パイプライン

OBP-601 (Censavudine)

新たな疾患領域への応用に期待

概要

OBP-601(Censavudine)は、RNAからDNAへの逆転写を阻害する核酸系逆転写酵素阻害剤(NRTI)です。
OBP-601は、重症感染症のHIV治療薬として開発することを目的に2006年にYale大学から導入し、2010年から2014年にかけてBristol-Myers Squibb Co.がPhase2臨床試験の完了まで開発を進めてきました。その後、HIV治療薬のマーケットが飽和状態となり、新規ライセンスの可能性が低い状況の中、感染症領域以外でのOBP-601の新規ライセンス契約締結に向けたビジネス活動を積極的に推進しました。
その結果、逆転写酵素阻害作用を重篤な疾患へ応用することを目的に設立されたTransposon Therapeutics, Inc.(以下「Transposon社」)との間で総額3億ドル超の新規ライセンス契約を2020年6月に締結しました。今後の開発はTransposon社が全世界で実施することになっています。

OBP-601 (Censavudine)

開発の状況

進捗に関しては、「パイプラインの概要:パイプラインの進捗一覧 」をご参照ください。
開発進捗に関する詳細は、決算短信に記載の「研究開発活動 」をご参照ください。

特許の概況

センサブジンは、平成29年1月末時点で日本を含む世界13ヶ国での特許取得が完了しています。

  • (特許取得済みの国)
  • 日本・米国・オーストラリア・カナダ・中国・香港・ロシア・イスラエル・韓国・メキシコ・ニュージーランド・ポーランド・シンガポール

詳しくはこちらもご参照ください。

発表論文

Efficacy, safety, bone and metabolic effects of HIV nucleoside reverse transcriptase inhibitor BMS-986001 (AI467003): a phase 2b randomised, controlled, partly blinded trial.

Gupta SK, McComsey GA, Lombaard J, Echevarría J, Orrell C, Avihingsanon A, Osiyemi O, Santoscoy M, Ray N, Stock DA, Joshi SR, Hanna GJ, Lataillade M
Lancet HIV. 2016 Jan;3(1):e13-22, 2016

The Nucleoside Analog BMS-986001 Shows Greater In Vitro Activity against HIV-2 than against HIV-1.

Smith RA, Raugi DN, Wu VH, Leong SS, Parker KM, Oakes MK, Sow PS, Ba S, Seydi M, Gottlieb GS; University of Washington-Dakar HIV-2 Study Group.
Antimicrob Agents Chemother. 2015 Dec;59(12):7437-46., 2015

Dried blood spot analysis without dilution: Application to the LC-MS/MS determination of BMS-986001 in rat dried blood spot.

Yuan L, Schuster A, Shen JX, Garrison-Borowski P, Aubry AF.
J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Oct 1;1002:201-9., 2015

Scalable Synthesis of the Potent HIV Inhibitor BMS-986001 by Non-Enzymatic Dynamic Kinetic Asymmetric Transformation (DYKAT).

Ortiz A, Benkovics T, Beutner GL, Shi Z, Bultman M, Nye J, Sfouggatakis C, Kronenthal DR
Angew Chem Int Ed Engl. 2015 Jun 8;54(24):7185-8., 2015

Nonclinical Safety Profile of BMS-986001, a Nucleoside Transcriptase Inhibitor for Combination Retroviral Therapy.

Mausumee G, Frank S, Shawn C, Dara H, Zhao Y, Soleil PM, Sanderson TP, Michael G, Marc D.
Int J Toxicol. 2014 May 20;33(3):204-218, 2014

Randomized, placebo-controlled single-ascending-dose study to evaluate the safety, tolerability and pharmacokinetics of the HIV nucleoside reverse transcriptase inhibitor, BMS-986001, in healthy subjects.

Urata Y, Paintsil E, Cheng YC, Matsuda T, Sevinsky H, Hawthorne D, Bertz R, Hanna GJ, Grasela D, Hwang C.
J Clin Pharmacol. 2014 Jun;54(6):657-64., 2014

Delayed emergence of HIV-1 variants resistant to 4'-ethynyl-2-fluoro-2'-deoxyadenosine: comparative sequential passage study with lamivudine, tenofovir, emtricitabine and BMS-986001.

Maeda K, Desai DV, Aoki M, Nakata H, Kodama EN, Mitsuya H.
CAntivir Ther. 2014;19(2):179-89., 2014

The antiretroviral drug pipeline: prospects and implications for future treatment research.

Flexner C, Saag M.
Curr Opin HIV AIDS. 2013 Nov;8(6):572-8., 2013

BMS-986001, an HIV nucleoside reverse transcriptase inhibitor, does not degrade mitochondrial DNA in long-term primary cultures of cells isolated from human kidney, muscle, and adipose tissue.

Wang F, Flint OP.
Antimicrob Agents Chemother. 2013 Dec;57(12):6205-12., 2013

In vitro cross-resistance profile of nucleoside reverse transcriptase inhibitor (NRTI) BMS-986001 against known NRTI resistance mutations.

Li Z, Terry B, Olds W, Protack T, Deminie C, Minassian B, Nowicka-Sans B, Sun Y, Dicker I, Hwang C, Lataillade M, Hanna GJ, Krystal M.
Antimicrob Agents Chemother. 2013 Nov;57(11):5500-8, 2013

Randomized placebo-controlled study of the safety, tolerability, antiviral activity, and pharmacokinetics of 10-day monotherapy with BMS-986001, a novel HIV NRTI, in treatment-experienced HIV-1-infected subjects.

Cotte L, Dellamonica P, Raffi F, Yazdanpanah Y, Molina JM, Boué F, Urata Y, Chan HP, Zhu L, Chang I, Bertz R, Hanna GJ, Grasela DM, Hwang C.
J Acquir Immune Defic Syndr. 2013 Jul 1;63(3):346-54., 2013

Comparison of supercritical fluid chromatography and reverse phase liquid chromatography for the impurity profiling of the antiretroviral drugs lamivudine/BMS-986001/efavirenz in a combination tablet

Alexander AJ, Zhang L, Hooker TF, Tomasella FP.
J Pharm Biomed Anal. 2013 May 5;78-79:243-51., 2013

Improved ruggedness of an ion-pairing liquid chromatography/tandem mass spectrometry assay for the quantitative analysis of the triphosphate metabolite of a nucleoside reverse transcriptase inhibitor in peripheral blood mononuclear cells.

Zhao Y, Liu G, Liu Y, Yuan L, Hawthorne D, Shen JX, Guha M, Aubry A.
Rapid Commun Mass Spectrom. 2013 Feb 15;27(3):481-8, 2013

Intracellular Metabolism and Persistence of the Anti-Human Immunodeficiency Virus Activity of 2',3'-Didehydro-3'-Deoxy-4'-Ethynylthymidine, a Novel Thymidine Analog

Elijah Paintsil, Ginger E. Dutschman, Rong Hu, Susan P. Grill, Wing Lam, Masanori Baba, Hiromichi Tanaka, and Yung-Chi Cheng
Antimicrobial Agents And Chemotherapy, 51(11):3870-3879, Nov. 2007

Comparison of the Phosphorylation of 4'-Ethynyl 2',3'-Dihydro-3'-Deoxythymidine with That of Other Anti-Human Immunodeficiency Virus Thymidine Analogs

Chih-Hung Hsu, Rong Hu, Ginger E. Dutschman, Guangwei Yang, Preethi Krishnan, Hiromichi Tanaka, Masanori Baba, and Yung-Chi Cheng
Antimicrobial Agents And Chemotherapy, 51(5):1687-1693, May 2007

Anti-Human Immunodeficiency Virus Type 1 Activity and Resistance Profile of 2',3'-Didehydro-3'-Deoxy-4'-Ethynylthymidine In Vitro

Takao Nitanda, Xin Wang, Hiroki Kumamoto, Kazuhiro Haraguchi, Hiromichi Tanaka, Yung-Chi Cheng, and Masanori Baba
Antimicrobial Agents and Chemotherapy, 49(8):3355-3360, Aug. 2005

Novel 4_-Substituted Stavudine Analog with Improved Anti-Human Immunodeficiency Virus Activity and Decreased Cytotoxicity

Ginger E. Dutschman, Susan P. Grill, Elizabeth A. Gullen, Kazuhiro Haraguchi, Shingo Takeda, Hiromichi Tanaka, Masanori Baba, and Yung-Chi Cheng
Antimicrobial Agents And Chemotherapy, 48(5):1640-1646, May 2004

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