Syntis Bio Doses First Patient in Phase 1/1b Trial of Novel Oral Obesity Treatment SYNT-101
Key Insights
Syntis Bio (search) has dosed the first patient in its Phase 1/1b SYNTIETY-1 clinical trial of SYNT-101, a once-daily oral pill designed to mimic gastric bypass surgery effects for obesity treatment.
SYNT-101 works by blocking nutrient absorption in the duodenum and redirecting nutrients to stimulate natural secretion of satiety hormones including GLP-1 (search), potentially preserving lean muscle mass.
The 28-day multi-ascending dose trial in Australia will evaluate safety, tolerability, and pharmacokinetics in healthy volunteers and overweight or obese patients.
Syntis Bio (search) has achieved a significant clinical milestone by dosing the first patient in its Phase 1/1b SYNTIETY-1 clinical trial of SYNT-101, the company's lead investigational program for obesity treatment. The novel once-daily oral pill is designed to redirect nutrient absorption past the small intestine's duodenum, mimicking the effects of gastric bypass surgery.
"Dosing of our first SYNTIETY-1 patient is a significant milestone for Syntis and for the SYNT-101 clinical program," said Rahul Dhanda, Chief Executive Officer of Syntis Bio (search). "This progress underscores the potential of our SYNT™ platform, which is designed to harness the biology of the small intestine to develop the next generation of oral therapeutics, either as monotherapy treatments or as co-formulations to enhance or combine the effects of other drugs."
Novel Mechanism Targets Duodenal Nutrient Exclusion
SYNT-101 works by transiently blocking nutrient absorption in the duodenum, the upper part of the small intestine, and redirecting nutrients to the distal small intestine to stimulate the natural secretion of satiety and metabolism-regulating hormones, including GLP-1 (search). 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 across both studies, with no adverse events reported.
Phase 1/1b Trial Design and Objectives
The Phase 1/1b trial is being conducted in Australia and is designed to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of SYNT-101 in healthy volunteers and in overweight or obese patients. The 28-day multi-ascending dose arm of the trial will also evaluate changes in relevant metabolic markers associated with weight management.
SYNT-101 may be used in conjunction with GLP-1 (search) agonists for potential additive or synergistic effects, positioning it as a potential combination therapy in the obesity treatment landscape.
SYNT™ Platform Technology
The drug leverages Syntis Bio (search)'s SYNT™ (SYNthetic Tissue-lining) technology, an oral therapeutic platform designed to enhance disease-modifying activity within the small intestine. 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.
Leadership Expansion
In conjunction with this clinical milestone, Syntis Bio (search) announced the appointments of David Rosenbaum, Ph.D., as Chief Development Officer, and Christo Shalish as Chief Business Officer, further strengthening the company's leadership team as it enters a pivotal phase of growth.
Dr. Rosenbaum brings more than two decades of experience in clinical development and regulatory strategy across gastrointestinal, metabolic and cardiovascular diseases. Prior to joining Syntis Bio (search), he served as Chief Development Officer at Ardelyx, where he led development efforts for multiple programs and guided Xphozah® and Ibsrela® through FDA approval for the treatment of hyperphosphatemia in chronic kidney disease and irritable bowel syndrome with constipation, respectively.
"I am thrilled to join Syntis at this inflection point," said Dr. Rosenbaum. "The company's mission and scientific approach have immense potential to help patients, globally and across the healthcare spectrum. Launching the SYNT-101 clinical program is a significant milestone that reflects our continued progress in advancing a differentiated obesity pipeline into the clinic."
Mr. Shalish joins with more than two decades of experience in business development, corporate strategy and strategic partnering across the biotechnology and pharmaceutical sectors. He previously served as Senior Vice President of Business Development and Strategy at Flagship Pioneering (search) and held senior roles at Frontier Medicines, Novo Nordisk, Dicerna Pharmaceuticals, Moderna, and other biotechnology companies.
"SYNT-101 and the SYNT platform represent a differentiated solution to oral therapeutics," commented Mr. Shalish. "As the program advances clinically, we are focused on forging strategic partnerships and building durable, long-term value for SYNT-101 and beyond."
Syntis Bio (search) is rapidly advancing a pipeline of oral therapies engineered for targeted activity in the small intestine, with programs spanning obesity and orphan metabolic diseases beyond its lead SYNT-101 program.