VYNE Therapeutics Announces Positive Phase 1b Efficacy Data From Phase 1b/2a Trial 

VYNE Therapeutics Inc. recently announced positive efficacy results from the Phase 1b segment of a Phase 1b/2a clinical trial evaluating FMX114 for the treatment of mild-to-moderate atopic dermatitis (AD).

FMX114 is VYNE’s proprietary investigational combination gel formulation of tofacitinib and fingolimod that is designed to address both the source and cause of inflammation in AD. FMX114 has the potential to be the first topical combination product for the treatment of AD.

The objective of the Phase 1b study segment was to evaluate the preliminary clinical safety, dermal tolerance, and pharmacokinetics of FMX114 and vehicle when topically applied to individual qualifying AD lesions for 2 weeks. Efficacy was also assessed over the two-week treatment period.

At the study baseline visit, each subject (N=4) had two AD lesions of comparable severity and extent based on the Atopic Dermatitis Severity Index (ADSI) scoring assessment. Target lesions were randomized and treated twice daily with either FMX114 or vehicle gel.

Efficacy data for the Phase 1b segment of the trial was assessed based on the absolute and percent change relative to baseline in ADSI score at week 2.

• Mean ADSI scores for FMX114 and vehicle treated lesions were 7.8 and 8.0, respectively, at baseline.
• Mean reduction in ADSI score from baseline was -6.3 (-81.4% mean reduction) for FMX114 treated lesions compared to -4.3 (-54.3% mean reduction) for vehicle treated lesions at week 2 (p=0.004, LOCF, ITT).

In addition, the effect of FMX114 on reducing pruritus (itch) was also assessed using the worst pruritus Numerical Rating Scale (NRS).

• Subjects reported a 96.4% mean reduction in worst pruritus NRS from baseline for lesions treated with FMX114 compared to a 45.8% mean reduction for vehicle treated lesions at week 2.

Dr. Iain Stuart, Chief Scientific Officer of VYNE, said “We are encouraged by these early efficacy results from this Phase 1b segment of the trial showing that, based on ADSI scoring, FMX114 treatment demonstrated a statistically significant improvement of the signs and symptoms of AD in 2 weeks. We look forward to topline results from the Phase 2a segment of the study in the second quarter.”

The Phase 1b/2a study is a randomized, double-blinded trial designed to compare the safety and efficacy of FMX114 gel with vehicle gel. The Phase 1b segment enrolled four subjects and the Phase 2a segment of the study is expected to enroll up to 25 subjects, with each subject serving as their own control. The enrollment criteria specifies that subjects must have two comparable target AD lesions for treatment upon entry. Participants will have FMX114 gel applied to one of these lesions and vehicle gel to the other.

During the Phase 1b segment, four subjects were initially treated twice daily with FMX114 and vehicle for up to 2 weeks to evaluate preliminary safety of FMX114 and the pharmacokinetics of each component (tofacitinib, fingolimod and the active metabolite, fingolimod 1-phosphate). There were no meaningful differences between FMX114 treatment and vehicle-treated lesions at baseline, according to ADSI, TLSS, pruritus NRS and lesion size.

The 25 subjects in the Phase 2a segment will receive FMX114, and vehicle treatment applied twice daily for 4 weeks in a double-blinded phase of the study to further evaluate safety, pharmacokinetics and efficacy. After completion of this phase, these subjects may continue into a two-week open-label treatment phase and will be able to apply the active drug to both lesions.

FMX114 is VYNE’s proprietary investigational combination gel formulation of tofacitinib and fingolimod. The product is designed to address both the source and cause of inflammation in AD through a combination of tofacitinib (a Janus kinase inhibitor) that acts with cells to reduce inflammation by inhibiting cytokine release from inflammatory cells) and fingolimod (a Sphingosine 1-phosphate receptor modulator) that acts outside of cells to reduce inflammation by inhibiting migration of inflammatory cells. In addition, fingolimod may also directly support skin barrier recovery because it is known to upregulate filaggrin, a protein that plays an important role in the skin’s barrier function. FMX114 has the potential to be the first topical combination product for the treatment of AD as well as the first topical product in clinical development that utilizes the sphingosine 1-phosphate receptor modulation mode of action.

Atopic dermatitis (AD) is a chronic, severe form of eczema that is characterized by the appearance of dry, red, and itchy skin. AD most commonly affects the cheeks, arms, and legs. Flare-ups often occur and symptoms can worsen leading to more-intense itching and worsening of disease. AD flares are triggered by stress, temperature changes, sweat, various skin irritants, and allergies. AD can have a wide-ranging impact on quality of life and there is a substantial monetary burden from direct and indirect costs to this patient population. While AD occurs most often in childhood, it can develop at any point in a person’s lifetime and affects approximately 30 million people in the U.S. alone. Approximately 22 million of those diagnosed are on treatment, with 19 million registering mild to moderate disease. According to Symphony Health data, there were over 7 million prescriptions written in 2019 alone for the treatment of AD.

VYNE’s mission is to improve the lives of patients by developing proprietary, innovative, and differentiated therapies for the treatment of immuno-inflammatory conditions. The company’s unique and proprietary pipeline includes FMX114 for the potential treatment of mild-to-moderate atopic dermatitis, and access to a library of bromodomain and extra-terminal (BET) domain inhibitors licensed from In4Derm Limited. The BET inhibitor platform includes lead programs VYN201 (pan-BETi) and VYN202 (selective-BETi) and access to a library of (BET) domain inhibitors for the potential treatment of immuno-inflammatory conditions. For more information, visit  www.vynetherapeutics.com.