Forward-looking: The rising popularity of GLP-1 receptor agonists like Ozempic and Wegovy has transformed obesity treatment and spurred competition among pharmaceutical companies to develop more effective alternatives. One such contender is Syntis Bio, a Boston-based biotech firm working on an oral medication designed to replicate the effects of gastric bypass surgery without the need for invasive procedures. The company recently unveiled promising early data at the European Congress on Obesity and Weight Management in Barcelona, highlighting the potential of its lead candidate, SYNT-101. SYNT-101 offers a novel approach to weight loss by temporarily altering nutrient absorption in the small intestine. Unlike GLP-1 drugs, which are administered via injection and often come with side effects such as nausea and vomiting, SYNT-101 is a once-daily pill that mimics the metabolic effects of gastric bypass surgery. The drug forms a temporary coating in the upper small intestine, redirecting nutrients to the lower intestine where satiety hormones like GLP-1 are naturally activated. This mechanism promotes feelings of fullness and supports sustainable weight loss, all while preserving lean muscle mass – a common concern with current anti-obesity medications. The science behind SYNT-101 is based on research conducted at MIT by gastroenterologist Giovanni Traverso and chemical engineer Robert Langer, who co-founded Syntis Bio with CEO Rahul Dhanda in 2022. SYNT-101 is meant to replicate the effects of gastric bypass surgery The drug's design leverages two key ingredients: dopamine and hydrogen peroxide. When ingested, these compounds interact with an enzyme called catalase in the small intestine to form a biocompatible polymer coating known as polydopamine. This coating lasts for approximately 24 hours before being naturally cleared through the body's mucosal turnover. // Related Stories In preclinical studies with rodents, SYNT-101 demonstrated consistent weight loss of one percent per week over six weeks, while preserving 100 percent of lean muscle mass. These findings were echoed in early human trials, where nine participants reported no adverse effects. Although the pilot study was not intended to measure weight loss, blood tests revealed promising hormonal changes: decreased levels of ghrelin, the "hunger hormone, "and increased levels of leptin, which helps regulate appetite. Tissue samples confirmed that the polymer coating formed as expected and was safely eliminated within a day. GLP-1 receptor agonists have challenges including high costs and the loss of lean muscle mass Syntis Bio's findings come at a pivotal moment in obesity treatment. While GLP-1 drugs have earned widespread acclaim for their effectiveness, they are not without drawbacks. High costs, insurance challenges, and unpleasant side effects have led many patients to discontinue their use. "With SYNT-101, we believe we can deliver sustainable, safe, effective weight loss by reducing fat while preserving lean muscle and stimulating natural production of satiety hormones," Dhanda said during the conference. Experts in the field have taken note of SYNT-101's potential. Dr. Louis Aronne, an obesity medicine specialist at Weill Cornell Medical College and a clinical adviser to Syntis Bio, emphasized the drug's promise as a first-line treatment. "A major pitfall of current GLP-1 drugs is related to gastrointestinal side effects as well as the loss of lean muscle that accompanies weight loss," Aronne noted. "SYNT-101's mechanism of action may avoid these issues entirely." Dr. Vladimir Kushnir, director of bariatric endoscopy at Washington University in St. Louis, praised the early data but cautioned that larger trials are necessary to fully assess the drug's efficacy and safety. "My anticipation is that this is going to have some digestive side effects like bloating and abdominal cramping," Kushnir told Wired. Despite these uncertainties, SYNT-101 could represent a significant advancement in obesity treatment. Syntis Bio plans to submit an Investigational New Drug (IND) application to the US Food and Drug Administration later this year and hopes to begin Phase 1 clinical trials shortly thereafter.