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The Drug Discovery World Podcast

Here at Drug Discovery World (DDW) we've been publishing articles written by leading experts in the Drug Discovery, Pharmaceutical, and BioPharmaceutical industries for over 20 years. DDW has grown as a quarterly business review of drug discovery and development, and now we've created this podcast to allow you to listen to our articles on the go.In our journal and this podcast, we cover topics surrounding: drug discovery; drug development; business; chemistry; enabling technologies; informatics; personalised medicine; screening; therapeutics, and much more. For the podcast we have selected recent, relevant and popular scientific articles, so that you can listen to all of the best content from Drug Discovery World. We hope you enjoy.

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R&D at Astrazeneca - Improving Drug Development Productivity With Better Predictivity

Changing demands in global healthcare over the past 15 years have led to greater complexity and spiralling costs in drug development. The average price tag of taking a new drug from discovery to completion of Phase III clinical trials is now $2.87 billion (1), which means informed decisions need to be made early on about which compounds to pursue. AstraZeneca’s new R&D framework, termed the ‘5Rs’, has introduced an increased scientific rigour and emphasis on quality, driving an almost five-fold increase in R&D productivity. AstraZeneca has surpassed the industry norm in recent years, moving from a 4% success rate in molecules progressing from candidate nomination to completion of Phase III trials in 2010, to more than 19% in 2017 (2). In our pursuit for continual improvement, the question now becomes how far can we push an even greater improvement in drug discovery productivity? One approach is by adopting new and evolving preclinical technologies to further improve clinical translation and reduce clinical attrition. Original article by Dr Lorna Ewart, Dr Richard Goodwin, Dr Stephen E. Fawell, Dr Pernille Hansen, Dr Catherine Priestley, Steve Rees, & Dr Menelas Pangalos If you'd like to view the original article then follow the link below: https://www.ddw-online.com/summer-2018-teasers/p322382-improving-drug-development-productivity-with-better-predictivity.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/131032/(2)-improving-productivity-with-better-predictivity.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

24mins

7 May 2019

Rank #1

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Immunotherapy - Knocking Out Cancer With a One-Two Punch

New immunotherapies that integrate innate and adaptive immune responses may increase efficacy against many cancers, and have the potential to expand the range of tumours and patients that can be treated with immunotherapy. Over the past decade, insights into the molecular mechanisms that cancer cells use to evade T-cells, antibodies/B cells and other adaptive immune defences have revolutionised oncology therapies. New understandings of how cancer evades innate immune defences – including macrophages, dendritic cells (DC) and Natural Killer (NK) cells – suggest a second, and perhaps even more significant, immunotherapy revolution may be at hand. Original article by Dr Mark Chao, Dr Ranjana Advani, and Dr Jens Peter Volkmer If you'd like to view the original article then follow the link below: https://www.ddw-online.com/therapeutics/p322916-knocking-out-cancer-with-a-one-two-punch.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/136062/(2)-knocking-out-cancer.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

19mins

12 Nov 2019

Rank #2

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Cell Therapy - Falling short of its potential?

Despite major investment in the field, few cell therapies have gained regulatory approval with limited commercial success. The success of therapeutic products is defined by three factors: safety, efficacy and scalability. Achieving these for cell therapy presents new challenges; overcoming transplant rejection (and GvHD in the case of immune cells), producing and culturing functional cells and developing an off-the-shelf therapy with a scalable manufacturing process. If you'd like to view the original article then follow the link below: https://www.ddw-online.com/therapeutics/p323014-cell-therapy-falling-short-of-its-potential.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/136359/(6)-cell-therapy.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

17mins

7 Jan 2020

Rank #3

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Antibiotics & Antimicrobial Resistance (AMR) - A Global Perspective

Antibiotic resistance is at a crossroad. In the world today, deaths in low income countries from Antimicrobial Resistance (AMR) are predicted to rise dramatically by 2050. We know how to stop this disaster, and some steps are being taken in the right direction. Will these steps be enough? Antibiotics for Critical Priority bacterial Pathogens are in the clinical trials stage, but, overall, the pipeline is described by the WHO as inadequate. Combinations of antibiotics and rejuvenation of old antibiotics are appearing in development and have potential alongside new chemical entities and new classes. Universal access to new antibiotics by both the rich and the poor may be feasible, but universal stewardship will be a difficult problem to solve. Long-term solutions, particularly for antibiotic development by the pharmaceutical industry are proposed in this episode. Original article by Professor Anthony Coates and Dr Yanmin Hu If you'd like to view the original article then follow the link below: https://www.ddw-online.com/summer-2018-teasers/p322384-antibiotics-&-antimicrobial-resistance-(amr)-a-global-perspective.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/131033/(3)-antibiotics-and-amr.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

27mins

8 Jan 2019

Rank #4

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Automating Automation - How close are we to Artificial Intelligence impact?

In terms of consistency, repeatability, known errors and sheer volume, there exists perhaps no better collection of data for computer learning than that emerging from automated processes. Many common lab procedures now run in parallel, miniaturised experiments – DNA synthesis, target screening, organoid culture, genetic analysis, organic reactions, safety assays – which are poised for extensive curation and algorithm development over the next 10 years. This article briefly outlines each area and offers opinions about how close we are to having artificial intelligence (AI), deep learning (DL) or machine learning (ML) influence each scientific domain. Original article by Dr Michael A. Tarselli, Dr Yohann Potier and Dr Alan E. Fletcher If you'd like to view the original article then follow the link below: https://www.ddw-online.com/enabling-technologies/p323010-automating-automation-how-close-are-we-to-artificial-intelligence-impact.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/136355/(2)-automating-automation.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

17mins

29 Oct 2019

Rank #5

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Induced Pluripotent Stem Cells (iPSCs) – Unlocking their full potential for Drug Discovery

Human stem cells were once viewed primarily as regenerative materials for tissue repair through cell therapies. However, advances in technologies and protocols mean that induced pluripotent stem cells (iPSCs) are now playing an increasingly important role in disease modelling and human cell-based screening assays. This episode explores what this means for drug discovery. The pharmaceutical industry’s current issue with attrition in the R&D pipeline is complex and multifaceted. However, few would disagree that one of the biggest factors contributing to the poor rate of success in drug discovery is the lack of reliable and translationally useful disease models. No matter how carefully studies are designed, animal models and immortalised cell lines cannot reflect the full complexity of human biology and disease mechanisms. While the use of human primary cells or human tissue samples is an attractive alternative for drug screening, these materials can be difficult to obtain, and require additional ethical considerations. Original article by Abby Edwards and Dr Richard Massey, of Biostrata If you'd like to view the original article then follow the link below: https://www.ddw-online.com/screening/p322574-unlocking-the-full-potential-of-induced-pluripotent-stem-cells-for-drug-discovery.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/133164/(5)-unlocking-the-full-potential-of-induced-pluripotent-stem-cells.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

24mins

19 Mar 2019

Rank #6

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Bringing Immuno-Oncology Together: How An Immunologist & Oncologist Collaborate

For many years, immunology and oncology operated as separate disciplines within drug discovery. However, recent advances in immuno-oncology (IO) have demonstrated what can be achieved when the two disciplines join forces in developing novel treatments for patients. From checkpoint inhibitors to CAR-T cells and model selection designed to reflect more personalised medicine approaches, immuno-oncology is shifting how both immunologists and oncologists approach drug discovery and development. In this Q&A, Dr Julia Schüler, DVM, Research Director at Charles River, which specialises in oncology, and Dr Louise Brackenbury, Principal Scientist for Cell Biology at Charles River’s newly acquired KWS BioTest, which specialises in immunology, will provide their unique perspectives on the ways in which IO is reshaping the industry. Original article by Dr Julia Schüler and Dr Louise Brackenbury If you'd like to view the original article then follow the link below: https://www.ddw-online.com/therapeutics/p322098-bringing-immuno-oncology-together:-how-an-immunologist-&-oncologist-collaborate.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/129239/(2)-bringing-io-together.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

24mins

29 Jan 2019

Rank #7

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The Future of Drug Discovery - Cutting-edge technologies meet traditional paradigms in assay development

With more than 1,500 drugs approved by the Food and Drug Administration (FDA) on the market, the easiest disease targets are already covered. Today’s scientists are challenged to find new compounds, acting alone or in combination, on intractable targets to treat multi-causal diseases including cancers, metabolic and psychiatric disorders. The technologies and assays coming to the market enable new avenues in drug discovery creating opportunities to study complex disease mechanisms and find cures. Original article by Dr Roger Bossé If you'd like to view the original article then follow the link below: https://www.ddw-online.com/drug-discovery/p322572-the-future-of-drug-discovery-cutting-edge-technologies-meet-traditional-paradigms-in-assay-development.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/133160/(1)-the-future-of-drug-discovery.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

22mins

19 Feb 2019

Rank #8

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How Mergers and Acquisitions Will Drive Oncology Research in 2019

2019 got off to a fast start for oncology drug discovery, with numerous mergers, acquisitions and collaborations announced in quick succession. These ventures provide a window into key trends in oncology research, where investigators are likely to focus their efforts, and the tools and technologies that will enable pharmaceutical and biotechnology companies to turn promise into efficacious therapies. While the pace of innovation is accelerating, the challenges of increasing competition, pricing pressures and regulatory complexity are squeezing ROI. In this environment, collaborative efforts will play a pivotal role in advancing oncology drug discovery effectively and efficiently. Original article by Dr Michael Seiler If you'd like to view the original article then follow the link below: https://www.ddw-online.com/business/p322915-how-mergers-and-acquisitions-will-drive-oncology-research-in-2019.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/136061/(1)-the-cure-for-going-it-alone.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

23mins

30 Jul 2019

Rank #9

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Integrated Platform Drug Discovery and Development Companies - Part 1

Technology was lauded as the saviour of the drug discovery and development process during the late 1990s. A myriad of independent companies developed and offered ‘innovative’ tools, technologies and platforms to pharmaceutical companies in order to mitigate the time, cost and risk of developing new therapeutic drugs. However, comparative analysis of FDA-approved New Molecular Entity (NME) and New Therapeutic Biologic (NTB) annual historical numbers announced does not reflect any significant productivity enhancement impact of such efforts. More recently there has been some attempt to amalgamate platform technologies within start-up and earlystage drug discovery and development (DDD) companies to increase drug candidate pipeline numbers. This strategy does not come without risks, but has quietly been implemented by a number of platform-DDD (PD3) companies. Original article by Dr Urban A. Kiernan and Dr Stephen Naylor If you'd like to view the original article then follow the link below: https://www.ddw-online.com/business/p322578-emerging-paradigm-of-integrated-platform-drug-discovery-and-development-companies.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/133163/(4)-emerging-paradigm-of-integrated-platform-drug-discovery.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

22mins

1 Oct 2019

Rank #10

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Systems Pharmacology - When multi-targeting is advantageous (Part 1 of 2)

The safety and efficacy of therapeutic drugs still requires improvement. However, the advent of both systems biology and precision medicine has stimulated a rethink on the process of therapeutic drug design and polypharmacology. More recently, the definition of polypharmacology has morphed to represent therapeutic drugs that have been designed deliberately for multi-targeting that affords beneficial effects to the patient. This emerging effort has been labelled ‘Systems Pharmacology’ and the products are referred to as multi-target or systems pharmacology drugs. This episode is part 1 of 2 episodes on the topic of systems pharmacology, and covers ­­human complexity, systems biology and precision medicine. Original article by Dr Kirkwood A. Pritchard Jr, Dr Dustin P. Martin and Dr Stephen Naylor If you'd like to view the original article then follow the link below: https://www.ddw-online.com/therapeutics/p322783-perspective-on-systems-pharmacology:-when-multi-targeting-is-advantageous.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/135186/(4)-perspective-on-systems.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

25mins

13 Aug 2019

Rank #11

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Automated Cell-based Assays: Novel tools overcome the barriers to drug discovery success

In this episode, we look at how commercial products and services are facilitating the automation of cell-based assays to advance drug discovery and accelerate the delivery of new medicines to patients. Cell-based assays are vital tools in modern drug discovery. Live cell cultures that replicate in vivo physiological conditions enable more reliable predictions about the safety and efficacy of drugs. Cellular assays have traditionally been complex and labour-intensive, however, automated technologies are now streamlining workflows as well as improving assay precision. By Helen Stewart-Miller and Kate Tointon If you'd like to view the original article then follow the link below: https://www.ddw-online.com/enabling-technologies/p323011-automated-cell-based-assays:-novel-tools-overcome-the-barriers-to-drug-discovery-success.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/136356/(3)-automated-cell-based-assays.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

15mins

26 Nov 2019

Rank #12

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How Phenotypic CRISPR Screening is Revolutionising Drug Discovery

Research in drug discovery and biotechnology increasingly exploits gene editing at industrial scale in order to identify and validate new biological targets for precision medicines. The discovery of CRISPR-Cas9 systems has fuelled a rapid expansion of gene editing adoption with particular interest in the increasingly prevalent area of functional genomic screening. As these technologies have matured and evolved, so have the applications to which they are deployed. While early efforts were heavily enriched for studies in cancer biology, the advent of more complex phenotypic analyses, coupled to CRISPR-based discovery efforts, have substantially broadened the impact of these tools to provide discovery opportunities in myriad disease areas with greater power for hit ID and fewer off-target effects than other screening tools. Original article by Dr Steffen Lawo and Dr Carlos le Sage If you'd like to view the original article then follow the link below: https://www.ddw-online.com/drug-discovery/p322579-how-phenotypic-crispr-screening-is-revolutionising-drug-discovery.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/133165/(6)-how-phenotypic-crispr.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

14mins

5 Mar 2019

Rank #13

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The Mass Spectrometry Innovations Simplifying Drug Discovery Workflows

Mass spectrometry (MS) has long been a valuable tool for drug discovery, and steady advances in its capabilities and performance have generated powerful insights for the pharmaceutical industry. The latest MS innovations are now helping biotherapeutics developers overcome challenges around sample preparation and large molecule analysis. The use of mass spectrometry in pharmaceutical discovery and development is rich and varied, spanning a wealth of applications from target discovery, medicinal chemistry, pharmacokinetics and bioanalysis workflows, to name just a few. Offering the selectivity, specificity and sensitivity required to answer a broad range of analytical questions, mass spectrometry has become one of the most powerful tools in the drug discovery toolbox. Mass spectrometry is a particularly powerful tool for the discovery and development of biotherapeutics. Today, biotherapeutic products account for a growing proportion of new drug approvals. Increased focus on the development of much larger, more complex therapeutics such as monoclonal antibodies, fusion proteins and antibody-drug conjugates has placed new demands on mass spectrometry. Original article by Helen Stewart-Miller and Dr Richard Massey If you'd like to view the original article then follow the link below: https://www.ddw-online.com/summer-2018-teasers/p322386-the-mass-spectrometry-innovations-simplifying-drug-discovery-workflows.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/131034/(4)-the-mass-spectrometry-innovations-simplifying-drug-discovery.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

19mins

18 Dec 2018

Rank #14

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Disruptive Approaches To Accelerate Drug Discovery and Development (Part 1) – Tools & Technologies

The staggering failure rate of experimental drugs in clinical trials indicates that despite huge investments in novel technologies, productivity gains in the pharmaceutical industry remain elusive. The pharmaceutical industry is facing a serious innovation deficit. The current biopharma model is therefore unsustainable and disruptive approaches are needed to remedy the status quo. It is incumbent upon the biomedical research community to harness the collective intelligence of pharma, biotech, academia, governmental agencies, non-profit research foundations and patient advocacy groups to accelerate innovation. In part 1 of this series of 3 episodes, we discuss tools and technologies. Original article by Ibis Sanchez-Serrano, Dr Tom Pfeifer and Dr Rathnam Chaguturu If you'd like to view the original article then follow the link below: https://www.ddw-online.com/business/p322101-disruptive-approaches-to-accelerate-drug-discovery-and-development-(part-1).html You can also download the original article pdf here: https://www.ddw-online.com/media/32/129242/(5)-disruptive-approaches-to-accelerate-drug-discovery--development.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

25mins

13 Nov 2018

Rank #15

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Treating Cancer - How Natural Killer Cell Therapy Will Transform Immunotherapy

Regulatory approval of CAR-T cell therapies in 2017 placed the spotlight on immunotherapy approaches that use live cells to attack tumours – a major shift in oncology treatment. Yet even this groundbreaking therapy has limitations, such as when patients already immuno-depressed from a first-line treatment do not have sufficient T-cells to modify or stimulate. For this reason, investigators are looking to natural killer cell therapy (NK cell therapy) as the next frontier of immunotherapy for the fight against cancer. As the evolution of precision medicine continues, NK cell therapy will play an important role in guiding efficacious treatments. Original article by Dr Azusa Tanaka and Dr Michael Seiler of Taconic Biosciences If you'd like to view the original article then follow the link below: https://www.ddw-online.com/therapeutics/p322104-how-natural-killer-cell-therapy-will-transform-immunotherapy.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/129245/(8)-natural-born-killers-cell-therapy-immunotherapy.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

17mins

27 Nov 2018

Rank #16

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Microfluidics - Driving Innovation and Streamlining Single Cell Analysis

Microfluidic platforms that harness picodroplet technology (picolitre volume aqueous droplets in stabilised oil emulsions) are unlocking the potential of single cell analysis to enable exciting new discoveries and advances with the potential to transform scientific research, drug development and precision medicine. These systems compartmentalise single cells and trap their released molecules, enabling tens of millions of novel single cell tests to be performed on each biochip per day. Our scientific understanding of cellular processes and signalling pathways has historically been informed by analyses of cellular populations, providing a global appreciation of molecular responses to external stimuli. However, this approach is inherently limited as it provides information only regarding the average response of the population and doesn’t account for heterogeneity (1). Original article by Dr Frank F. Craig If you'd like to view the original article then follow the link below: https://www.ddw-online.com/enabling-technologies/p322392-microfluidics-driving-innovation-and-streamlining-single-cell-analysis.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/131037/(7)-microfluidics-driving-innovation.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

19mins

30 Oct 2018

Rank #17