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Immuno-oncology drug development forges on despite COVID-19 Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-18 Samik Upadhaya; Vanessa M. Hubbard-Lucey; Jia Xin Yu
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Selectively triggering mitotic failure Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-17 Sarah Crunkhorn
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Targeting co-stimulatory molecules in autoimmune disease Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-16 Natalie M. Edner; Gianluca Carlesso; James S. Rush; Lucy S. K. Walker
Therapeutic targeting of immune checkpoints has garnered significant attention in the area of cancer immunotherapy, in which efforts have focused in particular on cytotoxic T lymphocyte antigen 4 (CTLA4) and PD1, both of which are members of the CD28 family. In autoimmunity, these same pathways can be targeted to opposite effect: to curb the over-exuberant immune response. The CTLA4 checkpoint serves
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Targeting the epigenetic regulation of antitumour immunity Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-14 Simon J. Hogg; Paul A. Beavis; Mark A. Dawson; Ricky W. Johnstone
Dysregulation of the epigenome drives aberrant transcriptional programmes that promote cancer onset and progression. Although defective gene regulation often affects oncogenic and tumour-suppressor networks, tumour immunogenicity and immune cells involved in antitumour responses may also be affected by epigenomic alterations. This could have important implications for the development and application
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First microbiome-based drug clears phase III, in clinical trial turnaround Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-11 Ken Garber
Seres Therapeutics’ stool-derived treatment for recurrent Clostridium difficile infection could become the first FDA-approved microbiome therapy. Several other live biotherapeutic microbial products are close behind.
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Trispecific antibodies take to the clinic Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-11 Asher Mullard
Sanofi and others are testing whether trispecific antibodies might have applications in cancer and infectious disease indications.
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Karen Akinsanya Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-11 Asher Mullard
Computational chemistry is already embedded in the drug discovery process. Schrödinger — a company that was founded more than 30 years ago to develop chemical simulation software for biopharmaceutical partners — believes that it should be more foundational still. Having co-founded several biotechs in the past decade, including Nimbus Therapeutics and Morphic Therapeutics, Schrödinger launched its own
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Novel chemistry for covalent inhibitors Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-10 Megan Cully
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Clinical trial recovery from COVID-19 disruption Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-10 John Z. Xue; Katarzyna Smietana; Pawel Poda; Kevin Webster; Guang Yang; Gaurav Agrawal
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Organs-on-chips: into the next decade Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-10 Lucie A. Low; Christine Mummery; Brian R. Berridge; Christopher P. Austin; Danilo A. Tagle
Organs-on-chips (OoCs), also known as microphysiological systems or ‘tissue chips’ (the terms are synonymous), have attracted substantial interest in recent years owing to their potential to be informative at multiple stages of the drug discovery and development process. These innovative devices could provide insights into normal human organ function and disease pathophysiology, as well as more accurately
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Upcoming market catalysts in Q4 2020 Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-08 Luis Pablos
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Phase 0/microdosing approaches: time for mainstream application in drug development? Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-08 Tal Burt; Graeme Young; Wooin Lee; Hiroyuki Kusuhara; Oliver Langer; Malcolm Rowland; Yuichi Sugiyama
Phase 0 approaches — which include microdosing — evaluate subtherapeutic exposures of new drugs in first-in-human studies known as exploratory clinical trials. Recent progress extends phase 0 benefits beyond assessment of pharmacokinetics to include understanding of mechanism of action and pharmacodynamics. Phase 0 approaches have the potential to improve preclinical candidate selection and enable
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Author Correction: Radiopharmaceutical therapy in cancer: clinical advances and challenges Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-07 George Sgouros; Lisa Bodei; Michael R. McDevitt; Jessie R. Nedrow
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Evolution of the COVID-19 vaccine development landscape Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-04 Tung Thanh Le; Jakob P. Cramer; Robert Chen; Stephen Mayhew
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FDA approves first GPCR biased agonist. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-03 Asher Mullard
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FDA approves first BCMA-targeted therapeutic. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-03 Asher Mullard
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FDA approves RNA-targeting small molecule. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-03 Asher Mullard
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COVID-19 must catalyse changes to clinical development. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-03 Rod MacKenzie,Peter Honig,Judy Sewards,Robert Goodwin,Marie-Pierre Hellio
The response to the COVID-19 pandemic has shown that exceptional efforts can dramatically accelerate the clinical development of vaccines. We propose that it is time to also take immediate actions to improve clinical trials in other areas to better serve all patients.
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Poly(ADP-ribose) polymerase inhibition: past, present and future. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-03 Nicola J Curtin,Csaba Szabo
The process of poly(ADP-ribosyl)ation and the major enzyme that catalyses this reaction, poly(ADP-ribose) polymerase 1 (PARP1), were discovered more than 50 years ago. Since then, advances in our understanding of the roles of PARP1 in cellular processes such as DNA repair, gene transcription and cell death have allowed the investigation of therapeutic PARP inhibition for a variety of diseases — particularly
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Fatty acid receptor gives lungs a breather. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-02 M Teresa Villanueva
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Soluble ligands as drug targets. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-02 Misty M Attwood,Jörgen Jonsson,Mathias Rask-Andersen,Helgi B Schiöth
Historically, the main classes of drug targets have been receptors, enzymes, ion channels and transporters. However, owing largely to the rise of antibody-based therapies in the past two decades, soluble protein ligands such as inflammatory cytokines have become an increasingly important class of drug targets. In this Review, we analyse drugs targeting ligands that have reached clinical development
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Degrading sialoglycans delays tumour growth. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-01 Sarah Crunkhorn
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Targeting TREM2 to enhance immunotherapy. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-01 Sarah Crunkhorn
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CRISPR-engineered fat cells prevent obesity. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-01 Sarah Crunkhorn
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Treating Dravet syndrome with TANGO. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-09-01 Sarah Crunkhorn
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Strengthening the sting of immunotherapy. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-08-25 Sarah Crunkhorn
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Targeting translation. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-08-18 Katharine H Wrighton
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Informing single-arm clinical trials with external controls. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-08-18 Ruthie Davi,Nirosha Mahendraratnam,Arnaub Chatterjee,C Jill Dawson,Rachel Sherman
Randomized controlled trials are the accepted standard for evaluating investigational therapies, but such trials are sometimes not an option for reasons of ethics or feasibility. Here, we discuss opportunities to address evidence gaps by using historical clinical trial data and real-world data in external control arms for single-arm trials, as well as the associated challenges.
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An RNA vaccine for advanced melanoma. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-08-17 Yvonne Bordon
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Tillman Gerngross. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-08-12 Asher Mullard
When Tillman Gerngross co-founded Adimab in 2007, his goal was to build a one-stop antibody-discovery shop for biopharma partners in need of biologic therapeutics. In the years since, the company has worked on over 350 programmes from more than 70 partners, helping advance 41 antibodies into the clinic — without ever being tempted into drug development programmes of its own. The onset of COVID-19 has
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Pharmaceutical firms commit US$1 billion to antibiotic development. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-08-12 Asher Mullard
Twenty-four large and medium-sized pharmaceutical firms are backing a US$1 billion fund to steward antibiotics through phase II and III trials. Can they also break an antibiotic reimbursement impasse?
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Advances in oligonucleotide drug delivery. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-08-11 Thomas C Roberts,Robert Langer,Matthew J A Wood
Oligonucleotides can be used to modulate gene expression via a range of processes including RNAi, target degradation by RNase H-mediated cleavage, splicing modulation, non-coding RNA inhibition, gene activation and programmed gene editing. As such, these molecules have potential therapeutic applications for myriad indications, with several oligonucleotide drugs recently gaining approval. However, despite
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Antitumour dendritic cell vaccination in a priming and boosting approach. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-08-06 Alexandre Harari,Michele Graciotti,Michal Bassani-Sternberg,Lana E Kandalaft
Mobilizing antitumour immunity through vaccination potentially constitutes a powerful anticancer strategy but has not yet provided robust clinical benefits in large patient populations. Although major hurdles still exist, we believe that currently available strategies for vaccines that target dendritic cells or use them to present antitumour antigens could be integrated into existing clinical practice
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COVID-19 vaccine guidelines. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-08-05 Asher Mullard
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RSV antibody showcases passive immunotherapy progress. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-08-05 Asher Mullard
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Anti-IL-6Rs falter in COVID-19. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-08-05 Asher Mullard
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Protecting β-cells in type 1 diabetes. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-08-04 Sarah Crunkhorn
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Multi-antigen-specific T cell therapy for multiple myeloma. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-08-04 Sarah Crunkhorn
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Exon skipping combats Batten disease. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-08-04 Sarah Crunkhorn
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Statin therapy improves endothelial dysfunction. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-08-04 Sarah Crunkhorn
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Protein degradation reaches further out. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-08-04 M Teresa Villanueva
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Radiopharmaceutical therapy in cancer: clinical advances and challenges. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-07-29 George Sgouros,Lisa Bodei,Michael R McDevitt,Jessie R Nedrow
Radiopharmaceutical therapy (RPT) is emerging as a safe and effective targeted approach to treating many types of cancer. In RPT, radiation is systemically or locally delivered using pharmaceuticals that either bind preferentially to cancer cells or accumulate by physiological mechanisms. Almost all radionuclides used in RPT emit photons that can be imaged, enabling non-invasive visualization of the
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The secret life of excipients. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-07-29 Katie Kingwell
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mRNA vaccines: intellectual property landscape. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-07-27 Cecilia Martin,Drew Lowery
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Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-07-24 Stephen C Cunnane,Eugenia Trushina,Cecilie Morland,Alessandro Prigione,Gemma Casadesus,Zane B Andrews,M Flint Beal,Linda H Bergersen,Roberta D Brinton,Suzanne de la Monte,Anne Eckert,Jenni Harvey,Ross Jeggo,Jack H Jhamandas,Oliver Kann,Clothide Mannoury la Cour,William F Martin,Gilles Mithieux,Paula I Moreira,Michael P Murphy,Klaus-Armin Nave,Tal Nuriel,Stéphane H R Oliet,Frédéric Saudou,Mark P Mattson
The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative
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Blocking GDF15 signalling reverses cachexia. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-07-23 Sarah Crunkhorn
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A metabolic safety switch for cell therapy. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-07-22 Joseph Willson
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Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-07-15 Lauren Mifflin,Dimitry Ofengeim,Junying Yuan
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a key mediator of cell death and inflammation. The unique hydrophobic pocket in the allosteric regulatory domain of RIPK1 has enabled the development of highly selective small-molecule inhibitors of its kinase activity, which have demonstrated safety in preclinical models and clinical trials. Potential applications of these RIPK1 inhibitors
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p53 programmes plough on. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-07-14 Asher Mullard
Despite recent setbacks with p53-activating small molecules including the nutlins, the cancer target keeps drug hunters coming back for more. Could immuno-oncology combinations, stapled peptides and targeted degraders unleash the therapeutic potential of the ‘guardian of the genome’?
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Leena Gandhi. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-07-14 Asher Mullard
Leena Gandhi, a thoracic oncologist, started working with cancer immunotherapies in 2008 in one of the first trials of the PD1 inhibitor nivolumab and has been hooked on the field ever since. In the subsequent decade, she coordinated dozens of immuno-oncology trials — first at Dana Farber Cancer Institute, then at New York University’s Perlmutter Cancer Center — including a seminal study defining the
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FDA new drug approvals in Q2 2020. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-07-10 Lisa Urquhart
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COVID-19 platform trial delivers. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-07-07 Asher Mullard
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FDA rejects NASH drug. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-07-07 Asher Mullard
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FDA rejects first DARPin. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-07-07 Asher Mullard
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Harnessing the PERx of covalent protein drugs. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-07-07 M Teresa Villanueva
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Targeting CD70 in acute myeloid leukaemia. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-07-06 Sarah Crunkhorn
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Inhibiting the HIV capsid protein. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-07-06 Sarah Crunkhorn
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ASO rescues Pelizaeus-Merzbacher disease. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-07-06 Sarah Crunkhorn
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Selectively targeting pathogenic TH17 cells. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-07-06 Sarah Crunkhorn
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RNA methyltransferase inhibitor reduces AML. Nat. Rev. Drug. Disc. (IF 64.797) Pub Date : 2020-06-29 Megan Cully
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