Move over, GLP-1s. Syntis launches with clinical-stage obesity pill to mimic gastric bypass surgery

GLP-1 agonists and their next-gen successors may still be center stage in the red-hot obesity space, but newly launched Syntis Bio is taking a different approach.

The Boston-based biotech’s lead program is called SYNT-101, a once-daily pill designed to mimic the effects of gastric bypass surgery by blocking the absorption of nutrients into the upper part of the small intestine. The company’s pipeline is further padded out by candidates recently acquired from enzyme engineering company Codexis.

SYNT-101 has already entered the clinic, with a full readout from the first-in-human trial to determine safety and efficacy expected later this year. The data will be used to seek an IND from the FDA in 2025 to conduct further human studies, Syntis said in a June 11 release.

The pill is based on so-called SYNthetic Tissue-lining tech developed by Massachusetts Institute of Technology’s Robert Langer and Giovanni Traverso, Ph.D., who, as well as being the company’s founders, are among its board members. The tech uses polymer chemistry inspired by nature—specifically, the water-dwelling mollusks known as mussels—to deliver a safe, transient polydopamine coating to catalase-rich tissues, like the duodenum.

This polydopamine lining diverts nutrients to the lower small intestine, where absorption is more controlled, stimulating satiety hormones such as GLP-1 and PYY. The lining is designed to last for up to 24 hours, after which it is naturally cleared from the body.

As well as slowing the absorption of nutrients, SYNT-101 can also be engineered to achieve a range of other therapeutic effects. More than 100 preclinical studies in pigs conducted by MIT and Syntis have shown that the tech can achieve 70% glucose blocking, 20 times improved enzyme activity and 4 times to 10 times increased oral drug bioavailability, according to the biotech’s release.

“While GLP-1 drugs have delivered new hope and unprecedented efficacy, there is significant demand for additional treatment options given ongoing issues with accessibility, cost, side effects and long-term maintenance,” Syntis’ CEO and co-founder Rahul Dhanda said in the release.

“We are excited by the encouraging results seen so far in human trials for our SYNT-101 program, which may offer an alternative or complementary obesity therapy in a convenient, accessible once-daily pill,” Dhanda said.

The company’s plans are funded by a $15.5 million seed round last year involving the likes of Safar Partners, BOLD Capital Partners, Touchdown Ventures, Colorcon Ventures and Portal Innovations.

Further back in Syntis’ pipeline is a portfolio of engineered enzymes picked up from Codexis in April. Syntis is targeting these assets on rare pediatric diseases with an initial focus on homocystinuria and maple syrup urine disease. Both diseases involve an inability to break down specific amino acids in the body, and patients don’t currently have access to any disease-modifying therapies. The hope is to file an IND application with the FDA for one of these programs next year.

“By unlocking the small intestine’s therapeutic value, we are pioneering more effective treatments across a vast spectrum of conditions—from widespread issues affecting millions, like obesity and diabetes, to rare conditions such as homocystinuria and maple syrup urine disease, where thousands suffer and options are scarce,” Dhanda added.

Codexis’ CEO Stephen Dilly, Ph.D., put the transfer of the assets in the context of the company’s decision last year to narrow its focus to its RNAi therapeutics manufacturing capabilities.

“Since announcing our strategic shift last year, the team at Codexis has been diligently working to find the right partners to continue advancing our biotherapeutics compounds,” Dilly said in Syntis’ release this morning. “We look forward to seeing what the combination of SYNT technology and the Syntis team can deliver for these rare disease patients.”