Syntis Bio, Inc., a clinical-stage biopharmaceutical company advancing novel oral therapeutics that uniquely leverage the small intestine, today announced results from its 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.

“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, Ph.D., 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 randomized, 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:

  • 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

  • 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

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.

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.”

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.”

About SYNT-101

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.

About SYNT™ Technology

Syntis Bio’s pipeline programs leverage the power of SYNT™ (SYNthetic Tissue-lining), an oral therapeutic technology designed to enhance disease-modifying activity within the small intestine, the body’s nexus for metabolic control, digestion, and drug absorption. SYNT™ employs mussel-inspired polymer chemistry to deliver a safe, transient polydopamine coating to catalase-rich tissues such as the duodenum. Following deployment in the gastrointestinal tract, the polydopamine lining is sustained for up to 24 hours and is then naturally and safely cleared from the body. In addition to nutrient exclusion, SYNT™ can be designed to install and sustain gut-restricted enzymes in the small bowel and enhance the oral bioavailability of drugs.

About Syntis Bio

Syntis Bio is a clinical-stage biopharmaceutical company with a growing pipeline across obesity and rare disease. Syntis Bio’s pill-based synthetic tissue platform unlocks the therapeutic potential of the small intestine by creating a safe, tolerable, and temporary lining that allows precise, programmable control of both nutrient and drug absorption. Syntis Bio is rapidly advancing a pipeline of oral therapies engineered for targeted activity in the small intestine, the body’s nexus for metabolic control, digestion and drug absorption. Alongside SYNT-101, the Company is advancing a portfolio of therapies in obesity and in orphan metabolic diseases. Syntis Bio is headquartered in Boston, MA. For more information, please visit www.syntis.bio and follow us on LinkedIn.

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