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Drug Discovery World
Drug Discovery World Spring 2018 - Issue Summary

Drug Discovery World Spring 2018 - Issue Summary

Dr. Roger Brimblecombe

Several articles in recent additions of Drug Discovery World have pointed out that the chances of producing meaningful therapeutic advances in a timely and cost-effective manner are increased significantly if there are appropriate collaborations between organisations with complementary skills and experience.

Often, expertise beyond the traditional teams of medicinal chemists, biochemists, pharmacologists and toxicologists is required and is unlikely to be found in any single company, no matter how large.

There are also signs of a willingness to share information which previously would have been kept within the confines of companies. Opinions probably differ about what constitutes ‘pre-competitive’ information but it would seem to be mutually beneficial and would enable the time, money and resources to be used more productively to learn, for example, that an approach being considered had been tried by others but resulted in failure.

This theme is pursued in one of our articles which describes the intention of Tesla, a US electric vehicle, energy storage and solar panel company, to implement and practise an ‘open source’ philosophy to its patent portfolio by which it undertakes not to pursue any legal action against anyone using its contents in good faith. Our authors, while admitting that it would be “a hard pill to swallow” for the biopharm industry, suggest that it ought to seriously consider such a strategy to enhance the pace of drug discovery and development. They describe the ‘Core Model’ using as an example the development of the anticancer drug bortezomib.

Cancer immunotherapy is a very fast-growing field in which there have already been significant advances. Immunological expertise, often not traditionally found in pharma companies, will be needed to progress this ‘personalised medicine’ approach even further. There is a discussion in the article of the potential use of NK (natural killer) cells, as opposed to T-cells, to attack specific tumours. There is a requirement now to ascertain whether or not the results from currently available animal models translate into the human clinical setting and, more generally, there is a need for “a better elucidation of the basic requirements for human tumour and immune cell recapitulation”.

On a related theme, two researchers – an immunologist and an oncologist – recount how recent interest in immuno-oncology (IO) has increased following, for example, the very promising clinical results with Ipilimumab alone and in combination with Nivoluhab. They, and others, have now realised that their two disciplines need to work together more closely to maximise the potential of this line of research.

The development of new technologies, or improvements in existing ones, to aid in the identification of new leads with a higher than the historical probability of success in the clinic, is another common theme in DDW. We carry a report of a meeting at which R&D IT experts from 30 top biopharm companies met to discuss the use of artificial intelligence (AI) in this context. There is a long list of potential opportunities – some near-term others for the future. Although there is great promise there are also challenges, particularly over what can be shared between companies pre-competitively and what might put intellectual property at risk, but again the point is made that “strong partnership and cross-functional teams... are essential to successful innovation”.

The question of the validity of some pre-clinical models in the search for new anticancer drugs is questioned by another author who points out that, as in other therapeutic areas, there is an unacceptably high failure rate of such drugs at some stage in their development. He believes that pharmaceutical companies should better recognise the importance of using ‘more robust’ methods such as primary cells and 3D culture models, especially now that new 3D technologies are aiming towards a higherthroughput approach. He also believes that there is a need for consistency in methodologies and reagents used by the many organisations involved in cancer research.

In an article dealing with kinases, it is stated that the human kinome comprises 518 known protein kinases and more than 20 lipid kinases. Many kinase inhibitors have made it to the market or are currently in development for the treatment of cancer and inflammatory diseases. It is believed that there are more to be discovered, especially now that new and innovative technologies, discussed in the article, are becoming available. The point is also made that some previously tested, but rejected, kinase inhibitors could now be retested using the new technologies.

In another article dealing with a technological advance, the authors discuss CRISPR-Cas9 which “has rapidly transformed our ability to perform targeted gene editing”. There have now been advances in its high throughput use which, it is stated, will enable genomic screening on an unprecedented scale. The data sets so produced will mean that more powerful tools will need to be developed to analyse them using bio-informatics approaches. It is probable that only a small subset of diseases are attributable to a single genetic mutation but for the future it should be possible to understand the role of the non-coding genome and to identify the multiple mutations associated with many diseases.

The need for a good and comprehensive scientific information system in a drug discovery organisation is emphasised in an article which discusses the key factors to be considered in setting up such a system. In drawing their conclusions, the authors draw on lessons learned from small molecule drug discovery. They note the differences in information generated in a small molecule, as opposed to a biologics, discovery programme and also discuss relevant current and near-term IT trends.

Dr Roger Brimblecombe PhD, DSc, FRCPath, FRSB