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‘Aspects of Modern Drug Discovery’ – Speaker Summaries

The first guest speaker to take to the podium at Sygnature’s symposium on October 7th 2014, was Dr Jonathan Rachman from MapMy Health. In the early 1990s, a small group of academic units around the world was taking an interest in the physiological effects of the gut hormone glucagon-like peptide-1 (GLP-1), with a view to its therapeutic potential. In recent years, through the efforts of “Mother Nature”, academics and the pharmaceutical industry, that therapeutic potential has been translated into multiple blockbuster agents that act through a GLP-1 mechanism, transforming the type 2 diabetes therapeutic landscape.
“Currently 10% of the NHS budget is being spent on treatments for diabetes, and this is expected to increase to 17% by 2035. Diabetes is truly a massive public health burden,” Dr Rachman commented.
“The journey of GLP-1 from ‘gut to glory’ faced so many challenges that most companies would have stopped the programme. But through persistence and determination, the result was a drug discovery success story in the therapeutic area of diabetes.”

Next to the podium was Dr Rana Lonnen from Axendos Therapeutics. Her case study was one of collaboration to develop first-in-class adjunctive therapies for hospitalised patients with community-acquired pneumonia (CAP). In the USA, CAP is the second most common cause of hospitalisation and the leading infectious cause of death in hospitals. Despite the use of effective antibiotics, poor health outcomes persist with long hospital stays and a high cost of care, leading to a high financial burden to healthcare systems.
Dr Lonnen shared her approach, which, if successful, will result in a major step forward in the effective treatment of pneumonia patients, delivering substantial savings to healthcare costs.

Dr Julian Golec from Vertex Pharmaceuticals talked to the audience about the journey of his business from start-up to the present day. The focus on a clear vision, entrepreneurial spirit and commercial growth were key factors in bringing three drugs to market and ultimately benefiting a huge number of patients. Not least, the development of Kalydeco, the first ever medicine to treat the underlying cause of cystic fibrosis, which was developed against the odds.

‘Most drug discovery scientists could (and should) be replaced by software systems’ was the title of Dr David Leahy’s (from Molplex Pharma) talk and was enough to cause a murmur in the audience. Small molecule drug discovery is a mature field with established methodologies, processes and best practice in place. Drug design is ultimately a multi-property search and optimisation process, with well-understood criteria for success. With the rapid growth of chemical structure and property databases – as well as the capacity for rapidly generating experimental data on a wide range of relevant biological, ADME and toxicity properties – Dr Leahy postulated that there is an opportunity to eliminate the medicinal chemistry bottleneck, as he described it, creating a step-change in productivity.

Dr Paul Leeson, formerly of AstraZeneca, shared his views on pursuing compound quality. Currently only about 4% of candidate drugs reach the market and compound-related risks in dose, exposure and toxicity have often been carried from discovery into more costly clinical development. However, compound quality is controllable, being fixed at the point of design, and varies substantially across organisations. Dr Leeson shared examples of how compound quality can be improved and emphasised how, through collaboration within the industry, sharing knowledge and working together can lead to greater success and a reduction in time (and resource) spent.

The University of Sussex is home to the Translational Drug Discovery Group, which was established in 2011. The group, which Professor Simon Ward is a part of, was formed to deliver both drug candidates into clinical development and novel chemical probes to enable validation of new therapeutic targets.
“Our philosophy is clear,” shared Professor Ward, “combining expertise in clinical and biological disease understanding with their pharma track record in drug discovery and development.”
Professor Ward went on to explain their strategy and research in the areas of DNA damage repair pathways for oncology and ion channel modulators for neuroscience indicators.

The closing talk was given by Professor Herbie Newell from Newcastle University’s Northern Institute for Cancer Research. Cancer is now the major cause of death from disease in the UK and other developed countries, and the incidence of malignancy is rising due to our aging population. Cancer survival has improved from 1:4 to 2:4 over the past 40 years and continued improvement will depend in part on the availability of novel treatments. The last 10 years have seen the advent of targeted cancer therapies, which for the first time exploit our evolving understanding of molecular pathology and disease. However, these therapies have challenges, which Professor Newell discussed, providing a perspective on recent developments and a future vision for cancer. As was the shared theme of the day, Professor Newell highlighted that there are too many groups – academic and commercial – all of whom are working on the same target and sometimes the same set of compounds.

Throughout the symposium there was a strong message about the clear shift, and continued need, to encourage greater collaboration and more effective sharing of knowledge cross drug discovery.

To close the presentation part of the symposium, Dr Simon Hirst remarked, “no one group has all of the answers no matter what the therapeutic area.”

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