SB414 - Inflammatory Skin Diseases

Novan is developing SB414 as a topical cream product candidate for the treatment of inflammatory skin diseases. 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 80% of atopic dermatitis patients with mild-to-moderate 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.

  • SB414 2%, a nonsteroidal topical therapy in development, had a favorable safety and tolerability profile
  • 71% of patients on SB414 2% achieved at least a 3-point improvement in worst-itch per a numeric rating scale (NRS) in 2 weeks
  • Patients treated with SB414 2% achieved statistically significant reductions in IL-13, IL-4R and IL-5 

Preclinical Data

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
  • 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 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. Nearly eighty percent of the atopic dermatitis population suffers from mild-to-moderate disease and are treated with first-line monotherapies, however, corticosteroids and calcineurin 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.

Stabilizing the disease and reducing the number and severity of flares are the primary goals of current treatment. The disease is characterized by 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 condition, triggering the “itch-scratch” cycle. The density of S. aureus colonization has been correlated with both the severity of atopic dermatitis lesions and the degree of cutaneous inflammation.