Mussels-inspired polymer helps Syntis Bio deliver drugs by coating the intestine

Rahul Dhanda is the head of a new therapeutic company, Syntis Bio, launched this week. But for Dhanda, the business began 20 years ago, when he cold-emailed Bob Langer, PhD, a professor in MIT’s department of chemical engineering (and, as of this week, a Kavli Prize winner .)

While Dhanda was finishing his MBA in Boston, less than a week before graduation, he sent Langer an email with a note saying he would love to meet him. His expectations for a response were low. But to his surprise, a response from Langer appeared in his inbox within minutes and a meeting was arranged. The two men have remained in contact since this first meeting.

Most recently, Dhanda recalled Langer. This time it was because he was considering his next move after leaving his position at Sherlock Biosciences, where he had been CEO for several years. This time the call was for advice. As before, Langer responded the same day. The call turned into a meeting with Giovanni Traverso, PhD, associate professor at MIT. Traverso, a gastroenterologist, and Langer, a bioengineer, worked together to identify a way to target the gut in a sustainable way. Together, the trio launched Syntis Bio, a Dorchester, Massachusetts-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 entire spectrum of healthcare, from rare genetic diseases to the world’s most prevalent conditions. . To do this, they focus on the small intestine, Dhanda said. GENERATIONan incredible location for therapeutic targeting as it provides the link between metabolic control, drug absorption and digestion.

At the heart of the company 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, such as the duodenum. After successful deployment in the gastrointestinal tract, the polydopaminergic mucosa persists for up to 24 hours, after which it is naturally eliminated from the body.

SYNT exploits the mechanism used by mussels to adhere to the ocean floor; mussels secrete a chemical that polymerizes and becomes sticky when wet. It also adheres to mucous membranes, such as in the small intestine. Once SYNT reaches the small intestine, where the enzymes that start the process are located, activation occurs and forms a tissue covering over the duodenum. To do this, SYNT introduces two main components: hydrogen peroxide and dopamine. Hydrogen peroxide is cleaved by catalase (found endogenously in the epithelial lining) into water and oxygen. The oxygen then acts as a catalyst for the polymerization of dopamine. Once exposed to oxygen, the polymerization process occurs rapidly. Within a few minutes, a tissue layer of polydopamine forms in the intestine.

SYNT becomes part of the mucosa and is then naturally secreted as the mucosa rebuilds. It can create a barrier and be combined with a drug or gut-restricted enzyme to keep them in one place rather than traveling freely through the gastrointestinal tract. Dhanda noted that this does not only affect the intestine, but could also act on the eyes, on bleeding wounds, cartilage, neurons, etc. Data from more than 100 preclinical studies in pigs conducted by MIT and Syntis demonstrate that SYNT can achieve 70% glucose blockade. , 20 times improved enzymatic activity and 4 to 10 times greater bioavailability of oral drugs.

The company’s first drug in development, SYNT-101, is intended for the treatment of obesity. Dhanda noted that when the company first started thinking about obesity, “no one wanted to get involved in obesity therapies because they thought there was nothing.” Today is 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 down the small intestine, where absorption is better controlled, and stimulates a full cascade of satiety hormones such as GLP-1 and the PYY. A formulation of SYNT-101 is currently undergoing human trials to establish preliminary safety, tolerability and blocking efficacy, with a full data readout expected 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 bariatric 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,” Traverso said. “SYNT-101 has the potential to enable significant and durable weight loss with a more favorable cost and tolerability profile than existing injectable GLP-1 therapies, which would significantly address current market gaps and unmet needs. patient satisfaction with obesity care.

Earlier this year, Syntis expanded its portfolio by acquiring a portfolio of technical enzymes from Codexis. Syntis’ initial goal is to develop first-in-class, orally administered treatments for homocystinuria (SYNT-202) and maple syrup urine disease (SYNT-203). Both conditions currently have no approved disease-modifying treatments. SYNT-202 and SYNT-203 have completed studies in non-human primates, and the company plans to file an IND application with the FDA for one of these drug candidates in 2025.