Boston — Syntis Bio reported positive initial safety, tolerability and pharmacodynamic data from the single ascending dose portion of a Phase 1/1b clinical trial evaluating SYNT-101 as a potential treatment for obesity.
SYNT-101 was well tolerated across all tested doses, with no serious adverse events, treatment-related gastrointestinal adverse events or discontinuations, the company said.
The drug is an investigational once-daily oral tablet designed to replicate some of the metabolic effects of bariatric surgery by creating a temporary, self-clearing lining in the small intestine. Syntis said the approach redirects nutrients to another section of the intestine, triggering hormones involved in satiety and metabolism.
The data are being presented at the 4th Obesity & Weight Loss Drug Development Summit 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 portion of the SYNTIETY-1 trial enrolled 32 healthy adults across four ascending-dose groups ranging from 857 milligrams to 3,428 milligrams, equivalent to one to four tablets.
The only treatment-related adverse event was mild, self-limited hypoglycemia during oral glucose tolerance testing, according to the company.
Continuous glucose monitoring during the testing showed a 17% reduction in glucose absorption compared with baseline over the measured period.
A single-tablet dose was also associated with 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 hormones are involved in appetite, satiety and metabolism.
Syntis said the findings build on earlier preclinical and first-in-human pilot data showing that SYNT-101 adhered to the intestine, was tolerated and cleared within 24 hours. Preclinical studies also suggested the drug could produce continued weight loss while preserving 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.”
Enrollment has been completed in a 28-day multiple ascending dose portion of the trial involving overweight or obese patients. That portion will evaluate changes in metabolic markers associated with weight management, with results expected later this year.
SYNT-101 works through a mechanism known as duodenal nutrient exclusion. The drug temporarily blocks nutrient absorption in the upper small intestine and redirects nutrients to the lower small intestine, where they stimulate the release of hormones including GLP-1.
The company is also evaluating whether SYNT-101 could be used with GLP-1 agonists to produce additive or synergistic effects.
