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Agreements

Date: 2017-09-14

Type of information: Development agreement

Compound: quizartinib, DS-3032,  DS-3201, and PLX51107

Company: Daiichi Sankyo (Japan) The University of Texas MD Anderson Cancer Center (USA - TX)

Therapeutic area: Cancer - Oncology

Type agreement: development

Action mechanism:

  • tyrosine kinase inhibitor/FLT3 kinase inhibitor/ MDM2 inhibitor/EZH1/2 inhibitor/BET inhibitor.
  • Quizartinib is an investigational oral small molecule that potently and selectively inhibits FLT3-ITD (FMS-like tyrosine kinase-3-internal tandem duplication), which is a growth driver of abnormal cells that contribute to the development of acute myeloid leukemia. Quizartinib has been granted orphan drug designation by the  FDA and European Medicines Agency (EMA) for the treatment of acute myeloid leukemia.  Quizartinib also has been granted Fast Track Designation by the FDA for the treatment of relapsed/refractory AML Quizartinib has been developed by Ambit Biosciences. Daiichi Sankyo acquired the company in November 2014,
  • DS-3032 is an orally available MDM2 (murine double minute 2) antagonist. MDM2, a zinc finger protein and a negative regulator of the p53 pathway, is overexpressed in cancer cells. DS-3032  binds to and prevents the binding of MDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53. By preventing this interaction, the proteosome-mediated enzymatic degradation of p53 is inhibited and the transcriptional activity of p53 is restored.
  • DS-3201 is an orally available selective inhibitor of the histone lysine methyltransferases enhancer of zeste homolog 1 (EZH1) and 2 (EZH2). EZH1/2, histone lysine methyltransferase class enzymes and catalytic subunits of the polycomb repressive complex 2, are overexpressed or mutated in a variety of cancer cells and play key roles in tumor cell proliferation, progression, stem cell self-renewal and migration. Inhibition of EZH1/2 specifically prevents the methylation of lysine 27 on histone H3 (H3K27). This decrease in histone methylation alters gene expression patterns associated with cancer pathways, enhances transcription of certain target genes, and results in decreased proliferation of EZH1/2-expressing cancer cells.
  • PLX51107 is a BET  (bromodomain and extra-terminal) inhibitor.

Disease: acute myeloid leukemia (AML)

Details:

  • • On September 14, 2017, The University of Texas MD Anderson Cancer Center and Daiichi Sankyo announced a multi-year collaboration focused on accelerating the development of novel therapies for acute myeloid leukemia. The collaboration will focus on numerous clinical trials using several investigational compounds from the Daiichi Sankyo pipeline and multiple agents in combination regimens. The collaboration will launch multiple phase 1 and 2 clinical trials conducted by MD Anderson with the aim of expediting delivery of new therapies. The studies will incorporate translational work, including exploration of novel biomarkers as well as pre-clinical studies of new agents aimed at mechanisms of resistance to existing treatments.
  • Compounds to be studied include quizartinib, a FLT3 inhibitor in late-stage clinical development, and three agents in early-stage development: DS-3032, an MDM2 inhibitor; DS-3201, a dual EZH1/2 inhibitor; and PLX51107, a BET inhibitor.

Financial terms:

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Is general: Yes