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EktaH, a clinical-stage biotechnology company developing first-in-class oral therapies for obesity and metabolic diseases, has announced positive preliminary phase I results and preclinical data for its lead compound NKS-3, a modified fatty acid molecule and the first oral therapy designed to address key limitations of current GLP-1 obesity treatments.
First-in-class oral mechanism triggers natural satiety hormones, addressing key limitations of GLP-1 therapies.
Phase I data demonstrate fat mass reduction, preservation of lean mass, 80% responder rate, and no serious adverse events.
While GLP-1 receptor agonists such as semaglutide and tirzepatide have demonstrated significant weight loss, patients typically regain their baseline weight within 18 months of discontinuing treatment. In addition, current therapies are associated with loss of lean muscle mass and gastrointestinal side effects that drive discontinuation rates above 60%. Equally important, up to one third of obese individuals do not respond to GLP-1 treatments.
EktaH’s approach directly targets these limitations. NKS-3 is an orally administered small molecule that reactivates the fat taste receptors CD36 and GPR120 in the tongue epithelium, which are downregulated in most obese individuals. Preclinical data have demonstrated that NKS-3 restores normal function to these receptors, triggers the body’s own natural release of satiety hormones including GLP-1, cholecystokinin, and peptide YY (PYY), and reduces food intake through the body’s endogenous signalling without the need of exogenous hormone administration.
“Our data demonstrate that fat taste receptor dysfunction is a measurable and treatable feature of obesity,” said Professor Naim Khan, CSO and co-founder of EktaH. “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. More importantly, this mechanism of action reduces the number of non-responders.”
NKS-3 Preclinical Data: 50% reduction in weight rebound after semaglutide discontinuation.
Diet-induced obese mice treated with semaglutide for two weeks were subsequently given either NKS-3 or vehicle for four weeks.
Animals receiving NKS-3 exhibited approximately 50% less weight rebound compared to control animals, while preserving lean body mass.
These findings suggest NKS-3 has significant potential as both a standalone treatment for obesity and as a maintenance therapy following GLP-1 treatment, addressing a critical unmet need in obesity management.
“Weight rebound is the biggest unresolved challenge in obesity treatment,” said Xavier Boidevezi, CEO and co-founder of EktaH. “Our preclinical data shows 50% less weight regains after stopping semaglutide, combined with a clinical profile that preserves muscle mass and shows no serious adverse events. This positions NKS-3 as the weight maintenance therapy urgently needed.”
EktaH has completed phase I clinical studies encompassing both a first-in-human safety trial in 27 healthy volunteers and is conducting a Single Ascending Dose/Multiple Ascending Dose study in 120 patients with obesity. Across all subjects dosed to date (87+), no serious adverse events have been reported.
Broad applicability: 80% of obese participants (15/18) demonstrated fat taste receptors responsive to EktaH’s modified fatty acid molecules (NKS-3 or NKS-5), indicating that the mechanism has potential to treat a wide segment of the obese population.
Mechanism confirmed in humans: 30-day treatment with NKS-3 or NKS-5 stabilized or increased fat taste receptor sensitivity in all responsive patients, confirming the preclinical mechanism of action.
Encouraging body composition changes: The NKS-5 cohort (n=7) showed an average fat mass reduction of 4.30% with a simultaneous slight 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.
Beyond its metabolic effects, NKS-3 demonstrated potent anti-inflammatory activity in multiple experimental models, with significant reductions in key pro-inflammatory cytokines and modulation of central inflammatory signalling pathways. These findings support the potential of EktaH’s approach to address the broader inflammatory component of obesity and metabolic diseases and represent an additional pipeline opportunity.
EktaH has received positive scientific advice from the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) on its Phase II clinical development plan. The phase IIa study (SERENITY-1) is a multicenter, double-blind, placebo-controlled, randomized, dose-finding study of NKS-3 in 126 obese subjects, with a 12-week treatment period and 12-week follow-up. Recruitment is planned to begin in the first half of 2027.
The company plans to share complete phase I results before the end of 2026 and is currently in discussions regarding its next financing round to support Phase II execution.
EktaH holds worldwide exclusive licenses on its core fat taste receptor technology (patents through 2044), with confirmed freedom-to-operate in Europe and the United States. The company’s pipeline includes two lead molecules (NKS-3 and NKS-5) for obesity, an anti-inflammatory program, and next-generation agonists in early development. EktaH is ISO 9001:2015 certified and is supported by an international Scientific Advisory Board. Founded in 2021, EktaH is headquartered in Dijon, France.
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