RARE Daily

Syntis Bio Launches to Develop Therapies for Obesity, Diabetes, and Rare Diseases

June 11, 2024

Rare Daily Staff

Syntis Bio has launched as a clinical-stage company with a mission to develop oral therapies that provide more accessible, effective, and sustainable solutions across the healthcare spectrum, from rare genetic disorders to the world’s most prevalent conditions.

By harnessing the small intestine’s unique biology as the nexus for metabolic control, digestion and drug absorption, the company is rapidly advancing a portfolio of programs addressing metabolic diseases ranging from obesity to rare pediatric indications homocystinuria (HCU) and maple syrup urine disease (MSUD).

MIT’s Robert Langer, Rahul Dhanda, and Giovanni Traverso co-founded the company. Syntis is advancing lead obesity program, SYNT-101, through human trials, as well as advancing a pipeline of rare disease assets into Investigational New Drug-enabling studies.

In 2023, the company raised a seed round of $15.5 million from Safar Partners, BOLD Capital Partners, Touchdown Ventures, Colorcon Ventures and Portal Innovations.

“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 HCU and MSUD, where thousands suffer and options are scarce,” said Dhanda, who serves as CEO of Syntis.

The company’s lead program, SYNT-101, is a once-daily pill that mimics the effects of gastric bypass surgery by transiently blocking nutrient absorption in the duodenum, the upper part of the small intestine. This mechanism, known as duodenal nutrient exclusion, diverts nutrients to the lower small intestine, where absorption is more controlled, and stimulates a full cascade of satiety hormones such as GLP-1 and PYY. A formulation of SYNT-101 is currently undergoing human trials to establish preliminary safety, tolerability and blocking efficacy, with a full data readout anticipated by the end of 2024. Syntis plans to leverage data from this initial study to support its IND application with the U.S. Food and Drug Administration in 2025.

SYNT-101 is powered by SYNT (SYNthetic Tissue-lining), an oral therapeutic technology developed by Langer and Traverso that uses mussel-inspired polymer chemistry to deliver a safe, transient polydopamine coating to catalase-rich tissues, like the duodenum. After successful deployment in the gastrointestinal tract (GI), the polydopamine lining is sustained for up to 24 hours, after which it is naturally and safely cleared from the body.

As a technology platform, SYNT is highly versatile and can achieve a variety of therapeutic effects. In addition to nutrient exclusion, SYNT can be engineered to install and sustain gut-restricted enzymes in the small bowel, enhance the oral bioavailability of drugs, and target new tissues throughout the body. Data from more than 100 preclinical pig studies conducted by MIT and Syntis demonstrate that SYNT can achieve 70 percent glucose blocking, 20 times improved enzyme activity, and 4-10 times increased oral drug bioavailability.

“What began as research to enhance the bioavailability of oral pediatric therapies quickly shifted to a vastly larger scale as we recognized that SYNT’s elegantly simple chemistry could help solve many global health challenges,” said Langer, who is also the David H. Koch Institute Professor at MIT. “The small intestine is the key to treating a broad spectrum of disorders and, by targeting this region, SYNT not only functions therapeutically on its own, but it also improves systemic drug bioavailability and local activity of biologic therapies, including enzymes.”

In April 2024, Syntis expanded its pipeline by acquiring a portfolio of engineered enzymes from Codexis. Syntis’ initial focus is on developing first-in-class, orally administered treatments for homocystinuria (SYNT-202) and maple syrup urine disease (SYNT-203). Both conditions currently lack any approved disease modifying therapies. SYNT-202 and SYNT-203 have completed non-human primate studies, and the company anticipates filing an IND application with the FDA for one of these drug candidates in 2025.

Syntis is actively developing next-generation formulations of SYNT-202 and SYNT-203 that leverage SYNT technology to improve local therapeutic activity and residence time for maximal patient benefit. Additionally, the company has several discovery-stage research projects underway exploring solutions for pancreatic insufficiency and peptic ulcers.

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