A new study, Pharmacological OGG1 inhibition decreases murine allergic airway inflammation, was published 17[th] of October in Respiratory pharmacology, Frontiers in Pharmacology, (DOI 10.3389/fphar.2022.999180, Tanner L, Bergwik J, Bhongir RKV, Pan L, Dong C, Wallner O, Kalderén C, Helleday T, Boldogh I, Adner M and Egesten A) and demonstrates that Oxcia’s potential clinical candidate OXC-201 (TH5487) may be a promising treatment for allergic asthma.
Allergic asthma is a complex inflammatory disease characterized by wheezing, dyspnea, coughing, chest tightness and variable airflow limitation for which there is no cure. It is symptomatically treated with inhaled corticosteroids, β2-agonists, and leukotriene receptor inhibitors. A large proportion of asthma patients experience side effects, resulting in suboptimal compliance. Molecular mechanisms underlying its complex pathogenesis are not fully understood. However, 8-oxoguanine DNA glycosylase-1 (OGG1), a DNA repair protein may play a central role, as OGG1 deficiency decreases both innate and allergic inflammation.
In the study, administration of OXC-201 significantly decreased mucus production and clearly improved the lung function in allergic airway inflammation disease model. OXC-201 treatment also decreased levels of activated NF-κB transcription factor and expression of proinflammatory mediators resulting in significantly lower accumulation of eosinophils and other immune cells in the lungs.
“The data presented in this study indicate that OXC-201 may be a potent pharmacological approach for the treatment of severe allergic asthma and we are really looking forward to investigate this further in coming studies” says Oxcia’s CEO Ulrika Warpman Berglund.
OXC-201 is a small molecule inhibitor of OGG1, potentially a ground-breaking approach for treatment of IPF, other fibrotic conditions as well as inflammatory diseases. By targeting the DNA repair enzyme OGG1 (8-oxo guanine DNA glycosylase 1), OXC-201 inhibits binding of OGG1 to DNA and thereby the modulation of gene transcription. OGG1 has significant roles in modulation of inflammation and fibrogenesis; genetic or chemical depletion of OGG1 have been shown to protect from inflammation and fibrosis in several experimental disease models.
OXC-201 has the potential to disrupt the market for anti-fibrotics and has also significant anti-inflammatory effects demonstrated in disease models of acute lung injury (ARDS) and allergic asthma.
Briefly about Oxcia AB
Oxcia AB is a pioneer in oxidative DNA damage and DNA Damage Response (DDR – the processes the body uses to repair the damage that occurs to DNA) with a focus on developing new safe treatments for patients suffering from diseases caused by cancer or inflammation. Oxcia currently has two DDR drug candidates, both with the potential to become first-in-class drugs. OXC-101 (Karonudib, TH1579) is being investigated in clinical phase 1 studies, one in advanced solid tumors and one in hematological cancers. OXC-201 (TH5487) is developed against inflammatory and fibrosis-related diseases, such as pulmonary fibrosis and allergic asthma, and is in the preclinical phase.
More information about Oxcia is available at www.oxcia.com