monlunabant (NN9440) / Novo Nordisk - LARVOL DELTA

Skye Bioscience Clinical Model Demonstrating Necessity of Peripheral CB1 Inhibition for Weight Loss Presented at European Congress on Obesity - "Skye Bioscience, Inc...presented a clinical pharmacokinetic ('PK') and pharmacodynamic ('PD') model that underscores the fundamental relationship between biodistribution and efficacy of CB1 inhibitors...Published clinical PK and potency data coupled with Phase 2 ('P2') and Phase 3 efficacy data from Novo Nordisk’s monlunabant and Sanofi’s rimonabant, respectively, as well as Phase 1 data from nimacimab were used to develop a model to determine whether peripheral CB1 inhibition alone is sufficient for weight loss, or if central inhibition is also required for optimal efficacy. The results showed that central inhibition of CB1 alone was not sufficient for weight loss with P2 data for monlunabant, and demonstrated that increasing drug levels in the brain did not improve efficacy."

Clinical data • PK/PD data • Obesity

A Study to Explore the PK and PD of INV-202 in Metabolic Syndrome (clinicaltrials.gov) - P1 | N=37 | Completed | Sponsor: Inversago Pharma Inc. | Phase classification: P1b ➔ P1

Phase classification • Dyslipidemia • Genetic Disorders • Hypertriglyceridemia • Metabolic Disorders • Obesity

Gut cannabinoid receptor 1 regulates alcohol binge-induced intestinal permeability. (PubMed, eGastroenterology) - "Additionally, a peripheral CB1R antagonist, (S)-MRI-1891 (INV-202/monlunabant), exhibited comparable binding affinity to CB1R in brain homogenates...Despite the effects on intestinal permeability, deletion of intestinal CB1R did not significantly affect metabolic parameters and liver disease. Our findings suggest that alcohol promotes leaky gut via the activation of gut epithelial CB1R and demonstrate that inhibition of CB1R with peripheral-restricted selective CB1R antagonists can prevent alcohol binge-induced intestinal permeability."

Journal • Gastroenterology • Gastrointestinal Disorder • Hepatology

Study of INV-202 in Patients With Obesity and Metabolic Syndrome (clinicaltrials.gov) - P2 | N=243 | Completed | Sponsor: Inversago Pharma Inc. | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Metabolic Disorders • Obesity

Monlunabant suppresses appetite through a central mechanism. (PubMed, Behav Pharmacol) - "These findings suggest that monlunabant suppresses appetite mainly through antagonism of central CB1 receptors. Consequently, monlunabant and other second-generation CB1 antagonists being developed for obesity may carry a similar risk of adverse psychiatric effects, as previously observed with rimonabant."

Journal • Genetic Disorders • Obesity • Psychiatry

A Research Study Investigating Safety and Concentration in the Blood After One Dose Tablet of the New Medicine Monlunabant in Healthy Weight Japanese and Caucasian Men (clinicaltrials.gov) - P1 | N=73 | Completed | Sponsor: Novo Nordisk A/S | Recruiting ➔ Completed

Trial completion • Genetic Disorders • Obesity

Phase 2 Study of INV-202 in Patients With Diabetic Kidney Disease (clinicaltrials.gov) - P2 | N=265 | Completed | Sponsor: Inversago Pharma Inc. | Active, not recruiting ➔ Completed

Trial completion • Diabetic Nephropathy • Nephrology • Renal Disease

A Research Study Investigating Safety and Concentration in the Blood After One Dose Tablet of the New Medicine Monlunabant in Healthy Weight Japanese and Caucasian Men (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

A Research Study Investigating Safety and Concentration in the Blood After One Dose Tablet of the New Medicine Monlunabant in Healthy Weight Japanese and Caucasian Men (clinicaltrials.gov) - P1 | N=72 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P1 trial • Genetic Disorders • Obesity

Cannabinoid Receptor 1 Inverse Agonist, INV-202, Increases Surfactant Phosphatidylcholines and Improves Lung Compliance in a Mouse Model of Asthma (ATS 2024) - "The peripherally acting CB1R inverse agonist INV-202 reduces airway reactivity in allergically inflamed mice and increases lung compliance by restoring airway surfactant phosphatidylcholines. This supports a significant role for the cannabinoid system on lung function. [1] Ackerman et al."

Compliance • Late-breaking abstract • Preclinical • Surfactant • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Phase 2 Study of INV-202 in Patients With Diabetic Kidney Disease (clinicaltrials.gov) - P2 | N=265 | Active, not recruiting | Sponsor: Inversago Pharma Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetic Nephropathy • Nephrology • Renal Disease

Advancements in Diabetic Kidney Disease Management: Integrating Innovative Therapies and Targeted Drug Development. (PubMed, Am J Physiol Endocrinol Metab) - "Emerging agents including GLP-1 agonists, anti-inflammatory agents like bardoxolone, and mineralocorticoid receptor antagonists show promise in mitigating DKD progression. Many novel therapies including monoclonal antibodies CSL346, Lixudebart, and tozorakimab, mesenchymal stem/stromal cell infusion, and cannabinoid-1 receptor inverse agonism via INV-202 are currently in clinical trials and present opportunities for further drug development."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Fibrosis • Hypertension • Immunology • Inflammation • Metabolic Disorders • Nephrology • Oncology • Renal Disease

Study of INV-202 in Patients With Obesity and Metabolic Syndrome (clinicaltrials.gov) - P2 | N=243 | Active, not recruiting | Sponsor: Inversago Pharma Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Metabolic Disorders • Obesity

Phase 2 Study of INV-202 in Patients With Diabetic Kidney Disease (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: Inversago Pharma Inc. | Trial primary completion date: Mar 2024 ➔ Jul 2024

Trial primary completion date • Diabetic Nephropathy • Nephrology • Renal Disease

Effects of CB1R inverse agonist, INV-202, in patients with features of metabolic syndrome. A randomized, placebo-controlled, double-blind phase 1b study. (PubMed, Diabetes Obes Metab) - "INV-202 was well tolerated, producing a signal for rapid weight loss with improvements in other metabolic syndrome markers in this population. These findings support further exploration and long-term assessment of cardiometabolic effects."

Clinical • Journal • P1 data • Gastrointestinal Disorder • Metabolic Disorders

Additive effect of SGLT2 inhibition and CB1R antagonism in the fight against diabetic nephropathy (EASD 2023) - "After 5 weeks, diabetic mice were divided into 4 groups and were treated either with control vehicle, the SGLT2i empagliflozin (0.3 mg/kg/day), the CB1R blocker INV-202 (0.5 mg/kg/day), or a combination of both by oral gavage for 28 days. Our results suggest that a poly-pharmacological approach combining both SGLT2i and CB1R antagonism might represent a promising therapeutic strategy for the management of DN."

Metabolic Disorders • CCL2 • COL1A1 • COL1A2 • DKK3 • KIM1 • NOX4 • SMAD3 • TGFB1 • WT1

Study of INV-202 in Patients With Obesity and Metabolic Syndrome (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: Inversago Pharma Inc. | Not yet recruiting ➔ Recruiting | N=100 ➔ 240

Enrollment change • Enrollment open • Genetic Disorders • Metabolic Disorders • Obesity

Therapeutic potential of a novel peripherally restricted CB1R inverse agonist on the progression of diabetic nephropathy. (PubMed, Front Nephrol) - "INV-202 reduced glomerular injury, preserved podocyte structure and function, reduced injury to PTECs, and ultimately reduced renal fibrosis in a streptozotocin-induced diabetic nephropathy mouse model. These results suggest that INV-202 may represent a new therapeutic option in the treatment of diabetic kidney disease."

Journal • Diabetes • Diabetic Nephropathy • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • Type 1 Diabetes Mellitus • NOX4 • NPHS1 • PODXL

Novo Nordisk to acquire Inversago Pharma to develop new therapies for people living with obesity, diabetes and other serious metabolic diseases (GlobeNewswire) - "Novo Nordisk A/S and Inversago Pharma today announced that Novo Nordisk has agreed to acquire Inversago for up to 1.075 billion US dollars in cash if certain development and commercial milestones are achieved. Inversago Pharma is a private, Montreal-based developer of CB1 receptor-based therapies for the potential treatment of obesity, diabetes and complications associated with metabolic disorders...The acquisition of Inversago includes the company’s lead development asset INV-202, an oral CB1 inverse agonist."

M&A • Diabetes • Metabolic Disorders • Obesity

Effects of CB1 Antagonist INV-202 in Patients with Metabolic Syndrome—A Randomized, Placebo-Controlled, Double-Blind Phase 1B Study (ADA 2023) - P1b | "Significant improvements were noted. Further studies on the long-term cardiometabolic effect of this novel CB1 blocker are warranted."

Clinical • P1 data • Metabolic Disorders • Obesity

Study of INV-202 in Patients With Obesity and Metabolic Syndrome (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: Inversago Pharma Inc.

New P2 trial • Genetic Disorders • Metabolic Disorders • Obesity

Cannabinoid Receptor 1 Inverse Agonist, INV-202, Induces Weight Loss and Reduces Airway Hyperreactivity in a Mouse Model of Obese Asthma (ATS 2023) - "This is the first study, of which we are aware, to investigate targeting the endocannabinoid system in obese asthma. This proof-of-concept study suggests the endocannabinoid system may be involved in airway reactivity in both lean and obese asthma and can also induce weight loss in obese mice. The mechanisms of action require further investigation, but this study suggests that the peripherally acting cannabinoid receptor-1 inverse agonist INV-202 may have efficacy in the treatment of obese asthma through direct effects on the airway and induction of weight loss."

Preclinical • Asthma • Genetic Disorders • Immunology • Inflammation • Metabolic Disorders • Obesity • Pulmonary Disease • Respiratory Diseases

Phase 2 Study of INV-202 in Patients With Diabetic Kidney Disease (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: Inversago Pharma Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetic Nephropathy • Nephrology • Renal Disease • CST3

A Study to Explore the PK and PD of INV-202 in Metabolic Syndrome (clinicaltrials.gov) - P1b | N=37 | Completed | Sponsor: Inversago Pharma Inc. | Active, not recruiting ➔ Completed | Trial completion date: Mar 2023 ➔ Oct 2022

Trial completion • Trial completion date • Dyslipidemia • Genetic Disorders • Hypertriglyceridemia • Metabolic Disorders • Obesity

Phase 2, Efficacy, Safety, and Pharmacokinetics Study of Two INV-202 Doses in Patients With Diabetic Kidney Disease (clinicaltrials.gov) - P2 | N=240 | Not yet recruiting | Sponsor: Inversago Pharma Inc.

New P2 trial • Diabetic Nephropathy • Nephrology • Renal Disease • CST3