Corbus Pharmaceuticals Holdings, Inc. · NASDAQ:CRBP
Corbus Pharmaceuticals — Obesity Week 2023
15 slides from Corbus Pharmaceuticals's conference presentation, Oct 16, 2023
Slide 1: Obesity Week 2023: CRB-913 Oral CB-1 Inverse Agonist
Obesity Week 2023 CRB-913: A Novel Oral Cannabinoid Receptor-1 (CB-1) Inverse Agonist Enhances Tirzepatide and Semaglutide Efficacy in a Diet Induced Obesity Mouse Model Andrew Kolodziej, Marshall Morningstar, Suzie Ferreira, Tracy Blumen, Rachael Brake and Yuval Cohen Corbus Pharmaceuticals, Inc. N
Slide 2: Forward-Looking Statements
FORWARD-LOOKING STATEMENTS This presentation contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including those relating to the Co
Slide 3: CB1 activation contributes to "Diabesity"
CB1 activation contributes to “Diabesity” 3 Source(s): Targeting the endocannabinoid system in diabesity: Fact or fiction?, Drug Discovery Today, Deeba et al. Mar 2021. HIGHLY CONFIDENTIAL - DO NOT DISTRIBUTE
Slide 4: The CB1 MOA is clinically validated in obesity
The CB1 MOA is clinically validated in obesity Rimonabant1 Taranabant2 RIO-Lipids Phase 3 study Completed Phase 3 studies (2 and 4 mg) (2 yr) Placebo (n=342); Placebo (n=417); 5 mg rimonabant (n=345); 20 mg rimonabant (n=346) 2 mg taranabant (n=414); 4 mg taranabant (n=415) % weight % weight loss lo
Slide 5: CRB-913 is a potent and selective CB1 receptor inverse agonist
CRB-913 is a potent and selective CB1 receptor inverse agonist • High selectivity over the CB2 isoform, improved potency across binding and functional assays vs. rimonabant Receptor Binding Affinity cAMP b arrestin % Inhibition of control % Efficacy specific binding % Efficacy log [CRB-913], M conce
Slide 6: CRB-913 PK demonstrates 21-fold lower brain exposure than rimonabant
CRB-913 PK demonstrates 21-fold lower brain exposure than rimonabant Plasma and Brain PK Brain conc. @ 1hr post dose Lean Mice Single Dose (10 mg/kg, PO) DIO Mice (dosing for 20 days) 6
Slide 7: CRB-913 induces significant dose dependent reduction in body weight
CRB-913 induces significant dose dependent reduction in body weight Body weight change (%) All cohorts P < 0.001 compared with vehicle Data were presented as Mean ± Sem;Two way ANOVA followed by Dunnett test by Prism GraphPad;n=6 • DIO mouse model with C57BL6/J mice (n=6/gp) fed a continuous high fa
Slide 8: Weight loss related to reduced food consumption and body fat
Weight loss is related to reduced food consumption and results in reduced body fat content but not lean mass ✱✱✱✱ 4.0 Daily Food Intake ✱✱✱✱ Fat and Lean Mass 3.5 ✱✱✱✱ Food intake per day(g) 3.0 ✱✱✱✱ ✱✱✱ 2.5 2.0 Weight (g) 1.5 1.0 0.5 0.0 2 4 6 8 10 12 14 16 18 Time (Day) Body Fat Lean Mass • DIO mo
Slide 9: CRB-913: additive weight loss in combination with semaglutide & tirzepatide
CRB-913: additive weight loss in combination with semaglutide & tirzepatide semaglutide tirzepatide **** vs mono agents **** vs mono agents Data were presented as Mean ± Sem;Two-way ANOVA followed by Dunnett test by Prism GraphPad; n=6. *P<0.05,****P<0.0001 DIO mouse model with C57BL6/J mice (n=10)
Slide 10: CRB-913 reduces leptin levels alone and in combination with incretin therapies
CRB-913 reduces leptin levels alone and in combination with incretin therapies ✱✱✱ ✱✱ ✱✱ CRB-913 - + - + - + Incretin vehicle semaglutide tirzepatide Data were presented as Mean ± Sem;Two-way ANOVA followed by Dunnett test by Prism GraphPad; n=6. # All cohorts P < 0.001 compared with vehicle *P<0.05
Slide 11: CRB-913 reduces liver triglycerides alone and in combination with incretin therapies
CRB-913 reduces liver triglycerides alone and in combination with incretin therapies Triglycerides (liver) Non-esterified fatty acid (liver) CRB-913 - + - + - + CRB-913 - + - + - + Incretin vehicle semaglutide tirzepatide Incretin vehicle semaglutide tirzepatide Data were presented as Mean ± Sem; Tw
Slide 12: CRB-913 treatment reduces liver fat storage alone and in combination
CRB-913 treatment reduces liver fat storage alone and in combination with incretin therapies semaglutide Liver fat (10 nmol/kg) CRB-913 (2.5 mg/kg) + semaglutide (10 nmol/kg) CRB-913 (2.5 mg/kg) + tirzepatide nmol/kg) CRB-913 tirzepatide vehicle • DIO mouse model with C57BL6/J mice (n=10) fed a cont
Slide 13: CRB-913 reduces peak insulin in oGTT alone or in combination
CRB-913 reduces peak insulin alone or in combination with semaglutide or tirzepatide in oGTT semaglutide tirzepatide CRB-913 & combo P < 0.001 compared with vehicle All cohorts P < 0.001 compared with vehicle ✱✱ ✱✱ • DIO mouse model with C57BL6/J mice (n=10) fed a continuous high fat diet for 22 wee
Slide 14: CRB-913 Summary
CRB-913 Summary • Orally available small molecule CB1 inverse agonist with dose dependent weight loss in preclinical animal models, attributed to reduced food intake and body fat content • Highly differentiated brain and plasma PK from 1st gen CB1 inverse agonists • Additive efficacy in driving weig
Slide 15: Acknowledgments
Acknowledgments Corbus Pharmaceuticals WuXi Apptec • Andrew Kolodziej • Xingjuan Wang • Marshall Morningstar • Zhu Lin • Suzie Ferreira • Chengcheng Wang • Tracy Blumen • Rachael Brake • Yuval Cohen 15