Syntis Bio says its experimental oral obesity drug SYNT-101 produced greater weight loss than placebo and triggered changes in key satiety hormones in a 28-day Phase 1/1b study, adding to early evidence for the company’s approach of targeting the small intestine rather than relying on systemic drug exposure.

 

The company reported that SYNT-101 was well tolerated across all three multiple ascending dose (MAD) cohorts, with gastrointestinal adverse events occurring at a rate comparable to placebo. No participants discontinued treatment or required a dose reduction.

 

The randomized, double-blind, placebo-controlled MAD portion of the SYNTIETY-1 trial included 23 adults with overweight or obesity who received daily doses ranging from 857 mg to 2,571 mg, equivalent to one to three tablets.

 

Syntis said participants receiving SYNT-101 lost more weight than those receiving placebo in each of the three dose cohorts. The company said the weight-loss signal was comparable to that observed with GLP-1 therapies over the same treatment period, although the Phase 1 study was small and exploratory.

 

The drug also produced changes in multiple hormones involved in hunger and satiety. According to Syntis, GLP-1 and PYY increased by two- to five-fold, while ghrelin, commonly known as the “hunger hormone,” decreased.

 

The company said the hormonal pattern was consistent with changes seen after gastric bypass surgery, supporting its hypothesis that SYNT-101 can reproduce elements of the metabolic response associated with bariatric surgery through an oral drug.

 

“SYNT-101 was designed to produce a specific multi-hormone signature, one that mimics the metabolic response of bariatric surgery but via a once-daily oral tablet,” said David Rosenbaum, Chief Development Officer of Syntis Bio. 

 

“Results from the 28-day MAD portion of the SYNTIETY-1 trial confirms the mechanism initially demonstrated in the SAD arm. The continued demonstration of tolerability across all dose cohorts, together with encouraging efficacy signals, reinforce the potential of a therapy that, unlike GLP-1s and other obesity drug candidates, is specifically designed to avoid systemic circulation. Overall, these data mark a significant de-risking milestone for SYNT-101 and provide a strong foundation for its advancement into Phase 2.”

 

Syntis previously reported initial results from the trial’s single ascending dose (SAD) portion in July. The company said those results showed early evidence of efficacy alongside favorable safety and tolerability.

 

The company’s approach is designed to work locally in the gut. SYNT-101 temporarily blocks nutrient absorption in the proximal small intestine, redirecting nutrients farther down the intestinal tract to stimulate the body’s natural production of hormones including GLP-1, PYY, ghrelin and GIP.

 

“Effective approaches to weight loss, from bariatric surgery to GLP-1 therapies, share a common endpoint: elevate circulating satiety hormones. What differs is how they achieve it, and at what cost,” said Rahul Dhanda, Chief Executive Officer of Syntis Bio. 

 

“Approved pharmacologic approaches such as GLP-1 therapies rely on sustained circulating drug levels to maintain their effect, which can produce gastrointestinal and other treatment-limiting effects, particularly as doses are escalated. By acting locally in the gut and forming a transient lining in the duodenum, SYNT-101 takes a fundamentally different approach.”

 

Dhanda continued, “SYNT-101 triggers a multi-hormone satiety response when food is consumed rather than through continuous systemic drug exposure, mimicking aspects of the natural response to a meal or bariatric surgery. 

 

"We believe this differentiated mechanism is reflected in the favorable tolerability observed to date in our daily pill and could position SYNT-101 as an important new option for weight management — either for patients who cannot tolerate existing therapies or potentially in combination to safely enhance GLP-1 therapy.”