78th Edition – April 2018

Servier and ScandiCure to collaborate on metabolic disease research

Servier, an independent international pharmaceutical company with its headquarters based in France, and Swedish spin-out ScandiCure, have entered into an agreement on the further development of ScandiCure compounds that show promise as treatments for type 2 diabetes and the liver disease non-alcoholic steatohepatitis (NASH). The seeds of the collaboration were sown when Margit Mahlapuu of the University of Gothenburg identified a drug target that could be used to reverse some of the metabolic complications of diabetes. Thanks to the European Lead Factory, she was able to identify a number of compounds that interact with the target. She then set up ScandiCure as a spin-out company to develop the compounds further. Under the new agreement, Servier will carry on the research started by ScandiCure, advancing the novel compounds through preclinical development. Servier will also provide ScandiCure with an upfront payment as well as pre-clinical and clinical milestones. ‘We have identified a new attractive target in metabolic diseases, and the European Lead Factory has provided an access to a high-quality compound library and a platform of expertise for high-throughput screening. This unique combination of a well-validated target with the high-quality output of the European Lead Factory has provided ScandiCure with strong starting points for new and transformative treatments in NASH and related diseases,’ said ScandiCure’s Dr Mahlapuu. ‘Our access to ScandiCure’s target-knowledge and novel chemistry allows us to explore an important pathway in metabolic diseases,’ said Claude Bertrand, General Director of Research and Development at Servier. ‘Our goal is to find effective treatments for patients who suffer from NASH, who are underserved by current therapies. This agreement illustrates Servier’s continued commitment to novel approaches to diseases where significant unmet medical needs still exist.’

ADVANCE develops interactive dashboard to monitor vaccine benefit and risk

The ADVANCE project has developed a web application with an interactive dashboard designed to make it easier to monitor the benefits and risks of vaccines in near real time. The tool is described in a paper in the journal Drug Safety. Once implemented, it would allow users to rapidly determine whether further regulatory or public health actions may be needed. The benefit-risk profile of vaccines that is determined initially in clinical studies may change during the vaccine’s life cycle, and needs to be further assessed once vaccines are on the market. In this study, the ADVANCE team assessed the feasibility and added value of using an interactive dashboard to monitor vaccine uptake, benefits and risks as well as composite benefit-risk measures. The dashboard was developed and demonstrated using simulated data mimicking the UK’s introduction of the rotavirus vaccine.  Feedback from stakeholders (including public health institutes, regulatory authorities, and pharmaceutical companies) revealed broad support for the dashboard, with users appreciating the interactive interface and the ability to visualise individual components. The stakeholders were however less in favour of the composite benefit-risk measures offered. The ADVANCE team concludes that ‘the proposed methodology is promising’ and they are now testing the dashboard with real-world data.

EMIF study challenges ‘obesity paradox’

According to the ‘obesity paradox’, it is possible to be overweight or even obese yet not have an increased risk of heart disease. Now, a study in the European Heart Journal shows that in fact the risk of heart and blood vessel problems such as heart attacks, strokes, and high blood pressure, rises as body mass index (BMI) increases beyond 22-23 kg/m². The research was funded in part by IMI through the EMIF project. The team followed 300 000 people in the UK over a number of years; all were healthy when they joined the study. Analyses of the data revealed that people with a BMI of 22-23 kg/m² had the lowest risk of heart disease. The risk rises by 13% for every 5.2 kg/m² increase in BMI in women and 4.3 kg/m² in men. The risk also rises with an increase in waist circumference. While some studies have suggested that the obesity paradox is true, the researchers say this could be due to factors such as smoking (which suppresses appetites) and undiagnosed diseases (which could cause weight loss). ‘This is the largest study that provides evidence against the obesity paradox in healthy people,’ said first author Stamatina Iliodromiti of the University of Glasgow in the UK. ‘By maintaining a healthy BMI of around 22-23 kg/m², healthy people can minimise their risk of developing or dying from heart disease.’ Acknowledging that this target may be difficult for some people to achieve and maintain, co-author Naveed Sattar added: ‘We know many cannot get to such low BMIs so the message is, whatever your BMI, especially when in the overweight or obese range, losing a few kilograms or more if possible, will only improve your health. There are no downsides to losing weight intentionally and the health professions need to get better at helping people lose weight.’

Read the University of Glasgow’s press release

CANCER-ID method marks step towards liquid biopsies for cancer patients

Scientists from the CANCER-ID project have developed a streamlined procedure for studying certain alterations in cancer cells found circulating in the blood stream. The method could prove useful in helping clinicians to better identify which treatments will work in which patients, and to monitor disease progression. Cancerous tumours regularly shed individual cells into the blood stream. If captured through a blood test, these ‘circulating tumour cells’ (CTCs) have the potential to provide a lot of information about the state of the tumour. This is particularly important for cancers that cannot be biopsied without major surgery, for example. This study focused on the analysis of copy number alterations (CNAs) in the tumour cells; CNAs are mutations where multiple copies of a gene are found in the genome. Different CNA profiles have been linked to increased response or resistance to different types of drugs. However, current techniques to analyse CNAs are complex and not easy to apply in the clinic. In PLoS ONE, the CANCER-ID team describes a robust yet simple, one-step method to detect the number of CNAs in single cells. According to lead author Nicolò Manaresi of Menarini Silicon Biosystems, the new technique, dubbed Ampli1, provides comparable or superior performance at lower cost than current methods. ‘Our streamlined workflow will further decrease the cost of copy number analysis in the future and pave the way to a simpler blood test to study cancer heterogeneity in liquid biopsy,’ he said.

Read the Menarini Silicon Biosystems press release

‘We made significant breakthroughs’ – an interview with the PREDECT project coordinators

When it comes to developing new cancer treatments, most drugs fail before they ever reach patients. This is partly because the models which scientists use to predict the success of future drugs in the laboratory have been too simple when compared to the real tumours. IMI's PREDECT project has developed new laboratory models that more accurately mimic the three-dimensional complexity of tumours, and their behaviour within the microenvironment of the patient’s body. These models could help researchers discover more effective treatments in the future, thereby boosting survival rates. In an interview the IMI Programme Office, project coordinator John Hickman of Servier, and academic coordinator Emmy Verschuren of the Institute for Molecular Medicine Finland at the University of Helsinki, explain the project’s most significant breakthroughs, and how these achievements will help in the future search for new drugs. ‘We have published a series of papers, which are open access, about how to create and work with these types of more complex cancer models,’ said Hickman. ‘That data is now available for everyone – it’s kind of a recipe book.’ Read the full interview

Patients are already benefiting from our project – an interview with the OncoTrack coordinators

Colorectal cancers are a very heterogeneous group of cancers and not all of them respond to the same drugs in the same way. By collecting tumour samples from patients and then analysing them in the laboratory, the OncoTrack project found molecular fingerprints of those tumours and then correlated them to how these tumours respond to various drugs. The project’s outputs are already helping doctors in choosing the right treatment for the right patient, and could also help in the future search for more effective drugs. As a result of the project, two spin out companies have been created and several patents filed, demonstrating tangible socio-economic benefits. In an interview with the IMI Programme Office, project coordinator, David Henderson of Bayer, and academic coordinator Hans Lehrach of the Max Planck Institute for Molecular Genomics, explain why all this wouldn’t have been possible without the public-private collaboration brought by IMI. ‘This was an extremely complex project,’ said Henderson. ‘In order to be successful with this degree of complexity you need a lot of know-how and a lot of detailed knowledge, and you can never find all of this in one place. So the big advantage of a public-private partnership is that you can bring in the different types of detailed knowledge that are available in an industrial setting, in a biotech start-up or in an academic setting. When you bring these together, the sum becomes much greater than its individual parts.’ Read the full interview

‘We made significant accomplishments in a very challenging field’ – an interview with MIP-DILI project coordinators

Many medicines are harmful to the liver, and drug-induced liver injury (DILI) ranks as one of the leading cause of liver failure and transplantation in western countries. However, predicting which drugs will prove toxic to the liver is extremely difficult, and often problems are not detected until a drug is already on the market. IMI’s MIP-DILI project deepened the understanding of the science behind drug-induced liver injury, and improved laboratory tests which are used to predict DILI in the early stages of drug development. This is already helping pharmaceutical companies to make better decisions on which drug molecule to take forward into further research, saving time and resources, and helping ensure that only the safest and most promising drugs reach patients. In an interview with the IMI Programme Office, Richard Weaver of Servier and academic coordinator, Kevin Park of the University of Liverpool, describe the project’s most important achievements, and explain how they are already benefitting industry, academia, and patients, while at the same time reducing the use of animals in research. ‘We went into this with a vision that we’re going to make a difference, and that energy drove us to see the project through in five years,’ said Weaver. ‘There were no ifs and buts on the way. That philosophy took us through some big hurdles and challenges, but it’s the satisfaction coming out on the other side of it that matters: we went in as a team, we came out as a team and we made significant accomplishments in a very challenging field.’ Read the full interview