Carbohydrate Binding Modules (CBMs): First in class glycan-targeted proteins for the treatment of respiratory tract infections and cancer
Pneumagen is using its platform technology, GlycoTarge, to develop novel biologics for the treatment of several diseases.
Pneumagen’s lead products are based on the carbohydrate-binding module Family 40 domain (CBM40 domain) derived from bacterial sialidases. Pneumagen has engineered oligomers of these monomeric CBM40s by genetically linking copies in tandem, with a trimerisation domain, resulting in multivalent proteins (mCBM40s) with a greatly increased binding affinity for sialic acid (sub nanomolar).
Transforming the treatment of Respiratory Tract Disease
Pneumagen has demonstrated that its engineered mCBM40s bind with extremely high affinity to sialic acid. These engineered mCBM40s have been shown to prevent and treat respiratory infections by masking epithelial cell surface sialic acid receptors present in the respiratory tract, used by several pathogens for entry and infection.
Advantages of mCBM40’s over anti-virals and vaccines
Influenza viruses continue to be a threat to human health and a burden on the health services. This burden is fuelled by annual seasonal outbreaks, the emergence of viruses with pandemic potential, and the development of resistance to current antiviral drugs. This resistance is caused as the virus rapidly mutates rendering the anti-viral drugs ineffective.
As Pneumagen’s mCBM40’s target the viral binding site in the respiratory tract rather than the virus itself, they have the advantage of not being subject to viral resistance. Significant time is required to develop a vaccine against a new virus strain and their effectiveness is limited, particularly in high-risk groups such as the elderly. By directly preventing the binding and entry of pathogens, CBMs have the advantage of being effective across multiple different viral strains including influenza viruses (IFVs), parainfluenza viruses, certain coronaviruses, enteroviruses and bacteria including Streptococcus pneumoniae.
A Revolutionary Approach to Cancer Treatment
Pneumagen is developing CBMs for the treatment of cancer by exploiting the growing understanding of the importance of the glycome in tumour proliferation and migration. Alterations in glycosylation have been shown to regulate the development and progression of cancer, such as the evasion of cell death and resistance to cancer therapy, enabling the survival and progression of cancer cells. An increased presence of glycans has been found to be present in metastasising tumours. Pneumagen has demonstrated that its engineered mCBMs inhibit of a number of cellular pathways associated with cancer cell types that are highly glycosylated.