Pipeline

OBP-601 (Censavudine)

Outline

OBP-601 (Censavudine) is a novel small molecule nucleotide reverse transcriptase inhibitor (NRTI) for HIV infection and is effective on a wide range of resistant virus strains. After getting exclusive worldwide license from Yale University in 2006, Oncolys completed preclinical, CMC, phase 1a, phase 1b/2a and phase 2b clinical studies and have been preparing phase 3 clinical study. OBP-601 has a potential to show better profile on safety having less side effects such as nerve damage, bone mineral density loss and abnormal lipid metabolism which have been a problems in existing anti-HIV drugs.

OBP-601 (Censavudine)

Target indication

HIV infection

Current status

In the phase 2b clinical trial involving 296 patients in 17 countries worldwide to explore optimal dosage of OBP-601, OBP-601 showed a potential to be a best-in-class type product for HIV treatment and Oncolys has investigated potential financial structure to conduct phase 3 study, including partnering with a third party. In May 2016, Oncolys signed an option agreement with LBR Regulatory & Clinical Consulting Services, Inc. (LBR), a professional firm based in Florence, Kentucky, USA, aiming to discuss and examine the strategy to advance to Phase 3 of OBP-601.

References

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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