Development of first-in-class antibody therapeutics and new partnership bring hope to patients with fibrotic and inflammatory diseases

• Clinicians and scientists from National Heart Centre Singapore, Duke-NUS Medical School’s Cardiovascular & Metabolic Disorders Programme (CVMD) and SingHealth Duke-NUS Academic Medical Centre (AMC)s’ discovery of a key driver of fibrosis and inflammation in human diseases is now moving rapidly toward the clinic.
• Discovery and development of therapeutic candidates led by Singapore-based biotech spin out company Enleofen Bio is a first for the SingHealth Duke-NUS AMC, as is its partnership with a major pharmaceutical company, Boehringer Ingelheim.
• Enleofen Bio could receive more than US$ 1 billion per product from Boehringer Ingelheim, which will further develop the therapies for multiple fibrotic human disorders, including non-alcoholic steatohepatitis (NASH) and progressive fibrosing interstitial lung diseases (PF-ILDs).

Singapore, 9 January 2020 – The breakthrough discovery of investigational therapies for multiple human diseases by a team of Singapore clinicians, clinician scientists and scientists from National Heart Centre Singapore (NHCS), Duke-NUS Medical School’s Cardiovascular & Metabolic Disorders Programme (CVMD), SingHealth Duke-NUS AMC and the Singapore-based biotech company Enleofen Bio, along with a newly forged partnership with Boehringer Ingelheim, brings hope to patients with fibro-inflammatory conditions worldwide.

Due to an incomplete knowledge of the fibrotic process, there are currently very limited effective therapies to treat many fibro-inflammatory diseases. The discovery of the role of a specific protein – interleukin 11 (IL-11) – in fibrotic diseases of the liver, lung, kidney, eye, skin and heart stimulated the development of bio-therapeutics called neutralising antibodies, to target and block IL-11 to reverse inflammation and improve fibrosis in diseased body organs. The findings of the various pre-clinical studies were published in high impact scientific journals¹.

“More than 225 million people worldwide suffer from heart and kidney failure, which resulted from the hardening of the organ tissues with no treatment. The development of anti-IL-11 therapies will offer hope to patients with end-stage heart, kidney, lung or liver failure, addressing the unmet medical needs of patients worldwide,” shared Professor Terrance Chua, Medical Director, NHCS and Group Chairman Medical Board, SingHealth.

A new strategic partnership between Enleofen Bio and the global pharmaceutical company, Boehringer Ingelheim, has been announced today. This partnership adds large value to the IL-11 programme and greatly accelerates the therapies towards the clinic. Boehringer Ingelheim is a global leader in the treatment of fibrotic lung diseases and in therapeutic antibodies. On top of its continued focus on fibrotic lung diseases, Boehringer Ingelheim is committed to targeting fibrosis and inflammation in multiple new areas, starting with liver disease. Boehringer Ingelheim also brings deep expertise in drug manufacturing and clinical development giving the IL-11 programme the best chance of success.

“We are very excited to engage Boehringer Ingelheim, a leading and innovative pharmaceutical company on this important phase of drug and clinical development. This marks a major biotechnology success in Singapore and we are extremely proud of the clinicians and scientists at NHCS and Duke-NUS,” said Professor Stuart Cook, Tanoto Foundation Professor of Cardiovascular Medicine, Director of Duke-NUS’ Cardiovascular and Metabolic Disorders Programme, and Senior Consultant at the Department of Cardiology, NHCS.

“This collaboration brings together Boehringer Ingelheim’s expertise in drug development and NHCS’ and SingHealth Duke-NUS AMC’s strengths in clinical care and translational research. This is a crucial step in the translational medicine process, and puts us in good stead to bring new anti-IL11 therapies and improve healthcare outcomes for patients in Singapore and beyond,” said Professor Ivy Ng, Group CEO, SingHealth.

“This is yet another example of the impactful research emerging from the Academic Medicine partnership between Duke-NUS and SingHealth, which integrates cutting-edge science with patient care. This new partnership between Enleofen Bio and Boehringer Ingelheim provides great promise for practical and clinical solutions to improve healthcare and patients’ lives,” said Professor Thomas M. Coffman, Dean of Duke-NUS Medical School.

The discovery science and drug target validation was made possible by the research done in the laboratories of National Heart Research Institute of Singapore (NHRIS) of NHCS, Duke-NUS Medical School’s Cardiovascular & Metabolic Disorders Programme and SingHealth Duke-NUS AMC. Funding from the National Medical Research Council (NMRC) underpinned the research on IL-11, which was patented over several years of scientific study at SingHealth Duke-NUS AMC.

¹Reference:

• Schafer, S., Viswanathan, S., Widjaja, A. et al. IL-11 is a crucial determinant of cardiovascular fibrosis. Nature 552, 110–115 (2017) doi: 10.1038/nature24676
• Widjaja, A. A., Singh, B. K., Adami, E., et al. (2019). Inhibiting Interleukin 11 Signaling Reduces Hepatocyte Death and Liver Fibrosis, Inflammation, and Steatosis in Mouse Models of Nonalcoholic Steatohepatitis. Gastroenterology, 157(3), 777–792.e14. doi: 10.1053/j.gastro.2019.05.002
• Ng, B., Dong, J., D’Agostino, G., et al. (2019). Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis. Science Translational Medicine, 11(511). doi: 10.1126/scitranslmed.aaw1237

Glossary for the Medical Terms

• Fibrosis is the formation of excessive connective tissue, causing scarring and failure of bodily organs and the skin. It is a common cause of cardiovascular and renal disease, where excessive connective tissue destroys the structure and function of the organ with scar tissue.
• Interleukin 11 (IL-11) − a critical protein that causes fibrosis and organ damage, which was initially thought to be anti-fibrotic until the SingHealth Duke-NUS AMC team of researchers overturned this misconception in a series of publications.
• Non-alcoholic steatohepatitis (NASH) – Liver inflammation and damage caused by a build-up of fat in the liver. It is a part of a group condition called non-alcoholic fatty liver disease. When NASH gets worse, it causes scarring of the liver, which leads to cirrhosis.