Syntis Bio oral SYNT-101 demonstrates weight-loss and satiety hormone modulation

Results from Syntis Bio’s 28-day multiple ascending dose (MAD) portion of its Phase 1/1b SYNTIETY-1 clinical trial, evaluating SYNT-101 as a potential treatment of obesity, revealed that SYNT-101 was well tolerated at all dose levels in the MAD cohorts (n=23), with no discontinuations and no dose reductions in any of the cohorts.

SYNT-101 is being developed as a once-daily pill for the treatment of obesity. SYNT-101 works by transiently blocking nutrient absorption in the proximal small intestine and redirecting nutrients to the distal small intestine to stimulate the natural secretion of satiety and metabolism-regulating hormones, including GLP-1, PYY, ghrelin, and GIP — a multi-hormone signature rather than a single-hormone effect.

This mechanism is a key contributor to the efficacy of gastric bypass surgery, which is considered a gold standard for quality weight loss and metabolic disease management. Preclinical data demonstrated 100% preservation of lean muscle mass with consistent 1% weekly weight loss in rodent models. Importantly, SYNT-101 displayed favorable safety and tolerability, along with preliminary weight loss and hormone modulation in the 55 subject Phase 1/1b SYNTIETY-1 (SYNThetic Intestinal ExclusIon Therapy for ObesitY) study in obesity.

“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 Dr 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.”

The randomised, double-blind, placebo-controlled MAD portion of SYNTIETY-1 evaluated changes in relevant metabolic markers associated with weight management in overweight or obese patients in 23 adult volunteers who were dosed across three ascending cohorts (857 mg to 2,571 mg, corresponding to one to three tablets). Data highlights include:

• Gastrointestinal (GI) adverse events occurred at a similar rate in SYNT-101 treated participants and placebo participants

• Exploratory pharmacodynamic assessments demonstrated SYNT-101 drove a concordant, multi-hormonal endogenous satiety response, consistent with hormonal changes observed after gastric bypass surgery, including: 2- to 5-fold increases in the satiety hormones GLP-1 and PYY, and a decrease in the “hunger hormone” ghrelin

• SYNT-101 participants lost more weight than those receiving placebo in each of the three dose cohorts – comparable to weight loss observed with GLP-1 therapies after the same treatment duration

These MAD data build upon positive initial data from the SAD portion of SYNTIETY-1, announced in July 2026, in which SYNT-101 was well tolerated and demonstrated early indications of efficacy. Preclinical models also indicate that SYNT-101 may result in consistent weight loss for the study duration, as well as preservation of lean muscle mass.

“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. 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 favourable 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.”

Detailed results will be featured in a late-breaking presentation at The Obesity Society's 44th Annual Meeting at ObesityWeek 2026, in Washington, DC from November 14-17, 2026.