KOMM: A Biologic Therapeutic for Pulmonary Fibrosis.

We have developed a new experimental drug targeting a key disease mechanism of progressive tissue fibrosis, i.e. the excessive formation of connective tissue and collagen (scar tissue) in an organ of the body. Progressive fibrosis is an important cause of organ failure in a number of chronic diseases. e.g. interstitial lung diseases (including a severe lung disease called idiopathic pulmonary fibrosis (IPF)), chronic kidney disease, heart failure, and chronic liver disease. Current treatment modalities directly targeting progressive fibrosis are insufficient in halting disease progression and are often associated with intolerable side effects reducing quality of life. Our experimental drug targets a novel mechanism of action, i.e. cell signaling elicited by key factors in the pathogenesis of diseases characterized by progressive fibrosis; including connective tissue growth factor, now known as CCN2. Following optimization of the drug candidate to enhance activity and stability, we have provided preliminary proof-of-concept that the molecule inhibits pulmonary fibrosis in a rodent model of IPF. Furthermore, we have shown that our experimental drug also inhibits kidney fibrosis in a disease model of chronic kidney disease in mice (unilateral ligation of ureter). In a subsequent escalating dose-efficacy study in the same experimental disease model we have confirmed that our experimental drug inhibits kidney fibrosis and we have determined the minimum effective dose. We have not observed any toxic effects of the drug candidate within the period of these studies. However, proper toxicity studies will have to await until the commercial production methods of the drug candidate have been finalized. We have scaled up the production of the experimental drug and shown that the experimental drug can be prepared at high concentrations and yet maintain both stability and biologic activity. Thus, we have convinced experts on biologic drug development and stakeholders from pharmaceutic industry that our experimental drug is suitable for production at industrial scale. We have also shown that our experimental drug inhibits relevant profibrotic mechanisms in fibroblasts isolated from human lungs. In other words, we have provided evidence that the experimental drug will target profibrotic disease mechanisms in humans. Our project partner, Inven2 AS, the TTO of Oslo University Hospital, have filed the PCT application (March 2020). The international search report as well as subsequent analyses of freedom to operate (FTO analyses) have not disclosed issues that may limit our chances to obtain IPR protection or limit the commercial uses of the biologic drug. In collaboration with Inven2, we have also actively been seeking industry partners or investors that may potentially be interested in developing our drug candidate towards clinical testing in man. In March 2021 Inven2 signed a license agreement with Tribune Therapeutics, the start-up company that will commercialize our drug candidate towards clinical testing in man. Two of the largest investors in clinical drug development in Scandinavia, HealthCap AB and Novo Holding, are the largest owners of Tribune Therapeutics. This project has thus achieved its major goal of developing our invention to the point where commercial partners may take center stage to secure commercial development of our drug candidate towards clinical testing in man. One of the inventors has now been hired by the company to take the role as chief scientific officer.

This project has verified that our biologic therapeutic targeting a key profibrotic protein family inhibits fibrosis in disease models of pulmonary fibrosis and chronic kidney disease in mice. We have also demonstrated that production of the biologic therapeutic can scaled up sufficient to convince pharmaceutical industry that commercial production of the biologic therapeutic is possible. Thus, two of the largest investors in pharmaceutical drug development in Scandinavia, HealthCap AB and Novo Holding, together with the inventors have established a start-up company, Tribune Therapeutics, with the aim of commercializing the biologic therapeutic towards clinical testing in man. Although it may take several years to bring the novel therapeutic to market, we have achieved our major goal of bringing the project to a point where a commercial partner will take center stage to develop the product towards clinical testing in man. Tribune Therapeutics has so far generated three jobs in Norway.