-centimeter adrenal adenoma... This case presents a patient with difficult-to-control T2D and additional comorbidities that could not be effectively managed despite long-term, extensive medical interventions. This case emphasizes the vital importance of promptly identifying and addressing hypercortisolism in patients with challenging metabolic..."

Clinical • Cardiovascular • Diabetes • Genetic Disorders • Hypertension • Hypotension • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Study to Determine the Prevalence of Hypercortisolism in Patients With Type 2 Diabetes and Treatment With Korlym® (Mifepristone) (CATALYST) (clinicaltrials.gov) - P4 | N=1000 | Recruiting | Sponsor: Corcept Therapeutics | Trial primary completion date: Jan 2024 ➔ Mar 2024

Trial primary completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

INIA Stress and Chronic Alcohol Interactions: Glucocorticoid Antagonists in Heavy Drinkers (clinicaltrials.gov) - P=N/A | N=65 | Completed | Sponsor: Johns Hopkins University | Recruiting ➔ Completed | N=150 ➔ 65

Enrollment change • Trial completion • Addiction (Opioid and Alcohol)

Abraxane® With or Without Mifepristone for Advanced, Glucocorticoid Receptor-Positive, Triple-Negative Breast Cancer (clinicaltrials.gov) - P2 | N=29 | Active, not recruiting | Sponsor: University of Chicago | N=64 ➔ 29

Enrollment change • Metastases • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Corcept attributes its revenue boost to better recognition of Cushing’s (Cushing's Disease News - Bionews) - "Corcept Therapeutics is expecting to earn nearly $500 million in revenue this year, which is due in large part to the increased recognition of Cushing’s syndrome...Corcept, which markets Korlym (mifepristone) — a therapy approved to control high blood sugar in certain adults with Cushing’s syndrome who have glucose intolerance or type 2 diabetes — reported $123.6 million in total revenue in this year’s third financial quarter."

Commercial • Sales • Cushing’s Disease

A Study of Enzalutamide, Enzalutamide in Combination With Mifepristone, or Chemotherapy in People With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=201 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

Combination therapy • Metastases • New P2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AR • HER-2 • PD-L1

Glucocorticoid receptor modulator CORT125385 alleviates diet-induced hepatosteatosis in male and female mice. (PubMed, Eur J Pharmacol) - "In this study, we set out to evaluate the novel glucocorticoid receptor modulator CORT125385, an analogue of the previously studied miricorilant but without mineralocorticoid receptor binding activity...In vivo, CORT125385 treatment did not influence PR-responsive gene expression in the oviduct, while mifepristone treatment strongly influenced these genes in the oviduct, thus excluding in vivo PR cross-reactivity of CORT125385 at a therapeutically active dose. We conclude that CORT125385 is a promising glucocorticoid receptor modulator that effectively reduces liver steatosis in male and female mice without affecting other steroid receptors at doses that lower hepatic lipid content."

Journal • Preclinical • Hepatology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • PGR

Phase 4 Study of Hypercortisolism in Patients with Difficult-to-Control Type 2 Diabetes Despite Receiving Standard-of-Care Therapies: Prevalence and Treatment with Mifepristone (ENDO 2023) - "In Part 1, approximately 1000 persons with difficult-to-control T2D will be screened with a 1-mg dexamethasone suppression test...Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*"

Clinical • P4 data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

"#CorceptTherapeutics World-Wide Sales for #KORLYM was 105.7m USD in Q1 2023 (Up 3%) https://t.co/XSEL3IpvyG" (@1stOncology)

Study to Determine the Prevalence of Hypercortisolism in Patients With Type 2 Diabetes and Treatment With Korlym® (Mifepristone) (CATALYST) (clinicaltrials.gov) - P4 | N=1000 | Recruiting | Sponsor: Corcept Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Study to Determine the Prevalence of Hypercortisolism in Patients With Type 2 Diabetes and Treatment With Korlym® (Mifepristone) (CATALYST) (clinicaltrials.gov) - P4 | N=1000 | Not yet recruiting | Sponsor: Corcept Therapeutics

New P4 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Selective and nonselective GR antagonists in combination with chemotherapy in ovarian cancer PDX models. (ASCO 2019) - P1, P2; "...Once tumor diameter reached 0.2 cm, mice were randomized into treatment arms (2-25 mice per arm) and treated intraperitoneal (i.p): control (9% saline, CTL) on day 0 (D0), 1, 7, 8, 14, 15, 21, 22; mifepristone (MIF), 15 mg/kg D0, 1, 7, 8, 14, 15, 21, 22; relacorilant (134), 20 mg/kg D0, 1, 7, 8, 14, 15, 21, 22; carboplatin (CBDCA) at the MTD, 51 mg/kg D1, 8, 15, 22; CBDCA + MIF; CBDCA + 134... Addition of GR antagonists can improve response to chemotherapy. Work is ongoing to identify the GR transcriptional network, tumor, and host characteristics which predict responses to GR antagonists. *model treated with CBDCA 10% (5 mg/kg), RAD51C mutated"

Combination therapy

Abraxane® With or Without Mifepristone for Advanced, Glucocorticoid Receptor-Positive, Triple-Negative Breast Cancer (clinicaltrials.gov) - P2 | N=64 | Active, not recruiting | Sponsor: University of Chicago | Trial primary completion date: Aug 2021 ➔ Dec 2022

Metastases • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR