**2.2 The chemical biology consortium Sweden (CBCS)**

Although much smaller than the MLP in the US, this example of a national consortium can highlight very well the particular strengths of a focused organization with only a few members. CBCS, with two nodes at the Karolinska Institutet and Umeå University, was founded as a non-for-profit research infrastructure for chemical biology in 2010 [8] by researchers from Biovitrum (former Pharmacia and Upjohn) and became an integrated platform of SciLifeLab, an already existing national centre for molecular biosciences, in 2013 [9]. The combined platform can investigate both chemical and genetic perturbations in biological systems. CBCS wants to enable high level basic research with open access publications while at the same time linking up academic and industrial groups. Complementary to CBCS, SciLifeLab offers a dedicated platform for drug discovery and development, with the clear goal of accelerating projects with translational potential. After nearly 10 years of operation, the consortium has produced more than 130 co-authored publications and 11 patent applications while scientific data provided the basis of six start-up companies [10].

Users are encouraged to discuss in more detail project proposals with the CBCS staff prior to the submission of the official application. A proposal template, user agreements and estimated costs of typical screening and chemistry projects are available online. Project proposals are evaluated by an independent 'Project Review Committee' (PRC), which meets biannually. Prioritized projects may be subsidized, with the remaining costs covered by the applicant. Implemented projects are periodically re-evaluated by the Project Review Committee as they progress to pre-defined milestones. A project plan for a so-called "large collaborative project" may run over a maximum of 2 years for which the user is expected to cover the costs for all reagents and consumables, including a compound access fee for plating of library compounds. There are also "small collaborative projects" which involve only limited CBCS

support for maximal 2 weeks, e.g. a short-term access to a specialized instrument such as an imaging plate reader. For these projects, no PRC application is required but they are undertaken with a "first come—first served" policy based on available resources [10]. In line with the open access data policy of the CBCS, the applicant and the CBCS agree upon a clear publication strategy before the implementation of the project. The target user group of CBCS are academic researchers at Swedish research institutions, who aim to develop chemical probes on a collaborative basis.

It is worth looking in more detail into the services CBCS can offer to their academic customers. The consortium assists in assay development for both biochemical and cell-based assays, gives access to the SciLifeLab compound collection and provides medicinal and computational chemistry expertise for hit validation and optimization. This model is very similar to the service offerings of the much larger European research infrastructure EU-OPENSCREEN which is being discussed below. In addition, mechanism-of-action studies can be performed with often specialized technologies such as cellular thermal shift assays (CETSA) [11]. In fact, the development of CETSA is a good example on how an expert consortium such as CBCS can impact and further develop disrupting technologies in collaboration with local academic groups and commercial partners (here: Pelago Biosciences). Starting life as a low throughput assay, CETSA is now amenable to high throughput screening [12]. Scientists usually come to the CBCS with the concept for a biological assay and first experimental data. They have then the chance to work further on the assay in the CBCS laboratories under guidance of their expert scientists, enabling in parallel scientific services and the education of users [10].

The CBCS compound collection consists of more than 200.000 compounds with high chemical diversity which are routinely quality controlled. While many of these compounds were donated by the pharmaceutical company Biovitrum, the library was further expanded with sets from commercial vendors and donations by other biotech companies. Importantly, the strategy has always been to build a modular collection of sub-libraries which can be adapted to the needs of each academic screening project, based mainly on assay throughput and cost per data point. For instance, in addition to a diverse primary screening set of 35.000 compounds, there are also focused libraries for particular target classes such as kinases, G-protein coupled receptors, agrochemicals etc., as well as a set of approved drugs [10]. This is very different to the concept of EU-OPENSCREEN which offers a high throughput screening set of 100.000 commercial compounds to their users, with the goal to have that set screened in almost all projects so that each compound becomes associated with "positive" and "negative" screening data from as many projects as possible (see below).

Overall, between 2010 and 2018 more than 400 collaborative projects with 236 individual users in Sweden were discussed. User interest grew continuously during these 8 years, currently leading to approximately one new project discussion per week. About 25% of discussions result in large project PRC applications while others obtain small project limited support, all documented in, on average, 20 publications per year [10].

#### **2.3 Public private initiatives: SGC and ELF**

In industry, chemical tool compounds play an important role as pharmaceutical modulators of novel drug targets. Typically, they are being used for testing a particular disease hypothesis and for validating the chemical tractability of newly discovered candidate proteins or signaling pathways for which otherwise comparatively little information is available. Sometimes their properties are even

**117**

cal companies.

*Accelerating Chemical Tool Discovery by Academic Collaborative Models*

instance epigenetic and other transcriptional modulators.

sufficient to act as starting points for drug discovery programs. The development of compounds with required potency and, most importantly, selectivity towards individual members of a protein class can be a formidable task even for larger pharmaceutical or biotech companies. It came therefore as no surprise that in 2009 several industrial partners decided to collaborate in a pre-competitive manner and initiated a public-private partnership (PPP) with leading academic institutes in the field of chemical biology. The aim was to develop high-quality chemical tool compounds for families of understudied proteins of potential therapeutic value, for

The chosen academic partners in that particular PPP were the universities of Oxford and Toronto which had already formed the so-called Structural Genomics Consortium (SGC) in 2004 with the goal of determining the three-dimensional structures of proteins with therapeutic relevance. The SGC advocates open access partnerships between industry and academia and is committed to make their chemical tool compounds available without any restrictions. In the last 10 years, and with financial support by several pharmaceutical companies, more than 50 chemical probes in the areas of epigenetics and kinase signaling were developed [13, 14]. Furthermore, seven pharmaceutical companies made their chemical tool compounds from older research programs available to the scientific community, including protocols, controls and associated data [15]. Efforts are now underway, under the umbrella of the Innovative Medicines Initiative (IMI), to expand the initial collection of compounds further by focusing not only on the protein classes which were selected in the past but also on the development of new technologies, making the identification and profiling of tool compounds generally faster and

Another PPP initiative supported by the IMI is the European Lead Factory (ELF) [17] which is a consortium of 20 partners, currently among them the universities of Oxford and Dundee while several other universities, research organizations and companies in the UK, Netherlands and Germany were former partners. The project was launched in 2013 and came to an end in 2018, with a follow-up five-year project funded in the same year [18]. During its lifetime, the ELF established a selection of about 550.000 compounds which are generally not commercially available. 300.000 of these were donated by seven participating pharmaceutical companies, while the rest was synthesized by medicinal chemistry partner companies during the last 5 years. Both the compound management facility in the UK and the high throughput screening center in the Netherlands were formerly part of pharmaceutical companies and able to perform screening operations and chemistry services such as hit optimization and modeling according to industry standards. The Oxford Biotechnology group of the SGC was selected as a key contributor of 3D co-crystal structures which are essential for compound optimization. During the lifetime of the project, more than 80 drug discovery programs across most therapeutic areas were pursued. By March 2018, two partnering deals between the respective project owner and one of the pharmaceutical company partners had emerged. Importantly, the ELF protects the IP rights of their academic collaborators against the pharmaceutical companies, ensuring that the academic researchers can always search for external partners in case that no development deal between them and one of the ELF industry partners could be fixed. This was one of the main concerns when the

It remains to be seen though if and how academic groups really benefit from these ambitious initiatives, especially when own research interests show little overlap with the essentially commercial interests of the participating pharmaceuti-

*DOI: http://dx.doi.org/10.5772/intechopen.91138*

more cost-effective [16].

project started in 2013 [19].

#### *Accelerating Chemical Tool Discovery by Academic Collaborative Models DOI: http://dx.doi.org/10.5772/intechopen.91138*

*Cheminformatics and Its Applications*

support for maximal 2 weeks, e.g. a short-term access to a specialized instrument such as an imaging plate reader. For these projects, no PRC application is required but they are undertaken with a "first come—first served" policy based on available resources [10]. In line with the open access data policy of the CBCS, the applicant and the CBCS agree upon a clear publication strategy before the implementation of the project. The target user group of CBCS are academic researchers at Swedish research institutions, who aim to develop chemical probes on a collaborative basis. It is worth looking in more detail into the services CBCS can offer to their academic customers. The consortium assists in assay development for both biochemical and cell-based assays, gives access to the SciLifeLab compound collection and provides medicinal and computational chemistry expertise for hit validation and optimization. This model is very similar to the service offerings of the much larger European research infrastructure EU-OPENSCREEN which is being discussed below. In addition, mechanism-of-action studies can be performed with often specialized technologies such as cellular thermal shift assays (CETSA) [11]. In fact, the development of CETSA is a good example on how an expert consortium such as CBCS can impact and further develop disrupting technologies in collaboration with local academic groups and commercial partners (here: Pelago Biosciences). Starting life as a low throughput assay, CETSA is now amenable to high throughput screening [12]. Scientists usually come to the CBCS with the concept for a biological assay and first experimental data. They have then the chance to work further on the assay in the CBCS laboratories under guidance of their expert scientists, enabling in

parallel scientific services and the education of users [10].

The CBCS compound collection consists of more than 200.000 compounds with high chemical diversity which are routinely quality controlled. While many of these compounds were donated by the pharmaceutical company Biovitrum, the library was further expanded with sets from commercial vendors and donations by other biotech companies. Importantly, the strategy has always been to build a modular collection of sub-libraries which can be adapted to the needs of each academic screening project, based mainly on assay throughput and cost per data point. For instance, in addition to a diverse primary screening set of 35.000 compounds, there are also focused libraries for particular target classes such as kinases, G-protein coupled receptors, agrochemicals etc., as well as a set of approved drugs [10]. This is very different to the concept of EU-OPENSCREEN which offers a high throughput screening set of 100.000 commercial compounds to their users, with the goal to have that set screened in almost all projects so that each compound becomes associated with "positive" and "negative" screening data from as many projects as

Overall, between 2010 and 2018 more than 400 collaborative projects with 236 individual users in Sweden were discussed. User interest grew continuously during these 8 years, currently leading to approximately one new project discussion per week. About 25% of discussions result in large project PRC applications while others obtain small project limited support, all documented in, on average, 20 publica-

In industry, chemical tool compounds play an important role as pharmaceutical modulators of novel drug targets. Typically, they are being used for testing a particular disease hypothesis and for validating the chemical tractability of newly discovered candidate proteins or signaling pathways for which otherwise comparatively little information is available. Sometimes their properties are even

**116**

possible (see below).

tions per year [10].

**2.3 Public private initiatives: SGC and ELF**

sufficient to act as starting points for drug discovery programs. The development of compounds with required potency and, most importantly, selectivity towards individual members of a protein class can be a formidable task even for larger pharmaceutical or biotech companies. It came therefore as no surprise that in 2009 several industrial partners decided to collaborate in a pre-competitive manner and initiated a public-private partnership (PPP) with leading academic institutes in the field of chemical biology. The aim was to develop high-quality chemical tool compounds for families of understudied proteins of potential therapeutic value, for instance epigenetic and other transcriptional modulators.

The chosen academic partners in that particular PPP were the universities of Oxford and Toronto which had already formed the so-called Structural Genomics Consortium (SGC) in 2004 with the goal of determining the three-dimensional structures of proteins with therapeutic relevance. The SGC advocates open access partnerships between industry and academia and is committed to make their chemical tool compounds available without any restrictions. In the last 10 years, and with financial support by several pharmaceutical companies, more than 50 chemical probes in the areas of epigenetics and kinase signaling were developed [13, 14]. Furthermore, seven pharmaceutical companies made their chemical tool compounds from older research programs available to the scientific community, including protocols, controls and associated data [15]. Efforts are now underway, under the umbrella of the Innovative Medicines Initiative (IMI), to expand the initial collection of compounds further by focusing not only on the protein classes which were selected in the past but also on the development of new technologies, making the identification and profiling of tool compounds generally faster and more cost-effective [16].

Another PPP initiative supported by the IMI is the European Lead Factory (ELF) [17] which is a consortium of 20 partners, currently among them the universities of Oxford and Dundee while several other universities, research organizations and companies in the UK, Netherlands and Germany were former partners. The project was launched in 2013 and came to an end in 2018, with a follow-up five-year project funded in the same year [18]. During its lifetime, the ELF established a selection of about 550.000 compounds which are generally not commercially available. 300.000 of these were donated by seven participating pharmaceutical companies, while the rest was synthesized by medicinal chemistry partner companies during the last 5 years. Both the compound management facility in the UK and the high throughput screening center in the Netherlands were formerly part of pharmaceutical companies and able to perform screening operations and chemistry services such as hit optimization and modeling according to industry standards. The Oxford Biotechnology group of the SGC was selected as a key contributor of 3D co-crystal structures which are essential for compound optimization. During the lifetime of the project, more than 80 drug discovery programs across most therapeutic areas were pursued. By March 2018, two partnering deals between the respective project owner and one of the pharmaceutical company partners had emerged. Importantly, the ELF protects the IP rights of their academic collaborators against the pharmaceutical companies, ensuring that the academic researchers can always search for external partners in case that no development deal between them and one of the ELF industry partners could be fixed. This was one of the main concerns when the project started in 2013 [19].

It remains to be seen though if and how academic groups really benefit from these ambitious initiatives, especially when own research interests show little overlap with the essentially commercial interests of the participating pharmaceutical companies.
