SB206 – Molluscum

Novan is developing SB206 as a topical antiviral gel for the treatment of viral skin infections, with a current focus on the treatment of molluscum contagiosum, a contagious skin infection caused by the molluscipoxvirus.

Phase 3 Molluscum Clinical Program

• Novan Reported Top-Line Efficacy Results from Phase 3 Trials of SB206 for Molluscum Contagiosum (B-SIMPLE1, B-SIMPLE2) in January 2020:
  • SB206 failed to achieve statistically significant results for the primary endpoint.
  • B-SIMPLE2 was statistically significant for multiple pre-specified sensitivity analyses.
  • Similar analyses with B-SIMPLE1 demonstrated the trial is reasonably consistent and supportive of B-SIMPLE2.
• Data from the prospectively Week 24 safety evaluation announced in March 2020
  • Safety and scarring profiles at Week 24 found to be favorable for SB206
• • FDA Type C meeting conducted on April 1, 2020
  • Based on verbal guidance received during the meeting, the Company understands the FDA will consider
    one additional pivotal trial (B-SIMPLE4), if successful, to be supported by the previously completed BSIMPLE2 trial
  • In addition, the FDA provided guidance with regard to both the study design for B-SIMPLE4 and
    expectations for a future NDA submission

Phase 2 Molluscum Clinical Trial Results

In a Phase 2 dose-ranging trial for the treatment of molluscum, clinical trial results include:

• For the primary endpoint, 12% once-daily was the most effective dose with 42% (mITT, p<0.05) and 38% (ITT, p<0.05) complete clearance rates compared to 20% and 18% for vehicle, respectively.
• For the secondary endpoint of mean percent change from baseline molluscum lesion count at each visit, patients treated with 12% once-daily experienced 29% (p<0.05), 37% (p<0.01), 56% (p<0.001) and 55% reductions in molluscum lesions at Week 2, 4, 8 and 12, respectively (mITT).
• No quantifiable levels of systemic exposure detected for SB206 12% twice-daily or once-daily following 12 weeks of treatment.
• The 12% once-daily treatment group had the lowest dropout rate out of all treatment groups, 9%, with 0 patients discontinuing treatment due to adverse event.

Preclinical Data

• SB206 exhibited a dose responsive pharmacologic effect with complete inhibition of papilloma growth compared to topical imiquimod in an in vivo model.
• NVN1000, the active pharmaceutical ingredient in SB206, exhibited a dose dependent decrease in HPV viral replication in human raft cell culture model.

Click the links below to learn more.

• Poster presentation at Society for Investigative Dermatology Annual Meeting – 2019
• Poster presentation at International Papillomavirus Conference – 2017
• Oral Presentation at American Academy of Dermatology Annual Meeting – 2017
• Oral presentation at Society for Investigative Dermatology Annual Meeting – 2016
  
• Poster presentation at Society for Investigative Dermatology Annual Meeting – 2016
  
• Poster presentation at Interscience Conference on Antimicrobial Agents and Chemotherapy – 2014

About Molluscum

Molluscum contagiosum is a common, contagious skin infection caused by the molluscipoxvirus, affecting approximately six million people in the U.S. annually, with the greatest incidence in children aged one to 14 years. Infected children typically present with 10 to 30 painless, yet unsightly lesions, and, in severe cases, they can have around 100 lesions. Due to the largely pediatric nature of the disease, parents are the caregivers for these children, in most cases, and tend to seek treatment. There are no FDA approved therapies for molluscum, and, upon seeking treatment, caregivers are faced with potentially painful in-office, dermatologist-administered physical procedures or cantharidin, or recommended off-label prescriptions and over-the-counter products. More than half of the patients diagnosed with molluscum are untreated and over 30% of those treated receive an off-label prescription with no molluscum indication or proven clinical efficacy. The average time to resolution is 13 months, however, some children experience lesions that may not resolve in 24 months. Further dissemination of this highly-contagious disease is common, and transmission to other children living in the household is reported to be 41%. There is a significant unmet need in the molluscum treatment landscape.

SB204 – Acne Vulgaris

Novan is developing SB204 as a once-daily, topical monotherapy for the treatment of acne vulgaris, a multifactorial disease with several mechanistic contributors to the disease pathology. Localized nitric oxide delivery may provide anti-inflammatory and antibacterial activity from a single active ingredient.

Clinical Trial Results

• Statistical significance at week 12 on all three co-primary endpoints in one of two pivotal trials:
  • The proportion of patients with IGA success
  • The absolute change in inflammatory lesions
  • The absolute change in non-inflammatory lesions
• Two Phase 2 trials with statistically significant efficacy with SB204 4% when compared to vehicle in both inflammatory and non-inflammatory lesion endpoints
• Sustained treatment benefit shown in long-term safety trial
• No measureable systemic exposure under maximal use conditions in adults or adolescents with moderate-to-severe acne

More About SB204:

• Oral presentation at Annual Meeting of the American Academy of Dermatology – 2018
• Poster presented at Winter Clinical Dermatology Conference – 2018
• Poster presentation at World Congress of Pediatric Dermatology – 2017
• Poster presentation at Summer Symposium of the Alabama Dermatology Society – 2017
• Poster presentation at Society for Investigative Dermatology Annual Meeting – 2017
• Poster presentation at Fall Clinical Dermatology Conference – 2016
• Oral presentation at Annual Meeting of the American Academy of Dermatology – 2016
• Poster presentation at World Congress of Dermatology – 2015
• Poster presentation at Society for Investigative Dermatology – 2014

SB208 – Fungal Skin Infections

Novan is developing SB208 as a broad-spectrum antifungal gel for the treatment of superficial cutaneous fungal infections of the skin and nails, such as tinea pedis and onychomycosis. Recent studies suggest that both the nail plate, interdigital space and surrounding cutaneous tissue may serve as an overlooked reservoir of dermatophytes, perpetuating reinfection and coinfection of onychomycosis and tinea pedis. Additionally, studies have demonstrated enhanced efficacy when tinea pedis and onychomycosis are treated concurrently, suggesting that an effective topical treatment, suitable for simultaneous application to the nail plate and skin, may lead to lower rates of recurrence and enhanced efficacy.

Clinical Trial Results

In a Phase 2 clinical trial enrolling 200 patients with tinea pedis, or athlete’s foot, SB208 demonstrated a statistically significant effect (p<0.05) compared to vehicle in reducing dermatophytes that cause these fungal infections.

• In the primary efficacy analysis of patients with evaluable culture results, 80.6% (p=0.002) of patients treated with SB208 4% and 74.2% (p=0.016) of patients treated with SB208 16% achieved negative fungal culture at day 14 versus 45.5% of patients treated with vehicle.
• The percentage of patients achieving mycological cure at the day 14 visit was 50.0% (p=0.009) of the patients treated with SB208 4% and 53.1% (p=0.010) of patients treated with SB208 16% versus 23.5% of patients treated with vehicle. Mycological cure is defined by having a negative laboratory culture and negative fungal clinical diagnosis.
  • At the end of a 4-week post treatment follow-up period, mycological cure was maintained at day 42 in both dose groups; 58.8% of patients treated with SB208 16% demonstrated a mycological cure compared to vehicle (p<0.05).

Click the links below to learn more about SB208

• Poster presentation at International Investigative Dermatology Conference – 2018
• Poster presentation at Winter Clinical Dermatology Conference – 2018 
• Poster presentation at ASM Microbe – 2016

Preclinical Data

In the ChubTur® infected human nail assay, a model utilized previously in the drug development of Kerydin® (tavaborole) Topical Solution, 5%, and Jublia® (efinaconazole) Topical Solution, 10%, nitric oxide-releasing formulations including SB208 demonstrated rapid penetration of the nail and effective fungal killing of Trichophyton rubrum in 24 hours following a single treatment application.

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About Onychomycosis

Onychomycosis is a chronic fungal infection of the nails that affects approximately 40 million Americans and accounts for one-third of cutaneous fungal infections. The prevalence of disease increases with age, and more than 50% of patients are 70 years or older. The infection, caused by dermatophytes such as Trichophyton rubrum, often results in painful thickening and deformation of the nail and sometimes the separation of the nail plate from the nail bed, leading to an inability of the nail to perform its natural protective function. Oral therapies used to treat the infection are associated with severe side effects, and topical therapies have modest efficacy profiles with complete cure rates of less than 20%.

About Tinea Pedis

Tinea pedis, often referred to as Athlete’s Foot, is a common fungal infection of the feet, affecting approximately 75 million Americans. Trichophyton rubrum is the most prominent dermatophyte in tinea pedis and also a causative pathogen in onychomycosis. Approximately one-third of onychomycosis patients also suffer from tinea pedis. Topical treatments are the first-line therapy for tinea pedis, while oral antifungals are prescribed when the infection is severe or the use of topical antifungals is not feasible. Currently, there is no approved single topical therapeutic agent that provides for the simultaneous treatment of the nail plate, bed, and surrounding cutaneous tissue.

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 and psoriasis patients with mild-to-moderate disease burden.

Clinical Trial Results

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

• 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.
  

Click the links below to learn more

• Atopic Dermatitis – Oral presentation at Society of Investigative Dermatology Annual Meeting – 2019
• Atopic Dermatitis – Poster presentation at Society of Investigative Dermatology Annual Meeting – 2019
• Atopic Dermatitis – Oral presentation at Inflammatory Skin Disease Summit – 2018
• Atopic Dermatitis – Poster presentation at Inflammatory Skin Disease Summit – 2018
• 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 

SB206 – External Genital Warts

Novan is developing SB206 as a topical antiviral gel for the treatment of viral skin infections, including external genital warts (EGW) caused by human papillomavirus (HPV).

Phase 2 External Genital Warts Clinical Trial Results

In a Phase 2 dose-ranging clinical trial for the treatment of external genital warts, clinical trial results include:

• In the primary efficacy analysis, 33% of patients achieved complete clearance of baseline warts by week 12 when treated with SB206 12% once-daily, compared to only 4% of patients achieving complete clearance with vehicle once-daily (p=0.0099).
• The proportion of subjects with complete clearance of all warts was 30% for SB206 12% once-daily and 4% for vehicle once-daily (p<0.02).
• Once-daily treatment arms were generally well-tolerated, including the most effective dose, SB206 12% once-daily.

Preclinical Data

• SB206 exhibited a dose responsive pharmacologic effect with complete inhibition of papilloma growth compared to topical imiquimod in an in vivo model.
• NVN1000, the active pharmaceutical ingredient in SB206, exhibited a dose dependent decrease in HPV viral replication in human raft cell culture model.

Click the links below to learn more.

• Poster presentation at Society for Investigative Dermatology Annual Meeting – 2019
• Poster presentation at International Papillomavirus Conference – 2017
• Oral Presentation at American Academy of Dermatology Annual Meeting – 2017
• Oral presentation at Society for Investigative Dermatology Annual Meeting – 2016
  
• Poster presentation at Society for Investigative Dermatology Annual Meeting – 2016
  
• Poster presentation at Interscience Conference on Antimicrobial Agents and Chemotherapy – 2014

About Human Papillomavirus (HPV) and External Genital Warts

HPV refers to a large family of double-stranded DNA viruses that induce abnormal growths on the skin or mucosal surfaces. HPV affects nearly 80 million Americans, and an estimated 14 million new cases of the virus are reported each year, according to the Centers for Disease Control and Prevention , or CDC. There are over 100 subtypes of the virus, characterized as low-risk or high-risk based on their cancer-causing potential. The virus is typically transmitted via direct skin-to-skin contact through disruptions in the normal skin barrier. All warts are caused by HPV, including genital and perianal warts, common warts and plantar warts.

Genital warts, mainly caused by HPV, affect approximately 1% of sexually active adults in the United States and Europe, and are among the world’s most common sexually transmitted diseases. Genital warts are usually flesh-colored growths that can be raised, flat or cauliflower-shaped and are typically found on the surface of the external genitalia or in and around the anus. In males, they can appear on the surface of the penis and scrotum, and in females inside the vagina or on the cervix. Genital warts carry a substantial psychosocial burden due to the shame and embarrassment related to having a sexually transmitted disease as well as the inconvenience and discomfort of current treatment modalities. Current treatment options for genital warts consist of ablative procedures that cut, burn or freeze the warts but do not address the underlying viral infection, and there are no currently approved oral or topical prescription products indicated for the treatment of genital warts with a direct anti-viral mechanism of action.

WH504 – High-Risk HPV

Novan is developing WH504 for the treatment of cervical intraepithelial neoplasia (CIN).

About Cervical Intraepithelial Neoplasia (CIN)

Cervical intraepithelial neoplasias (CIN), or precancerous lesions of the cervix caused by persistent high risk-HPV infection, are categorized by HPV genotype and the depth of the infection within the epithelial tissue of the cervix, with grades 1 and 2 considered precancerous and grade 3, carcinoma in situ. While there are an estimated 250,000 to 1 million women diagnosed with CIN annually in the U.S., there are no minimally invasive therapies with direct antiviral activity for the treatment of CIN and excisional procedures are often associated with pain, fertility issues and recurrence. Despite the availability of the prophylactic HPV vaccines, the incidence of HPV-induced cancer is steadily increasing, due to (a) the inability of the vaccine to cure preexisting infections; (b) a great majority of adolescent populations is not vaccinated; and (c) high rate of population growth. According to a survey on U.S. cervical cancer mortality rates, each year, nearly 12,000 women in the U.S. will be diagnosed with cervical cancer and more than 4,000 will die from the cancer.

WH602 – High-Risk HPV

Novan is developing WH602 for the treatment of cervical intraepithelial neoplasia (CIN).

About Cervical Intraepithelial Neoplasia (CIN)

Cervical intraepithelial neoplasias (CIN), or precancerous lesions of the cervix caused by persistent high risk-HPV infection, are categorized by HPV genotype and the depth of the infection within the epithelial tissue of the cervix, with grades 1 and 2 considered precancerous and grade 3, carcinoma in situ. While there are an estimated 250,000 to 1 million women diagnosed with CIN annually in the U.S., there are no minimally invasive therapies with direct antiviral activity for the treatment of CIN and excisional procedures are often associated with pain, fertility issues and recurrence. Despite the availability of the prophylactic HPV vaccines, the incidence of HPV-induced cancer is steadily increasing, due to (a) the inability of the vaccine to cure preexisting infections; (b) a great majority of adolescent populations is not vaccinated; and (c) high rate of population growth. According to a survey on U.S. cervical cancer mortality rates, each year, nearly 12,000 women in the U.S. will be diagnosed with cervical cancer and more than 4,000 will die from the cancer.