COMPACT

Biopharmaceuticals, medicines based on biological molecules such as proteins and nucleic acids, have already delivered effective treatments for a number of serious, often hard to treat diseases, such as Crohn’s disease and multiple sclerosis, dramatically improving patients’ quality of life.

The pharmaceutical industry is keen to expand its work on these novel drugs, but biopharmaceuticals still have a number of drawbacks which are hampering their broader application. For example, because these molecules tend to be complex and delicate, most biopharmaceuticals have to be injected; if they were administered orally (a more patient-friendly route), they would be destroyed by the harsh environment of the stomach. Furthermore, even once biopharmaceuticals are in the body, their large size means it is hard for them to get to their molecular targets.

By bringing together 14 academic groups, 7 pharmaceutical companies and 2 SMEs, the COMPACT project set out to reduce delivery and targeting bottlenecks for developing innovative biopharmaceuticals.

Better understanding of nanomedicines

One of the most significant project achievements is related to getting biopharmaceuticals from the injection site to the target that is causing the disease. For that purpose, researchers use nanocarriers, modifying their surface so that they bind to specific cells. COMPACT researchers discovered why this modification works in certain cases and not in others, which led to a better understanding of how nanomedicines work. The project also developed a novel nanoparticle to get a new type of therapeutic oligonucleotide into the lungs via inhalation.

More patient-friendly ways of administering drugs

Another important project outcome has to do with making the delivery systems for biological molecules more patient friendly. For example, insulin is a very effective treatment for diabetes but it has to be administered via injections. The COMPACT project researchers investigated whether insulin and similar biologicals could be delivered via tablets, which would be a more patient-friendly route. They showed that when insulin is taken via oral delivery, certain cell penetrating peptides can help in getting the molecules over the intestinal barrier into the blood. This represents the first important step towards the oral delivery of biological molecules.

Additionally, the project developed microneedles which can deliver peptides directly into the skin using a nanomedicine type of approach. These microneedles are so fine that they dissolve after they are inserted into the skin, representing a more patient-friendly alternative to traditional injections.

Important breakthrough in the blood-brain barrier

Another important achievement concerns the blood-brain barrier. The brain is a really isolated organ as there is a tight barrier between the blood and the brain cells. Getting across this barrier is a huge limitation in drug delivery. In this project, researchers identified potential new targets that can be used to get drugs into the brain. This is only at the target identification level at this stage but has led to a new IMI project which will explore those possibilities in more detail.

Database, cell banks and other achievements

Other important project achievements include:

• a wide repertoire of drug delivery systems, fully characterised and tested;
• in vitro and in vivo tools to study delivery, including transgenic reporter mice;
• a manually curated database containing over 1 200 entries with useful searchable information from the scientific literature on nonlipid nanoparticles and neurotrophic viruses;
• cell banks containing the most relevant cell lines and standardised protocols and a serum source to be used by all the partners throughout the consortium;
• a strong network of industry and academia to further explore collaborations via bilateral agreements and European funding.

Socio-economic benefits

In addition to the scientific achievements, the project generated significant socio-economic benefits. For example, during the course of the project two patents were filed: one for brain delivery and another for the nanocarrier system for lung delivery.

In order to build on the project achievements, a biotech company has also spun out from Oxford University. The company will look into developing exosomes –nano-sized lipid vesicles which shuttle proteins and genetic information between cells for the delivery of oligonucleotide-based therapeutics. The system is still at an early stage, but once developed, could be of great interest for pharmaceutical companies.

Furthermore, several companies which were not part of COMPACT are now also showing interest in the delivery systems developed within the project. They are collaborating with some of the COMPACT academic partners to see if these delivery systems could be used for their therapeutics. In the long run, these new collaborations could lead to the development of a new line of therapeutics.

For the benefit of industry, academia, SMEs

For academic partners this project was a great opportunity to work with the industry, use their R&D infrastructure, and learn what kinds of problems they encounter during the drug development process. The project also contributed to training of a new generation of pharmaceutical scientists that have a better understanding of the needs and limitations of the drug development process. During the course of the project, 19 PhD students got their doctorate degrees and 5  found jobs at the companies of industry partners.

The pharmaceutical companies benefitted from being able to test novel nanocarrier based delivery approaches directly with academic partners. They also benefitted from the network that has been created within the project, not just with academic partners and SMEs but also with other key players in industry.

The SMEs in the project benefitted from access to industry knowledge and resources, getting a close-up view of the drug development process, and from being treated as an equal partner in the project.

Benefits for patients

Biopharmaceuticals have the potential to improve the lives of many patients with diseases and conditions that are currently hard or even impossible to treat. By finding more effective ways of administering these drugs, and improving their ability to travel through the body to where they are needed, the COMPACT project outcomes will allow more patients to benefit from biopharmaceuticals. Furthermore, designing less invasive administration routes and reducing the dose (and therefore the side effects) and frequency of administration will help to improve patient compliance with treatments.

What’s next

The project resulted in both tangible and non-tangible assets that will be useful for further research. Among the tangible assets are the transgenic mice for analysing biodistribution of nanocarrier systems. These are already accessible to researchers through a commercial company.

Non-tangible assets include more than 65 publications and the know-how that has been generated and will be further developed by researchers in the field, including those in follow-on IMI projects.

Interview with project coordinators