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Respiratory

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.

Respiratory assays

Established respiratory assays in use at Sygnature include:

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Fibrotic diseases

Sygnature Discovery’s integrated teams of medicinal chemists, bio scientists, DMPK and translational scientists have developed significant expertise in drug discovery in the fibrosis field, with a particular focus on kidney, liver and lung fibrosis.

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Metabolic diseases

Sygnature’s scientists have extensive experience in the field of metabolic disease, from early medicinal chemistry right through to in vivo testing. The integrated teams at Sygnature Discovery have a track record of delivering validated drug candidates to clients.

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Oncology and Immuno-oncology

We have successfully delivered more than 16 pre-clinical oncology projects, utilising our Integrated Drug Discovery expertise to develop small molecule drug candidates to treat a variety of cancers such as leukaemia, breast and prostate cancer. From initial screening and profiling through to clinically relevant Biomarkers, our DMPK and bioscience group can provide full support for your discovery projects.

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Anti-Infectives

Sygnature have a history of enabling discovery success in the field of anti-infectives. Our Integrated Drug Discovery teams have worked in close collaboration with many clients to design potent and efficacious compounds. Our Bioscience team can provide cytopathic effect and viability screening assays to assess compounds designed to inhibit virus attachment, entry or replication in human host cells.

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Neuroscience

Our scientists have a well-developed understanding of the challenges associated with the design and optimisation of compounds that target the central nervous system (CNS). Our experience is both broad, reaching across a number of neurodegenerative diseases (such as Alzheimer’s, Parkinson’s and Amyotrophic Lateral Sclerosis) and neuropathic pain, and deep-rooted, with members of our senior team having 10+ years in CNS drug research.

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Respiratory

We have an excellent track record of success in the field of respiratory diseases using our extensive in-house expertise, accelerating 5 compounds to the clinic and a further 4 into preclinical development for our clients. Our collaborative approach to drug discovery and our established network of KOLs in the field have been invaluable to the progression of our clients’ projects

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Inflammation and Immunology

Our scientists have a rich heritage in this therapeutic area and provide significant experience in developing in vitro assays utilising Peripheral Blood Mononuclear Cells (PBMCs), T lymphocytes (e.g. CD4+/CD8+), leukocytes, and phagocytes, amongst others, that assess various inflammation and immunological biomarkers, processes, and endpoints.

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