Syntis Bio reported encouraging 28-day MAD results from its Phase I/Ib SYNTIETY-1 study of SYNT-101, an investigational once-daily oral pill for obesity. In 23 overweight or obese adults across three dose levels (857–2,571 mg), SYNT-101 raised GLP-1 and PYY by 2–5x, lowered ghrelin, and produced greater weight loss than placebo. The company says the hormone pattern resembles that seen after gastric bypass and plans to advance the program to Phase II.
Syntis Bio Reports Promising Phase I/Ib MAD Results for Oral Obesity Candidate SYNT-101
SYNT-101 is an oral therapy intended for the potential treatment of obesity. Credit: Monkey Business Images / Shutterstock.com.
Syntis Bio has released results from the multiple ascending dose (MAD) part of its Phase I/Ib SYNTIETY-1 study evaluating SYNT-101, an investigational once-daily oral therapy for obesity.
The 28-day MAD cohort enrolled 23 adults who were overweight or living with obesity and tested three dose levels (857 mg, 1,714 mg and 2,571 mg). The study assessed safety, exploratory pharmacodynamic markers and short-term weight change.
Key Findings
Tolerability: SYNT-101 was well tolerated across all dose cohorts. There were no participant withdrawals or dose reductions, and gastrointestinal adverse events occurred at frequencies similar to placebo.
Hormone Effects: Exploratory pharmacodynamic measures showed 2- to 5-fold increases in the satiety hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), together with reductions in the hunger hormone ghrelin. The company reports this multi-hormone signature resembles the metabolic changes typically seen after gastric bypass surgery.
Weight Change: Participants receiving SYNT-101 lost more weight than those on placebo in each dose cohort. The magnitude of short-term weight loss was described by the company as comparable to what is often observed with GLP-1 therapies over a similar timeframe.
Proposed Mechanism and Next Steps
Syntis Bio says SYNT-101 is designed to act locally in the gut: the compound forms a transient lining in the duodenum that is intended to trigger satiety responses at mealtimes while avoiding systemic circulation. The company views the MAD data as a de-risking milestone and plans to advance SYNT-101 into Phase II testing.
David Rosenbaum, Chief Development Officer, Syntis Bio: "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."
"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 II."
The MAD results build on earlier findings from the single ascending dose (SAD) arm of SYNTIETY-1 reported in July 2026. Syntis Bio first dosed a patient in the trial in March 2026.
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