A new interleukin target for NASH spawns Singaporean biotech steered by well known players
A Singaporean biotech looking to break into the big NASH field has offered a glimpse of the preclinical data that’s stoked its confidence in targeting an oft-overlooked cytokine.
Researchers from Duke-NUS Medical School and National Heart Centre Singapore started with hepatic stellate cells, which “are pivotal in the pathogenesis of NASH and give rise to up to 95%” of disease driving cells known as liver myofibroblasts. Here’s how they summarized the current NASH landscape, from their new paper in Gastroenterology:
A number of factors are implicated in HSC activation and transformation, including the canonical pro-fibrotic factors transforming growth factor-B1 (TGFB1) and platelet derived growth factor (PDGF) and also pro-inflammatory factors such as CCL2, TNFA and CCL5.. Perhaps reflecting this complexity and implicit redundancy, no single upstream initiating factor has been targeted successfully in NASH and there are no approved NASH drugs. Currently, there are a number of drugs in clinical trials for NASH but many of these target metabolism and it is not clear if they will improve liver fibrosis, which predicts clinical outcomes.
To simultaneously get at the fat accumulation, inflammation and scarring present in NASH, they need a better target. And the scientists believe they have found the answer in interleukin 11, or IL11.
By inhibiting the protein in mice that have been fed a diet full of fatty food and sugary drinks, the scientists found that they were able not only to prevent fatty liver disease but also reverse its course, according to first author Anissa Widjaja.
“Intriguingly, genetic or pharmacologic inhibition of IL11 is associated with lower serum triglycerides, cholesterol and glucose,” the researchers added. “This aspect of IL11 inhibition is a desirable feature for a potential NASH therapy, as patients with NASH often suffer from cardiovascular diseases.”
It will take years for Enleofen, the biotech spinout entrusted to bear this theory out, to catch up with frontrunners like Intercept (armed with mixed Phase III data) and NGM (supported by a deep-pocketed Merck). But until — or even when — a new drug is approved, you can be sure to see big and small players angling for a slice of the enormous market. Last month, Gilead pungled up $50 million to kickstart a partnership with the AI experts at Insitro, which involves as many as 5 new NASH drugs — and that’s in addition to several assets it’s already blending together in a cocktail.
Stuart Cook, an author of the study and a professor in cardiovascular medicine at Duke-NUS, is a co-founder at Enleofen alongside Sebastian Schäfer. Like him, Andrew Khoo of Tessa Therapeutics and Jeffrey Lu of Engine Biosciences are also directors, adding some star power from two of the small country’s biotech stars. Tim Lu, a pioneer in the synthetic biology field who’s had plenty of experience launching his own startups, is also on board as an adviser.