The biopharma firm has filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) for the initiation of a phase 2 clinical study of nimacimab in patients with obesity and chronic kidney disease.
Nimacimab is a negative-allosteric modulating antibody targeting the cannabinoid 1 receptor (CB1), which has been implicated as an important target in multiple cardiometabolic diseases including obesity and renal complications.
“The global overweight and obesity epidemic affects over a billion people worldwide and in the US is estimated to affect over 40% of the adult population. Even with the recent approvals of new drugs for the treatment of obesity, this number is only expected to grow,” said Punit Dhillon, CEO and chair of Skye.
In addition, obesity and kidney disease are highly correlated, as 80% of patients who have kidney disease are also obese, while 30% of obese patients have kidney disease.
“GLP-1 and GIP receptor agonists have demonstrated that obesity can be treated therapeutically with safe and effective drugs and have exposed a market opportunity that is just the tip of the iceberg. Despite the excitement and success around these drugs, a significant portion of the patient population cannot tolerate them and there is recognition of a need for differentiated therapeutic mechanisms,” Dhillon added.
“This need is underscored by recent activity of large pharmaceutical companies to acquire drugs with complimentary mechanisms of action to treat obesity and highlights a trend toward combinations targeting two or even three mechanisms. As we look to a likely future where most major pharmas will have their own GLP-1 agonist, we see nimacimab as a key potential component of future combination therapies.”
The role of CB1 as an important regulator of appetite and diabetic renal complications has been demonstrated preclinically, as well as clinically, with a number of small molecule inverse agonists and antagonists.
However, their efficacy has been hampered by mechanism-based safety issues related to side effects of the central nervous system (CNS).
Unlike these examples, based on preclinical and early clinical studies, Skye claims that nimacimab is able to inhibit CB1 signaling and is devoid of the CNS liabilities typically seen by small molecule drugs that target the CB1 receptor because it does not cross the blood-brain barrier.
The most recent phase 1b study of the drug, in non-alcoholic fatty liver disease (NAFLD) patients with diabetes or prediabetes, demonstrated no serious adverse events with ‘encouraging’ trends seen in exploratory biomarkers of cholesterol, liver enzymes and liver function in patients receiving nimacimab versus placebo after the three-week dosing period.
Moving forward, the company is planning a phase 2 study in patients with obesity and chronic kidney disease in the first half of 2024.
“The safety profile of nimacimab from preclinical and clinical studies is encouraging, and we believe it exceeds what others have demonstrated with small molecule drugs that also act to block the CB1 receptor,” said Tu Diep, chief development officer of Skye.
“Because of the potential of this class of drug to treat a range of metabolic conditions, we believe a phase 2 study to treat patients with obesity and comorbid chronic kidney disease offers the potential to evaluate multiple meaningful clinical endpoints beyond weight loss, such as changes in albuminuria to evaluate kidney function, that will guide the future development of nimacimab.”
Moreover, pharmacokinetic assessment of nimacimab highlighted a half-life of approximately three weeks, potentially allowing for monthly dosing, giving the treatment an edge in the crowded market.
“The promising PK data from the phase 1 study suggests that nimacimab can be dosed once-a-month subcutaneously, which we believe would be a significant competitive advantage over once-a-week subcutaneous dosing of the current peptidic GLP-1 receptor agonists or even orally dosed GLP-1 receptor agonists due to their less desirable tolerability profile,” Diep added.