Domainex Ltd., based in Cambridge UK, is a leading provider of integrated drug discovery services. As a result of the work carried out by Domainex during an in-house research programme to identify inhibitors of protein kinases TBK1 and IKK-epsilon, DMXD-011 has been nominated as a preclinical drug candidate. The molecule is orally-bioavailable and highly selective. The recent human ex-vivo data outlined below indicates this drug should be effective in the treatment of interferonopathies such as lupus, Sjögren’s syndrome, and scleroderma.

The literature (e.g. Hasan et al, 2016, Louis et al, 2018) suggests that inhibitors of TBK1 and IKK-epsilon should be highly-effective disease-modifying drugs for the treatment of interferonopathies, as well as for other inflammatory diseases such as rheumatoid arthritis. Domainex has previously demonstrated the efficacy of DMXD-011 in animal models of lupus and rheumatoid arthritis, in full accordance with these mechanistic observations from the scientific literature, without any evidence of side effects or toxicity.

Most recently, ex-vivo laboratory studies using blood samples taken from hospital patients suffering from a variety of interferonopathies were carried out by Domainex in collaboration with Dr Marjan Versnel of the Erasmus University Medical Center in Rotterdam. DMXD-011 was added to the patients’ blood samples, and the levels of inflammatory biomarkers in the blood were measured before and after chemical stimulation of the immune cells to mimic a flare-up of the auto-immune disease. DMXD-011 showed a strong dose-dependent reduction in the expression of these biomarkers. It is noteworthy that in analogous studies, AstraZeneca has reported that its recently-approved type 1 interferon receptor antibody anifrolumab (SaphneloTM) showed a similar effect, and it used the same biomarkers to demonstrate patient responses in some of the clinical studies with this drug (Brohawn, 2015, Tanaka, 2020).

“We are very encouraged by the outcome of the ex vivo studies conducted by Dr Versnel and her team in the Netherlands,” commented Dr Tom Mander, CEO of Domainex. “It indicates that the TBK1/IKKe inhibitors in our granted-patent estate could have disease-modifying potential in interferonopathies and other inflammatory conditions. We have a very attractive opportunity for a licensing partner to take these compounds into pre-clinical and clinical development.”

To learn more about DMXD-011, and Domainex’s capabilities in inflammatory research, please visit: https://www.domainex.co.uk/services/inflammatory-diseases.

DMXD-011 is available for out-licensing. Interested parties should contact: tom.mander@domainex.co.uk.