Corcept Therapeutics Incorporated · NASDAQ:CORT
Corcept Therapeutics — Technical Presentation (April 2023)
13 slides from Corcept Therapeutics's technical presentation, Apr 14, 2023
Slide 1: Selective Glucocorticoid Receptor Modulation Reveals a New Role for CLEC10A in Patients With Solid Tumors
Selective Glucocorticoid Receptor Modulation Reveals a New Role for CLEC10A in Patients With Solid Tumors Nicoletta Colombo, Toon Van Gorp, Ursula A. Matulonis, Ana Oaknin, Rachel N. Grisham, Diane Provencher, Gini F. Fleming, Alexander B. Olawaiye, Erkut H. Borazanci, Russell Z. Szmulewitz, Subhagy
Slide 2: Disclosure Information
Disclosure Information Grace Mann I have the following relevant financial relationships to disclose: Employee of: Corcept Therapeutics Consultant for: N/A Speaker’s Bureau for: N/A Grant/Research support from: N/A Stockholder in: Corcept Therapeutics Honoraria from: N/A My additional financial relat
Slide 3: SGRMs Can Enhance Chemotherapy Efficacy
Selective Glucocorticoid Receptor Modulators (SGRMs) Can Enhance Chemotherapy Efficacy • GR activation by endogenous cortisol can induce genes that suppress chemotherapy-mediated apoptosis • The SGRM relacorilant selectively antagonizes the GR to enhance chemotherapy efficacy Intermittent SK-OV-3 xe
Slide 4: Objective: Identify Biomarkers of GR Activity
Objective: Identify Biomarkers of GR Activity • The effects of short-term, super-physiological glucocorticoids on cells and tissue have been characterized • We used oral relacorilant to probe the GR activities of endogenous cortisol in blood GR, glucocorticoid receptor. Presented by: Grace Mann, PhD
Slide 5: Discovery Data Set: Phase 2 Study in Platinum-resistant Ovarian Cancer
Discovery Data Set: Phase 2 Study in Patients With Platinum-resistant Ovarian Cancer (NCT03776812) • A randomized, controlled, 3-arm study of relacorilant + nab-paclitaxel vs. nab-paclitaxel alone1,2 • Crossover post-progression: Nab-paclitaxel alone to continuous relacorilant + nab-paclitaxel • RNA
Slide 6: Identified Genes Affected by Relacorilant + Nab-paclitaxel, but not Nab-paclitaxel Alone
Identified Genes Affected by Relacorilant + Nab-paclitaxel, but not Nab-paclitaxel Alone • Showing the 4 most suppressed and the 4 most induced genes by relacorilant – Testing the fold change in each gene between treatment arms resulted in P<0.05 Continuous Relacorilant + Nab-paclitaxel Nab-paclitax
Slide 7: Crossover Analysis Confirms That These Genes Are Modulated by Relacorilant
Crossover Analysis Confirms That These Genes Are Modulated by Relacorilant • Genes were not altered on nab-paclitaxel alone • Significant modulation observed after crossover to continuous relacorilant + nab-paclitaxel • Confirms that these genes are markers of GR activity TNFRSF17 BRIP1 FPR3 CLEC10A
Slide 8: Modulation of GR Activity Markers Confirmed in Pancreatic Ductal Adenocarcinoma
Modulation of GR Activity Markers Confirmed in Other Solid Tumor Types: Pancreatic Ductal Adenocarcinoma (NCT04329949) • A single-arm, open-label study of relacorilant + Pancreatic cancer: nab-paclitaxel in patients with metastatic PDAC1 Relacorilant + nab-paclitaxel • Effect of relacorilant on gene
Slide 9: Modulation of GR Activity Markers Confirmed in Other Solid Tumor Types
Modulation of GR Activity Markers Confirmed in Other Solid Tumor Types (NCT02762981, NCT03674814, NCT03437941) • Similar pattern of change were observed across distinct: – Disease types – Concomitant medications (G-CSF, nab-paclitaxel, enzalutamide) – Selective GR modulators (relacorilant, exicorila
Slide 10: CLEC10A: A Particularly Sensitive Marker of GR Activity
CLEC10A: A Particularly Sensitive Marker of GR Activity • CLEC10A is strongly decreased by GR agonists and strongly increased by relacorilant – In healthy volunteers1, the GR agonist prednisone – In a mCRPC study2, low baseline CLEC10A was rapidly decreased CLEC10A associated with high baseline 24-h
Slide 11: CLEC10A Induction by Relacorilant Is Associated With Longer Overall Survival in Ovarian Cancer
CLEC10A Induction by Relacorilant Is Associated With Longer Overall Survival in Patients With Ovarian Cancer • In a post-hoc, exploratory analysis, patients treated with relacorilant + nab-paclitaxel1 with CLEC10A induction experienced improved OS compared to nab-paclitaxel alone – No significant di
Slide 12: Conclusions
Conclusions • We identified reliable indicators of GR activity in whole blood RNA. • Consistent pharmacodynamic effects were observed in multiple tumor types. • CLEC10A was a particularly sensitive marker of GR activity. – CLEC10A is induced by SGRMs and suppressed by synthetic and endogenous glucoc
Slide 13: Thank you!
Thank you! The authors want to thank all those who participated in this study: • The study patients and their families, • the investigators, and • the sponsor team. Presented at AACR 2023, Apr. 14–19, 2023, Orlando, FL Presented by: Grace Mann, PhD Presented at AACR 2023, Apr. 14–19, 2023, Orlando,
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