Positive Preclincal Data Seen for VYN201 in Human Skin Model of Vitiligo

VYNE Therapeutics, a biopharmaceutical company focused on developing proprietary, innovative, and differentiated therapies for the treatment of immuno-inflammatory conditions, released positive preclinical data in an ex vivo skin model of vitiligo. In the preclinical model, VYN201 (VYNE Therapeutics) a pan-bromodomain and extra-terminal (BET) inhibitor reduced the expression of key pro-inflammatory biomarkers relevant to the pathogenesis of vitiligo, and demonstrated marked reduction in melanocyte loss, according to the release.

This study aimed to evaluate the ability of VYN201 to reduce matrix metalloproteinase-9 (MMP-9) secretion, reduce soluble adhesion molecule, E-cadherin, minimize the loss of melanocytes by assessing melanin pigment content, and affect the expression of genes commonly associated with melanogenesis.

The study usedreconstituted human epithelial skin cultures that were stimulated with tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-ɣ) cytokines to induce a vitiligo phenotype. The stimulated cultures were topically treated with vehicle, VYN201 at varying concentrations ranging from .001% - 1%, or an active control, topical ruxolitinib cream (Opzelura, Incyte Dermatology), 1.5%, at 3 mg/cm2. The topical treatments were applied to the skin cultures 24 hours prior to, and concomitantly with, cytokine induction, the released explained.

The data showed:

• VYN201 produced a dose dependent reduction in MMP-9 and soluble E-cadherin:
  • Applications with VYN201 at each of the .1% and 1% concentrations resulted in statistically significant reductions in MMP-9 when compared to vehicle, with a 94.7% reduction in secreted MMP-9 for the VYN201 1% treatment (p<.0001).
  • Applications with VYN201 at each of the .1% and 1% concentrations resulted in statistically significant reductions in the release of soluble E-cadherin relative to vehicle, with a 32.6% reduction in soluble E-cadherin for the VYN201 1% concentration (p<.01).
  • VYN201 .1% and 1% were both numerically superior to topical ruxolitinib cream, 1.5% in reducing the secretion of MMP-9 and soluble E-cadherin.
• VYN201 at each of the .1% and 1% concentrations substantially reduced the loss of melanin pigment in the basal layers of skin:
  • Quantified melanin levels for VYN201 1% treated skin cultures were approximately 10-fold higher as compared to VYN201 vehicle treated skin cultures (p=.03).
• VYN201 positively impacted the expression of several genes implicated in the pathogenesis of vitiligo:
  • VYN201 .1% and 1% resulted in a statistically significant reduction in the expression of inflammatory cytokines interleukin (IL)1-α and IL1-β relative to vehicle (VYN201 1%, p<.0005).
  • VYN201 significantly upregulated the WNT signaling pathway at the .1% and 1% concentrations relative to vehicle, with a 10-fold increase observed at the 1% concentration (p<.01).

“We are encouraged by the evolving therapeutic potential of our locally-administered pan-BET inhibitor, VYN201,” said David Domzalski, VYNECEO. “This latest set of pre-clinical data in vitiligo reflects the potential broad utility for this molecule. We look forward to providing additional updates as we continue to advance this program toward in-human clinical trials later this year.”

Reference:

VYNE reports positive preclinical data for lead bet inhibitor, vyn201, in human skin model of vitiligo. BioSpace. Press release. Published March 7, 2022. Accessed March 8, 2022. https://www.biospace.com/article/vyne-reports-positive-preclinical-data-for-lead-bet-inhibitor-vyn201-in-human-skin-model-of-vitiligo/