What is the purpose of the collaboration?

The objective of the company is to enable the creation a bank of stem cells, open protocols and standardised systems in stem cell technology that will enable consistent differentiation of stem cells into stable homogenous populations of particular cell types, with physiologically relevant phenotypes suitable for toxicology testing in high throughput platforms.

The Stem Cells for Safer Medicines consortium is therefore interested in the potential of differentiating human embryonic stem cells into normal human cells, such as those in the liver (hepatocytes) and heart muscle (cardiomyocytes). If this is possible in a reproducible and consistent way, these cells could be used to evaluate the effect a potential new medicine has on specific cells, and to provide a more accurate prediction of drug metabolism and toxicity outcomes in man. We believe this would represent a significant step forward in increasing the human relevance of studies at an earlier stage of development of a potential new medicine and would help us to overcome the current limitations that a restricted supply of normal cells presents.

The consortium will draw upon scientific expertise within the pharmaceutical companies – especially in relation to safety assessment of new medicines – academic stem cell experts in the UK and third parties including biotechnology companies.

Why is Government supporting this collaboration?

There are clear benefits in terms of UK Government strategy and for the public good that justifies Government support:

• in the longer term, if successful this will lead to improved patient safety, in clinical trials and in clinical practice

• enhancing basic research capability in the UK and maintaining the UK’s global lead in stem cell research

• to help speed the development of new medicines to patients, though this pre- competitive research collaboration.

Are there other benefits?

Yes. The benefits to the UK of such an initiative may well be substantial, including:

• enhancing academic-industry collaboration

• acting as a focus for UK stem cell expertise and international experts in safety assessment

• opening up exploitation opportunities for small and medium enterprises, who will be encouraged to engage with the collaboration

• enhancing UK competitive advantage to retain and attract more pharmaceutical companies to locate their research and development and safety assessment activities in the UK, promoting future inward investment.

Why use stem cells in developing new medicines?

The attrition of medicines in clinical studies remains a critical issue for pharmaceutical companies. Unexpected safety issues remain a key reason for failure in first in man and larger late-stage clinical studies. While animals continue to give essential information on safety, efficacy and dosing calculations for first in man studies, human cell based assays offer the opportunity of early identification of those that are likely to fail when first tested in volunteers or patients.

How does the consortium allocate research projects?

The allocation process works by open competitive tendering by scientific groups. The Scientific Advisory Board advises on the calls for proposals which are approved by the Members of the company. The SAB is especially important in mapping out the calls for research proposals beyond the pilot phase.

In later stages company laboratories, working in partnership with academics and third party organisations, will carry out research to assist identifying the standards and protocols that would be useful for drug discovery research. Validating these technology platforms, standards and protocols will be critical in realising the vision for the project.

Will the consortium fund research to use stem cells in therapies?

No, the collaboration is only interested in developing stem cells for early screening in predictive toxicology to assess the safety of medicines. However, the knowledge developed in the programme could also be relevant to the use of Stem Cells in medicine particularly since validation of differentiation protocols is a common issue.

Will this research replace the use of animals in research?

The concept is not directly to replace the use of animals in safety testing and for the foreseeable future they will remain an essential element of developing a new medicine. Animals research will continue to give critical information on safety and efficacy of candidate medicines in whole animals (as opposed to organs, which the stem cell assays are akin to), as well as provide results that allow the first dose in man to be calculated safely.

However by screening out compounds with possible human safety issues early in the drug discovery process, the number of animals used in research for compounds that fail in clinical studies should be reduced and refine the use of animals by focusing their use only in areas where animal data adds value.

What is predictive toxicology?

Predictive toxicology is the term used to describe pre-clinical experiments to ascertain any toxic effects of drugs to guide subsequent research in patients or healthy volunteers.

What are stem cells?

The human body contains different types of cells that usually have a specific purpose (e.g. liver cells, brain cells etc). Stem cells are different in that they have not yet developed in to a specific type of cell. If we can create liver cells in a consistent manner, then these could be used in in vitro assays – high throughput screens to test a large number of compounds in early drug discovery.

What type of tool can be made from stem cells?

It is hoped that we will be able to produce standardised systems in stem cell technology leading to stem cells to be consistently developed into stable populations of particular cell types, especially liver cells. These can then be used in tests and trials to predict what toxicity effects new medicines might have on humans.

What is a stem cell line?

A stem cell line is a stable population of stem cells maintained in a culture for successive generations. Once the cell line is created no further samples are required from sources for stem cells.

Not all stem cells are equal though. Some can only give rise to particular cell types (for example bone marrow contains stem cells that can only give rise to blood cells, these are adult stem cells). Others, such as those sourced from human embryonic stem cells typically give rise to a much wider range of cell types. It has been very difficult to derive liver cells from adult sources.

A number of research groups around the world are looking to identify alternative sources of stem cells, such as from umbilical cord blood. However it is not the intention of the consortium to utilise these at the current time. The Scientific Advisory Board will keep relevant developments under review and the Ethics Advisory Board, when created in 2008, will advise on the framework in which such cells lines could be considered in the longer-term scientific strategy.

What type of stem cells will you be using?

During the pilot phase, the work will look to develop a tool to predict the toxicity of new medicines, utilising human embryonic stem cells that are already banked with the UK Stem Cell Bank. Any cells used must comply with the Ethics Policy and research groups will be audited to ensure this has been followed.

Liver cells are the most relevant to toxicity for most medicines and therefore in the first year, those most likely to be able to be differentiated into liver cells (hepatocytes) will be the most relevant.

Why is this research important?

If stem cells can be developed in a consistent way to enable their use in predicting such adverse effects then failures could be detected at a lot earlier stage, reducing investment loss and improving the safety of medicines for patients in the longer term.

Pharmaceutical companies invest huge amounts of money in developing new medicines. Due to the nature of the development process, much of this investment can be lost if unexpected reactions occur when candidate medicines are first tested in man. Such failures mean that the investment is not successful.