Biopharmaceutical Pipeline
- Product Pipeline Overview
- Respiratory
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TREATING RESPIRATORY DISEASES
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Respiratory System Diseases
Hypersecretion of mucus into the airways is an important contributor to morbidity and mortality in many patients with severe chronic lung diseases, such as chronic obstructive pulmonary disorder (COPD), asthma and cystic fibrosis. Excessive mucus in the airways can limit airflow; and its presence is a particular risk factor for those patients with COPD that are prone to chest infections.
Clearing Airways
Syntaxin are pioneering new biopharma medication products for patients who have airway mucus hypersecretion related diseases such as COPD and chronic brochitis. The inhaled delivery of Syntaxin's novel proteins target respiratory epithelial cells.
COPD is a severe chronic inflammatory disease of the respiratory tract that comprises three conditions, namely chronic bronchitis (long-standing airway mucus hypersecretion), small airways disease and emphysema.
It is increasing worldwide in prevalence and economic burden. In COPD, patients with chronic mucus hypersecretion have a significantly increased risk of hospitalisation and death compared with patients without a marked bronchitic component. Current treatments for COPD are palliative and do not halt disease progression, and there is no specific treatment for the mucus hypersecretion.
Effect of COPD medication
Effect of SXN187 on intracellular mucin in A549 cells:
The level of mucus created by these cells is reduced and mucin was retained inside the treated cells.
Due to the absence of effective therapy for any aspect of COPD pathophysiology, development of treatments for mucus hypersecretion and is much warranted. The ability to clear mucus from the lungs, via airway cilia movement, depends on the mucus' viscosity and elasticity. These properties are determined by the proportion of mucin glycoproteins. In patients with COPD, levels of the mucins MUC5AC and MUC5B are both increased in the respiratory mucus, though proportionally more MUC5B is secreted. Mucins are secreted into the airways by goblet cells in the epithelium and seromucous glands in the submucosa.
One possibility for inhibiting mucus secretion is to utilise the anti-secretory activity of proteases of clostridial neurotoxins, targeted to the mucin secreting cells of the airway using Syntaxin's novel recombinant proteins.
To create a therapeutic protein that could potentially inhibit secretion of mucins from lung epithelium, and thus aid mucus clearance from airways, Syntaxin explored a number of peptide ligands to receptors known to be present on mucin secreting cells of the respiratory epithelium, and proteases from serotypes of botulinum neurotoxin known to cleave SNARE proteins found within these cells. A variety of proteins were created in this manner that demonstrated a potent inhibition of stimulated mucin release from airway epithelial cells in vitro, in a concentration-dependent fashion.
The target product profile for this programme is a recombinant therapeutic protein that can be administered on an infrequent basis by inhalation to patients with a mucus hypersecretory component to their chronic respiratory condition such as COPD.
The aim being sustained inhibition of mucus hypersecretion leading to a reduction in mucus obstruction and improved respiratory function. There are currently no effective therapeutics that address the mucus hypersecretion that is a contributing component of a number of chronic respiratory system diseases. The Syntaxin approach offers a novel and effective approach to treat this aspect of chronic respiratory system disease and to do so with duration of action that is well suited to the long term relief of chronic disease making it perfect for COPD medication and treatment.