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.
About OXC-201
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