VYNE Therapeutics Reports Results From Phase 1a Trial of VYN202
VYNE Therapeutics Reports Results From Phase 1a Trial of VYN202
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.
VYNE Therapeutics公司（納斯達克：VYNE）（簡稱"VYNE"或"公司"）是一家臨牀階段生物製藥公司，致力於開發針對高未滿足需求的慢性炎症和免疫介導疾病的差異化療法，今天宣佈其VYN202的1a期SAD/MAD試驗的多個遞增劑量（"MAD"）部分的積極結果。1a期試驗是針對健康志願者進行的兩部分、雙盲、安慰劑對照的劑量遞增研究，包括單遞增劑量（"SAD"）和MAD元件，以評估VYN202的安全性、耐受性、藥代動力學（"PK"）和藥效學。
Key Findings from the Top-line Phase 1a MAD Results for VYN202:
VYN202 1a期MAD結果的主要發現：
- 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.
- VYN202顯示出良好的安全性和耐受性，沒有與早期一代、選擇性較差的溴結構域和額外末端結構域（"BET"）抑制劑相關的藥物不良事件，包括血小板減少症、中性粒細胞減少症或胃腸毒性發現。
- 沒有嚴重不良事件（AEs），因不良事件而中斷治療或臨牀上有意義的治療出現不良事件（TEAEs）。所有TEAEs被認爲是輕度或中度嚴重。
- 沒有與實驗室結果相關的藥物不良事件。沒有任何嚴重程度的AEs與血小板減少症相關，而血小板減少症是早期一代BET抑制劑相關的已知劑量限制性毒性。
- 顯示出VYN202的良好PK特徵：
- 數據支持每日一次的給藥方案。
- VYN202顯示出劑量依賴性暴露，在7次每日一次的給藥後達到穩態。
- VYN202血液水平在所有劑量下至少24小時內均處於對BD2 BRD4的關鍵抑制閾值IC50至IC90之間。
- 當VYN202與甲氨蝶呤聯合使用時，未觀察到藥物相互作用，甲氨蝶呤是治療慢性免疫炎症疾病中常用的藥物。
- 在體外檢測中，VYN202在靶向結合和炎症生物標誌物上顯示出強大的藥效學活性：
- VYN202誘導靶向結合生物標誌物HEXIm-11隨劑量依賴性增加，最大效果在0.5mg至1.0mg QD時觀察到。
- VYN202抑制與Th17、Th1/髓樣和Th1/Tc失調活性相關的多個炎症生物標誌物的產生，這與VYN202的臨牀前模型一致。