Pipeline & Programs

* including other metabolic disorders: Non-Alcoholic Steatohepatitis (NASH), Obesity, Type 1 and Type 2 Diabetes, Cardiometabolic disease, Hypertriglyceridemia (HTG). 

Monlunabant (formerly INV-202) is a potential first-in-class small molecule CB1 receptor (CB1r) blocker being developed for the treatment of metabolic disorders. It is specifically designed to preferentially block CB1 receptors in peripheral tissues such as the kidneys, gastro-intestinal tract, liver, pancreas, adipose tissues, muscles, and lungs. The therapeutic effects of a peripheral CB1r blockade in a range of cardiometabolic and fibrotic diseases are well-documented, paving the way for potential treatment of a large number of patients with current unmet needs. In a first-in-human study examining the safety and tolerability, oral absorption, and pharmacokinetics of monlunabant, results supported rapid progression into a phase 2 study. It also demonstrated potential for decreased appetite—a relevant pharmacodynamic marker of early efficacy of Inversago’s lead program.

As a complication of type 1 and type 2 diabetes, DKD affects approximately 1 in 3 people living with diabetes in the United States. Poorly controlled diabetes causes DKD, leading to chronic kidney disease and requiring either dialysis or transplant in late stage. No cure exists for this indication and available medications only help slowing the progression of the disease and control related complications.

Overactivity of peripheral CB1 receptors plays a key role in DKD and research in preclinical models has shown that the inhibition of CB1r signaling has the potential to significantly reduce the progressive impairment of kidney function.

Inversago believes that the development of peripherally-acting CB1r blockers represents a promising therapeutic avenue for metabolic disorders. We believe that by leveraging the benefit of a potentially safe and more potent peripheral CB1r blockade it may be possible to address a significant unmet medical need affecting a growing number of patients globally. Based on positive results obtained in a Phase 1b, Inversago has initiated an additional phase 2 trial in subjects with obesity. Both phase 2 studies are expected to complete in the second half of 2025.

PHASE 2A TRIAL IN OBESITY

Completed in the second half of 2024, this trial investigated the efficacy and safety of a once-daily 10 mg, 20 mg and 50 mg dose of monlunabant compared to placebo on body weight after 16 weeks in 243 people with obesity and metabolic syndrome ¹. People were equally randomised among the four treatment arms.

From a baseline body weight of 110.1 kg, all doses of monlunabant achieved a statistically significant weight loss compared to placebo. After 16 weeks of treatment, people treated with a once-daily 10 mg dose of monlunabant achieved a weight loss of 7.1 kg compared to a reduction of 0.7 kg with placebo ². Limited additional weight loss was seen at higher doses of monlunabant.

In the trial, the most common adverse events were gastrointestinal, with the vast majority being mild to moderate and dose dependent. Reporting of mild to moderate neuropsychiatric side effects, primarily anxiety, irritability, and sleep disturbances, was more frequent and dose dependent with monlunabant compared to placebo. No serious adverse events were reported in relation to neuropsychiatric side effects.

Based on the results, Inversago expects to initiate a larger phase 2b trial in obesity to further investigate dosing and the safety profile of monlunabant over a longer duration in a global population. The phase 2b trial is expected to be initiated in 2025.

¹ Metabolic syndrome defined as the presence of at least 3 of 5 key clinical features of abdominal obesity, elevated triglycerides and cholesterol, impaired glucose tolerance, and elevated blood pressure.

² Hypothetical estimand corresponding to if all people adhered to treatment.

The INV-300 series is Inversago’s next generation of CB1r blockers based on the company’s growing knowledge of blocker biology such as advanced G-Protein Coupled Receptor (GPCR) biology and β-arrestin biased signaling. These next generation candidates are designed to maximize potency and safety.

INV-347, an oral, small molecule CB1r blocker, is currently assessed in a phase 1 trial to investigate its safety, tolerability and pharmacokinetics. 

INV-101 (zevaquenabant) is a small molecule, peripherally acting CB1r blocker being developed for the treatment of idiopathic pulmonary fibrosis (IPF), including progressive fibrosis interstitial lung diseases (e.g.: systemic sclerosis, Hermansky-Pudlak Syndrome). Fibrosis is when an excessive deposition of extracellular matrix components interferes with normal organ function. IPF is when the underlying cause of the fibrosis is unclear. In the lung, fibrosis interferes with normal gas exchange and reduces lung volumes, leading to shortness of breath. Patients with progressive lung fibrosis typically have a poor prognosis with a median life expectancy of only 2.5–3.5 years after diagnosis. As such, there is a high unmet need for anti-fibrotic therapies that slow progression of fibrosis. Recent studies show that CB1 receptors are upregulated in the lungs of patients with pulmonary fibrosis.

Nonclinical studies in animal and human tissues show CB1 receptors are upregulated in fibrotic tissues, whilst CB1r blockers reduce or slow the progression of fibrosis.

Inversago believes that appropriate peripheral CB1r blockade has potential in multiple disease areas including diabetes, non-alcoholic steatohepatitis (NASH), and fibrotic disorders. In diabetes, CB1 receptor blockade may increase insulin production by protecting beta-cells in the pancreas and help manage insulin resistance in other tissues. In NASH, clinical study results demonstrate a broad effect through multiple pathways downstream of the CB1 receptor. In pulmonary fibrosis, recent studies indicate that CB1 receptors are unregulated in the lungs of these patients and in nonclinical study models, blocking the CB1 receptor slows the progression of IPF. Similarly, CB1r blockade results in reductions in fibrosis in other organs, including the liver, kidneys, and skin.