Fibrosis-targeted Therapies Will Be Focus of Start-up Based on Discovery at Singapore Lab

Research into key drivers of fibrosis will be used by a Singapore-funded biotechnology start-up, Enleofen Bio, to possibly develop first-in-class therapeutics for pulmonary fibrosis (PF) and other fibrosis-related diseases.

The intellectual property that came from the work performed at two Singapore institutions, Duke-NUS Medical School (Duke-NUS) and National Heart Centre Singapore (NHCS), was licensed to Enleofen Bio.

Findings were reported at the Annual Congress of the European Society of Cardiology in Barcelona on Aug. 28, in a presentation titled “Integrated target discovery screens identify a novel therapeutic target for cardiovascular fibrosis.”

In their joint work, scientists investigated new genes important for fibrosis in order to better understand the disease’s biology and to potentially discover new drug targets.

Researchers first established primary fibroblast cultures from biopsies of patients with cardiac fibrosis. Fibroblasts are a type of cell involved in fibrosis development. Then, through a genome wide analyses, the team identified — and later verified — interleukin-11 (IL-11) as the leading pro-fibrotic molecule present in the fibroblast samples.

Besides being evident at high levels on fibroblast cultures, IL-11  was found by the researchers to be an important player in collagen deposition and fibroblast activation — two features of fibrotic processes.

Further work in mice models of cardiac and renal fibrosis showed that inhibiting IL-11 activity protected the animals from fibrosis development.

“We discovered that a specific cytokine [IL-11] is a key driver and potentiator of TGF-beta in cardiac fibrosis. Ironically, it has been in plain sight for many years, but unfortunately for patients, this target was completely mischaracterized and hence overlooked,” Stuart Cook, who led the research, said in a press release.

Cook, director of the Cardiovascular & Metabolic Disorders program at Duke-NUS and director of the National Heart Research Institute Singapore (SingHealth), is also director and a co-founder of Enleofen Bio.

Moving such “bench” findings into clinical work was encouraged and supported by Duke-NUS, NHCS and the National Health Innovation Centre of Singapore to support the research and assist in the development of therapeutic applications with a commercial use.

“We are very excited to see this great Singapore-derived therapeutics platform now under development at Enleofen Bio,” said David Epstein, director of the Centre for Technology and Development and Duke-NUS vice dean for Innovation and Entrepreneurship. “We have found the right partners to take Professor Cook’s work to the next level of clinical application to improve peoples’ health and lives.”

In related news

The British Lung Foundation (BLF), in collaboration with GlaxoSmithKline (GSK) has awarded £1.3 million (about $1.68 million) in grants to three lung disease experts to support research projects on finding new therapeutic targets for personalized medicine in idiopathic pulmonary fibrosis (IPF), bronchiectasis and chronic obstructivepulmonary disease (COPD).

One of the three recipients is Toby Maher, clinical investigator at the National Heart and Lung Institute (NHLI), Imperial College London, and consultant respiratory physician at Royal Brompton Hospital’s Interstitial Lung Disease Unit.

Maher and his team are studying the underlying mechanism that causes the tissue scaring that leads to IPF. He is also identifying groups of patients who may respond well to personalized treatments.