CB1 receptor antagonists

De-risked approach to CB1 receptor antagonism: clinical efficacy without adverse side effects

Dysregulated endocannabinoid signaling can lead to several diseases. Past attempts to leverage the benefits of CB1 receptor antagonists produced adverse effects in certain groups of vulnerable patients. Artiam Bio has discovered breakthrough antagonist compounds utilizing cutting-edge receptor pharmacology and medicinal chemistry approaches, effectively eliminating these unwanted side effects.

Targeted solution: Non-alcoholic steatohepatitis (NASH)

Blockade of CB1 receptors expressed in brain and peripheral tissues have been clinically proven to induce weight-loss, improve lipid profile, provide cardio-protection and reverse insulin resistance.  Most importantly, a 100+ patient clinical study confirmed that CB1 antagonism can reverse NAFLD. After one year of treatment using the first-generation CB1 blocker rimonabant, three times as many patients reversed their fatty liver index to normal values over patients receiving a placebo. Because unresolved fatty liver disease (NAFLD) progresses to NASH, reversal of NAFLD can lead to resolution of NASH. Artiam’s refined CB1 blockers achieve these same effects but do not produce adverse psychiatric effects in animal studies, thereby providing an incredible opportunity to safely target a clinically proven receptor.

Despres et al. Arterioscler Thromb Vasc Biol. 2009;29:416-423

Targeted solution: Cannabis Use Disorder

Blocking the rewarding and reinforcing effects of a drug of abuse is a proven strategy for addiction therapies that do not have a strong physical withdrawal component. Rimonabant was effective in reversing many of the psychoactive effects of marijuana and was also successful clinically as a smoking cessation agent. However, because of adverse side-effects, rimonabant and other similar first-generation CB1 antagonists were not approvable for these indications. Artiam’s CB1 receptor antagonists are differentiated. They are efficacious without producing adverse effects – marking a distinct and powerful breakthrough in CB1 therapeutic technology.  Addiction related disorders have a ripple effect on patients, families and care givers and our objective is to provide a durable, attainable treatment solution.

Huestis et al. Psychopharmacology. 2007; 194:505-15

Targeted Solution: Prader-Willi Syndrome (PWS)

For many patients living with this genetic disorder, corresponding obesity can lead to an increased risk of diabetes, cardiac insufficiency, sleep apnea, respiratory problems, and other serious, life-threatening complications. A clinical study with rimonabant produced encouraging results but the risk of adverse effects nullified the use of this compound in PWS. Artiam’s lead compound produces potent-weight loss and hunger-satiety effects in preclinical studies while eliminating adverse effects. Our approach provides a unique and groundbreaking therapy for PWS.

Motaghedi et al. Eur J Med Gen. 2011;54:14-8

Learn more about our exciting programs and latest advancements towards bringing our patented portfolio of small molecule CB1 receptor antagonists to the market.