VYNE Therapeutics Inc. (NASDAQ:VYNE) ("VYNE" or the "Company"), a clinical-stage biopharmaceutical company focused on developing differentiated therapies to treat chronic inflammatory and immune-mediated conditions with high unmet need, today announced positive results from the multiple ascending dose ("MAD") portion of its Phase 1a SAD/MAD trial of VYN202. The Phase 1a trial was a two-part, double-blind, placebo-controlled dose-escalation study in healthy volunteers consisting of single ascending dose ("SAD") and MAD components to evaluate the safety, tolerability, pharmacokinetics ("PK") and pharmacodynamics of VYN202.

Key Findings from the Top-line Phase 1a MAD Results for VYN202:

• VYN202 demonstrated a favorable safety and tolerability profile with no drug-related adverse events historically associated with earlier generation, less selective bromodomain and extra-terminal domain ("BET") inhibitors, including thrombocytopenia, neutropenia or gastrointestinal toxicity findings
  • No serious adverse events (AEs), discontinuations due to an AE or clinically meaningful treatment emergent adverse events (TEAEs). All TEAEs were considered mild or moderate in severity.
  • No drug-related adverse events associated with laboratory results. There were no AEs of any severity grade relating to thrombocytopenia, which is a known dose-limiting toxicity associated with earlier generations of BET inhibitors.
    
• Favorable PK profile demonstrated for VYN202:
  
  • Data supports once-daily dosing regimen.
  • VYN202 demonstrated dose dependent exposure that reached steady-state after 7 once-daily doses.
  • VYN202 blood levels were within key inhibitory thresholds of IC50 to IC90 against BD2 BRD4 for at least 24 hours at all doses.
  • No drug-drug interaction was observed when VYN202 was co-administered with methotrexate, a treatment commonly used in the management of chronic immuno-inflammatory conditions.
    
• VYN202 demonstrated robust pharmacodynamic activity on target engagement and inflammatory biomarkers in ex vivo assays:
  
  • VYN202 induced a dose-dependent increase in the target engagement biomarker HEXIM-11 with a maximal effect observed at 0.5mg to 1.0 mg QD.
  • VYN202 inhibited the production of multiple inflammatory biomarkers related to Th17, Th1/myeloid and Th1/Tc dysregulated activity, consistent with preclinical models of VYN202.