Skye Bioscience starts CBeyond Phase 2 clinical trial with

SAN DIEGO, Aug. 22, 2024 (GLOBE NEWSWIRE) — Skye Bioscience, Inc. (Nasdaq: SKYE) (“Skye”), a clinical-stage biopharmaceutical company focused on developing new therapeutic avenues for metabolic health, has begun screening patients for a Phase 2 clinical trial (CBeyond^TM) of its novel peripheral CB1 inhibitor nimacimab, a negative allosteric modulating antibody. The study is designed to evaluate the ability of nimacimab as a next-generation weight loss therapeutic to safely and effectively reduce weight in patients with obesity, assessing parameters that are increasingly considered important for the long-term quality and/or sustainability of weight loss, including gastrointestinal (GI) tolerability and maintenance of muscle mass.

“There is clearly a need for alternative mechanisms of action that can provide physicians and patients with improved overall health outcomes in weight loss beyond those achieved with GLP-1 and GIP drugs. We believe peripheral CB1 inhibition and nimacimab, a unique biologic drug within this class, have properties that can help achieve such outcomes, and we look forward to our goals of presenting interim data from this Phase 2 obesity trial in the second quarter of 2025 and final data in the fourth quarter of 2025,” said Punit Dhillon, Chief Executive Officer of Skye. “Research on CB1 inhibition has shown that it has the potential to directly promote energy expenditure and fat loss¹Improving leptin sensitivity² and peripherally modulate hunger and satiety ³We are excited to evaluate nimacimab as monotherapy, but also to conduct a preliminary evaluation of our peripheral CB1 inhibitor in combination with a GLP-1 drug.”

“As we evaluate CB1 inhibition as a potential alternative mechanism for weight loss, we believe it is important to consider health consequences beyond gastrointestinal intolerance and muscle loss, such as neuropsychiatric side effects that may compromise the long-term use of these drugs necessary for sustainable results,” added Tu Diep, Skye's Chief Development Officer. “The first generation CB1 inhibitor, rimonabant, was a small molecule acting on the CNS. It demonstrated efficacy in weight loss ⁴Dose-dependent psychiatric side effects were also observed ⁵ including anxiety, depressed mood, depression and suicidality. Current second-generation CB1 inhibitors, small molecules that may be more peripherally restricted than rimonabant, continue to show accumulation in the brain⁶ in preclinical models, suggesting a potential ongoing safety issue with this approach. Nimacimab, a monoclonal antibody (large molecule), is significantly more effectively kept away from the brain⁷ and there were no psychiatric side effects in our preclinical studies⁷ or Phase 1 study⁷ in patients with nonalcoholic fatty liver disease (NAFLD). We believe the positive safety and tolerability profile of nimacimab gives Skye a competitive advantage over small molecule CB1 inhibitors.”

“We are very honored to participate in this study of nimacimab as an adjunct therapy for the treatment of obesity. This innovative approach targeting the CB1 receptor is a logical next step following the results of promising early studies,” said Harold Edward Bays, M.D., Medical Director/President of the Louisville Metabolic and Atherosclerosis Research Center/Your Body Goal. “We hope that investigating this additional mechanism of action will ultimately expand treatment options for patients with obesity.”

CBeyond^TM Design of Phase 2 clinical trials

The clinical trial protocol for this Phase 2 study of Nimacimab consists of the following elements:

• 120 patients will be enrolled in four treatment groups.
  • In a double-blind design, 80 patients will receive either 200 mg nimacimab or a nimacimab-matching placebo subcutaneously once weekly.
  • 40 patients will receive either Nimacimab + Wegovy^® or Nimacimab-matching placebo + Wegovy^® once a week in a partially blinded design. Wegovy^® is administered once weekly according to the prescribing information up to a maximum weekly dose of 2.4 mg.
• Patients will be treated for 26 weeks and followed for a further 13 weeks.
• Primary endpoint: Assessment of weight loss in the nimacimab arm compared to placebo. Designed to detect an 8% difference in mean weight loss between active and placebo with 80% power.
• Secondary endpoints: safety and tolerability, neuropsychiatric and cognitive assessment, change in body composition by dual energy X-ray absorptiometry (DEXA).
• Exploratory endpoints: Changes in key metabolic parameters, including triglycerides, insulin sensitivity and leptin sensitivity; evaluation of the combination of nimacimab and Wegovy^®; Evaluate the difference in weight loss between Nimacimab and Wegovy^®; Assess the difference in body composition between Nimacimab and Wegovy^®; Improve sleep.
• The study will enroll patients with obesity (≥ 30 kg/m2 to ≤ 45 kg/m2) OR overweight (≥ 27 kg/m2 and
• In addition, a subset of 40 patients from all study arms will have sleep quality assessed by EEG quantification of sleep patterns. Sleep quality disturbances may be associated with sleep apnea, a condition for which obesity is a major risk factor. Data will be collected over multiple nights after screening and at weeks 13, 26, and the follow-up period. Data will be collected and analyzed using Beacon Biosignal's FDA 510(k) cleared Dreem headband and its advanced sleep monitoring technology platform.
• Patients with diabetes are excluded.
• This study will be conducted at 18 clinical trial sites in the United States
• Interim data will be announced after 50% of enrolled patients have completed the treatment period. Final data will be announced after completion of treatment and follow-up of all enrolled patients.

1 Ruiz de Azua et al., J Clin Invest. 2017
2 Tam et al., JCI. 2010; Tam et al., Cell Metabolism 2012
3 Tam et al., JCI. 2010; Tam et al., Cell Metabolism 2012
4 RBC Capital Markets (February 2024); Després et al., NEJM. 2005
5 FDA Briefing Document, NDA 21-888, Zimulti (rimonabant) Tablets, 20 mg, Sanofi Aventis, Advisory Committee – June 13, 2007
6 Liu et al., ACS Pharmacol Transl Sci. 2021.
7 Skye data.

About Nimacimab

Nimacimab is a first-in-class humanized monoclonal antibody that acts as a negative allosteric modulator and inhibits CB1 signaling in the periphery. CB1 inhibition has demonstrated antifibrotic, anti-inflammatory and metabolic mechanisms of action and offers the potential to treat a broad spectrum of diseases with unmet medical needs, such as obesity, chronic kidney disease and metabolic dysfunction-associated steatohepatitis (MASH).

In July 2024, Skye hosted a KOL event on obesity with key opinion leaders and Skye management highlighting the mechanisms of peripheral CB1 inhibition and the properties and potential role of nimacimab in the obesity therapeutic landscape. The presentation and a recording of the call are available on the company's website. website.

About Skye Bioscience

Skye is focused on developing new therapeutic avenues for metabolic health by developing next-generation molecules that modulate G-protein-coupled receptors. Skye's strategy leverages biological targets with substantial proof of mechanism of action in humans to develop first-in-class therapeutics with clinical and commercial differentiation. Skye is conducting a Phase 2 clinical trial for the treatment of obesity with nimacimab, a negative allosteric modulating antibody that peripherally inhibits CB1. This trial is also evaluating the combination of nimacimab and a GLP-1R agonist (Wegovy).^®). For more information, please visit: Contact us at X and LinkedIn.

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