EktaH links novel obesity drug to fat loss, muscle retention in early-phase trial

Dijon, France-based EktaH is building on work Naim Khan performed at the University of Bourgogne. The research showed CD36 and GPR120, fat taste receptors in the tongue epithelium, are downregulated in most people with obesity. Khan and his collaborators proposed that the downregulation of the receptors impaired people’s 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,” Khan, chief scientific officer and co-founder of EktaH, said in a statement. “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.”

Synthesizing agonists of CD36 and GPR120 enabled the researchers to study the impact of reactivating the fat taste receptors. EktaH shared data on two oral candidates, CD36 agonist NKS-3 and CD36/GPR120 agonist NKS-5, on Tuesday.

The update included data from 18 people with obesity enrolled in an ongoing multiple ascending dose study. EktaH said fat taste receptors in 15 of the patients responded to its modified fatty acid molecules NKS-3 and NKS-5, fueling the biotech’s belief that the mechanism can treat a wide segment of the population. Fat taste receptor sensitivity stabilized or increased in all responsive patients.

After four weeks of treatment, EktaH saw an average fat mass reduction of 4.30% in the seven people who received NKS-5. Skeletal muscle mass increased by 0.36% in the NKS-5 cohort over the same period. In contrast, fat mass increased by 2.48% in people who received a placebo or had receptors that did not respond to the drug candidate. 

The competition

EktaH is trailing large biopharma companies in the race to bring oral weight-loss drugs to market. Novo Nordisk and Eli Lilly, the market leaders in the injectable space, have won U.S. approvals for oral GLP-1 drugs, and other companies are advancing rival assets. The companies have delivered fast, steep weight loss, with Roche reporting a 7.3% reduction in body weight after four weeks of treatment in 2024.

The bar set by oral GLP-1 drug developers leaves limited room to compete on weight loss, but EktaH has identified other ways to differentiate its candidates. Some people do not respond to GLP-1 medicines, and those who do respond may lose lean muscle mass, experience gastrointestinal side effects that can lead them to discontinue treatment and regain some lost weight after coming off treatment. 

EktaH presented preclinical data in diet-induced obese mice that received semaglutide, which Novo sells as Ozempic and Wegovy, for two weeks before switching to either NKS-3 or placebo for four weeks. Mice that received NKS-3 regained about 50% less weight than the control animals while preserving lean body mass, EktaH said. The data suggest NKS-3 could be used as a maintenance drug after GLP-1 treatment. 

The company is working to generate more data. EktaH expects to complete the full, 120-subject clinical trial in December. In parallel, the company is engaging with regulators about a planned Phase 2 trial that will evaluate the effects of giving NKS-3 to 126 people with obesity for 12 weeks. EktaH is talking to investors about raising money to fund the Phase 2 trial.