The MRC/AstraZeneca Centre for Lead Discovery (CLD) aims to support academic researchers in discovering potential starting points for small molecule therapeutic approaches with a clear line-of-sight to therapeutic use.
Academic researchers will benefit from unprecedented access to over two million molecules in AstraZeneca’s compound library, as well as its state-of-the-art high throughput screening facilities.
Following completion of the HTS campaign, sufficient ‘hit’ data should be available to enable applicants to seek follow-on funding internally through confidence in concept or through the MRC’s Development Pathway Funding Scheme (DPFS).
‘Classical’ development of new investigational medicinal products (IMPs) has been based on the manufacture of active chemical substances (drugs), and accounts for approximately 90% of the drugs available for treatment of medical conditions today. High throughput screening is a tool that has been used by big Pharma for decades to search for small molecule starting points for their internal R&D pipeline projects
The MRC/AZ Centre for Lead Discovery will form a unique cornerstone for academic and industrial drug discovery projects by supplying high throughput screening (HTS) infrastructure (NiCoLA-B). Whilst some academic institutions have developed drug discovery screening facilities the AZ facility will offer access to advanced compound management facilities, a large compound collection, advanced screening robotics and multiple state of the art assay platform technologies which together do not exist in academia.
AstraZeneca has carefully curated a collection of ~2 Million compounds within its corporate HTS collection. The full collection is available for screening within this initiative, if suitable assays are derived, providing the same opportunity for applicants as for AstraZeneca’s internal R&D teams, thereby maximising the chance of the academic groups identifying tractable hits which may be advanced into chemistry development programmes.
The MRC will provide funding to support up to 5-10 projects per year. In the first instance, the competition will be run once a year, for an initial five year period. As capacity is limited, projects will be prioritised for funding and for timeslots within the facility. The timeframe for commencement of the studies will vary; although the expectation is within 12 months of the funding decision. If further assay development is required this time-frame may be extended.
AZ may offer to fund a project in its entirety if, based on the application, it considers that route to be the most appropriate funding mechanism for that individual study. In such cases, these will be taken forward through direct collaboration with the company without any further MRC involvement. Applicants who do not wish to accept this offer may continue to seek MRC support through the initiative.
Assay transfer and high-throughput screening activities will be conducted at the AstraZeneca facility in Alderley Park (Cheshire), prior to the relocation to the Cambridge Biomedical Campus in 2019, with costs met by MRC; typically, applicants will not be able to request costs associated with this component of the project.
The MRC Panel, in consultation with technical input from AstraZeneca, may agree to provide limited funding to support assay optimisation prior to transition to the CLD. If this work is conducted within the RO, AstraZeneca will nominate a contact to provide advice.
Following the completion of the HTS campaign the Panel will consider providing additional limited funding to facilitate re-synthesis of tool compounds arising from the screen, additional in-vitro selectivity data and preliminary in-vivo PK. Costs will be limited and the studies will need to be delivered and reported on within a three month window. It is envisages that these activities will take place at Clinical Research Organisations, but may also be available directly from AZ or within the applicants host institution.