California-UK collaborative opportunity in translational stem cell research: disease team III
The Medical Research Council (MRC) has agreed to partner the Californian Institute of Regenerative Medicine (CIRM) in its Disease Team Therapy Development Awards III Request for Applications (RFA 13-01), which aims to progress late preclinical and early clinical translational stem cell research. The MRC is therefore calling for proposals from UK groups active in the late preclinical and early clinical domain that can link to Californian research teams, to establish high quality, multidisciplinary translational research programmes. Funded programmes will be milestone-driven and have the maturity and critical mass to complete early clinical testing within the four-year period of support.
- Background
- Aim of call
- Eligibility
- Funding available for invited proposals
- Application process
- Eligibility criteria for proposals seeking MRC support
- Terms and conditions of the MRC award
- Intellectual property
- Consortium agreement
- Monitoring Performance
- Publishing results
- Contact
Background
Stem cell research offers enormous potential for the development of novel therapies, derived from or targeting stem cells,for the treatment of disease and serious injury. The application of stem cell research to clinical problems has matured to the stage that stem cell-based therapies are now poised to progress into clinical testing. Such research is an inherently multidisciplinary process, requiring the combined strengths of academic and clinical researchers, together with the expertise of the biotechnology and pharmaceutical sector. Collaborative arrangements between these different partners are likely to be needed in order to assemble teams with the requisite complementary expertise to successfully translate promising pre-clinical findings into viable therapeutics.
Applications to this call will seek to establish such partnerships, based on scientific excellence and involving teams in both the UK and California, in order to deliver an interdisciplinary programme of translational stem cell research able to delivery early stage clinical trials.
Aim of call
The aim of the California Institute of Regenerative Medicine (CIRM) Disease Team Therapy Development Awards III RFA 13-01call is to accelerate clinical proof of concept for potential therapies based on stem cell research through the completion of Phase I and/or Phase 2 clinical studies
- Phase I Objectives: Demonstrate preliminary safety, range of safe doses to be studied in subsequent trial, and to assess measures of biologic/clinical activity in humans; and/or
- Phase 2 Objective: Evaluate efficacy of the therapeutic in a target indication.
To facilitate this goal, CIRM intends to support actively managed multidisciplinary teams engaged in milestone-driven translational research, in partnership with collaborative funding partners. The MRC has agreed to partner CIRM in this effort, and will fund the participation of a limited number of UK groups within this programme. The mission of the programmes funded under this call will be to conduct the necessary research and regulatory activitiesrequired to complete early clinical testing of a single therapeutic entity per programme.
There is an additional opportunity under this call for submissions from CIRM-funded Early Translational awardees seeking support for earlier phases of pre-clinical development, to enable a IND filing. Further details can be found on the CIRM RFA 13-10 website.
Eligibility
The call is open to projects meeting the following eligibility criteria:
Therapeutic Candidate –
This call will support the following types of therapeutic candidate:
- A cell therapy derived from pluripotent stem cells
- Allogeneic adult stem cells or progenitor cells for repair and/or regeneration, except for those out of scope identified below
- Genetically- or pharmacologically-modified allogeneic adult stem cells or progenitor cells (e.g. hematopoietic stem cells) for repair and/or regeneration
- Tissue engineered (e.g. utilizing a cell scaffold or biomaterial in combination with a stem or progenitor cell) functional tissues for implantation in vivo
- A small molecule or biologic demonstrated to target normal endogenous stem cells as the primary mechanism of action (MOA) (in vivo) for regeneration and repair
- Any therapeutic candidate developed under a Disease Team Research I (RFA 09-01) award
Therapeutic candidates that fall outside the scope of this call include the following:
- Unmodified hematopoietic stem cells (HSCs)
- Small molecules and biologics, unless targeting endogenous stem cells as primary MOA (in vivo) for regeneration or repair
- Autologous mesenchymal stem cell (MSC) approaches
- Autologous tissue-derived stem cell-derived approaches
- Minimally manipulated bone marrow or minimally manipulated cord blood
Programme Readiness –
• Single final therapeutic development candidate chosen, for which there is a strong scientific and clinical rationale.
• Strong preclinical proof-of-concept (POC) evidence has been shown with the development candidate in the target disease/injury; for example, reproducible evidence of disease-modifying activity in a relevant animal model using the intended therapeutic candidate.
• Applicants with projects commencing with definitive late-stage preclinical development must, by the Letter of Intent (LOI) due date (March 13, 2013) (see below), provide a record of discussion with the FDA and, as necessary, the Medical and Healthcare Products Regulatory Agency (MHRA), indicating
- either the completion of a pre-IND meeting with the FDA or evidence of a FDA-confirmed date for a pre-IND meeting that will take place prior to the application due date (May 15, 2013); and
- if proposing UK clinical trial site(s), either completion of a scientific advice meeting with the MHRA (covering the same topics as a pre-IND meeting with the FDA), or evidence of a MHRA-confirmed date for such a meeting that will take place prior to the application due date (May 15, 2013).
• Applicants with projects beginning with a clinical trial must
- have filed a complete IND application package with the FDA, by the LOI due date (March 13, 2013); and
- if proposing UK clinical trial site(s), have filed a complete Clinical Trial Authorisation (CTA) application package with the MHRA and provided evidence of this filing to the MRC by September 13, 2013, this being shortly prior to the MRC review meeting
• For projects proposing to start a Phase 2 clinical trial, applicants must have Phase 1 data demonstrating preliminary safety in the target population by the application due date (May 15, 2013).
In addition to MRC, CIRM has agreed to partner with the Chinese Ministry of Science and Technology (MOST), the National Institutes of Health (NIH), and the Andalusian Initiative for Advanced Therapies (InitiativaAndaluza en TerapiasAvanzadas, “IATA”) of Andalusia, Spain. Through this ‘Collaborative Funding Partner’ programme, California-based Principal Investigators (PIs) can collaborate with researchers eligible for funding by any of these agencies, such that if a collaborative funding proposal is approved, CIRM will fund all project work done within the State of California and the partner will fund all project work within its jurisdiction. Thus MRC will fund the UK component of awarded collaborative projects under standard arrangements, subject to the available funds.
Funding available for invited proposals
• Under RFA 13-01, CIRM intends to commit up to $100 million to support up to 5 awards. Projects will be funded for up to four years, with justifiable total project costs of between $5 and $20 million per project for California-based activity. Only in extraordinary circumstances is it expected that a project would be funded at the higher end of the range.
• MRC has made up to £5m available to support UK participation in the CIRM Disease Team III RFA.It is anticipated that the MRC will fund the UK-based activity in one or two of the top-ranked fundable proposals involving a UK team.
• UK participation will be funded as an MRC award to the eligible UK organisation under standard arrangements. Funding will be provided at 80 per cent fEC.
Application process
Submission of an application for the CIRM Disease Team Research RFA involves a two-step process. Teams with UK participants must first submit to CIRM a single joint Letter of Intent (LOI), to the LOI due date (March 13, 2013). LOIs will be assessed by CIRM for fit to RFA 13-01 eligibility. Please refer to CIRM RFA 13-10 website for further details.
The likely overall funding request associated with the UK component should be indicated although details of the resource request need not be specified at the LOI stage. The proposed clinical trial must include at least one clinical trial site in California and may include site(s) in the UK. The UK site can be the lead site.
Applicants meeting the eligibility criteria will be invited to submit a full application. In the case of applicants seeking both CIRM and MRC support, full submissions, using where possible common forms, will need to be made to both CIRM and MRC (details of the MRC submission process will be provided to relevant successful LOI applicants).Following submission, parallel and independent reviews will be undertaken by each organization with a positive recommendation of support from each being required in order for a joint award to be made.
Key assessment criteria for the full submissions will be:
- Significance and Impact
- Scientific Rationale and Risk/Benefit
- Therapeutic Development Readiness
- Design and Feasibility of the Project Plan
- Principal Investigator, Development Team and Leadership Plan
- Budget
- Quality of Collaborations, Assets, Resources and Environment; and
- Intellectual Property
Application timetable
Submission |
Deadline |
Review |
Letter of Intent |
CIRM - 5 pm (PDT)13 March 2013 |
CIRM - March 2013 |
Full Application |
CIRM - 5 pm (PDT), 15 May 2013 |
CIRM - August 2013 |
MRC –4 pm (GMT),15 May 2013 |
MRC - September - October 2013 |
Please bear in mind that all proposals to MRC 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.
Full applications will be reviewed by CIRM’s Grants Working Group (GWG), at its meeting in August 2013, and by the relevant MRC Translational Funding Scheme Panels (DPFS or RMRC), at their meetings in September or October 2013, to reach recommendations of support.
Final funding decisions will be made by CIRM’s Independent Citizens' Oversight Committee (ICOC), at its meeting in Q4 2013. Applications seeking MRC support will need to secure both a recommendation of support from the MRC’s Translational Funding Scheme Panel and a positive funding decision from CIRM’s ICOC.
The earliest that funding could start, contingent upon collaboration agreement approval (see below),is January 2014.
Please note that the decisions of the MRC’s Panels will not be open to appeal and that the MRC reserves the right to amend its application process, in agreement with CIRM.
Eligibility criteria for proposals seeking MRC support
- Proposals must involve UK activity that is critical to the progression of the collaboration
- UK based applicants must have strong collaborative links with Californian PIs.
- MRC support will be provided to fund the UK component of competitive proposals where the UK team leader has the status of Co-PI and is fully involved in the project’s leadership plan.
- UK based applicants will need to meet standard MRC eligibility rules apply; please see the MRC applicants’ handbook and the Research Council UK website.
- Commercial links can be accommodated under EU state-aid rules. Funding requests will need to meet MRC Industry Collaboration Application eligibility criteria. In general, MRC will not meet industrial collaborator costs.
- All UK applicants must have first discussed their proposal with MRC Head Office. Please contact Dr Jonathan Pearce (jonathan.pearce@headoffice.mrc.ac.uk)
Terms and conditions of the MRC award
Standard MRC terms and conditions will apply to the UK component of a collaborative disease team award. These are specified in the applicants’ handbook, and encompass:
- the core Research Councils UK terms and conditions
- the additional MRC-specific terms and conditions relating to medical research
- the MRC supplementary terms and conditions for research grants involving human stem cells, where relevant
Further additional terms will also apply to the CIRM-MRC collaborative Disease Team Therapy Development Awards III, such that it will be a condition of MRC funding that:
- The consortium partners (CIRM-funded or otherwise) agree to abide by the Code of Practice for the UK Stem Cell Bank and for the Use of Stem Cell Lines. This includes the requirement to deposit any hESC line derived using MRC funds in the UK Stem Cell Bank, and to seek approval from the Steering Committee for the UK Stem Cell Bank for the import, export or use of any hESC lines in the UK.
- The consortium partners (CIRM-funded or otherwise) agree to provide free access to the UK research community to all publication related biomedical materials generated during the course of the project, to provide consistency with the CIRM requirements for California.
Intellectual property
- Intellectual property generated in the course of the collaborative project through MRC funding will be owned by the host UK institution, who will have the right to manage and exploit the project intellectual property.
- Participating UK groups will be bound by the specified CIRM IP provisions in relation to activities within the State of California. UK partners would only be required to comply with the CIRM IP provisions relating to joint inventions when these were directly linked to CIRM funded research.
- MRC wishes to assure itself that the funded UK institutions are able to manage and exploit effectively the intellectual property generated from the MRC-funded research. In agreement with the CIRM position, MRC will reserve march-in rights to ensure that IP generated during the course of the project using MRC funding can be fully exploited for the national benefit and that of the research organisation involved.
Consortium agreement
- The terms of the collaboration funded under the Disease Team Therapy Development Awards III RFA must be determined early in a proposal’s development and relevant agreements put in place by the start of the project. Collaboration arrangements should ensure transparency in the project design and in the analysis and publication of results (including if these are negative). Consideration should also be given to issues such as: relative responsibilities, governance arrangements, indemnity, intellectual property rights, reporting and access to data and samples.
- MRC funding will not be released until an appropriate consortium agreement has been agreed and signed by all collaborative partners, and approved by MRC and CIRM (and any other collaborative funding partner).
Monitoring Performance
- For collaborative disease team awards involving UK groups, MRC and CIRM will be involved with the project PIs in the active management of the projects. In addition to annual Progress Reports, the PIs will be expected to provide 1) quarterly updates; 2) routine communication by the PI or Project Manager; and 3) participation in Evaluation Meetings. MRC and CIRM will have access to all grantee-generated progress and financial reports across the full scope of the project’s work.
- MRC and CIRM will meet periodically to review the progress of the collaboratively funded projects, and funding may be withdrawn should there be a failure in making satisfactory progress. These Evaluation Meetings will typically occur at the key decision points in development projects, at which time go / no go decisions will be made.
Publishing results
- Results of MRC-funded clinical studies (whether positive or negative) must be published within a reasonable period* following the conclusion of the study. Results should be reported in accordance with the recommendations in the CONSORT statement [Schulz et al. BMJ 2010;340:c332]. Data should be made available in line with the MRC Data Sharing Policy. *Generally within a year of completion
Contact
If you wish to discuss this call, please contact Dr Jonathan Pearce, MRC Programme Manager with responsibility for regenerative medicine (jonathan.pearce@headoffice.mrc.ac.uk)