EktaH's Novel Obesity Drug Shows Promise in Reducing Weight Rebound After GLP-1 Treatment Discontinuation
核心洞察
EktaH (搜索)'s lead compound NKS-3 (搜索) demonstrated approximately 50% reduction in weight rebound compared to control animals in preclinical studies following semaglutide discontinuation.
Phase I clinical data from 18 patients showed NKS-5 (搜索) achieved 4.30% fat mass reduction while preserving skeletal muscle mass, with 80% of participants responding to the treatment.
The novel mechanism targets fat taste receptors CD36 (搜索) and GPR120 (搜索) to restore natural satiety signaling, potentially addressing key limitations of current GLP-1 (搜索) therapies including muscle loss and high discontinuation rates.
French biotechnology company EktaH (搜索) has reported promising preclinical and Phase I clinical data for its novel obesity (搜索) treatment NKS-3 (搜索), which targets fat taste receptors to address key limitations of current GLP-1 (搜索) therapies. The Dijon-based company's approach offers a potential solution to weight rebound, muscle loss, and non-response issues that plague existing obesity treatments.
Targeting Fat Taste Receptor Dysfunction
EktaH (搜索)'s therapeutic strategy is based on research by Chief Scientific Officer Naim Khan at the University of Bourgogne, which identified that fat taste receptors CD36 (搜索) and GPR120 (搜索) in the tongue epithelium are downregulated in most people with obesity (搜索). This downregulation impairs the ability to detect lipids, leading to increased fat intake.
"Our data demonstrate that fat taste receptor dysfunction is a measurable and treatable feature of obesity (搜索)," Khan stated. "By restoring the body's own ability to sense dietary fat and regulate satiety, we are addressing obesity at its physiological origin rather than overriding the system with exogenous hormones."
The company's oral small molecule candidates, NKS-3 (搜索) and NKS-5 (搜索), are designed to reactivate these receptors and trigger the body's natural release of satiety hormones including GLP-1 (搜索), cholecystokinin (CCK), and peptide YY (PYY).
Preclinical Data Shows Reduced Weight Rebound
In preclinical studies, diet-induced obese mice treated with semaglutide for two weeks were subsequently given either NKS-3 (搜索) or placebo for four weeks. Animals receiving NKS-3 exhibited approximately 50% less weight rebound compared to control animals while preserving lean body mass.
"Weight rebound is the biggest unresolved challenge in obesity (搜索) treatment," said Xavier Boidevezi, CEO and Co-founder of EktaH (搜索). "Our preclinical data show 50% less weight regain after stopping semaglutide, combined with a clinical profile that preserves muscle mass and shows no serious adverse events."
Phase I Clinical Results Show Promise
EktaH (搜索) has completed Phase I studies in 27 healthy volunteers and is conducting an ongoing multiple ascending dose study in 120 patients with obesity (搜索). Preliminary data from 18 patients in the ongoing study revealed encouraging results after 30 days of treatment.
The company reported that 80% of obese participants (15 out of 18) demonstrated fat taste receptors responsive to NKS-3 (搜索) or NKS-5 (搜索), indicating broad potential applicability. Fat taste receptor sensitivity stabilized or increased in all responsive patients, confirming the mechanism of action in humans.
Patients receiving NKS-5 (搜索) showed an average fat mass reduction of 4.30% with a simultaneous increase in skeletal muscle mass of 0.36% at four weeks. In contrast, the placebo and non-responder group gained 2.48% fat mass over the same period.
Across all 87+ subjects dosed to date, no serious adverse events have been reported, suggesting a favorable safety profile.
Competitive Landscape and Differentiation
While EktaH (搜索) trails large pharmaceutical companies like Novo Nordisk and Eli Lilly in the oral weight-loss drug race, the company has identified key differentiators. Current GLP-1 (搜索) therapies face limitations including non-response in up to one-third of patients, lean muscle mass loss, gastrointestinal side effects driving discontinuation rates above 60%, and weight regain within 18 months of treatment cessation.
The competition has set a high bar, with companies like Roche reporting 7.3% reduction in body weight after four weeks of treatment in 2024. However, EktaH (搜索)'s approach addresses the underlying physiological dysfunction rather than overriding natural systems with exogenous hormones.
Development Timeline and Regulatory Progress
EktaH (搜索) has received positive scientific advice from the UK's Medicines and Healthcare products Regulatory Agency (MHRA) for its Phase II development plan. The Phase IIa study (SERENITY-1) will be a multicenter, double-blind, placebo-controlled, randomized, dose-finding study of NKS-3 (搜索) in 126 obese subjects, with a 12-week treatment period and 12-week follow-up.
The company expects to complete its full 120-subject Phase I trial in December 2026 and plans to begin Phase II recruitment in the first half of 2027. EktaH (搜索) is currently in discussions regarding its next financing round to support Phase II execution and plans to share complete Phase I results before the end of 2026.
Additional Therapeutic Potential
Beyond metabolic effects, NKS-3 (搜索) demonstrated potent anti-inflammatory activity in multiple experimental models, with significant reductions in key pro-inflammatory cytokines. These findings support potential applications in addressing the broader inflammatory component of obesity (搜索) and metabolic diseases, representing additional pipeline opportunities for the company.