Lead program SYNT-101 now in human trials to validate potential as a once-daily oral obesity therapy

Orphan pediatric portfolio acquired from Codexis expands pipeline with first-in-class oral enzyme replacement therapies for homocystinuria and maple syrup urine disease; both programs ready for IND-enabling studies

Proprietary SYNT technology optimizes therapeutic effects in the small intestine, the body's nexus for metabolic control, digestion and drug absorption

BOSTON--(BUSINESS WIRE)--Syntis Bio, Inc. (Syntis) today announced its launch as a clinical-stage biopharmaceutical 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).

Co-founded by industry veteran Rahul Dhanda and Massachusetts Institute of Technology (MIT) visionaries Robert Langer, Sc.D., and Giovanni Traverso, M.B., B.Chir., Ph.D., Syntis is advancing its lead obesity program, SYNT-101, through human trials, as well as advancing a pipeline of rare disease assets into Investigational New Drug (IND)-enabling studies. In 2023, the company raised a seed round of $15.5 million from leading life sciences and strategic investors, including Safar Partners, BOLD Capital Partners, Touchdown Ventures, Colorcon Ventures and Portal Innovations.

"Obesity is a global epidemic projected to affect 1.5 billion people by 2030. 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," said Mr. Dhanda, who serves as Chief Executive Officer of Syntis. "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. 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."

SYNT-101 once-daily pill for obesity

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 & Drug Administration (FDA) in 2025.

"While weight loss surgery remains the gold standard for obesity and diabetes management, SYNT-101 represents a pioneering non-invasive, non-surgical way to replicate this mechanism of action in a simple pill," said Dr. Traverso, who is also an Associate Professor of Mechanical Engineering at MIT and an Associate Professor of Gastroenterology at Brigham and Women's Hospital, Harvard Medical School. "SYNT-101 has potential to achieve significant, sustainable weight loss with a more favorable cost and tolerability profile than existing injectable GLP-1 therapies, which would meaningfully address current market gaps and unmet patient needs in obesity care."

SYNT-101 is powered by SYNT (SYNthetic Tissue-lining), an oral therapeutic technology developed by Drs. 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% 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 Dr. 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."

Rare pediatric disease portfolio

In April 2024, Syntis expanded its pipeline by acquiring a portfolio of engineered enzymes from Codexis, Inc. 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.

"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. We are delighted to partner with Syntis for further development of two potential first-in-class treatments for homocystinuria and maple syrup urine disease," said Stephen Dilly, MBBS, Ph.D., Chief Executive Officer of Codexis. "We look forward to seeing what the combination of SYNT technology and the Syntis team can deliver for these rare disease patients."

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.

The Syntis board of directors is composed of Mr. Dhanda and Drs. Langer and Traverso, as well as highly experienced corporate strategists and company builders Teymour Boutros-Ghali, Ph.D., co-founder and Managing Partner of BOLD Capital, and Martin Madaus, D.V.M., Ph.D., Operating Executive at the Carlyle Group.

About Syntis Bio

Syntis Bio is a clinical-stage biopharmaceutical company developing oral therapies that harness the small intestine's unique biology to provide more accessible, effective and sustainable solutions across the healthcare spectrum, from rare genetic disorders to the world's most prevalent conditions. Syntis is rapidly advancing a pipeline of oral therapies engineered for optimization in the small intestine, the body's nexus for metabolic control, digestion and drug absorption. The company's lead program, SYNT-101, is a once-daily oral pill for the treatment of obesity that mimics the effects of gastric bypass surgery. SYNT-101 leverages the power of SYNT (SYNthetic Tissue-lining), an oral technology developed by Syntis founders that delivers a safe, transient polymer coating to the duodenum that controls nutrient uptake, as well as enhances both gut-restricted enzyme efficacy and systemic drug absorption for up to 24 hours. The company is also developing a portfolio of enzyme replacement therapies to treat orphan metabolic and broad digestive disorders. Syntis is headquartered in Boston and has raised $15.5 million to date from leading life sciences and strategic investors. For more information, please visit and follow on LinkedIn.

Media Contact:
Dan Budwick, 1AB
dan@1abmedia.com

Investor Contact:
IR@syntis.bio