EktaH Reports Positive Early Clinical Data for Oral Obesity Candidate NKS-3

EktaH has announced positive preliminary Phase I and preclinical results for its lead obesity candidate NKS-3, an oral small molecule designed to overcome several limitations associated with current GLP-1-based obesity treatments.

The company says NKS-3 works through a first-in-class mechanism targeting fat taste receptors and could potentially address major challenges in obesity treatment, including weight regain, muscle loss, gastrointestinal side effects and non-responsiveness to existing therapies.

A Different Approach to Obesity Treatment

Current GLP-1 receptor agonists such as Ozempic and Mounjaro have transformed obesity management by delivering significant weight loss.

However, several important limitations remain, including:

• Weight regain after treatment discontinuation
• Loss of lean muscle mass
• Gastrointestinal side effects
• High treatment discontinuation rates
• Lack of response in a significant portion of patients

According to EktaH, up to one-third of obese individuals do not adequately respond to GLP-1 therapies.

The company believes NKS-3 may offer an alternative by targeting obesity earlier in the physiological signalling pathway.

How NKS-3 Works?

Unlike injectable GLP-1 drugs that deliver external hormone stimulation, NKS-3 is designed to reactivate fat taste receptors known as CD36 and GPR120 in the tongue epithelium.

These receptors are reportedly downregulated in many obese individuals. According to the company, restoring receptor activity helps trigger the body’s natural release of satiety hormones, including:

• GLP-1
• Cholecystokinin (CCK)
• Peptide YY (PYY)

This endogenous signalling pathway is intended to reduce food intake naturally without relying on exogenous hormone administration.

Professor Naim Khan, co-founder and chief scientific officer at EktaH, said the findings suggest fat taste receptor dysfunction may represent a measurable and treatable biological feature of obesity.

Phase I Data Show Encouraging Safety and Body Composition Findings

EktaH reported that Phase I development included:

• A first-in-human safety study in 27 healthy volunteers
• An ongoing Single Ascending Dose/Multiple Ascending Dose study involving 120 obese participants

Across more than 87 subjects dosed to date, the company stated that no serious adverse events have been observed. Key preliminary findings included:

80% Responder Rate

According to the company, 15 out of 18 obese participants demonstrated fat taste receptors responsive to either NKS-3 or the related compound NKS-5.

This suggests the mechanism could potentially be applicable across a broad obesity population.

Mechanism Confirmed in Humans

Thirty-day treatment with NKS-3 or NKS-5 reportedly stabilized or improved fat taste receptor sensitivity in responsive patients, supporting translation of the preclinical mechanism into humans.

Fat Loss With Lean Mass Preservation

In the NKS-5 treatment cohort:

• Average fat mass decreased by 4.3%
• Skeletal muscle mass increased slightly by 0.36%

By comparison, placebo-treated and non-responder patients reportedly experienced a 2.48% increase in fat mass over the same period.

Preserving lean muscle mass has become an increasingly important focus in obesity drug development, particularly as muscle loss remains a known concern with many rapid weight-loss therapies.

Preclinical Data Suggest Reduced Weight Regain After GLP-1 Discontinuation

One of the most notable findings involved preclinical studies evaluating weight rebound after discontinuation of semaglutide treatment. In diet-induced obese mice:

• Animals first received semaglutide for two weeks
• Mice were then switched to either NKS-3 or placebo for four weeks

According to the company, animals receiving NKS-3 demonstrated approximately 50% less weight regain compared with controls while maintaining lean body mass. EktaH believes these findings position NKS-3 as both:

• A standalone obesity therapy
• A potential maintenance treatment following GLP-1 discontinuation

CEO Xavier Boidevezi described post-treatment weight regain as one of the biggest unresolved challenges in obesity management.

Potential Beyond Weight Loss

Beyond metabolic effects, EktaH also reported that NKS-3 demonstrated anti-inflammatory activity across several experimental models. The company observed:

• Reduction in pro-inflammatory cytokines
• Modulation of inflammatory signalling pathways

These findings may support future development opportunities beyond obesity, particularly in metabolic and inflammatory disorders.

Phase II Plans Already Underway

Medicines and Healthcare products Regulatory Agency (MHRA) has reportedly provided positive scientific advice regarding EktaH’s planned Phase II program. The upcoming SERENITY-1 study will be:

• Multicenter
• Randomized
• Double-blind
• Placebo-controlled
• Dose-finding

The trial is expected to enroll 126 obese participants and will include:

• 12 weeks of treatment
• 12 weeks of follow-up

Recruitment is planned to begin during the first half of 2027.

Intellectual Property and Pipeline Expansion

Founded in 2021 and headquartered in Dijon, EktaH holds worldwide exclusive licenses for its fat taste receptor platform technology, with patent protection extending through 2044. The company’s pipeline currently includes:

• NKS-3 for obesity
• NKS-5 for obesity
• Anti-inflammatory programs
• Next-generation receptor agonists

EktaH stated that it is currently preparing for its next financing round to support Phase II development.

Why This Matters?

The obesity treatment landscape is rapidly evolving, but major gaps remain around:

• Long-term weight maintenance
• Muscle preservation
• Tolerability
• Patient adherence
• Treatment response variability

If future clinical studies confirm the early findings, NKS-3 could represent a differentiated oral obesity therapy with a novel biological mechanism and potential use both during and after GLP-1 treatment.

The concept of restoring endogenous satiety signalling rather than replacing it with external hormones may also open a new direction in obesity drug development beyond current GLP-1 approaches.