FDA Approves Skye's Phase 2 Trial for Nimacimab in Obesity and CKD

Skye Bioscience, a pharmaceutical firm, has been given the green light by the FDA to start a Phase 2 clinical trial for nimacimab, a drug that targets the cannabinoid 1 receptor (CB1), in patients with obesity and chronic kidney disease. The trial is set to commence in mid-2024. Nimacimab is a novel antibody that modulates CB1 negatively, which is linked to cardiometabolic disorders such as obesity and kidney disease. With a significant overlap between these conditions—80% of kidney disease patients are obese and vice versa—nimacimab presents a potential solution for their shared pathological processes.

Preclinical studies indicated that nimacimab has minimal central nervous system (CNS) penetration, a significant advancement over previous CB1 inhibitors that faced safety concerns due to CNS accumulation. Phase 1b trials in non-alcoholic fatty liver disease (NAFLD) patients with diabetes or prediabetes showed no serious adverse events and demonstrated positive trends in cholesterol, liver enzymes, and liver function after a four-week treatment period. The drug's pharmacokinetics suggest a half-life of about three weeks, which could allow for monthly dosing, a notable advantage over the weekly dosing required for current GLP-1 receptor agonists.

Third-party research supports the role of CB1 inhibition in enhancing insulin and leptin sensitivity, preserving muscle mass, and promoting long-term weight loss. Nimacimab's unique profile could make it a significant alternative for treating obesity and other related conditions, either as a standalone therapy or in combination with others.

Tu Diep, Skye's Chief Development Officer, expressed confidence in nimacimab's safety profile, which surpasses that of small molecule CB1 inhibitors. The company is eager to assess clinical endpoints in the Phase 2 trial, such as weight loss and changes in kidney function biomarkers, to guide future development. Punit Dhillon, CEO and Chair of Skye, highlighted the importance of peripheral CB1 inhibition in future combination therapies for obesity, positioning nimacimab as a key component.

The endocannabinoid system (ECS) is a critical regulator of energy balance, with CB1 playing a role in various tissues. In obesity, endocannabinoids like anandamide and 2-arachidonoyl-glycerol can increase, impacting insulin-sensitive tissues negatively. Peripheral CB1 inhibition can reduce food intake and promote weight loss through various mechanisms, including increased gut incretin expression and reduced ghrelin levels. The ECS also plays a role in lipid and glucose metabolism, with CB1 blockade known to improve insulin sensitivity.

Nimacimab, as a first-in-class humanized monoclonal antibody, inhibits peripheral CB1 signaling and has shown potential in treating diseases like obesity, chronic kidney disease, and NASH. The drug's limited brain accumulation in preclinical studies and favorable safety profile in Phase 1b studies are promising. The drug's dosing frequency, once a month, could offer an advantage over current treatments.

Skye Bioscience is dedicated to harnessing the ECS's pharmaceutical potential to address diseases involving inflammation, fibrosis, and metabolism. With support from leading investors, Skye develops first-in-class therapeutics with significant clinical and commercial potential. The company is set to initiate a Phase 2 study for nimacimab in obesity and chronic kidney disease and is also studying a CB1 agonist in glaucoma and ocular hypertension patients.