MRC/AZ Centre for Lead Discovery (CLD) FAQs
What are the aims of the MRC/AZ Centre for Lead Discovery?
- Give academics access to AstraZeneca’s high throughput screening infrastructure
- Deliver lead molecules for academic drug discovery projects with clinical line of sight
Who will own the IP?
- The academic groups will own all the resulting IP.
- AZ will have the first option to enter a negotiation to license any resulting programmes of relevance to the company’s therapeutic areas of interest.
What therapeutic areas are within scope?
- All areas – this call is NOT limited to areas of interest to AZ
- Exclusion criteria – existing or previous AZ internal or open innovation projects; existing 3rd party arrangements, technical feasibility / tractability that would prevent the adoption of the screen.
What constitutes a fundable project?
- Significant unmet need
- Strong scientific rationale
- Good evidence
- Technical validated
Is the call restricted to applicants with prior/current MRC funding?
- NO. This call follows standard RCUK eligibility criteria and is open to UK-based researchers who can show they will direct the proposed research and be actively engaged in carrying it through.
Is this call a one off or will it be run in future years?
- The MRC collaboration with AstraZeneca will run for an initial period of five years. This call will be run annually throughout this initial five year period.
What are the technical requirements?
- Please see Applicants guidance for a detailed explanation of technical requirements.
- The preferred minimum requirements are (these are guidelines and should be considered as a whole when deciding the quality of your proposed HTS screen)
- Tolerability of assay to DMSO within the range 0.1 -10% v/v.
- Signal to Background ratio ideally >3
- %CV for max activity/DMSO vehicle plates ideally <10%
- Robust Z’ ideally ≥ 0.5
- Assay must be amenable to miniaturisation into 384 or 1536 well plates
- Data from a minimum of 3 independent, 384well plate runs. 96 well plate runs will be accepted but data generated in 384 plates preferred.
- Small scale protein production and /or cell culture achieved. Consideration must be given to whether protein production or cell culture can be scaled up and to what degree to allow an estimate of the size of HTS achievable. Use of an external supplier is acceptable. Any licences required to use assay reagents in a commercial setting should be highlighted.
- Stability of reagents assessed. This should cover storage as well as on bench and in assay stability.
- Identify secondary assays that can confirm any hits from the primary assay
- Identify selectivity assays if required – these will be specific to the target and should focus on related targets that would be detrimental to the therapeutic index of your primary target.
If I have a strong scientific rationale for my discovery target, why is it important to have an assay developed?
- The aim of this scheme is to enable academics to access lead discovery infrastructure to deliver lead molecules for academic drug discovery projects, via high throughput screening of a high quality compound library.
- Your HTS campaign will involve the single point testing of up to 2 million compounds. Imagine if you tested a compound twice, on day 1 a compound produced a result of 40% and on day 2 only 20%, if the cut-off for the assay was set at 30%, then on day 1 your compound would be determined as a hit, and on day 2 it would not be selected. This can impact in 2 ways,
- If this compound isn’t active, then on day 1 it has been selected as a false positive, whilst this would ultimately be detected in confirmation studies, if the campaign has a high false positive hit rate, then you may end up with too many hits to run XC50 confirmation assays on.
- If this compound is active, then on day 2 it was not selected, and you end up with a false negative, and its ability to be detected may be lost. This ‘hit’ may have ended up as the best starting point for a lead optimisation programme, but will now never be reported.
What types of assay format are acceptable?
- The NiCoLA-B system can be configured to multiple assay formats and plate readers. The table below summarises the current existing and future detection platforms and HTS reader technologies.
Where will the work be carried out?
- The work will initially be carried out at AstraZeneca’s facilities at Alderley Park, prior to the companies relocation to the Cambridge Biomedical Centre.
What is the application process?
- A single stage Full Application process
- There is NO expression of interest or Outline application stage
What is the decision making process?
- A freedom to operate assessment will be undertaken by AZ prior to the applications being sent out for external Peer Review
- Prioritisation decisions will be made by an independent Panel, made up of representatives from MRC’s DPFS Panel, Research Boards and other experts, AZ will have no input in to this scientific assessment
- Prioritised applications will be assessed by a technical Panel, which will be responsible for feedback on additional work required, allocation of slot at AZ, and any follow-up funding, AZ will be involved again at this stage of the project.
What are the timescales?
- Screens will be scheduled at AZ in the 12 months following agreement of the work plan, timing will be dependent on assay readiness, transfer to AZ CLD, confirmation of reagent stability and assay performance at AZ, and available time on the NiCoLA-B.