Funding opportunity

Expression of interest: Prosperity partnerships: advanced therapies safety and toxicity

• Opportunity status: Open
• Funders: Medical Research Council (MRC)
• Funding type: Grant
• Total fund: £10,500,000
• Award range: £2,000,000 - £4,000,000
• Publication date: 30 August 2024
• Opening date: 30 August 2024 9:00am UK time
• Closing date: 6 November 2024 4:00pm UK time

Apply for funding to support emerging or established research partnerships between businesses and academic partners (lead must be UK-based).

Co-developed programmes should enhance knowledge of the safety and toxicity of advanced therapies, developing tools and resources to assess and mitigate safety risks. The research will integrate discovery and translational science, aiming to propel future advanced therapies into clinics.

Where justified, multiple partners can participate on either side of the partnership, with MRC funding academic costs of £2 million to £4 million FEC for up to five years. Equal contribution is expected by the business partner(s).

Who can apply

You must complete the mandatory expression of interest stage and be invited to the full stage. See ‘How to apply’ for more information.

Applications must be co-developed and led by an academic lead and a lead business project partner (the primary business partner in the partnership). Submission of applications will be undertaken through the UK Research and Innovation (UKRI) Funding Service by the academic ‘project lead’ (PL).

Who is eligible to apply

Research organisations can act as the academic lead if they are eligible to receive UKRI funding.

Businesses can act as the lead project partner if they are:

• a UK-based business or have UK-based research activity
• a business in the private sector driven by profit, or from an organisation with a commercial arm which generates independent revenue
• able to contribute to the UK national prosperity through increasing their investment in research and development activities and subsequent product, service, or technology development in the UK

Businesses may be a contributor to other applications as a project partner. Other businesses can collaborate in the partnership as project partners, but the majority of the matched contribution is expected from the lead business partner.

Before applying for funding, check the Eligibility of your organisation.

UKRI has introduced new role types for funding opportunities being run on the new Funding Service.

For full details, visit Eligibility as an individual.

A research organisation may lead or partner on more than one application and applications may comprise more than one research organisation.

For applicants who do not have a contract of employment for the duration of the proposed programme, by submitting an application the research organisation is confirming, if it is successful:

• contracts will be extended beyond the end date of the programme
• all necessary support for the programme and the applicants will be provided, including mentorship and career development for early career researchers

Who is not eligible to apply

You are not eligible to apply for this opportunity as academic lead if you are based at an international research organisation. This does not include MRC Unit The Gambia or MRC/UVRI Uganda Research Unit at the London School of Hygiene and Tropical Medicine that are eligible to apply as project lead. Before applying for funding, check the Eligibility of your organisation.

International applicants

You can include international applicants as project co-leads (international), where they will make a major intellectual contribution to the design or conduct of the programme. The contribution and added value to the research collaboration should be clearly explained and justified in the application.

Equality, diversity and inclusion

We are committed to achieving equality of opportunity for all funding applicants. We encourage applications from a diverse range of researchers.

We support people to work in a way that suits their personal circumstances. This includes:

• career breaks
• support for people with caring responsibilities
• flexible working
• alternative working patterns

Find out more about equality, diversity and inclusion at UKRI.

What we're looking for

Aim

Toxicity issues with advanced therapies (ATs) include, but are not limited to, immune reactions, off-target gene effects, and tumourigenesis. The long-term safety of many advanced therapies remains uncertain, with potential for unexpected toxic effects over time.

Therefore, advancing our understanding of how these therapies can be safely and effectively delivered to patients holds significant potential for breakthroughs, particularly in treating complex and previously untreatable conditions.

This funding opportunity aims to establish core resources and capabilities in advanced therapy toxicology for the UK, fostering connectivity among business, academia, and regulatory bodies, and gaining insights into the biological processes through which ATs can cause harm.

Research into the toxicity of advanced therapies, including the advanced therapy medicinal product (ATMP) classification of cell and gene therapies, regenerative medicine and nucleic acid therapies such as oligonucleotide base therapies and base or gene editing techniques, are all in scope.

Aims include modelling short and long-term adverse effects and translating research evidence into harmonised standards and definitions of future regulatory pathways. Additionally, this initiative aims to influence policy and standards in the AT sector and support skills and training in toxicology and regulatory science.

Prosperity partnerships should aim to address at least one of the following challenge areas in at least one area of advanced therapies:

• mechanisms governing safety and toxicology of ATs
• persistence, localisation and distribution of ATs in vivo
• translation of mechanistic insights into tools and assays, and development of a standardised approach to assessment of safety and toxicology of ATs

For more information on these three challenge areas see the Additional information section.

Prosperity partnerships funded through this initiative will be co-developed with academia and business addressing significant challenge areas in safety and toxicology. These partnerships will form a UK-wide network that goes beyond the individual partnerships, coalescing the field and providing both connectivity and critical mass.

The strategic partnership can be newly established or based on existing, long-term relationships. It should be recognised by both parties and have a clear path for future collaboration, possibly formalised by a memorandum of understanding (MoU) or a collaboration agreement.

The research programme must be co-created, driving shared research challenges, with both business and academic researchers making distinct intellectual contributions.

This is an expression of interest stage, and the information about the full application stage may change. You can only apply for the full funding opportunity if we have invited you to do so following a successful expression of Interest.

The full funding opportunity will open in November 2024. More information will be available on this page then.

Scope

Applications should articulate co-developed research programmes addressing clear challenges in safety and toxicology of advanced therapies, and clearly described business-academic partnerships.

Academic and business partner project leads should ensure that:

• the business and academic partners have a demonstrable emerging or established research-based relationship
• there are clear plans to evolve this relationship via shared research challenges and the prosperity partnership is a key component of the plans to evolve and strengthen this relationship
• partners are committed to the co-creation of a jointly delivered large scale research programme addressing a clearly defined key challenge area within the funding opportunity remit
• the business partners can commit to matching funding for the prosperity partnership with at least a matched contribution. This must consist of at least 50% in cash with a maximum of 50% of the matched contribution being in-kind
• a definitive list of eligible cash contributions is set out in the ‘Definitive list of eligible cash contributions for business leads and partners’ section
• no UKRI, public, or government funding will be used as co-investment, and the partners are able to clearly demonstrate an auditable transfer during the grant duration
• the lead business partner must be:from a business in the private sector driven by profit or from an organisation with a commercial arm which generates independent revenue
• the lead business partner must be in a position to contribute to the nation’s prosperity through increasing their investment in UK based research and development activities and subsequent product development in the UK

The following is the definitive list of eligible cash contributions by business partners.

We expect the time of researchers, research and innovation associates, technicians, and grant managers to be fully costed onto projects depending on how much time a person would spend on it.

In the application, it is expected that the role and responsibilities of costed persons are detailed, and it is demonstrated clearly how their experience and skills are linked to work packages and outcomes. The appropriateness of the time devoted to the project will be assessed at the full application stage.

Gross salary can be claimed as matched funding (that is, including indirect costs such as pension, National Insurance, and taxes) but not business overheads or profits. The salary of a single member of staff (researcher, research and innovation associate or grant manager) can be covered in partnership by the business partner and Medical Research Council (MRC) funds in a ratio that best suits the project.

Below we state the eligible cash contributions for business leads and partners.

Researcher salaries

All or part of the pro rata, gross salary cost associated with researchers employed by research organisations (including project co-leads).

Research and innovation associates’ salaries

All or part of the gross salary cost associated with research associates employed by research organisations to work exclusively on the prosperity partnership.

Research associates can also be employed directly by the businesses in the partnership and the appropriately costed gross salary can be claimed as a cash contribution depending on how much time the person spends on the prosperity partnership.

Professional grant manager salaries

Pro rata gross salary cost of a professional grant manager.

Technician salaries

Pro rata gross salary cost of technicians.

Software licences

New software licences needed for the project and their maintenance cost for the duration of the project. Software licences or intellectual property (IP) owned by the business which are already accessible by the partners will apply at marginal cost, not at market rate.

New equipment

Equipment essential for the successful delivery of the proposed research.

Items of multiple-use equipment (where the equipment is necessary for the pursuit of the proposed research but will not be fully occupied on it) may also be included.

The application must explain the other proposed uses and the overall benefit to MRC research of the equipment.

Equipment produced by the business

Equipment produced by the business is only claimable at the cost of manufacture (not market) rate.

Access to equipment and facilities

Access to specific equipment and facilities critical to achieve the outcomes of the project. If the facility is based at the academic or business partner’s facility, the cash contribution will be valued at cost.

Facilities development

Facilities development can be an eligible business cash contribution if the upgrade will increase the capability of the facilities with specific benefit to the proposed work. This contribution must be justified in addition to any estate costs already factored in. Any facilities development contributions require discussion with us prior to submission.

Business cash contribution

Business cash contributions which will be provided to the academic partners, for the academic partners to manage in line with the project objectives.

Skills and talent training

Skills and training activities such as higher apprenticeships, continuing professional development of the project’s research and innovation team, exchanges, and secondments.

For more information on the background of this funding opportunity, go to the Additional information section.

Duration

The duration of this award is up to a maximum of five years.

Funding available

The full funding amount of £10.5 million will be delivered in a single funding opportunity with programmes being up to five years. The academic full economic cost (FEC) of your programme can be between £2 million and £4 million.

MRC will fund 80% of the FEC and 100% of permitted exceptions

Find out more about full economic costing.

The business partner(s) must provide at least a matched (financial and in-kind) contribution to the programme.

What we will fund

MRC will fund the academic partner’s costs which can include:

• staff costs
• equipment and other items required to carry out the programme
• costs related to impact
• travel and subsistence
• skills and talent training costs

You can also request costs for work to be undertaken at international organisations by international project co-leads. We will fund 100% of the full economic cost.

The total of such costs requested for international applicants from high income countries (those not on the OECD DAC List of ODA Recipients), India and China must not exceed 30% of the total resources requested.

There is no cap on costs requested for international applicants from DAC list countries.

For more information on international costs and what we will and will not fund see costs we fund overseas and the Collaborate with Researchers in Norway guidance.

Supporting skills and talent

We encourage you to follow the principles of the Concordat to Support the Career Development of Researchers and the Technician Commitment.

Trusted Research and Innovation (TR&I)

UKRI is committed in ensuring that effective international collaboration in research and innovation takes place with integrity and within strong ethical frameworks. Trusted Research and Innovation (TR&I) is a UKRI work programme designed to help protect all those working in our thriving and collaborative international sector by enabling partnerships to be as open as possible, and as secure as necessary. Our TR&I Principles set out UKRI’s expectations of organisations funded by UKRI in relation to due diligence for international collaboration.

As such, applicants for UKRI funding may be asked to demonstrate how their proposed projects will comply with our approach and expectation towards TR&I, identifying potential risks and the relevant controls you will put in place to help proportionately reduce these risks.

Further guidance and information about TR&I, including where applicants can find additional support.

How to apply

We are running a mandatory expression of interest (EOI) stage to provide information to prospective applicants about the alignment of their programmes with the scope and remit of our opportunity. Download the EOI template (DOCX, 273KB) complete and send to prosperitypartnerships@mrc.ukri.org by 4:00pm, 6 November 2024.

We are running the full funding opportunity on the new UK Research and Innovation (UKRI) Funding Service so please ensure that your organisation is registered. You cannot apply on the Joint Electronic Submissions (Je-S) system. We will publish full details on how to apply when the full funding opportunity opens.

At the full application stage, applications will be submitted by the academic programme lead via the Funding Service.

Deadline

The expression of interest stage will close on 6 November 2024 at 4:00pm UK time.

The full opportunity is expected to open on 27 November 2024 and close on 12 February 2025. Please follow future announcements for confirmed dates.

Personal data

Processing personal data

MRC, as part of UKRI, will need to collect some personal information to manage your Funding Service account and the registration of your funding applications.

We will handle personal data in line with UK data protection legislation and manage it securely. For more information, including how to exercise your rights, read our privacy notice.

How we will assess your application

Assessment process

We will assess your application using the following process:

• a mandatory expression of interest (EOI) stage: consists of examination by an expert MRC panel and constructive feedback
• a full application stage: involves a review and shortlisting process by an expert panel, which will shortlist applications for the final interview stage
• an interview stage: conducted by an expert panel who will make a funding recommendation to Medical Research Council (MRC)

Expression of Interest

This stage is mandatory. Expression of interest (EOI) forms will undergo a preliminary review by a panel of experts. The aim of this review is to evaluate alignment with the funding opportunity’s remit and scope. Feedback will be provided to all applicants prior to submission of a full application.

Full application stage assessment and interview

Full stage applications will be assessed during a shortlisting meeting, where a subset of applicants will be shortlisted for the final interview stage. In this final stage, an expert panel will evaluate both the quality of the full application and the applicant’s performance during the interview. The panel will then make a funding recommendation.

We expect interviews to be held on 28 or 29 April 2025.

Principles of assessment

We support the San Francisco declaration on research assessment and recognise the relationship between research assessment and research integrity.

Find out about the UKRI principles of assessment and decision making.

We reserve the right to modify the assessment process as needed.

Evaluation areas for EoI

EoIs will be examined for their fit to the scope and remit of the funding opportunity using the following evaluation areas:

• vision: the extent to which the proposed work will achieve transformative impacts through a strong, co-developed vision, with clear short-term and medium-term benefits. Assessors will evaluate the potential and timeliness of the work, its alignment with the opportunity aims, and its capacity to impact research, society, and the economy
• additionality and added value: the unique added value and benefits of the prosperity partnership, including evidence of business partner buy-in and co-creation of the proposed research programme
• applicant and team capability to deliver: the leadership and team structure, including evidence of effective collaboration between business and academic programme leads where appropriate, and potential to manage a large, complex programme with diverse stakeholders

Contact details

Get help with your application

If you have a question and the answers aren’t provided on this page

IMPORTANT NOTE: The helpdesk is committed to helping users of the UKRI Funding Service as effectively and as quickly as possible. In order to manage cases at peak volume times, the Helpdesk will triage and prioritise those queries with an imminent opportunity deadline or a technical issue. Enquiries raised where information is available on the Funding Finder opportunity page and should be understood early in the application process (for example, regarding eligibility or content/remit of an opportunity) will not constitute a priority case and will be addressed as soon as possible.

Contact details

For help and advice on costings and writing your application please contact your research office in the first instance, allowing sufficient time for your organisation’s submission process.

For questions related to this specific funding opportunity please contact prosperitypartnerships@mrc.ukri.org

For general questions related to MRC funding including our funding opportunities and policy please contact rfpd@mrc.ukri.org

Any queries regarding the system or the submission of applications through the Funding Service should be directed to the helpdesk.

Email: support@funding-service.ukri.org

Phone: 01793 547490

Our phone lines are open:

• Monday to Thursday 8:30am to 5:00pm
• Friday 8:30am to 4:30pm

To help us process queries quicker, we request that users highlight the council and opportunity name in the subject title of their email query, include the application reference number, and refrain from contacting more than one mailbox at a time.

For further information on submitting an application read How applicants use the Funding Service.

Sensitive information

If you or a core team member need to tell us something you wish to remain confidential, email prosperitypartnerships@mrc.ukri.org

Include in the subject line: [the funding opportunity title; sensitive information; your Funding Service application number].

Typical examples of confidential information include:

• individual is unavailable until a certain date (for example due to parental leave)
• declaration of interest
• additional information about eligibility to apply that would not be appropriately shared in the ‘Applicant and team capability’ section
• conflict of interest for UKRI to consider in reviewer or panel participant selection
• the application is an invited resubmission

For information about how UKRI handles personal data, read UKRI’s privacy notice.

Additional info

Background

The Medical Research Council (MRC) is committed to supporting the development, scale-up, and delivery of advanced therapies (ATs) to patients. This initiative leverages MRC’s longstanding investment in toxicology and AT to facilitate the translation of discovery science into clinically relevant outcomes and to enhance skills in regulatory science for ATs.

Current safety and toxicological assessments do not adequately address novel medicines like ATs, restricting innovation and patient benefit. To overcome these limitations, the following three interconnected focus areas are needed:

• understanding the mechanisms influencing the safety and toxicity of ATs
• monitoring their persistence, localisation, and interactions in vivo
• developing tools and assays to translate these findings into clinically relevant outcomes

Mechanisms governing safety and toxicology of ATs

A greater understanding of factors affecting safety and toxicology of ATs is needed. The recent demonstration of unexpected out-of-frame peptides by RNA-based medicines highlights the potential risk that insufficient safety assessment of these novel therapies presents, and therefore the need for more in-depth understanding.

ATs typically persist in the human body for considerably longer timeframes than traditional medicines, for example small molecules, and so understanding the pharmacokinetic (PK) and pharmacodynamic (PD) effects is critical but extremely challenging where the PK/PD of ATs is therapy, patient-specific, donor-specific or both and not reflected well by preclinical models.

Not all conventional pharmacokinetic parameters, for example absorption, distribution, metabolism and excretion, apply to advanced therapies or are sufficient to assess their safety. The safety and pharmacokinetics of cell therapies can be affected by factors such as recognition of healthy tissue, graft failure, graft versus host disease (GVHD), oncogenic potential or donor-related product attributes, migration from the target site (localised treatments), ectopic tissue formation (stem-cell derived products), replication, and triggering of unwanted immune responses.

For gene therapies and gene editing techniques, there is a risk of random gene integration or unintended mutations. The consequences of these risks are not yet fully understood, but off-target gene editing can introduce mutations that may lead to tumourigenicity or uncontrolled cell growth, raising significant safety concerns. Although the toxicity profiles of gene and nucleic acid (NA) therapies have improved over the past decade, some therapies still pose risks of liver and kidney toxicity, which remains inadequately understood.

There is a need for more advanced and predictive in vitro and in vivo studies to better assess the risks of toxicity and tumourigenicity. Additionally, a deeper understanding of the types of mutations resulting from gene editing and their potential risks in gene and cell therapy products is necessary to establish acceptable limits within mutagenic profiles. For nucleic acid therapies, such as antisense oligonucleotides, safety is sequence-dependent, yet there is limited knowledge about how sequence changes or conjugation to delivery moieties affect their safety profiles.

For viral vectors, addressing the risk of inadvertent germline transmission or viral shedding is crucial. Concerns about genomic integration of vectors, including those like AAV which are generally considered non-integrating, pose risks that could undermine the success of these treatments. Additional toxicities include integration-site specific hazards, immunotoxicity, and for CAR-T cells, acute on-target/off-tumour, off-target, and neurological toxicities.

A better understanding of therapeutic thresholds, especially in CAR-T therapies, is essential and could be enhanced through improved modeling to determine tolerable levels of on-target/off-tumour toxicity. While mitigation strategies exist to reduce patient toxicity risks, clinical and preclinical safety approaches need to be strengthened, and knowledge should be shared across the AT landscape.

For all ATs, validated predictive biomarkers for toxicity of treatments remain essential to ensure greater and safer uptake. Linking human based in vitro systems with clinical expertise and patient organisations is key to achieving these outcomes.

Persistence, localisation and distribution of ATs in vivo

The disposition and persistence of any therapeutic product must be understood before administering the first dose to humans. This is essential in all AT development, as even a single dose of an AT can persist for months or years, and gene therapy products could potentially remain in the body for life. The persistence of cell therapies can vary between patients, necessitating real-time monitoring.

A shortage of appropriate model systems and techniques to study the localisation of ATs over time in vivo is a major barrier to their development. Development of suitable imaging technologies to track and monitor ATs would therefore be advantageous. The sector needs more physiologically relevant large animal models, including pig and sheep, as well as access to suitable facilities to perform these experiments. Development of agreed model systems and knowledge sharing across the sector is key to proactively streamlining the regulatory pathway.

Translation of mechanistic insights into tools and assays, and development of a standardised approach to assessment of safety and toxicology

It is critical for the field to generate underpinning biological evidence that will improve patient safety and enhance regulatory decision-making across product lifecycles, supporting policy formulation and enabling agile and proportionate regulation.

The more permissive regulatory system in the UK continues to be a benefit to AT development, however, there is room for improvement with potential for streamlining. Indeed, there is an increasing focus by the Medicines and Healthcare products Regulatory Agency (MHRA) on promoting regulatory science. There are opportunities to work with the Agency for mutual benefit to generate essential reference standards needed by academia and business alike, and to streamline and actively promote the translational and regulatory path. Connecting these insights with regulatory experts and recent Innovate UK investment in Regulatory Innovation Networks would be beneficial.

Overall, this investment in the safety and toxicology of ATs aims to create a robust framework that ensures these innovative treatments are safe and effective. This involves building a strong foundation in toxicology research, fostering collaboration across sectors, and continuously improving safety assessments to keep pace with advancements in therapeutic technologies.

Additional disability and accessibility adjustments

UKRI can offer disability and accessibility support for UKRI applicants and grant holders during the application and assessment process if required.

Webinar for potential applicants

We will hold a webinar on 10 October 2024 at 11:00am. This will provide more information about the funding opportunity and a chance to ask questions.

Register for the webinar (passcode: 11223344)

Research disruption due to COVID-19

We recognise that the COVID-19 pandemic has caused major interruptions and disruptions across our communities. We are committed to ensuring that individual applicants and their wider team, including partners and networks, are not penalised for any disruption to their career, such as:

• breaks and delays
• disruptive working patterns and conditions
• the loss of ongoing work
• role changes that may have been caused by the pandemic

Reviewers and panel members will be advised to consider the unequal impacts that COVID-19 related disruption might have had on the capability to deliver and career development of those individuals included in the application. They will be asked to consider the capability of the applicant and their wider team to deliver the research they are proposing.

Where disruptions have occurred, you can highlight this within your application if you wish, but there is no requirement to detail the specific circumstances that caused the disruption.

Supporting documents

Expression of interest template (DOCX, 273KB)