Let’s begin with TSLP
Abrax’s technologies center around a cytokine called thymic stromal lymphopoietin (TSLP). TSLP is produced by skin keratinocytes upon stimulation with Vitamin D3. Abrax’s co-founder, Dr. Taku Kambayashi, found that TSLP increases regulatory T cells and has been investigating the utility of TSLP-elevating agents such as MC903 in the treatment of autoimmune and inflammatory diseases. Furthermore, Dr. Kambayashi more recently discovered that TSLP-elevating agents also causes an extremely robust and selective loss of white adipose tissue (visceral and subcutaneous fat) in normal and obese mice. The mechanism behind the loss of fat was through secretion of an energy-rich substance known as sebum from the skin. Given the high caloric content of sebum, he showed that its overproduction/secretion can lead to adipose tissue loss with far-reaching impact on obesity-related disorders such as type 2 diabetes.
First thing first
Sebum is mainly composed of lipids and secreted by sebaceous glands associated with hair follicles of the skin. Sebum moisturizes the skin, enhances skin barrier function, and promotes a healthier skin environment. Thus, we are compelled to believe that MC903/TSLP-induced sebum secretion will improve disrupted skin barrier conditions such as seen in eczema, aging skin, and alopecia.
Abrax’s lead development program is designed to rapidly establish the proof-of-concept that a topical TSLP-elevating agent, MC903, can induce increased sebum and meibum secretion in human subjects and patients. As MC903 is an FDA-approved drug for treatment of psoriasis, it has an excellent safety profile, which makes it attractive as a reformulation target. Topical application of MC903 can induce overproduction of sebum, which can improve skin barrier function for the patients with eczema. This concept will be tested in humans in Australia in early 2024.
Expanding the horizon
As TSLP can affect a wide variety of diseases and conditions, Abrax has a clear plan to expand the applications of its products to other indications. For instance, your eyes produce sebum-like substance called meibum. Meibum is responsible for the formation of the tear film’s outer layer, thus reducing the evaporation of tears from the front surface of the eye. TSLP induces the inner eyelids to produce meibum, which can improve dry eye conditions. Additionally, in mouse studies, MC903 treatment robustly increased the triglyceride content of sebum, which lowered serum triglycerides and caused adipose tissue loss. Based on these discoveries, Abrax is currently evaluating potential applications in hypertriglyceridemia as well as other lipid metabolism disorders. Future pipeline drug indications will also include obesity, type 2 diabetes, autoimmune diseases (e.g. multiple sclerosis), allergic disorders, and nonalcoholic steatohepatitis.
