SB414 - Inflammatory Skin Diseases
Novan is developing SB414 as a topical cream product candidate for the treatment of inflammatory skin diseases such as psoriasis and atopic dermatitis. Inflammatory skin disorders are the results of immune system reactions that involve the skin. Biologic therapies are often used to treat patients with severe disease. A non-steroidal topical therapy that targets key inflammatory cytokines could address an unmet need for the 6 million psoriasis patients and 14 million atopic dermatitis patients with less severe disease burden.
- In a psoriasis mouse model, SB414 significantly (p<0.05) reduced composite psoriasis scores and also inhibited the production of pro-inflammatory cytokines, including interleukin-17, or IL-17a and IL-17f.
- In two in vivo models that assess critical components of atopic dermatitis disease pathology, SB414 displayed potent anti-staphylococcal activity in partial-thickness skin wounds infected with a methicillin- resistant S. aureus strain isolated from an AD patient. Additionally, SB414 demonstrated a dose-dependent inhibition of inflammation in a preclinical mouse model comparable to that of betamethasone, a mid-potency corticosteroid used to treat eczema patients.
Click the links below to learn more
- Atopic Dermatitis - Poster presentation at International Investigative Dermatology Conference - 2018
- Psoriasis - Poster presentation at Society of Investigative Dermatology Annual Meeting – 2017
- Atopic Dermatitis - Oral presentation at Society of Investigative Dermatology Annual Meeting – 2017
- Atopic Dermatitis - Poster presentation at Society of Investigative Dermatology Annual Meeting – 2017
About Inflammatory Skin Diseases
According to a recent, peer-reviewed article in the British Journal of Dermatology, IL-17, a key inflammatory cytokine, is known to be or is likely to be related to the mechanism and severity of a number of inflammatory skin disorders. IL-17 activation leads to propagation of several pro-inflammatory signaling cascades. Binding of IL-17 to its cognate receptor signals keratinocytes and other cell types to generate and release pro-inflammatory cytokines IL-1ß and IL-6 resulting in enhanced inflammasome activation.
Psoriasis is a chronic inflammatory skin disease that affects approximately 7.5 million people in the United States. The disease is characterized by an errant immune-system response that drives inflammation and thickening of the skin caused by rapid turnover of skin cells. This typically results in patches of plaques, or thick, red raised skin with silvery-white scales. There is no cure for psoriasis. The healthcare market has seen an increase in the introduction of systemic therapies, including biologics, to treat patients with higher disease burden, but the current systemic therapies are indicated only for patients with moderate-to-severe disease. For the approximately 80% of patients with mild-to-moderate psoriasis, prescription treatment options include topical corticosteroids, retinoids and vitamin D3. Vitamin D3 is not efficacious enough as monotherapy and topical corticosteroids and retinoids have well-known side effects and restrict the chronic use.
About Atopic Dermatitis
Atopic dermatitis, also known as atopic eczema, is the most common chronic relapsing inflammatory skin disease, affecting nearly 18 million people in the United States with no FDA-approved cure. Stabilizing the disease and reducing the number and severity of flares are the primary goal of current. The diseases is characterized by recurrent red plaques, intense itching, dry skin with red papules and plaques ,“weeping” clear fluid , crust and scaling. Immune cells in the deep layers of skin release inflammatory signals, causing an itchy rash. Scratching leads to defects in the skin barrier function, allowing environmental triggers, such as the bacteria Staphylococcus aureus, to penetrate the skin barrier and further exacerbate the immune cells. A recent study showed that the entry of S. aureus into the dermis triggers immune abnormalities seen in atopic dermatitis skin. Nearly eighty percent of the atopic dermatitis population suffers from mild-to-moderate disease and are treated with first-line monotherapies, however, corticosteroids and calcineruin inhibitors have side effects and are not well-suited for chronic use. Recently, the first biologic treatment for atopic dermatitis targeting IL-4 and IL-13 was approved, but it is reserved for patients with moderate to severe disease. Topical PDE4 inhibitor was also recently approved after more than a decade of absence of new mechanism of action.