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Introduction


introduction I


n the 20 years or so since Drug Discovery World was first pub- lished there have been many advances – scientific, technological and organisational – which have undoubtedly led to the discov-


ery and development of many novel and useful therapeutic agents, some for conditions which were previously untreatable or only poorly treated. However, as has been frequently discussed in our pages, there is still concern about the high costs and the long time involved in producing these new agents. This is due, to a consider- able extent, to the high attrition rate in the development pipeline and, as always, several of the articles in this number of DDW are, in one way or another, concerned with improving this situation. Organisationally, partnerships have had to be set up since no


company, however large, can undertake all the various activities involved in taking a ‘gleam in a scientist’s eye’ through to an approved and marketable product. Among the most common arrangements are those in which academia or relatively small dis- covery organisations supply lead molecules to larger development companies which may, in turn, contract out some work – clinical trials, for example. One of the articles herein discusses ‘the partnership model in


practice’ mentioning some arrangements made by large companies to facilitate academia/industry collaboration. It goes on to describe in more detail, and with examples, the partnership activities of Mundipharma, a network of independent associated companies from around the world, the stated purpose of which is ‘To Move Medicine Forward’. The authors note that “not every partnership we have explored has come to fruition, however those that have continued to yield considerable benefits”. Another organisation that has featured previously in these pages


is the Pistoia Alliance, a global non-profit organisation including life science companies, technology suppliers, publishers and aca- demic groups which work together to prepare members for changes in the world of drug discovery and development. In this edition they write a report as it may appear in 2030 looking back at the previous decade, ie starting from now. The overall message is that if the industry embraces the “substantially and continually develop- ing technical and scientific advances in the life sciences” then many opportunities will have arisen, especially if the emphasis is switched from treatment to prevention of disease. This will fit well with socio-political changes moving in the direction of healthcare increasingly being seen as a human right. The authors of another article point out that unlike the retail and


consumer sectors, the pharmaceutical industry has invested very lit- tle in evaluating the experience of users, although they state that “since 2017 we have seen the slow and steady adoption of User experience (UX) within the life sciences”. They discuss the implica- tions and mechanisms for adopting UX and suggest that it will be key to the inevitable changes which will occur in R&D over the coming decades. As evidenced by a number of articles in recent issues of DDW


there is an ever-increasing interest in precision or personalised medicine. This is dependent on relevant biomarkers being


Drug Discovery World Winter 2019/20


detectable in samples from patients. To date, diseases have been profiled mainly through genomics or transcriptomics, but the authors of anoth- er article state that there is a lack of val- idated


proteomic


biomarkers and dis- cuss how the modi- fied proteome can be harnessed to increase diagnostic power in a number of diseases. Te c h n o l o g i c a l


advances in processes which are in regular use in R&D labora- tories are regularly reviewed in these pages, and in this edition liquid handling is one such subject. The accurate measurement and transport of liquids from one vessel to another is one process and, as the authors point out, there has been “a dramatic evolution… from the humble Pasteur pipette to today’s automated liquid handling instruments”. They review currently-available instruments and conclude that there have been improvements in the precision, accuracy, speed and repeatability of workflows. These improvements should, in turn, contribute to dramatic reductions in drug discovery timescales. Another technology reviewed here is cryo-electron microscopy


(cryo-EM) which the authors state should also reduce development time and guesswork of lead compound design. This technology enables structural analysis of protein complexes thus giving better insight into such biomolecules which are notoriously difficult to work with. Recent publications from pharmaceutical companies have shown that the technology has given critical structural insights unattainable by other methods. Examples are given of the benefits of cryo-EM in studying viruses and antibodies, enzymes, ion chan- nels, GPCRs and hormone receptors, as well as small molecules. Novel methods of drug delivery are always of interest and in


another article the potential in this regard of extracellular vesicles (EVs) is described. These vesicles, which range in size from 30 to 100nm, play a role in normal homeostasis. They are found in cir- culating blood and serum and other biological fluids. The authors acknowledge that designing and engineering EVs carrying specific cargoes and targeting desired cells “poses significant challenges” but advances are being made and these are described in the article.


Dr Roger Brimblecombe PhD, DSc, FRCPath, FRSB 7


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