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Volume 18 Issue 10, October 2019

Next-generation regulatory T cells, inspired by the Review on p749.

Cover design: Susanne Harris.


  • Real-world evidence is increasingly valued by regulators and payers. Central to this evidence base is patient-reported outcome data describing the impact of drugs on quality of life, daily activities and symptoms. Here, we highlight key challenges with current real-world, patient-reported outcome data and describe collaborative next steps for international stakeholders to overcome these issues.

    • Melanie J. Calvert
    • Daniel J. O’Connor
    • Ethan M. Basch


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News & Analysis

  • Target 2035 — an ambitious open-science proposal to develop a suite of chemical genomics tools to modulate every protein in the proteome — faces many challenges ahead.

    • Asher Mullard
  • News in Brief

  • Biobusiness Briefs

  • An Audience With

    • In 1989, Stanley Crooke left his job heading up R&D at Smith Kline Beckman, a predecessor of the pharmaceutical giant GlaxoSmithKline, to found and run the antisense-oligonucleotide start-up Ionis Pharmaceuticals (initially called Isis Pharmaceuticals). With just over US$5 million funding at the time, Crooke’s ambitious plan was not just to develop a new RNA-targeted modality that could lower protein expression, but also to tackle industry’s productivity crisis while delinking drug development from commercialization. As broader interest in antisense technologies waxed and waned, Ionis faced some tough years. But it now has three antisense products on the market with partners, three products including a pioneering treatment for Huntington disease in phase III trials and more than ten candidates that could enter phase III trials by the end of 2020. After 30 years at the helm of Ionis as CEO, Crooke will transition to the executive chairman role in January. He spoke with Asher Mullard about Ionis’s long road to success, and the future of antisense drug technology.

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

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Research Highlights

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  • Our increased understanding of how regulatory T cells suppress immune responses has led to their use in early-phase clinical trials for inflammatory disorders, with promising results. This Review describes the key advances and prospects in designing and implementing regulatory T cells as multifaceted, adaptable smart therapeutics in autoimmunity and transplantation.

    • Leonardo M. R. Ferreira
    • Yannick D. Muller
    • Qizhi Tang
    Review Article
  • Cyclic nucleotide phosphodiesterases (PDEs) have roles in numerous biological processes and their dysfunction has been associated with various diseases including those affecting the nervous system, the cardiovascular system, fertility, immunity, cancer and metabolism. Here, Kelly and colleagues assess the current status of therapeutic PDE inhibitors, and highlight emerging novel strategies to therapeutically target PDE function.

    • George S. Baillie
    • Gonzalo S. Tejeda
    • Michy P. Kelly
    Review Article
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  • Adaptive platform trials, which can study multiple therapeutic interventions in a disease in a perpetual manner, offer the potential to improve the efficiency of drug development. This article reviews common features and issues that arise with such trials, and puts forward recommendations to promote best practices in their design, conduct, oversight and reporting.

    • Derek C. Angus
    • Brian M. Alexander
    • Janet Woodcock
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Amendments & Corrections

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