Rahul Dhanda is at the helm of a new therapeutics company, Syntis Bio, which launched this week. But for Dhanda, the company got its start 20 years ago, when he sent a cold email to Bob Langer, PhD, institute professor in the department of chemical engineering at MIT (and, as of this week, Kavli Prize award winner).
When Dhanda was wrapping up his MBA in Boston, with less than a week until graduation, he sent Langer an email with a note saying that he would love to meet him. His expectations for a response were low. But to his surprise, a reply from Langer appeared in his inbox within minutes and a meeting was arranged. The two have stayed in touch since that initial meeting.
More recently, Dhanda called Langer again. This time, the call was for advice. Dhanda was thinking about his next move after leaving his post at Sherlock Biosciences—where he had been CEO for several years. Like before, Langer responded quickly. The call turned into a meeting with Giovanni Traverso, PhD, associate professor at MIT. Traverso, a gastroenterologist, and Langer, a bioengineer, had been working together to identify a way to target the intestine in a sustained way. Together, the trio started Syntis Bio—a Dorchester, MA-based company that has raised $15.5 million to date.
Syntis Bio’s mission, they say, is 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. To do that, they are focusing on the small intestine which is, Dhanda told GEN, an incredible location for therapeutic targeting because it is the nexus of metabolic control, drug absorption, and digestion.
At the company’s core is SYNT (SYNthetic Tissue-lining) an oral therapeutic technology 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, the polydopamine lining is sustained for up to 24 hours, after which it is naturally cleared from the body.
SYNT leverages the mechanism that mussels use to adhere to the ocean floor; the mussels secrete a chemical that polymerizes—and becomes sticky—when it’s wet. It also sticks to mucosal linings, such as in the small intestine. Once SYNT reaches the small intestine, where the enzymes that start the process are found, activation occurs and it forms a tissue coating over the duodenum. To do this, SYNT introduces two main components: hydrogen peroxide and dopamine. The hydrogen peroxide is cleaved by catalase (which is endogenously found in the epithelial lining) into water and oxygen. Oxygen then acts as a catalyst for dopamine to polymerize. Once it’s exposed to oxygen, the polymerization process occurs quickly. Within minutes, a polydopamine tissue coating is formed in the intestine.
SYNT becomes part of the mucosal lining and then is naturally secreted as the mucosal lining gets replenished. It can create a barrier and be combined with a drug or a gut-restricted enzyme to hold them in a location rather than freely traveling through the GI tract. Dhanda noted that this is not just for the intestine, but could work in the eye, on bleeding wounds, cartilage, neurons, etc. 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.
The first drug in the company’s pipeline, SYNT-101, is for obesity. Dhanda noted that, when the company first started thinking about obesity, “nobody wanted to get involved in obesity therapies because they thought there was nothing there.” Today, it’s a different story.
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 FDA in 2025.
“While weight loss surgery remains the gold standard for obesity and diabetes management, SYNT-101 represents a pioneering noninvasive, nonsurgical way to replicate this mechanism of action in a simple pill,” said Traverso. “SYNT-101 has the 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.”
Earlier this year, 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 nonhuman primate studies, and the company anticipates filing an IND application with the FDA for one of these drug candidates in 2025.
