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Volume 19 Issue 11, November 2020

Targeting the epigenetic regulation of antitumour immunity, inspired by the Review on p776.

Cover design: Susanne Harris.

Comment

  • Consortia are enabling drug discovery in areas that individual organizations are unable to support alone because of the high risk or the need to pool information. This article discusses desirable features that can underpin the success of such consortia.

    • Peter B. Simpson
    • Graeme F. Wilkinson
    Comment

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News & Analysis

  • Small-molecule integrin inhibitors are catching the attention of pharmaceutical firms, with fibrosis joining gut dysfunction as a key indication for integrin-based interventions.

    • Megan Cully
    News
  • Fragment-based screening methodologies are proliferating, fuelled by interest in novel target space and targeted degraders.

    • Asher Mullard
    News
  • News in Brief

  • Biobusiness Briefs

  • An Audience With

    • Between 2000 and 2010, Pfizer racked up three of the ten largest biopharmaceutical deals of all time, with a US$90 billion acquisition of Warner-Lambert, a $60 billion merger with Pharmacia and a $68 billion acquisition of Wyeth. The last deal, especially, was aimed at bolstering Pfizer’s flagging pipeline and protecting its revenue base from an upcoming patent cliff. More than a decade on — having walked away from an attempted takeover of AstraZeneca and a merger with Allergan — the company is celebrating an R&D turnaround. Pfizer CSO Mikael Dolsten has overhauled the firm’s scientific approach, focusing on five therapeutic areas, halving the number of candidates the company has in the clinic, and expanding its modality capabilities beyond the small molecules it used to focus on. And he believes the results are in: Pfizer’s phase II success rate has tripled in recent years, he said at a recent investor day. Dolsten spoke with Asher Mullard about Pfizer’s clinical success rate, its focus on speedy drug development and its approach to modality expansion in recent years.

      • Asher Mullard
      An Audience With
  • From the Analyst's Couch

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Research Highlights

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Reviews

  • cis-Regulation therapy (CRT) — modifying the activity of gene-regulatory elements — is emerging as a potential approach to treat genetic diseases. Here, Matharu and Ahituv assess emerging CRT technologies and present proof-of-concept studies in cell and animal models. Key factors to be considered for the translation of CRT into the clinic are discussed.

    • Navneet Matharu
    • Nadav Ahituv

    Collection:

    Review Article
  • Aberrant epigenetic processes can influence tumour immunogenicity and immune cells involved in the response to cancer. This Review highlights how epigenetic regulators can be modulated with small-molecule drugs to promote antitumour immune responses, and discusses the opportunities and challenges for developing cancer treatment regimens that combine epigenetic therapies with immunotherapies.

    • Simon J. Hogg
    • Paul A. Beavis
    • Ricky W. Johnstone
    Review Article
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Perspectives

  • Phase 0 approaches, including microdosing, evaluate subtherapeutic exposures to novel drugs, potentially enabling safer, cheaper and quicker first-in-human studies. Here, Burt et al. discuss the fundamentals and applications of phase 0 approaches, highlight the potential advantages of their application in drug development and address the associated limitations.

    • Tal Burt
    • Graeme Young
    • Yuichi Sugiyama
    Perspective
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Amendments & Corrections

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