VYNE Therapeutics Announces First Subjects Dosed in Phase 1a/b Clinical Trial Evaluating Pan-BET Inhibitor for the Treatment of Vitiligo

VYNE Therapeutics Inc. recently announced the first subjects have been dosed in a Phase 1a/b clinical trial evaluating VYN201 for the treatment of vitiligo. VYN201 is a locally administered, small molecule, pan-bromodomain and extra-terminal domain (BET) inhibitor that is being developed for the treatment of immuno-inflammatory diseases. The clinical trial is a first-in-human study designed to generate safety and pharmacokinetic data in healthy volunteers as well as provide early clinical proof-of-concept data in vitiligo patients.

“We believe BET inhibitors have the potential to become a major new drug class for the treatment of vitiligo and other immuno-inflammatory diseases,” said David Domzalski, President and Chief Executive Officer of VYNE. “The initiation of this clinical trial for VYN201, the first of several planned programs for our InhiBET BET inhibitor platform, is a major milestone in our mission to improve the lives of patients suffering from immuno-inflammatory diseases. We look forward to topline data for both the Phase 1a and Phase 1b portions of the study, expected in the first half of 2023.”

The Phase 1 study will be conducted in US-based clinical centers. The Phase 1a portion of the study will evaluate single ascending/multiple ascending doses in up to 30 healthy volunteers with VYN201 applied topically once daily for up to two weeks. The primary objective of this portion of the study is to characterize the preliminary safety and pharmacokinetics of VYN201 and to determine the safe starting dose for the Phase 1b portion of the study.

In the Phase 1b portion, up to 30 patients with a clinical diagnosis of non-segmental vitiligo will receive VYN201 once daily in up to three dose cohorts. Patients will receive treatment for an initial 8-week period based on currently available nonclinical safety data. The company expects to extend the treatment period for up to an additional 12 weeks, subject to ongoing nonclinical safety assessments. The primary objective of the Phase 1b portion of the study will be to evaluate the safety and pharmacokinetics of VYN201. In addition, exploratory efficacy of VYN201 in non-segmental vitiligo patients will also be assessed. Clinical assessments will include safety, pharmacokinetics, local skin tolerance, efficacy, pharmacodynamic biomarkers and photography.

“By utilizing a soft-drug approach, topical VYN201 is designed to maximize target engagement in the skin and minimize systemic exposure. In an ex vivo human tissue model of vitiligo, VYN201 demonstrated a dose-dependent reduction in the loss of melanin pigment in the basal layers of skin and positively impacted key biomarkers that drive dyspigmentation in vitiligo. Further, VYN201 was found to upregulate the WNT signaling pathway which is an important mediator of both melanogenesis and melanocyte differentiation and is known to be dysregulated in patients with vitiligo,” said Dr. Iain Stuart, Chief Scientific Officer of VYNE. “Based upon these data, we believe VYN201 could be a promising and differentiated new therapy to address the unmet needs of patients with vitiligo.”

VYN201 is a locally-administered pan-bromodomain BET inhibitor, designed as a “soft” drug to address diseases involving multiple, diverse inflammatory cell signaling pathways while providing low systemic exposure. To date, VYN201 has produced consistent reductions in pro-inflammatory and disease-related biomarkers, improvements in disease severity and a demonstrated local activity through several preclinical models. The company believes these data suggest potential broad utility for VYN201 across multiple routes of administration.

Vitiligo is a chronic autoimmune depigmenting disorder of the skin, characterized by the loss of pigment producing cells known as melanocytes. Vitiligo is the most common depigmenting skin condition, with a prevalence estimated at 0.5%-2% of the world population. There is currently only one FDA-approved product for the treatment of vitiligo.

BET proteins play a key role in regulating gene transcription via epigenetic interactions (“reading”), and recent research has determined a key role for these BET proteins in regulating B cell and T cell activation and subsequent inflammatory processes. As epigenetic readers, BET proteins regulate the recruitment of transcriptional factors that are key to the production of several pro-inflammatory cytokines. BET inhibitors have the potential to treat a range of immuno-inflammatory and fibrotic diseases by blocking pro-inflammatory cytokine transcription with additional potential myeloproliferative neoplastic disorders.

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 bromodomain and extra-terminal (BET) domain platform includes lead programs VYN201 (pan-BETi) and VYN202 (selective-BETi), and access to a library of small molecule BET inhibitors for the potential treatment of immuno-inflammatory conditions licensed from Tay Therapeutics Limited. For more information, visit www.vynetherapeutics.com.