HONG KONG – Enleofen Bio Pte Ltd., of Singapore, said it has discovered a key target for the treatment of fibrosis, which could significantly improve the therapies by offering more effective options with fewer side effects to the patients.

Fibrosis is the formation of excessive connective tissue; it can disrupt the structure and function of the organ where it forms. That process may affect many areas within the body and is the main pathology behind heart and renal failure.

The newly discovered interleukin-11 (IL-11) factor, according to data published in Nature, is another major cause of fibrosis and scarring of body organs other than the transforming growth factor beta 1 (TGF-B1), which has been the base of existing fibrosis therapies. The scientists showed that inhibiting IL-11 prevents fibrosis through a wide range of pathways, putting it in the very center of the fibrotic process.

"Currently there are no treatments for fibrosis on the market that work well," said Stuart Cook, director and co-founder of Enleofen. "Those that exist are old, have side effects and are not consistent in their effects."

The existing therapies that try to target the TGF-B1 protein are based on switching off the gene for TGF-B1 and have severe side effects, as that protein plays other important nonfibrosis roles in the body.

"IL-11 is like a master switch for fibrosis – all profibrotic stimuli need it to make fibrosis. IL-11 is specific for fibroblasts, so if you turn it off you only turn off fibroblasts," Cook told BioWorld. "TGF-B1 is important for fibroblasts but also lots of other cells. Turning off TGF-B1 also turns off the immune system leading to infection and cancer.

"We are convinced that IL-11 is even more important than TGF-B1 for fibrosis, as inhibiting IL-11 prevents fibrosis through a wide range of pathways of which TGF-B1 is just one. While it is surprising that the importance of IL-11 has been overlooked for so long, it has now been very clearly demonstrated," he added.

Toxicity associated with inhibiting IL-11 is not expected, as mice lacking the IL-11 receptor have no significant abnormalities. Furthermore, humans who are mutant for the receptor of IL-11 have only a minor developmental abnormality and are otherwise normal; they also are not unusually susceptible to diseases and have normal life spans.

Backed by Duke-National University of Singapore (NUS), Enleofen is a biotech startup with focuses on human fibrosis assays, human-based genetic and genomic discovery, models of human disease, and human genetic data that support drug safety. A suite of patents and products have been licensed from the university into the spin-out. (See BioWorld, Sept. 25, 2017.)

The company aims to develop its lead antibodies in clinical trials within a two-year time frame with the goal of creating a drug that can be used to treat multiple diseases for which there are currently no treatment options.

"We are working together with the company Abzena for the development of our first-in-class antibody therapeutics for the treatment of fibrotic human diseases," said Cook.

Abzena plc is a life sciences group providing services and technologies to enable the development and manufacture of biopharmaceutical products.

"We have developed a wide range of potent IL-11 inhibitors and our fully human antibody development program is being advanced with the use of Abzena's Composite CHO cell line technology," said Cook. "We may in the future opt to progress with large scale manufacturing at Abzena's San Diego facility."

Abzena will also support Enleofen through the development of alternative strategies to block IL-11 signaling. Abzena's wide range of protein engineering technologies will help to translate findings from successful proof-of-concept studies in preclinical models of disease to the clinic.

"We are funded to go a long way in drug development but would look for further funding to expedite this process at some time in the future," Cook said. "The potential indications for anti-IL-11 therapy are very many such as fibrosis in liver, lung, heart, retina, skin. . . and as a small biotech we would not be able to take all these on in phase II clinical trials and we would welcome working with others."

Cook, who is also a professor and director of the cardiovascular and metabolic disorders program at Duke-NUS Medical, said the startup has benefited from the university's "active translation model" that allows faculty members to carry on with basic research and gives them access to additional funds, as well as exposure to those who have led industrial research.