The respiratory system is persistently exposed to airborne disease-causing insults, including pollution, dust mites, viruses, bacteria, and fungi. These contagions significantly contribute to or cause common chronic respiratory disease including COPD, asthma and acute and chronic lung infections. Other lung disease, for example idiopathic pulmonary, are more complex in their origin, and some are genetic, such as cystic fibrosis (CF). These diseases share features with other diseases, typically inflammation and fibrosis, so an argument can be made that the respiratory field is as much about drug delivery as it is about novel disease pathology.
For any project that looks to treat a disease where the lung is the primary target, there must be a robust argument as to why to go inhaled. Developing an inhaled medicine is more expensive, longer and more complex when compared to their oral counterparts. Pharmacology that is not tolerated systemically, and/or the need to have significant local drug concentration, are genuine reasons to pursue inhaled delivery. Drugs which are delivered by inhalation often require exquisite potency and a method of retaining them in the lung, which requires different tactics depending on the nature of target and disease.
Sygnature’s scientists have broad experienced across all of these approaches. Having the right in vitro biosciences and DMPK is essential to drive a successful respiratory project
Our skilled bioscientists use a wide range of assay platforms and systems to assess the molecules. They are adept at developing bespoke assays, as well as adapting existing assays to meet the precise needs of individual respiratory projects. Importantly, they also have experience in developing in vitro assays using airway epithelial cells, endothelial cells and alveolar macrophages. The cells are sourced from our in-house human blood donor panel, as well as via our links with local hospitals, universities and commercial vendors.
We have worked across all indications that affect the respiratory system, from asthma and COPD to infectious diseases and CF. Sygnature’s multi-disciplinary, integrated, and collaborative way of working have delivered twelve compounds to preclinical development and six compounds have entered clinical trials. The most advanced of these, PC945, is entering phase III clinical trials to treat life threatening respiratory fungal infections.
Established respiratory assays in use at Sygnature include:
- Biophysics to explore potential protein or epigenetic targets and protein-protein interactions
- Gene expression
- Measurement of secreted or cellular inflammatory mediators
- Cellular assays