A new study, “Small-molecule-mediated OGG1 inhibition attenuates pulmonary inflammation and lung fibrosis in a murine lung fibrosis model” (freely translated: Pharmacological OGG1 inhibition reduces acute lung injury and lung fibrosis in mice), was published on January 26 in Nature Communications ( https://doi.org/10.1038/s41467-023-36314-5, L. Tanner, A. B. Single, R. K. V. Bhongir , M. Heusel , T. Mohanty, C. A. Q. Karlsson, L. Pan, C-M. Clausson, J. Bergwik , K. Wang, C. K. Andersson, R. M. Oommen, J. S. Erjefält, J. Malmström, O. Wallner, I. Boldogh, T. Helleday, C. Kalderén & A. Egesten) shows that OXC-201 (TH5487) may be a promising treatment for idiopathic pulmonary fibrosis (IPF).
IPF is a progressive lung disease that dramatically reduces lung function and eventually leads to lung collapse. Survival for IPF patients is only 3-5 years after diagnosis. The medical treatment available today does not improve lung function but only slows the ongoing deterioration of lung capacity, for many patients at the cost of troublesome side effects. Today there are approximately 2,000 people in Sweden and over 700,000 globally who have been diagnosed with IPF, but it is likely that there are a lot of unreported cases.
The DNA repair enzyme OGG1 (8-oxoguanine DNA glycosylase-1) has been shown to play an important role in inflammation and fibrosis. The study demonstrates that by genetically knocking out OGG1 or inhibiting the enzyme with OXC-201 (TH5487), acute inflammation and pulmonary fibrosis can be reduced. Administration of OXC-201 to mice with bleomycin-induced pulmonary fibrosis and inflammation markedly reduced lung injury compared to untreated mice. Treatment with OXC-201 reduced the levels of activated NF-κB transcription factor, the infiltration of immune cells into the lung, and the production of inflammatory and fibrotic substances linked to pulmonary fibrosis such as TGF-β, TNF-α, and collagen 1A1.
“IPF is a serious disease that has a major impact on the quality of life and life expectancy, which lacks good medical treatment and thus represents a major medical need. Therefore, it is gratifying that the data presented in the study indicate that OXC-201 has the potential to be developed into a new potent pharmacological treatment of IPF. We are now taking the next step to develop OXC-201 further towards the clinic,” says Oxcia’s preclinical manager Christina Kalderén.
OXC-201 is a small molecule inhibitor of OGG1, a potential breakthrough approach for the treatment of IPF (idiopathic pulmonary fibrosis), other fibrotic conditions and 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 plays a significant role in modulating inflammation and fibrogenesis; genetic downregulation or chemical inhibition of OGG1 has been shown to protect against inflammation and fibrosis in several experimental disease models. OXC-201 is patent protected and Oxcia AB has exclusive rights under the patent to develop and commercialize OXC-201.
As communicated in the press release on February 24th, the EIC (European Innovation Council) has awarded Oxcia AB a grant of 2.5 million euros within the EIC-Transition program for the next phase of the development of OXC-201.
For further information please contact:
Christina Kalderén, Pre-clinical Director, firstname.lastname@example.org
Ulrika Warpman Berglund, CEO, email@example.com
Briefly about Oxcia
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 is in early clinical development as novel cancer therapy. OXC-201 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