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Federal Governments Medical Research Future Fund provides grant to biotech company, Cincera Therapeutics

Cincera Therapeutics Pty Ltd, a biotech company with operations in Adelaide and Melbourne, has been granted $1 million by the Biomedical Translation Bridge (BTB) Program. The funding will progress its research in developing a drug to treat severe and life-threatening obesity-related health conditions such as NASH, an advanced form of non-alcoholic fatty liver disease, which can lead to liver failure or cancer.

The company will use the BTB funds to enhance its development of a drug that effectively changes the balance between healthy fats and toxic fats stored around various organs in the body. This rebalancing of fats will promote beneficial effects that can potentially treat an array of serious life-threatening diseases.

A third of Australians are considered to be obese and at high risk of developing the kinds of severe metabolic disorders that Cincera’s drugs will aim to treat. This includes NASH (non-alcoholic steatohepatitis), a disease that can lead to severe ‘scarring’ of the liver that reduces organ function leading to death in the absence of a liver transplant.

NASH is considered an emerging epidemic in Australia, due to increased rates of obesity.

Dr Michael Bettess, Executive Director at Cincera, says that early prevention by maintaining a healthy lifestyle is key to reducing the impact of metabolic disorders. However, Dr Bettess says that research into therapies that treat serious obesity-related disorders is critical as sometimes, drug-based treatments are the last and only option for people who need urgent therapy.

“While weight loss and healthy lifestyle are important to ease the stress that toxic fat accumulation can place on an organ, this isn’t always sufficient to repair the damage the disease has already done – especially in the more severe cases” says Dr Bettess. “We’re going a step further at Cincera, aiming to create a new drug that blocks the production of toxic or ‘bad’ fats and increases the level of ‘good’ or healthy fats in the body. Our research shows these good fats can promote disease modifying responses that may help treat the damage done to the organ.”

There are many types of important fats or ‘lipids’ that support many different biological processes in the body. These bioactive lipids include the type of fats targeted by Cincera’s drug, termed ceramides.

The main goal of Cincera’s research is to create a drug that can increase the ‘good’ type of ceramide called dhCeramide, which has been shown to reduce disease progression and encourage the body to produce anti-inflammatory and anti-fibrotic (anti-scarring) responses to treat disease.

Cincera’s therapy aims to do this by inhibiting a key enzyme called Des-1. Research has found inhibiting Des-1 boosts the levels of dhCeramide in the body and that this has profound and beneficial effects in various models of disease.

Cincera’s co-founder and CEO, Associate Professor Bernard Flynn, says that the anti-fibrotic response elicited by the company’s Des-1 inhibitor drug, means that there are applications beyond obesity-related health issues.

“The implications of this are enormous, as it means we can help the body mount a balanced immune and scarring response to disease,” says Associate Professor Flynn. “Excessive inflammation and scarring (fibrosis) is the leading cause of organ failure and disease related death globally, so being able to utilise a drug in the body to control these processes is a hugely important research area.”

Cincera’s co-founder and CSO, Professor Stuart Pitson, says that while Cincera is presently researching the effect of lipid conversion for liver disease, the company’s studies also show incredible potential for treating lipid-related diseases in other organs, such as the kidney, heart, lung and even skin.

“This new BTB funding will allow us to take our research to the next level, through further testing the concept and our compounds in various models of human disease. This is the first step towards our major objective of progressing into clinical testing with a once daily, orally administered drug candidate.”

Cincera was founded in 2018 as a spinout from the and Monash Institute of Pharmaceutical Sciences (MIPS) in Melbourne and Centre for Cancer Biology (CCB) Adelaide with venture capital investment from the Medical Research Commercialisation Fund (MRCF).

The Biomedical Translation Bridge program is an initiative of the Medical Research Future Fund, providing up to $1 million in matching funding to develop new medical therapies, technologies, and medical devices. Cincera is among several organisations who received funding from the BTB programme this year.

Cincera Therapeutics Pty Ltd (“Cincera”) has launched with an AU$7 million venture capital commitment from the Medical Research Commercialisation Fund (MRCF).

The Company has been founded to develop new therapies to target conditions relating to an unhealthy Western diet, including serious and highly prevalent diseases associated with obesity. The company will initially focus on treatments for the emerging epidemic of a liver disease termed ‘NASH’ (non-alcoholic steatohepatitis).

Cincera secured its vital venture capital support from the AU$200 million Brandon Capital managed ‘MRCF3’ fund. The MRCF was established in 2007 and promotes the creation of early stage medical technology companies across Australia and New Zealand, with the $200 million MRCF3 fund raised in 2015.

Obesity and Western diets, high in saturated fats and processed carbohydrates, can alter the abundance (in both quantity and quality) of fats in the body. The subsequent accumulation of excessive and ‘toxic’ fats in the peripheral organs can induce inflammation and tissue fibrosis (scarring), which can ultimately compromise function and lead to organ failure. Cincera aims to treat diseases like NASH by reducing the excessive abundance of specific ‘toxic’ fats in the body.

The Company is harnessing high-potential research from the Centre for Cancer Biology, an alliance between the University of South Australia and SA Pathology in Adelaide, and Monash University’s Institute of Pharmaceutical Sciences (MIPS) in Melbourne. Founding scientists of Cincera, Associate Professor Bernard Flynn from MIPS, who is also CEO, and Professor Stuart Pitson from the CCB, have been developing novel therapies that modulate an important target involved in a number of diseases.
Medicinal chemist and serial entrepreneur Associate Professor Flynn says, “Cincera is a great example of how partnering great teams and technologies with capital, and the right expertise, can facilitate the translation of Australian medical research.”

“In our collaboration with Professor Pitson of CCB and Associate Professor Bing Wang of Monash Clinical Epidemiology, we have brought the science of disease biology and drug-discovery together in a unique and effective manner. Through the rapid assembly of initial research compounds, we were able to identify the most important enzymatic targets that contribute to inflammatory and fibrotic disease – and then develop drug-like lead compounds to specifically intercept these new targets.” “MIPS is taking Australian innovation to the world through the development of novel therapies and we are delighted to have won the support from MRCF to take our innovative new therapies to the next stage,” Professor Flynn says.

Professor Pitson, a world leader in cell signalling and CSO of Cincera, says, “Through collaboration with the team at Monash, we have drug candidates that are potent and broad-acting antiinflammatory and anti-fibrotic agents that show strong potential to become new treatments.”

“There are many aspects of the disease that could be improved by these drugs, from treating liver or kidney dysfunction through to possible treatments for certain cancers. Making a difference is what drives researchers at the CCB and forming a company like Cincera will be important for translating our research into better treatments for patients.”

“The Cincera founders have developed a highly differentiated approach to treating inflammation and fibrosis,” says Dr Michael Bettess, Investment Manager at Brandon Capital Partners and Director of Cincera. “When combined with high-quality Australian science and the extensive commercial experience of the team, Cincera became a clear early-stage investment for the MRCF.” “It’s important to lead and maintain a healthy lifestyle as diseases like NASH are often associated with poor dietary choices and therefore largely preventable. However, for the many people who do suffer from this serious disorder a drug based treatment is really their only option and needed urgently,” Dr Bettess says.

The MRCF investment will be used by Cincera to show efficacy in disease models and support the ongoing optimisation of compounds to select drug candidates that will be suitable for clinical trials in three to four years.