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. 

Clinical Data

In a Phase 1b trial for mild-to-moderate atopic dermatitis, 48 adults were randomized to receive one of 2% SB414 cream, 6% SB414 cream, or vehicle, twice daily for two weeks. Results of this trial are shown below.

  • Biomarkers from the Th2 and Th22 inflammatory pathways known to be highly relevant and indicative of atopic dermatitis, including Interleukin-13, or IL-13, IL-4R, IL-5 and IL-22, were downregulated after two weeks of treatment with SB414 2%, achieving statistically significant 10.5, 2.5, 7.1 and 7.5-fold reductions over vehicle, respectively.
  • The changes in Th2 and Th22 biomarkers and clinical efficacy assessed as the percent change in Eczema Area Severity Index (EASI) scores were highly correlated in the SB414 2% group.  
  • Additionally, the proportion of patients achieving a greater than or equal to 3-point improvement on the pruritus (itch) numeric rating scale (NRS) after two weeks of treatment was 71% for patients treated with SB414 2% compared to 43% for vehicle.  

Preclinical Data

  • 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.

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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.


About Psoriasis

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.