Skye Bio obesity medication fails in phase 2; hope to ride higher doses and combination therapy now
Patients taking experimental Skye Bioscience obesity did not lose enough weight to meet the goals of the mid-term study, which allowed the biotech setback to resume bidding for a range of drugs due to safety risks. These did not have these complications in clinical trials, Skye executives said the drug could prove to have higher drug delivery capabilities.
The Skye drug Nimacimab is an antibody designed to block CB1, and its physiological effects include regulating appetite. San Diego-based Skye is evaluating weekly injectable medications in 136 patients in the 2A study. Preliminary results reported on Monday showed that participants received Skye's Nimacimab because monotherapy lost an average of 1.52% of their weight after 26 weeks, while the placebo group lost 0.26% of their weight, which was not enough to be statistically significant.
The study drug combined with Wegovy from Novo Nordisk was better, compared with a clinically meaningful average weight loss of 13.2%, compared with 10.25% on arms receiving Wegovy and placebo. Although these results are not statistically significant, weight loss did not reach a steady state at 26 weeks, and the company said patients may continue to lose weight, while longer medications may continue to lose weight.
Skye shares opened at $1.81 on Monday, down nearly 62% from Friday's closing price.
CB1 has both clinical and regulatory validation from SANOFI, which was approved in Europe in 2006 that Rimonabant is an oral small molecule inhibitor of this target. Targeting CB1 in the gastrointestinal tract can help patients lose weight, but this receptor has also been found in the central nervous system. Rimonabant hits these receptors in the brain, causing suicide thoughts in some patients. In 2008, Sanofi pulled the drug from the market.
Skye designed Nimacimab is peripherally restricted, blocking CB1 in the gastrointestinal tract but avoiding CNS. In an interview last year, Chief Development Officer Tu Diep explained that as an antibody, Nimacimab is too large to penetrate into the obstructions of the blood-brain barrier, which should avoid the risk of complications observed by Rimonabant. Skye said that in the results of Phase 2A, Nimacimab was used alone and combined with Wegovy, showing safety for cleaning. Not only are there no additional gastrointestinal side effects, but no neuropsychiatric adverse events have been reported.
Patients who completed the 26-week study were eligible for the 26-week extended study. Enrollment rates have been completed and Skye is expected to provide data in the first quarter of next year. More detailed results for the initial 26-week period will be presented during the Obesity Weekly held in Atlanta next month.
Skye said in an investor introduction that the 200 mg once weekly dose was based on modeling of the Phase 1 test, indicating that the drug’s peripheral exposure was significant, but with little exposure in the brain. The company says preclinical data and modeling of Nimacimab's pharmacokinetics (PK) — how the body interacts with the drug during exposure throughout the body — suggests the potential of the drug to higher doses.
“With our preclinical data, toxicology safety profits and PK modeling, we believe we have a pathway to support higher doses and we are evaluating the next phase of the development phase to optimize doses in potential future clinical trials,” Chief Medical Officer Puneet Arora said in a Skye announcement.
Skye attempts to distinguish itself among a small number of companies working to restore CB1 inhibition as a way to treat obesity. Novo Nordisk's 2023 acquisition of Inversogo Pharma brings a lead program, now known as Monlunabant, an oral small molecule inhibitor of CB1. Although the drug has interim data showing statistically significant weight loss, the results showed neuropsychiatric effects. Corbus Pharmaceuticals' CRB-913 is also an oral small molecule inhibitor of CB-1's peripheral restriction; the company is expected to start a 1B dose range study in the fourth quarter of this year.
Skye said in an investor speech that it will focus on the combination strategy with Wegovy while continuing to evaluate higher doses of Nimacimab as a monotherapy. The company will also evaluate Nimacimab's potential as a maintenance treatment for patients who achieve target weight loss through GLP-1 weight loss medication. In clinical trial results so far, nimaximab did not increase the frequency or severity of gastrointestinal side effects, a common reason for discontinuing treatment. This can give Skye drugs the advantages of safety and tolerance over long-term use of GLP-1 drugs.
William Blair analyst Andy Hsieh said that to make Skye continue to do a higher dose as a monotherapy, it is necessary to reduce the burden on patients, currently two injections, 100 mg per syringe. Hsieh is more interested in the potential uses of Skye Drug and Wegovy. The results showed that the two drugs together resulted in 13% placebo-adjusted weight loss, which was only far from Wegovy's treatment in a note sent to investors, said in a note.
“We are disappointed with the clinical setbacks of Nimacimab,” Hsieh wrote. “However, we hope that using higher doses (such as 600 mg or 1,000 mg per week) Nimacimab can exhibit greater monotherapy activity and emphasize its ability to use in combination with Wegovy.”
Photo: Peter Dazeley, Getty Images
