VYNE Therapeutics Inc. announced new preclinical data showing the positive effect of its novel pan-BET inhibitor, VYN201, in a preclinical model of idiopathic pulmonary fibrosis (IPF). Bleomycin-Induced Mouse Model: IPF is a chronic, life-threatening, fibrosing lung disease with few treatment options. Patients experience debilitating symptoms, including shortness of breath and difficulty performing daily activities.

The current standard of care treatment options for IPF have been shown to have only a modest impact on slowing the progression of the disease and have been associated with significant side effects. In this well-validated preclinical model for IPF, lung fibrosis was induced in mice using a single intratracheal dose of bleomycin. Fibrosis was left to develop for seven days, and thoracic tomography images were obtained to stage fibrotic development.

Animals were assigned to six treatment groups: untreated and unstimulated control, placebo, and one of four doses of VYN201 (0.1, 0.2, 0.5, and 1.0 mg/ml) (N=6/group). Each treatment group was dosed intratracheally every other day for 14 days. Changes in blood oxygen saturation, Ashcroft scoring (a standardized numerical scale used to quantify the extent of lung fibrosis in histological samples), lung hydroxyproline (a tissue biomarker for fibrosis), and volumetric lung function were assessed.

Key findings: Ashcroft Scoring and Hydroxyproline Levels: VYN201 at 0.5 mg/ml and 1 mg/ml demonstrated statistically significant reductions in Ashcroft scores (a measurement of lung fibrosis) and levels of the tissue fibrosis biomarker, hydroxyproline, compared to the placebo control group at day 21. Mean control-adjusted lung fibrosis scores for VYN201 1 mg/ml were 65.8% lower compared to the placebo control group at day 21. Blood Oxygen Saturation: VYN201 demonstrated a dose-dependent improvement in blood oxygen saturation.

Mean blood oxygen saturation for the VYN201 1 mg/ml group was 92.4% at day 21, an 8.8% improvement compared to the placebo group (83.6%). Mean blood oxygen saturation for the untreated and unstimulated control group was 95.2%. Volumetric Lung Function: Thoracic tomography revealed that VYN201 treatment groups demonstrated a dose-dependent improvement in functional lung volume compared to the placebo control group.

These data correlate with an increase in blood oxygen saturation and reduction in Ashcroft fibrosis scores. Treatment with VYN201 1 mg/ml resulted in a 51.8% mean improvement in functional lung volume compared to animals receiving placebo treatment. VYN201 is a pan-bromodomain BET inhibitor designed to be locally-administered 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 and improvements in disease severity, and demonstrated local activity in several preclinical models (using several different routes of administration). The Company believes that these data suggest the potential broad utility for VYN201 across multiple routes of administration. VYNE has completed a Phase 1a study of a topical formulation for VYN201 in healthy volunteers and is now evaluating the topical formulation in a Phase 1b study in patients with non-segmental vitiligo.

The Phase 1a study showed that VYN201, administered topically, performed as expected. In particular, VYN201 had minimal systemic exposure and none of the common adverse events commonly associated with systemically administered pan-BD BET inhibitors, such as thrombocytopenia. VYNE expects to report topline results from the Phase 1b study in mid-2023.