Aston University scientists are working with start-up company, Isterian Biotech, part of Cambrian BioPharma, to develop novel drugs to treat fibrotic diseases such as lung disease.

The focus of preclinical-stage biotechnology company Isterian Biotech is on developing novel drugs to stop or reverse the pathological accumulation of crosslinked proteins commonly observed in all major organs with age.

As we age a chronic increase of crosslinked proteins occurs in the extracellular matrix (ECM), that surround, support, and give structure to the cells and tissues in the body. These crosslinked proteins are difficult for the body to degrade and over time can make organs stiff and dysfunctional, ultimately resulting in fibrosis. Reversing the accumulation of these pathological crosslinks will greatly contribute to reducing fibrosis.

The start-up is working to develop small molecule inhibitors of transglutaminase 2 also known as TG2, which is one of the major crosslinking enzymes in the human body, that becomes more active during ageing – thus resulting in fibrotic diseases such as a type of lung disease known as idiopathic pulmonary fibrosis (IPF).

Isterian President and Chairman of the Board, Georg C Terstappen, PhD said: “Isterian’s strategy of combining rational drug design with efficient multiparametric profiling of synthesized small molecules has been both impressive and highly productive. Notably, for one of our highly potent and selective TG2 inhibitors, we have recently demonstrated efficacy in a mouse model of lung fibrosis for the first time.

“Using this state-of-the-art approach to drug discovery combined with an impressive team gives us great confidence in the future of this novel company.”

IPF is a progressive, irreversible disease that is characterized by pathological crosslinking of extracellular matrix (ECM) proteins (a large network of proteins and other molecules that surround, support, and give structure to the cells and tissues in the body) leading to excessive deposition of collagen.

This means that in IPF scar tissue or fibrosis builds up around the air sacs (alveoli) in the lungs and reduces the ability to transfer oxygen that is breathed into the blood, resulting in severe restriction of lung capacity and function.

IPF is the most common form of pulmonary fibrosis. The disease affects between 200,000 and 300,000 people globally. Statistics from the charity Action for Pulmonary Fibrosis suggest there are about 30,000 people living with IPF in the UK with an estimated 6,000 new cases of the condition each year. The disease usually develops in people aged 70 and older and is more common in men. But it can occur in younger individuals, particularly if there is a family history of idiopathic pulmonary fibrosis.

The company was founded by capitalising on over 35 years of scientific research from the laboratory of Professor Martin Griffin and his team Dr Dan Rathbone and Dr Vivian Wang at Aston University.

Their work with small molecule inhibitors selective for TG2 has demonstrated reduction of fibrosis in multiple organs in a number of animal models. In 2019, Aston University partnered with Cambrian to form Isterian Biotech with a mission to develop safe and effective TG2 inhibitors to treat Idiopathic pulmonary fibrosis (IPF), a devastating fibrotic disease of the lung.

Professor Martin Griffin, Biosciences Research Group, Aston University said: “We are delighted to continue our work with Isterian researching how we can further develop TG2 inhibitors to help tackle this awful disease.”

CEO of Cambrian BioPharma, James Peyer, commented: “As Cambrian continues on its mission to build medicines that will redefine healthcare in the 21st century, we are very thankful to find brilliant scientists such as Martin and his team that are willing to break the mold. Isterian and its work to reduce fibrosis are a perfect fit alongside the other pipeline companies our team has announced in 2022.”

The company’s current pipeline includes an advanced preclinical-stage TG2 inhibitor for inhaled administration and several structurally unrelated back-up compounds for the treatment of IPF.