亞盛醫藥-B(06855.HK):EED抑制劑APG-5918獲中國I期臨牀試驗許可,將推進晚期實體瘤或血液惡性腫瘤的臨牀開發
格隆匯11月10日丨亞盛醫藥-B(06855.HK)發佈公吿,公司在研原創1類新藥胚胎外胚層發育蛋白(EED)抑制劑APG-5918獲得國家藥品監督管理局(NMPA)藥品審評中心(CDE)臨牀試驗許可,將開展治療晚期實體瘤或血液系統惡性腫瘤的I期臨牀試驗。在此之前,該在研品種已在美國獲批開展針對晚期實體瘤或血液腫瘤適應症的臨牀試驗,是公司“中美雙報”策略推進的又一重大成果。APG-5918是首個進入臨牀階段的中國原研EED抑制劑。
根據披露,這是一項多中心、開放性的I期劑量遞增及劑量擴展臨牀試驗,旨在評估晚期實體瘤或血液系統惡性腫瘤患者口服APG-5918的安全性、藥代動力學和療效。中國臨牀腫瘤學會理事長、中山大學腫瘤防治中心主任、院長徐瑞華教授將擔任該項臨牀試驗的主要研究者(PI)。
EZH2在多種人類癌症中呈現高表達並且促進癌症發生和惡變,靶向抑制EZH2的甲基轉移酶活性已被證明是一種成功的癌症治療策略。儘管如此,EZH2的二次突變可產生獲得性耐藥,且其同源性EZH1也具有甲基轉移酶活性,均會導致EZH2 抑制劑活性受限。研究發現,PRC2複合物的多蛋白性和EZH2活性對EED的支架和調節作用的高度依賴性。抑制PRC2亞基EED的化合物可破壞EED-EZH2的蛋白質-蛋白質相互作用(PPI),隨後使PRC2的功能受損,導致受H3K27me3激發的 PRC2活性喪失,並阻止H3K27的三甲基化。因此,近年來靶向EED蛋白作為抑制PRC2的替代失活策略獲得了極大的關注。
APG-5918是亞盛醫藥在研具有口服活性、新型強效、高選擇性EED蛋白小分子抑制劑,具有高度結合親和力,通過調節腫瘤組織表觀遺傳學及腫瘤微環境,在血液腫瘤、實體瘤和非腫瘤適應症上具有廣闊的臨牀應用前景。APG-5918能選擇性地與EED蛋白上的H3K27me3結構域結合,導致EED H3K27me3結合口袋發生構象變化,阻止EED與組蛋白甲基轉移酶EZH2的相互作用。初步數據證明了 APG-5918在多個腫瘤細胞系的體外抗腫瘤細胞增殖活力,以及在EZH2突變的B 細胞非霍奇金淋巴瘤、INI1-陰性惡性橫紋肌樣瘤,BAP1突變的間皮瘤和前列腺癌的PDX/CDX模型中的抗腫瘤活性。
Follow us
Find us on
Facebook,
Twitter ,
Instagram, and
YouTube or frequent updates on all things investing.Have a financial topic you would like to discuss? Head over to the
uSMART Community to share your thoughts and insights about the market! Click the picture below to download and explore uSMART app!

Disclaimers
uSmart Securities Limited (“uSmart”) is based on its internal research and public third party information in preparation of this article. Although uSmart uses its best endeavours to ensure the content of this article is accurate, uSmart does not guarantee the accuracy, timeliness or completeness of the information of this article and is not responsible for any views/opinions/comments in this article. Opinions, forecasts and estimations reflect uSmart’s assessment as of the date of this article and are subject to change. uSmart has no obligation to notify you or anyone of any such changes. You must make independent analysis and judgment on any matters involved in this article. uSmart and any directors, officers, employees or agents of uSmart will not be liable for any loss or damage suffered by any person in reliance on any representation or omission in the content of this article. The content of the article is for reference only and does not constitute any offer, solicitation, recommendation, opinion or guarantee of any securities, virtual assets, financial products or instruments. Regulatory authorities may restrict the trading of virtual asset-related ETFs to only investors who meet specified requirements. Any calculations or images in the article are for illustrative purposes only.
Investment involves risks and the value and income from securities may rise or fall. Past performance is not indicative of future performance. Please carefully consider your personal risk tolerance, and consult independent professional advice if necessary.