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Terns Pharmaceuticalsが2020年デジタル国際肝臓学会議で複数の NASHプログラムに関するデータを発表へ



- 第1相臨床試験でTERN-201の単回投与は、安全性と良好な忍容性を示すとともに、強力で選択的・持続的なSSAO阻害を実証し、血漿SSAO活性のほぼ完全な阻害を観察 -



- TERN-501は前臨床NASHげっ歯類モデルにおいて、強力で選択的なTHR-β作動作用を実証し、脂肪肝、線維症、肝障害の血清マーカーを有意に低減 -

米カリフォルニア州フォスターシティ--(BUSINESS WIRE)--(ビジネスワイヤ) -- 肝疾患を治療するベストインクラスの単剤療法および併用療法の開発に傾注するバイオ製薬企業のTerns Pharmaceuticals, Inc.(上海拓臻生物科技有限公司)は本日、2020年8月27~29日に開催予定の2020年デジタル国際肝臓学会議にて、2つ主力プログラムに関し3件のポスター発表を行うと発表しました。ポスター発表にはセミカルバジド感受性アミンオキシダーゼ(SSAO)阻害薬TERN-201の臨床/前臨床データと、前臨床段階の甲状腺ホルモン受容体β(THR-β)作動薬TERN-501をげっ歯類モデルで検討したin vivoデータが含まれます。TERN-201とTERN-501はいずれも非アルコール性脂肪肝炎(NASH)の治療を目的としています。




Ternsの社長兼最高医学責任者(CMO)であるエリン・クワーク(M.D.)は、次のように述べています。「来るデジタル国際肝臓学会議で、当社のSSAO阻害薬TERN-201の複数の研究から得たデータと、THR-β作動薬TERN-501の最初のデータを発表できるのは当社にとって大きな喜びです。TERN-201とTERN-501のそれぞれの重要な作用機序はNASHに対する当社の併用療法戦略に含まれるものです。TERN-201の臨床データは、同薬が強力なターゲットエンゲージメントを示し、一般的に安全で忍容性が良好であることを証明しており、TERN-201がNASHにおける炎症と線維症に影響を及ぼす可能性があることを示しています。また両プログラムとも、強力な前臨床データを示しています。高コレステロール血症および線維症性NASHのげっ歯類モデルで、TERN-501は血清コレステロールを速やかに低下させ、脂肪肝を逆転させて肝臓の炎症と線維症を改善し、単独療法と、おそらくより重要な点として当社の他の主力NASH治療薬候補との併用療法の両方で使用できる可能性を持つベストインクラスのTHR-β作動薬として、患者に大きな利点をもたらす可能性を持つことが示されています。」



発表の詳細は下記の通りです。



発表の表題: 「新規の選択的セミカルバジド感受性アミンオキシダーゼ(SSAO)阻害薬TERN-201の単回投与は、健康な試験参加者において、安全性と良好な忍容性を示し、SSAO活性の持続的な低減をもたらす」(Single doses of TERN-201, a novel selective semicarbazide-sensitive amine oxidase (SSAO) inhibitor, are safe, well-tolerated, and result in sustained reduction of SSAO activity in healthy participants)

発表番号: FRI-088

セッション: NAFLD:治療

日付: 2020年8月28日

発表者: Martijn Fenaux

注目データ:

すべての投与量のTERN-201が健康な試験参加者で安全性と良好な忍容性を示し、1 mg~10 mgの単回経口投与の場合、臨床的に意味のある有害事象は1件も報告されなかった。血漿SSAOアミンオキシダーゼ活性の阻害と、血漿メチルアミン(MMA)の用量依存的上昇は、TERN-201の単回投与後、最長1週間まで維持され、強力な共有結合性のターゲットエンゲージメントを示唆しており、短い血漿内半減期にもかかわらず、1日1回の投与を支持。



ポスターの表題: 「コリン欠乏高脂肪食飼料を用いた非アルコール性脂肪肝炎ラットモデルにおけるセミカルバジド感受性アミンオキシダーゼ阻害薬TERN-201の抗炎症・抗線維化作用」(Anti-inflammatory and anti-fibrotic activity of TERN-201, a semicarbazide-sensitive amine oxidase inhibitor, in a rat choline-deficient high-fat diet non-alcoholic steatohepatitis model)

発表番号: SAT-032

セッション: NAFLD: 実験および病態生理学

日付: 2020年8月29日

発表者: Martijn Fenaux

注目データ:




  • TERN-201投与はラットNASHモデルで肝臓の炎症(p<0.001)および炎症と関連した遺伝子発現を有意に低減。


  • TERN-201は線維症(p<0.005)および肝障害(p<0.05)の遺伝子発現マーカーも低減させ、NASH患者での本薬のさらなる開発を支持。



ポスター表題: 「甲状腺ホルモン受容体ベータの強力な選択的作動薬であるTERN-501は、げっ歯類モデルの非アルコール性脂肪肝炎に伴う病態の組織学的特徴とバイオマーカーを大幅に低減」(TERN-501, a potent and selective agonist of thyroid hormone receptor beta, strongly reduces histological features and biomarkers of non-alcoholic steatohepatitis associated pathology in rodent models)

発表番号: SAT-066

セッション: NAFLD: 実験および病態生理学

日付: 2020年8月29日

発表者: Martijn Fenaux

注目データ:




  • TERN-501は強力で選択的なTHR-β作動作用(THR-β EC50=100nM;THR-α EC50=2,600nM)と良好な薬物動態特性を発揮。


  • ラットの高コレステロール血症モデルで、最大71%(賦形剤に対してp <0.0001)と強固で用量依存的な総コレステロール低減が観察。


  • マウスのNASHモデルで、TERN-501は対照マウスとの比較で脂肪症を有意に低減。試験で用いられたすべての用量で血清総コレステロール、トリグリセリド、ALTの各値の有意な低下も観察。


  • またTERN-501はNASHの進行と関連する複数の線維化促進性星細胞経路で遺伝子発現も有意義に調整。



TERN-201とセミカルバジド感受性アミンオキシダーゼ(SSAO)阻害について



VAP-1(血管接着タンパク質-1)としても知られるSSAOは、H2O2の生成を通じて酸化ストレスを増大させる二重機能アミンオキシダーゼで、肝臓への白血球補充を促進し、結果的に酸化ストレス、炎症、肝線維症を増大させます。表在性SSAOの濃度は炎症組織の血管系で上方制御され、NASH患者では可溶性SSAOの濃度が上昇します。SSAOの阻害は、NAFLD、NASH、その他の慢性線維性肝疾患に対する治療効果を持つと考えられています。TERN-201は、酸化ストレスと肝臓への白血球補充を低減することで、NASHに対する追加的な治療メカニズムを提供する強力なSSAO阻害薬です。インビトロではSSAOの選択指数がオフターゲットとしてのモノアミンオキシダーゼ(MAO)と比較して7000倍超と選択的なものとなっています。一定のMAOはNASH患者層であり得る薬物相互作用に関連する可能性があります。



TERN-501と甲状腺ホルモン受容体ベータ(THR-β)について



甲状腺ホルモン受容体ベータ(THR-β)は、肝臓で高度に発現する核内ホルモン受容体で、脂質代謝、血中コレステロール/トリグリセリド濃度の調節、肝臓における過度の脂肪蓄積を原因とする脂肪症の予防に中心的な役割を果たします。脂肪症は、脂肪性肝炎として知られる肝臓の炎症を特徴とする重篤な進行性肝疾患であるNASHの主因です。THR-βの低分子作動薬は、代謝を高め、血中脂質のパラメーターを正常化し、脂肪症を低減する能力を備えているため、有望なクラスのNASH治療薬です。Ternsは、肝臓のTHR-βを選択的に活性化することで、他の組織における潜在的なオフターゲット作用を回避する新規治療法を追求しています。TERN-501は、極めて強力で選択的な低分子THR-β作動薬です。



NASHについて



非アルコール性脂肪肝炎(NASH)は非アルコール性脂肪性肝疾患(NAFLD)の重症型であり、NAFLDは肝臓における脂肪の過剰な蓄積が原因で発症します。NASHには慢性肝炎と肝細胞損傷が伴い、線維症、肝硬変、最終的には肝がんや肝不全をもたらす場合があります。世界におけるNAFLDとNASHの発症率は肥満率の上昇に伴い、急上昇しています。現在、承認済みのNASH治療薬はありません。



Terns Pharmaceuticalsについて



Terns Pharmaceuticals, Inc.は臨床段階のバイオ医薬品企業として、非アルコール性脂肪肝炎(NASH)を治療する経口薬候補のパイプラインを含め、肝疾患を治療するためのベストインクラスの単剤療法および併用療法の開発に傾注しています。当社の肝臓選択的FXR作動薬TERN-101は現在、多施設・ランダム化・二重盲検・プラセボ対照第2a相臨床試験の患者を組み入れ中です。本試験は、NASHが疑われる患者96人にプラセボまたはTERN-101をさまざまな用量にて12 週間投与して有効性、安全性、薬物動態を評価するようにデザインされています。Ternsは最近、当社の高選択的SSAO阻害剤TERN-201についての良好な第1相臨床データを発表し、強力で持続的なターゲットエンゲージメントを実証しました。当社はさらに、甲状腺ホルモン受容体β作動薬TERN-501につき、NASH単剤療法および他のNASH治療薬パイプライン資産との併用療法にて検討する臨床試験を開始する計画を積極的に進め、また低分子GLP-1R作動薬プログラムを前進させています。Ternsの出資者にはオービメッド、Vivo Capital、リリー・アジア・ベンチャーズ、Decheng Capital(徳誠資本)が含まれます。



本記者発表文の公式バージョンはオリジナル言語版です。翻訳言語版は、読者の便宜を図る目的で提供されたものであり、法的効力を持ちません。翻訳言語版を資料としてご利用になる際には、法的効力を有する唯一のバージョンであるオリジナル言語版と照らし合わせて頂くようお願い致します。


Contacts


US Media Contact:
Investor Relations Contact:

Mark Vignola

investors@ternspharma.com



Media Contact:
Margaret Robinson

info@ternspharma.com

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      Line: 217
      Function: render

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
      Line: 238
      Function: render

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
      Line: 116
      Function: _execute

      File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
      Line: 45
      Function: fetch

      File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
      Line: 32
      Function: view

      File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
      Line: 292
      Function: require_once

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    Severity: Notice

    Message: Trying to access array offset on value of type null

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    Line Number: 29

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php
    Line: 29
    Function: _error_handler

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d136f97_11902452

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 384
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 416
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 248
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 186
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 156
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
    Line: 88
    Function: instanceBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3cb92fa0_94546305

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 116
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 71
    Function: endChild

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_675a781dcbf339_49719938

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 238
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 116
    Function: _execute

    File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
    Line: 45
    Function: fetch

    File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
    Line: 32
    Function: view

    File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
    Line: 292
    Function: require_once

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    Severity: Notice

    Message: Undefined offset: 1

    Filename: smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php

    Line Number: 41

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _error_handler

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 416
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 248
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 186
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 156
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
    Line: 88
    Function: instanceBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3cb92fa0_94546305

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 116
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 71
    Function: endChild

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_675a781dcbf339_49719938

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 238
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 116
    Function: _execute

    File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
    Line: 45
    Function: fetch

    File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
    Line: 32
    Function: view

    File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
    Line: 292
    Function: require_once

    A PHP Error was encountered

    Severity: Notice

    Message: Trying to access array offset on value of type null

    Filename: smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php

    Line Number: 24

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php
    Line: 24
    Function: _error_handler

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d136f97_11902452

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 384
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 416
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 248
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 186
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 156
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
    Line: 88
    Function: instanceBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3cb92fa0_94546305

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 116
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 71
    Function: endChild

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_675a781dcbf339_49719938

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 238
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 116
    Function: _execute

    File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
    Line: 45
    Function: fetch

    File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
    Line: 32
    Function: view

    File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
    Line: 292
    Function: require_once

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    Severity: Notice

    Message: Trying to access array offset on value of type null

    Filename: smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php

    Line Number: 29

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php
    Line: 29
    Function: _error_handler

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d136f97_11902452

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 384
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 416
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 248
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 186
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 156
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
    Line: 88
    Function: instanceBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3cb92fa0_94546305

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 116
    Function: _subTemplateRender

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