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European Biopharmaceutical Review

Compound Interest

In recent years, corporate compound collections have been used as tools to promote innovation, in order to encourage external involvement in enhancing drug discovery. Facilitating outside access to pharmaceutical collections requires enablers, either internal or external, who have the means to manage the compound inventory, logistics, associated data and intellectual property to support successful collaborations – a capability generally lacking in academia and small and medium enterprises (SMEs), as well as in larger organisations under resource pressure.

The clear and steady decline in approved therapeutics is leading the pharma industry to redefine its drug discovery strategies. One outcome is the initiation of intercompany and academia collaborations to drive innovation (1). Pharma organisations are aiming to maximise their productivity, providing support in areas they are strongest in, by offering open access to core assets in return for enterprise. The emerging models offer a new approach to aspects of drug discovery traditionally viewed as competing activities.

Collaboration Value

Success in drug discovery is dependent on combining well-validated targets with a compound lead series that reduces attrition risks, such as safety. Currently, there exist many potentially good therapeutic targets in organisations without access to suitable compound collections. Meanwhile, discovering ways to access this novel biology, and the associated knowledge from academia and biotechnology firms, has been shown to boost early-stage productivity. This is particularly important for developing areas of biology, where even with good target validation and support, there is no guarantee of finding a suitable hit that can be optimised from current compound collections – with poor hit rates reported for many new target types. Compound collections, therefore, need to continue to develop in diversity – and contain druglike starting points – as new assay technologies and new target classes open up drug disease pathways.

Compound collections are recognised as being valuable drug discovery assets to pharma companies. In the past 5-10 years, medium and large pharma corporations have spent many millions of dollars investing in both compounds and the infrastructure to manage them. It is therefore worth considering how to maximise the return on investment from these assets. However, there are clear challenges with the cost and risk of opening access to a compound collection, compared with the obvious rewards and attractiveness for collaborative partners.

Models of external access to corporate compound collections have emerged, with individual companies sharing their collections with academic groups (such as AstraZeneca, Pfizer, Sanofi, GlaxoSmithKline (GSK) and Roche), business forming partnerships (AstraZeneca and Bayer, Astellas and Daiichi Sankyo), and creations of largescale, multi-partner collaborations (Innovative Medicines Initiative (IMI) and European Lead Factory (ELF)).

Benefits of Sharing

There are a number of reasons why companies may benefit from open access to their compound collections:

Novel Chemical Space
Compound collections have generally been created on a historical basis, built around an organisation’s therapeutic area of interest, with compounds either synthesised or selected for purchase, using rules of acceptability created by an internal chemistry team. As a result, the collections of individual companies are quite unique, which means they are not suited to a wider range of needs (2,3). It is important to create a mechanism to rapidly enhance collections with highquality complements.

For successful identification of hit compounds for novel biological targets, a collection is required that represents the maximum diversity possible, carefully designed to contain multiple representatives of each central pharmacophore. Finding hits for new targets, and the ability to use new biology assays, strongly suggests that diversity of collection is an advantage – which cannot be guaranteed from existing internal collections. Accessing other collections designed by different methods – covering alternative chemistry, but still being of pharma quality in terms of synthetic tractability, pharmacokinetics and toxicology – provides novel possibilities for the successful progression of a project.

Diversity can be brought about by combining collections from different partners with experience of working on different indications. Following the merger of Bayer Healthcare and Schering AG, the compound collections of both companies were compared (2,3). Only around 1.5% of duplicated structures were found between the over 2 million compounds from Bayer and around 900,000 from Schering – most being the result of combinational chemistry or synthetic intermediates. There was virtually no overlap between medicinal chemistry compounds from each collection.

In 2010, AstraZeneca and Bayer were the first companies to report sharing their chemistry assets for selected drug targets – a collaboration reported to have successfully identified promising starting points for both businesses. Recognising the need for an increased compound management resource, the companies agreed to share biology assays, rather than the compound collections. In April 2014, two large Japanese pharma companies – Astellas and Daiichi Sankyo – agreed to accelerate open innovation through sharing around 400,000 compounds from their collections. In both cases, the rights to develop and commercialise hits were granted to the target owner.

Academia and Startups
Providing access to a corporate collection can be used to increase exposure to novel biology and potential new drug targets that could be partnered or internalised. Innovation centres – where external groups can work directly with pharma – are one such mechanism for achieving this. The Pfizer Centres for Therapeutic Innovation, GSK’s Tres Cantos Open Lab, and Neomed – a not for profit, public/ private pharma alliance sponsored by AstraZeneca, Pfizer and Janssen – are all designed to promote open innovation drug discovery, facilitating the sharing of resources and biology between pharma and academia. These centres enable external groups to benefit from significant resources and experience, while allowing the host company to carefully control the use of its assets.

External sharing of collections with academic institutes is also being promoted by many companies. AstraZeneca provides access to around 250,000 compounds from its screening library to the Academic Drug Discovery Consortium, and to the Medical Research Council Technology, which performs screening, hit validation and optimisation of selected compounds, controlled by a joint screening committee.

Biological Data
Specifically designed compound sets with a known mode of action can be provided as a resource to enhance links with expert external research groups of benefit to R&D activities. St Jude Children’s Research Hospital, Novartis and GSK have created – in collaboration with Medicines for Malaria Venture – a ‘Malaria Box’, where 200 diverse probe-like compounds with a known mode of action have been combined with 200 drug-like compounds selected for maximum diversity (with additional predicted oral absorption and removed toxicophores). The purpose of this compound set is to enhance basic research into disease mechanisms, ensuring that data generated is collated in an open access database.

In addition, specific compound sets can be shared with relevant academic groups to confirm a compound selection process – defined by a novel computational model against a new target class. By increasing the exposure of the collection to related targets, the potential success of the collection can be assessed ahead of internal discovery projects.

Commercialised Collections
In some cases, external collaborations are initiated – in part to introduce external innovation into a company – but also to generate revenue from a particularly novel and attractive set of compounds by selling access to the collection.

European Lead Factory
Initiated by Bayer Healthcare and now into its second year, the ELF is a unique public-private partnership supported by the European IMI to enhance drug discovery by innovation. With the Joint European Compound Collection (JECC) at its core, seven European pharma companies have collectively contributed at least 300,000 small molecules (4). Creating a collection from multiple partners greatly raises the diversity available, increasing the chances of identifying promising leads.

This unique asset is enhancing early-stage discovery output through a number of mechanisms. Firstly, each of the seven pharma contributors are able to screen the JECC internally – against targets of their choice – introducing novel chemistry to their projects. Furthermore, the JECC has been used to find new therapeutic targets from European SMEs and academia using crowd sourcing, combined with the offer to screen the collection for free.

Further crowd sourcing is being utilised to gather an additional 200,000 compounds for the JECC. These compounds are being selected from submitted proposals to enhance both diversity and novelty, while maintaining the drug-like properties inherent in the collection. Combining these different innovation streams in one place creates great potential to enhance the output of the respective pharma partners, beyond that of a reciprocal compound agreement.

Key to Success

The management of such collaboration is highly complex and requires significant resources. In order to satisfy contributors’ demands, there needs to be a central manager – a neutral third party – who can ensure the maximum use of the collection and satisfy the demands of every partner.

The compound management, logistics and associated infrastructure has a central role in facilitating all the activities necessary for successful collaboration; management of the compound collection and associated data; organisation of the inventory; and administration of rules set up to share the data. The collection needs to be housed in a secure location, capable of correctly storing the compounds to ensure integrity is maintained. In addition, efficient logistics are essential to guarantee the supply and re-supply to multiple locations in suitable formats. Data needs to be handled carefully, sharing sufficient information to allow testing of compounds, but with restrictions carefully managed to ensure the safety of intellectual property.

The ELF has created a model with a clear framework for multiple partner sharing. Using a neutral compound management partner as a central management and logistics hub allows the sharing of compound collections among a large consortium to become a reality. This allows the JECC to be fully exploited in a search for promising drug candidates. In addition, the ELF provides a structure that allows the secure sharing of compound collections, while limiting access to structural information. Computational selection methods allow mining without revealing structures, ensuring the collection is correctly designed for non-overlap, maximum diversity, with multiple examples of each pharmacophore (5).

Even when collections are to be shared between only a few partners, compound storage, management and logistics capacity can be an issue preventing successful collaboration – something that can be readily solved through using an experienced third-party compound management partner.

Shared Future

Open innovation offers the greatest chance of reversing the decline in approved therapeutics. It is in the best interests of pharma companies to find models that work for them and are attractive to external institutions. With each organisation possessing different objectives, each model needs to be specifically tailored. As a result, the use of corporate compound collections as a sharable asset to engage in enterprising collaborative projects looks set to prove both promising and valuable.


1. Hunter J, Collaboration for innovation is the new mantra for the pharmaceutical industry, Drug Discovery World Spring: pp9-15, 2014
2. Schamberger J, Grimm M, Steinmeyer A and Hillisch A, Rendezvous in chemical space? Comparing the small molecule compound libraries of Bayer and Schering, Drug Discovery Today 16: pp636-641, 2011
3. Kogei T et al, Big pharma screening collections: More of the same or unique libraries? The AstraZeneca- Bayer Pharma AG case, Drug Discovery Today 18: pp1,014-1,024, 2013
4. Mullard A, European Lead Factory open for business, Nature Review Drug Discovery 12: pp173-175, 2013
5. Besnard J, Jones PS, Hopkins AL and Pannifer AD, The Joint European Compound Library; A screening collection to boost precompetitive research in Europe, Drug Discovery Today, In press

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Dr Simon MacKenzie, Chief Executive Officer at BioAscent Discovery Ltd, has a PhD in Biochemistry from the University of Dundee. He has broad experience in early-stage drug discovery, working for pharma, biotechs, CROs and in academia. Prior to joining, he was Director, Product Strategy Centre at Kyorin Pharmaceutical Company, with responsibility for the pipeline enhancement of the Respiratory Disease franchise.

Dr Sylviane Boucharens is Chief Operation and Scientific Officer and co-founder of BioAscent Discovery Ltd. She attained her PhD in Cellular and Molecular Biology from the University Joseph Fourier, France, and has more than 20 years’ experience in scientific research and the drug discovery environment. Sylviane was Head of Global Compound Repository and In Vitro Screening at Organon, Schering-Plough, and Merck Sharp & Dohme.
Simon MacKenzie
Sylviane Boucharens
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