Development of a monoclonal antibody to treat systemic sclerosis

The project aimed to develop a monoclonal antibody as a clinical drug candidate targeting rare fibrosis diseases. Throughout the project duration, we successfully established the production of the antibody in compliance with regulatory standards for clinical studies. Furthermore, we conducted safety studies (toxicology) in animals to ensure adherence to safety protocols. In 2023, in accordance with the projected schedule, we initiated a phase-1 clinical study. Dosing on healthy volunteers was completed, and we diligently followed all participants for 100 days post-dosing. Preliminary findings indicate that the drug is safe and shows no significant adverse effects in the study participants. To enhance our understanding of the drug's mechanism, we conducted additional preclinical studies. Notably, one of these studies was published this year in the Annals of The Rheumatic Diseases, the leading scientific journal in rheumatology with the highest Impact Factor. It is noteworthy that the project has consistently progressed in alignment with the timelines set in 2019.

Outcomes: The project has enabled the development of a monoclonal antibody for the treatment of rare fibrotic diseases including systemic sclerosis and pulmonary fibrosis. The project has contributed to the successful completion of preclinical development of our drug candidate and the initiation of a clinical phase 1 study. This progress the company has made over the project period recently resulted in a large series A fundraising (75 million EUR) and the merger with a Dutch biotech company to form a new company called Calluna Pharma. The lead candidate of Calluna Pharma is the monoclonal antibody developed in part with the support of the grant. Impact: Over the course of the project period, the company has added three additional employees in Norway and is now and established Norwegian biotech company with plans for further hires in the near term.

Arxx Therapeutics is a Norwegian start-up biotechnology company that aims to develop a disease-modifying therapeutic for systemic sclerosis and other rare fibrotic diseases by targeting a novel biological mechanism with a monoclonal antibody developed by the founding scientists of the company. Systemic sclerosis is a rare, progressive and life-threatening disease that afflicts mostly women (80%) between the ages of 30 and 60, causes extensive fibrosis of multiple organs (eg skin, lungs, heart, gastro-intestinal system) and leads to premature morbidity and mortality. There are currently no approved disease-modifying agents available and the unmet need is extremely high. The therapeutic target is a pro-fibrotic and pro-inflammatory mediator that has been demonstrated to play a key role in the development and progression of fibrosis. Arxx has a patent-protected high affinity, selective monoclonal antibody that effectively neutralizes the target both in vitro and in vivo and confers anti-inflammatory and anti-fibrotic effects. The aim of the project is to conduct studies that will enable the monoclonal antibody to be ready for clinical testing in patients. The activities planned include: 1) Additional pre-clinical studies (in vivo and in vitro) to further characterize the mechanism of action; 2) Cell-line development, bioanalytical work and toxicology studies in animals to establish the safety of the drug prior to testing in humans; 3) A first-in-human study to establish the safety and pharmacokinetic properties of the drug. The activities will be performed at the Oslo University Hospital (Professor Finn Olav Levy) and University College London (Professor Christopher Denton) and by a world-leading contract research organization.