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MRC/AstraZeneca Centre for Lead Discovery

  • Status: Closed
  • Open date: 2 Aug 2017
  • Closing date: 27 Sep 2017 16:00 GMT+1
  • Type: Calls

Introduction

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).

Background

‘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.

Further information on the collaboration with AstraZeneca can be found at https://www.youtube.com/watch?v=el2tCW2w-IU  

Further information on NiCoLA-B – the most advanced drug discovery robot in the world can be found at https://www.astrazeneca.com/media-centre/articles/2016/meet-nicola-b-the-most-advanced-drug-discovery-robot-in-the-world-06122016.html#?vid=az5237352153001

Funding available

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 5 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 timeframe 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 3 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.

Note. There are a number of minimum assay development guidelines (see Applicants Guidance) which when considered as a whole will need to provide evidence that minimum requirements have been met prior to application. The less well developed the assay, and the more work that is required prior to transfer to the CLD, the less competitive the proposal will be.

Who can apply

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.  Eligible institutions include UK higher education institutions, Research Council Units and Institutes, and eligible Independent Research Organisations (IROs). All IROs listed on the RCUK web page are eligible to apply.

Research proposals that are led by commercial entities are not eligible. Applications may not include collaborations with additional commercial parties.

Application process

Proposals must be submitted using the Research Council’s Joint electronic Submission (Je-S) System.

Applicants should read the MRC/AZ Centre for Lead Discovery Application Guidance before preparing their proposal. To submit an application, the applicants must complete the MRC/AZ Centre for Lead Discovery Case for Support form, and submit this as a PDF, along with all other documentation detailed in the application guidance.

Please bear in mind that all proposals have to be submitted via your research organisation’s administrative department. Please ensure sufficient time to complete their parts of the proposal before the MRC deadline dates. Standard MRC terms and conditions will apply to this scheme.

Assessment

Applications will be assessed by expert peer-review and prioritised for funding by the MRC, via a bespoke expert assessment Panel including members of MRC’s DPFS Panel, MRC’s Research Boards and external experts, with AZ providing guidance to confirm that projects are technically feasible, that there are no 3rd party agreements preventing AZ from undertaking the project, and that no equivalent screen has been conducted as part of  AZ’s internal R&D programme or through any prior open innovation collaboration.

The Panel will consider all applications against the criteria outlined below:

  • Need: Does the identified need exist? Would meeting this need significantly reduce disease burden and/or provide a valuable commercial opportunity and/or alleviate an important development bottleneck? If the need is not significant now, will it become so in the future? Is the need met or unmet? If unmet, will it likely be unmet at the time that the proposed solution is in place? Has the applicant identified the key competing solutions and their status or are they aware of other similar or complementary research underway elsewhere? Has the applicant identified the key competitive advantages of their proposed solution? How likely is it that the proposed solution, if achieved, would be widely adopted?
  • Rationale: Is there a good medical/scientific rationale for the project? Is there a reasonable body of evidence to support the proposed rationale?
  • Deliverability: Are upstream or downstream development hurdles surmountable?

The Panel will, independent of AZ input, determine the applications that merit support and rank them by order of priority. If modifications to the approach or provision of additional data would potentially make a re-application worthy of support, declined applications may receive ‘Positive Feedback’. The decision of the Panel is final and will not be open to appeal and the MRC reserves the right to amend the application process.

Post-award scheduling

Applications will be supported in order of priority, taking into account the view of a subsequent joint AZ and technical review sub-Panel meeting. Applicants may be required to provide further information in advance of this Meeting, and to potentially join by telephone.

Intellectual property

All projects funded under this initiative will be collaborative studies between academic researchers and AZ. The investigators will work under a pre-agreed standard collaborative research agreement, jointly signed by the Research Organisation and AZ, based closely on the Lambert Agreement for preclinical studies. Release of funds will be contingent on receipt of the signed agreement by MRC.

The Research Organisation will own all generated IP. AZ will have the first right to negotiate for an exclusive licence to any arising and relevant background. AZ can declare an interest (in writing) in exercising their option at any point in the project and up to 6 months after the project end. If AZ do not exercise their option or are unable to agree terms, any jointly generated IP will be assigned to the HEI at the relevant period with AZ signing away any claim over exploitation or profit.

Timeline

Call open

2 August 2017

Call close

27 September 2017

Panel Meeting

tbc (Mid February 2018)

Technical Meeting

tbc (Mid March 2018

Screening

Q3/Q4 2018

Contact

You are encouraged to discuss your proposal with the MRC Programme Manager before submission:

Email: highthroughputscreen@headoffice.mrc.ac.uk

For further information please refer to the FAQ web page.