After a decade in the type 2 diabetes game, Fractyl Laboratories recharges with a fresh $100M and a new name
Harith Rajagopalan compared the way type 2 diabetes is managed to sticking your fingers in a dam that’s leaking from a number of places.
You can take drugs to lower your blood sugar, cholesterol, or blood pressure, but you’re not addressing what he says is the core issue — the metabolic abnormality that causes the disease.
“We’re so busy plugging the holes in the dam, we don’t have time to see that the whole infrastructure is at risk,” he said. “That infrastructure is a full-body systemic metabolic abnormality called metabolic syndrome, that we’re ignoring while we’re so busy trying to treat all of the individual symptoms of the condition.”
Following evidence that the gut is a key driver of metabolic control, Rajagopalan launched Fractyl Laboratories with a $5.5 million Series A round back in 2011. Almost exactly a decade later, the company’s back with a $100 million Series F round and a shiny new name to continue the hunt for therapies to reverse metabolic disease.
Fractyl Health will use the Series F funds to advance its endoscopic therapy, Revita DMR, in late-stage studies across the spectrum of type 2 diabetes. The technology recently received breakthrough device designation, and is expected to complete a registrational trial in insulin-treated patients in the US in 2023.
Why the subtle name change? “We want to stand really firmly on the side of improving health for patients and for society, rather than managing disease,” Rajagopalan told Endpoints News.
The company has raised about $280 million so far. But when asked whether he has plans to go public, Rajagopalan responded: “We don’t have any news to share on that as of now.”
Revita DMR makes use of a balloon catheter to inject saline into the walls of the duodenum, the first part of the small intestine immediately beyond the stomach. Duodenal lining thickens over time due to modern diets high in fat in sugar. This “cushion of saline” thickens the lining, in order to separate it from deeper structures. The balloon then heats up to about 90 degrees Celsius (194 degrees Fahrenheit), essentially stripping away that excessive layer. Then the body heals itself, regenerating a new, healthy lining which Fractyl believes could restore insulin sensitivity.
“The reason we target the duodenum is because there’s a lot of evidence that, in people with type 2 diabetes and obesity, there’s a dysfunctional duodenal signal that’s triggering insulin resistance in the liver, and that we believe to be one of the very first events in the metabolic syndrome,” Rajagopalan explained.
Fractyl began enrolling in the registrational trial, dubbed REVITA-T2Di, in the first half of this year. The primary endpoint in that study is the percentage of patients who achieve glycemic control (defined as HbA1c levels less than or equal to 7%) without the need for insulin after 24 weeks.
In a trial conducted in Europe and Brazil, Revita DMR didn’t reach statistical significance in reduction of HbA1c levels in the combined populations, though Rajagopalan said the Brazil group was underpowered. In just the European population, median HbA1c change from baseline was –6.6mmol/mol (17.5mmol/mol) in the Revita group, versus –3.3mmol/mol (10.9mmol/mol) in a sham group, with a p-value of 0.033, according to data published in the BMJ.
While Rajagopalan believes the procedure can benefit patients for “a very long time,” he’s still unsure exactly how often patients might need to repeat it.
“We’re looking forward to doing some studies in which we can show the repeatability after several years,” he said.