Skye Bioscience’s nimacimab fell short of investor and company expectations, but showed encouraging weight-loss results when combined with Wegovy, according to analysts at William Blair.
Skye Bioscience’s cannabinoid receptor 1-targeting candidate nimacimab failed to outpace placebo at reducing body weight in adults with overweight or obesity—but nevertheless elicited encouraging signals of potential efficacy when used as part of a combination drug regimen.
Topline results from the company’s Phase IIa CBeyond trial, released Monday, showed that patients experienced “lower than expected” exposure to nimacimab, suggesting the need to test higher doses of the drug, according to the company. Nimacimab alone resulted in a placebo-adjusted reduction in body weight of 1.26% at 26 weeks, an effect that failed to reach statistical significance.
However, Skye touted “meaningful add-on efficacy” for nimacimab when used alongside Novo Nordisk’s blockbuster GLP-1 drug Wegovy. Patients who received both treatments lost 13.2% of their body weight at 26 weeks, as compared with 10.25% in those on Wegovy alone. This equated to a significant 2.95% benefit attributed to add-on nimacimab.
Writing to investors on Monday, analysts at William Blair chalked the combo benefit up to an “intriguing synergy” between nimacimab and Wegovy.
“We are intrigued by the synergistic effect when nimacimab is combined with Wegovy and the apparent increase in weight loss magnitude over time” versus Wegovy monotherapy, they said. Still, the analysts cautioned that this potential combo benefit remains “speculative in nature.”
Aside from overall weight loss, Skye also looked at nimacimab’s effect on body composition. Results showed that those who were treated with nimacimab plus Wegovy had a significantly better lean mass-to-fat mass ratio at 26 weeks versus those on Wegovy alone.
As for safety, Skye pointed to a “clean” profile for nimacimab, with “placebo-like tolerability.” When used with Wegovy, the biotech did not detect an uptick in gastrointestinal side effects. Of note, Skye also reported no concerning neuropsychiatric signals, with no documented increases in anxiety, insomnia or depression. Psychological side effects such as these doomed earlier cannabinoid receptor 1–targeting drugs. Last November, Novo announced mid-stage data from its own CB1 candidate, monlunabant, including reports of “mild to moderate neuropsychiatric side effects,” such as anxiety, irritability and sleep disturbances.
Skye is looking at the potential of launching another Phase II study for nimacimab in obesity. The biotech has also promised to present more detailed findings from CBeyond at the upcoming ObesityWeek meeting in November.
Despite being “disappointed” by the Phase IIa fail, William Blair analysts noted that they “are hopeful that with higher doses (such as 600 mg or 1,000 mg per week), nimacimab could show more substantial monotherapy activity” while also boosting its combination benefits with Wegovy.
