Syntis Bio Reports Positive Initial Phase 1/1b Single Ascending Dose Data for SYNT-101, Supporting its Novel Approach to Obesity Treatment

SYNT-101 was well tolerated across all doses with no related GI adverse events, no serious adverse events, and no discontinuations

Data confirm SYNT-101's intended mechanism of nutrient redirection, with reduced glucose absorption and favorable changes in satiety hormones after a single dose

Additional data from the multiple ascending dose arm of the trial in obese patients is expected later this year

BOSTON--(BUSINESS WIRE)--Syntis Bio, Inc. a clinical-stage biopharmaceutical company advancing novel oral therapeutics that uniquely leverage the small intestine, today announced initial safety, tolerability, and pharmacodynamic data from the single ascending dose (SAD) arm of its ongoing Phase 1/1b SYNTIETY-1 clinical trial evaluating SYNT-101.

SYNT-101, the Company’s lead investigational program for the treatment of obesity is an investigational once-daily oral tablet designed to replicate the metabolic effects of bariatric surgery via a transient, self-clearing synthetic intestinal lining. These data will be presented at the 4^th Obesity & Weight Loss Drug Development Summit being held July 14-16, 2026, in Boston.

“Results from the SAD arm validate SYNT-101’s core mechanism of action, affirm its potential for best-in-class tolerability among weight management therapies, and demonstrate early indications of efficacy,” said David Rosenbaum, Ph.D., Chief Development Officer of Syntis Bio. “SYNT-101 is built on the premise that by altering where nutrients are sensed in the gastrointestinal tract, the hormonal response will be activated similarly to gastric bypass surgery, but without surgical intervention. Observing delayed nutrient absorption alongside notable increases in satiety hormones GLP-1 and PYY after a single tablet is direct evidence that SYNT-101 triggered that same distal-gut signaling pathway we set out to replicate.”

The randomized, double-blind, placebo-controlled SAD portion of SYNTIETY-1 was designed to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of SYNT-101 in healthy volunteers. Thirty-two healthy adult volunteers were dosed across four ascending cohorts (857 mg to 3,428 mg, corresponding to one to four tablets). Data highlights include:

• SYNT-101 was well tolerated at all dose levels, with no discontinuations, no serious adverse events, and no related GI adverse events
• The only treatment-related adverse event observed was mild, self-limited hypoglycemia occurring during oral glucose tolerance testing (OGTT)
• Continuous glucose monitoring during OGTT showed direct evidence of nutrient redirection with a 17% reduction in glucose absorption versus baseline over the measured duration
• Single-tablet dosing was associated with favorable shifts in post-prandial endogenous satiety-related hormones, including: a 58% increase in total GLP-1, a 125% increase in peptide YY, a 21% reduction in ghrelin, and a 100% increase in leptin

These results build on earlier preclinical and first-in-human pilot findings demonstrating SYNT-101's adhesion, tolerability, and clearance within 24 hours. Preclinical models also indicate that SYNT-101 may result in consistent weight loss without a plateau, as well as preservation of muscle mass.

"These SAD results give us confidence in SYNT-101’s potential to deliver meaningful weight-loss benefit, which we expect to be further informed by the multiple ascending dose data later this year. The degree of nutrient redirection observed, together with favorable tolerability, further validates both SYNT-101’s mechanism and the broader potential of our SYNT platform,” said Rahul Dhanda, Chief Executive Officer of Syntis Bio. “We believe SYNT-101 offers a differentiated, complementary approach to GLP-1s, while our platform creates a unique opportunity to combine synergistic weight loss mechanisms – including existing and next generation GLP-1s and programs from our own obesity pipeline – in a single pill.”

The 28-day multiple ascending dose (MAD) arm of the SYNTIETY-1 trial will evaluate changes in relevant metabolic markers associated with weight management in overweight or obese patients. Enrollment in the cohort is now complete and Syntis Bio expects to announce data from this arm later this year.

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. This mechanism, known as duodenal nutrient exclusion, 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, while first-in-human data showed that SYNT-101 demonstrated strong evidence of nutrient redirection and satiety hormone modulation. Importantly, SYNT-101 displayed strong safety and tolerability with no treatment-related adverse events. SYNT-101, which is being currently evaluated in the Phase 1/1b SYNTIETY-1 (SYNThetic Intestinal ExclusIon Therapy for ObesitY) study in obesity, may be used in conjunction with GLP-1 agonists for potential additive/synergistic effects.

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, enhance the oral bioavailability of drugs, and enable targeting of new tissues throughout the body.

About Syntis Bio

Syntis Bio is a clinical-stage biopharmaceutical company with a growing pipeline across obesity and rare disease. The Company has completed enrollment in a Phase 1/1b clinical study to evaluate lead program SYNT-101 in obesity. 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.