LXR Agonist for Immuno-Oncology & Atopic Dermatitis
Liver X Receptors [LXRs] play a crucial role in cholesterol metabolism, lipogenesis, glucose homeostasis, inflammation and innate immunity and are highly druggable targets. Based on these properties, LXRs have been widely explored as promising targets in a number of disease indications, including atherosclerosis, diabetes, Alzheimer's disease, atopic dermatitis [AD] and cancer. The Innovimmune team is developing several novel structural series that selectively target LXR-alpha and LXR-alpha/beta (“pan” LXR agonists) for development in both cancer and AD.
Targeting LXRs is a highly promising strategy for cancer treatment, particularly for those cancers which do not currently have effective treatment options. Numerous studies have demonstrated the robust anti-cancer activity and suppression of metastases by LXR agonists in a wide range of well-established animal models of multiple human cancer types. LXR agonists have pleiotropic effects upon cancer cells, from targeting the cell cycle machinery and promoting apoptosis to inhibiting invasion and metastasis by increasing Apolipoprotein E, an LXR target gene. In addition, LXR agonists have direct effects upon cells within the tumor micro-environment; for instance by boosting immune surveillance of resident macrophages and even perturbing endothelial cell functionality, resulting in reduced angiogenesis. Innovimmune anticipates that INV-25 will obtain FDA Orphan Drug Designation in several solid tumor types of high-unmet need, particularly drug-resistant malignancies and could be exploited as a combination therapy (with immune checkpoint inhibitors) in addition to stand-alone therapy.
INV-25 is concurrently being developed as a topical treatment for AD (eczema), a common inflammatory skin disease characterized by a loss of barrier function of the skin and skin inflammation. Innovimmune believes there is significant opportunity to develop a novel therapy for AD that will be more effective and with a superior safety profile than commonly used topical therapies (glucocorticoids and calcineurin inhibitors). INV-25 is anticipated to concomitantly improve both barrier function and decrease inflammation in AD by activating LXRs in skin keratinocytes, a mechanism crucial for maintaining the impermeable barrier of skin and promoting an anti-inflammatory environment.