Maple Syrup Urine Disease

By leveraging the small intestine’s role in metabolic control, digestion and drug absorption, the company is progressing with a portfolio of programmes. Credit: Billion Photos / Shutterstock. Clinical-stage biopharmaceutical company Syntis Bio has announced the launch of developments for oral therapies targeting a range of metabolic diseases, from obesity to rare conditions such as homocystinuria (HCU) and maple syrup urine disease (MSUD). Recommended Buyer's Guides Buyer's Guide Leading Guide to Compliance Software for the Pharmaceutical Industry Buyer's Guide Leading Guide to Clinical Packaging Companies in contract Manufacturing for the Pharmaceutical Industry By leveraging the small intestine’s role in metabolic control, digestion and drug absorption, Syntis Bio is progressing with a portfolio of promising programmes. In 2023 the company secured $15.5m in a seed funding round from investors including Safar Partners, Touchdown Ventures, BOLD Capital Partners, Colorcon Ventures and Portal Innovations. The company’s lead obesity programme, SYNT-101, is currently undergoing human trials, while other rare disease assets are moving towards investigational new drug (IND)-enabling studies. It is a once-a-day oral medication designed to replicate the effects of gastric bypass surgery by temporarily obstructing nutrient uptake in the duodenum, the small intestine’s upper part. See Also: Takeda signs option agreement with Ascentage for CML drug UK’s new Netflix-style funding model for antibiotics goes live The drug aims to reroute nutrients to the lower small intestine, enhancing controlled absorption and triggering a series of satiety hormones such as GLP-1 and PYY. Preliminary safety, tolerability and efficacy data from human trials of a SYNT-101 formulation are expected by the end of 2024, which will inform an IND application to the US Food and Drug Administration planned for 2025. Syntis CEO Rahul Dhanda stated: “We are excited by the encouraging results seen so far in human trials for our SYNT-101 programme, 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.” The company expanded its pipeline through the acquisition of engineered enzymes from Codexis in April 2024. Syntis Bio will initially focus on the development of orally administered therapies for HCU (SYNT-202) and MSUD (SYNT-203), both of which lack approved disease-modifying therapies. After successful non-human primate studies, the company anticipates an IND submission for one of these candidates.

Syntis Bio's 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. 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.”

Syntis Bio emerged from stealth on Tuesday with ambitions to mimic the effectiveness of weight-loss surgery with a once-daily oral therapy. The company – which counts mRNA pioneer Robert Langer as one of its co-founders – is hoping to exploit the small intestine’s unique biology to not only combat obesity, but a range of rare metabolic diseases.“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,” noted co-founder Rahul Dhanda, the start-up's chief executive. The biotech is using the fact that the small intestine serves as the nexus for metabolic control, digestion and drug absorption. Its lead programme, SYNT-101, is designed to mimic the effects of gastric bypass surgery by transiently blocking nutrient absorption in the upper part of the small intestine. Syntis explained that this 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 peptide YY. IND filing in 2025A formulation of SYNT-101 – which is powered by the company’s SYNT oral therapeutic technology – is currently in human testing, with full data due by the end of 2024. Findings from the study are expected to support an IND application with the FDA next year."What began as research to enhance the bioavailability of oral paediatric therapies quickly shifted to a vastly larger scale as we recognised that SYNT’s elegantly simple chemistry could help solve many global health challenges," remarked Langer. The technology uses mussel-inspired polymer chemistry to deliver a polydopamine coating to catalase-rich tissues, like the small intestine, which lasts for 24 hours before being naturally cleared from the body.Key to many disorders"The small intestine is the key to treating a broad spectrum of disorders,” Langer noted, with the SYNT platform also able to install and sustain gut-restricted enzymes in the small bowel, enhance the oral bioavailability of drugs, and target new tissues throughout the body. Earlier this year, Syntis acquired a portfolio of engineered enzymes from Codexis, including SYNT-202 for homocystinuria and SYNT-203 for maple syrup urine disease. The company is now working on next-generation formulations of the oral drugs and expects to submit an IND for one of them to the FDA next year.Syntis is backed by Safar Partners, BOLD Capital Partners, Touchdown Ventures, Colorcon Ventures and Portal Innovations, and raised $15.5 million in seed financing in 2023.For related analysis, see Vital Signs: Updating the oral obesity efficacy landscape – can they compete with injectables?