2021-03-31-accounts

FRAME Annual Report

www.frame.org.uk | [e-mail] | [phone]

2020-2021 1/24/22

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Word from FRAME Chair of Trustees

This past year we have passed a major milestone for FRAME, celebrating 30 years of the FRAME Laboratory in partnership with the University of Nottingham. We are incredibly proud of the FRAME Laboratory, which was the first dedicated research centre focusing entirely on human-based methods that will help replace animal research in the UK, but we are also aware that, although much has been achieved since FRAME was founded, there are still millions of animals in the UK and worldwide that are used in medical and scientific research, often without eliciting much, if any, progress to understand and cure human diseases.

In 2020, 2.88 million scientific procedures involving live animals were conducted in the UK alone. Whilst an immediate end to all animal testing is not possible without halting certain areas of medical research, we believe this number of animal experiments is unnecessary.

I am privileged to be a part of FRAME as Chair of the Trustees in advocating the 3Rs – Replacement, Reduction, and Refinement. Through these principles, we can help reduce animal suffering immediately as well as pave the way for non-animal methods to take the lead in the future.

We are working hard to push for a drastic reduction in the number of procedures involving live animals by focusing on four key pillars:

• Funding research – through the ongoing work of the FRAME Laboratory, our Summer Studentships and our brand-new Innovation Grants. We are at the forefront of creating, validating, and sharing non-animal methods.

• Sharing information – with our non-animal science-centred publication, ATLA, and our education and outreach work, we are sharing the importance of human-centred science around the world. Our Training School also continues to be a leader in training researchers on how to reduce and refine animal use in experiments where no non-animal methods are currently available.

• Creating change – we are working hard to promote non-animal methods within scientific communities around the world and influence positive changes in policy.

• Building resilience – we are passionate about our work and our vision for a better future, but we know change takes time. We are working hard to increase the resilience of FRAME and the sustainability of our funding, ensuring we will be around until we achieve our vision.

I hope you enjoy reading more about our work in these areas in this report.

Finally, I would like to say a huge thank you, to you - our supporters. We are immensely grateful to have such a warm group of advocates helping us through offering partnerships and providing donations and critical advice. We are honoured to be able to work on your behalf to create a future where non-animal methods are considered scientific best practice and animals are no longer used in medical or scientific research.

Together we can create a more humane world, benefitting animals and humans alike.

Dr Anna Cadogan, FRAME Chair of Trustees

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2

Welcome from FRAME CEO

The past year has been challenging year for us all, but one thing the COVID-19 pandemic has highlighted is the urgent need for good – by which I mean robust, reliable, efficient, and effective – science as well as the important role of information sharing and collaboration within both academia and the scientific industry. The search for possible vaccines and treatments has created an unprecedented level of openness in the research community and has shone a light on the alternative, non-animal technologies being used to gather data about the virus.

Throughout the pandemic, FRAME’s work to research alternatives to the use of animals in medical and scientific research, education and testing has continued, and we cannot thank our supporters and corporate sponsors enough for their continued support, interest, and enthusiasm for our vision of a world where nonanimal methods are accepted as scientific best practice.

Despite the challenges of the pandemic, work in the FRAME Laboratory continued, with our scientists focusing on desk-based research when the lab temporarily closed due to lockdown. We’re proud that the FRAME Lab has worked on a number of successful, human-relevant projects this year, including developing an in vitro model to study chemotherapy-associated liver disease; collaborating with the University of Helsinki to investigate gut microbiota in IBS, and working with the MRC Versus Arthritis Centre for Musculoskeletal Ageing Research on a human dietary study.

Every year, FRAME delivers an annual FELASA (Federation of European Laboratory Animal Science Associations) accredited Training School, held in collaboration with the University of Nottingham. Due to the pandemic, the event moved online but the course was delivered successfully through live lectures and group discussions that encouraged interactivity and collaboration.

The pandemic also led us to make changes to our Summer Studentship programme, developed to support undergraduates in undertaking research projects in an area relating to the development of alternative methods. We anticipated that laboratory research projects weren’t going to be possible, so redirected the funds to other forms of research and were pleased to award three studentships looking at important areas of policy, practice, and regulation of animal research.

In June 2020, we revealed the results of our global study: ‘Fact or fiction? Mapping perceptions of animal testing ’ which we commissioned to understand current public attitudes and perceptions of animal testing and research for medical, chemical, and cosmetic purposes. Amongst its findings, the study revealed that the overwhelming majority of people (93.4%) think more needs to be done to replace and reduce the use of animals in testing and research. We’d like to say a big thank you to those who took the time to complete the survey – the information and insights we gathered will help to inform our outreach strategy and focus our key messages for the public, the education sector, policymakers, and businesses.

The events of this year will hopefully allow gains from animal research to be evaluated, alongside the important contribution of non-animal methods, to assess the current state of animal testing and – crucially – influence a future without it.

Together, it is possible to improve outcomes for human health and prevent animal suffering.

Celean Camp

FRAME Chief Executive Officer

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Strategy and governance

Our vision

Our vision is a world where non-animal methods are accepted as scientific best practice.

Our mission

Our mission is to support the timely development and implementation of scientifically valid methods which will provide reliable data and replace the need for animal experiments in medical and scientific research, education, and testing.

Our values

To help us to achieve our vision we have a clear set of values that help guide us in the work we do and the decisions we make. Our values are:

• Brave - we inspire change, by questioning and constructively challenging the use of animals in scientific and medical research.

• Thoughtful - our approach is research-led and considered, using expert scientific sources to demonstrate that humane and human-focussed science is better science.

• Collaborative - we work with academics, industry scientists, policymakers, and regulators. We don’t dictate, berate, or preach; we stand alongside those working within the sector to create practical solutions for better human health.

• Resourceful - we act prudently and creatively, using our resources strategically to create maximum impact.

• Supportive - we are supportive of our staff and community, open to new ideas and viewpoints and loyal to our supporters and partners. We seek to inform, inspire, and nurture the next generation of researchers.

Our strategy

FRAME works to achieve its goals via the following strategic areas of activity:

• Funding research - To ensure scientific methods for biomedical research that improve upon the use of animals continue to be developed and implemented.

• Sharing information - To ensure that information about non-animal methods, how to find, and how to use them is disseminated and shared as widely as possible within the scientific community at all levels.

• Creating change - To actively promote uptake of non-animal methods, ensure that barriers to adoption are reduced, and engage in constructive challenge around the inherent problems of animal models.

• Building resilience - To ensure that FRAME is a sustainable and resilient organisation with sufficient skills, support, and income to continue its work in the long term.

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Strategy and governance

FRAME believes that the use of animals in research has always been scientifically questionable, and there is a growing evidence base supporting this view. Combined with the development of better alternatives and changing attitudes towards animals within society, we believe that animal research should now not be considered appropriate for the majority of research into human diseases and their treatments.

The current system of research, funding, regulation, discovery, and publication has evolved around the requirements for animal research and attempts to control and justify the use of animals. As a result, it can be difficult to make a change both at an individual and a system level.

We believe that lasting change needs to involve everyone – current and future scientists to embrace new methods, regulators to put more stringent requirements on animal research and enforce these, funders to encourage work that involves non-animal methods to build the evidence base, journal editors to ensure that high quality original research conducted in new ways can be shared and that where animal studies are published they are of high quality and reproducible, and the public to get involved in research and consider donating tissue or organs for scientific research.

Theory of change

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Funding research

The FRAME Laboratory

FRAME continues to provide the FRAME Laboratory at the University of Nottingham Medical School with an annual block grant to support the laboratory, staff and students in their research work using humanrelevant, non-animal methods. The experimental work carried out in lab marries excellent basic science with practical scientific alternatives to the use of animals in medical experiments.

Practical research at the FRAME Laboratory halted temporarily during lockdown and some students took up opportunities to support COVID testing facilities in the early stages of the pandemic. Laboratory research swiftly resumed under social distancing guidelines.

Despite the challenges of the pandemic, students continued to work on their PhD projects with two completing them. A study involving the FRAME Lab looking at time restricted feeding on insulin sensitivity in men as opposed to mice models was also published in the American Journal of Nutrition. Several other papers were worked on, and manuscripts written and prepared for submission, including work on scaffolds for growing 3D cell models, and liver injury models.

Work in the FRAME Laboratory is based around three key pillars:

• Neuroinflammation – The lab’s interest in neuroinflammation is driven by the significant influence it has on human health. Our scientists are building human-based models to allow them to figure out how and why neuroinflammation occurs with the ultimate aim of developing new treatments. The lab is conducting this research using induced pluripotent stem cells – stem cells which can be turned into cells such as neurones, astrocytes and microglia that can be combined to create a mini organ. The scientists also work on proteins with pre-identified drug targets that have shown promise at phase I and II trials for conditions such as Parkinson’s.

• The liver - The liver is an important focus of the lab’s research as there are currently no available treatments for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In NAFLD, fat accumulates in the liver. Over time, this leads to inflammation and then fibrosis – scarring of the liver. To model this process, the lab uses all the primary human cells involved in the liver, including hepatocyte cells, Kupffer cells, stellate cells and cells with liver disease (fibrosis), all derived from liver samples which are ethically sourced from hospitals in the East Midlands region. The lab is also isolating the cells that our scientists believe are adult stem cells and is growing and differentiating these to produce hepatocytes. Scientists then produce ‘scaffolding’ from donated human liver tissue that has had the original cells removed. New cells (healthy or diseased) can be inserted by our researchers to produce mini organs that can be used to investigate liver diseases, toxicity, and the effectiveness of potential drugs.

• Biomaterials - The lab is researching ways to produce 3D and 2D materials that will provide an ideal environment for building cells. One project includes the creation of electrospun scaffolds – a synthetic biomaterial that can mimic cell architecture found in the human body. This will improve the quality and accessibility of in vitro models as viable alternatives to animals across a range of research areas.

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Funding research

The FRAME Summer Studentship Programme is an annual initiative that offers grants to undergraduate students to allow them to carry out a summer research project in an area relating to the development of alternative methods.

Despite the ongoing COVID-19 pandemic, we were still keen to support undergraduate research projects. Lockdown meant that many grants for practical research projects had to be postponed, as students and supervisors were unable to carry out laboratory work. To ensure we could continue to support students, we decided to redirect the funds during 2020 to allow applications for desk-based research projects and reviews only.

We were pleased to receive a number of interesting applications for our revised grant call and to award three grants. The funded projects were:

The use of animal models in respiratory diseases research – Martina Bonassera, Cardiff University

Martina’s project looked at the use of Non-Technical Summaries (NTSs) to sustain the Replacement, Reduction and Refinement of animal use in Respiratory Disease Research. Her research found that in many cases the accuracy and transparency of the NTS was poor, but that changes to the EU requirements in 2020 had improved this. As the only publicly available source of information on what individual studies are being carried out on animals, the NTS is a valuable source of information, and also allows for independent scrutiny of the application of the licensing legislation. She concluded that studies that assess the quality of NTS reporting in different fields of research could be a valuable source of information not only for the general public but also for competent authorities and the whole scientific community.

Single species testing in pharmaceutical drug development – Caterina Dixon, University of Cambridge

Caterina’s project used bioinformatics (computer-based technology and tools for analysing and understanding biological data) to collate and analyse available biological data to identify specific physiological differences between animal species and the impact this has on their response to different drugs. Whilst her results were inconclusive, this project highlights possible avenues to create potential tools for assessing species relevance through the use of available data and suggests possible next steps.

Commenting on the experience, Caterina said: “ To put simply, I could not have done my project without FRAME. They have supported me throughout the process, giving advice, checking that the project was on track and making me feel like I was part of a group much larger than just me and my supervisor. I feel truly honoured to have been given a chance to conduct research in such a vital branch of science. Thank you FRAME for this opportunity.”

Tackling Alzheimer’s disease: how well do mouse models work? – Gréta Utassy, Cardiff University

Gréta’s project reviewed mouse models used in published Alzheimer’s disease research over the past decade. Gréta identified the strain of mice used in each project and used a scoring sheet to assess the physical and behavioural characteristics of the mouse strain in comparison to the presentation of Alzheimer’s disease in people. She concluded that whilst the mice strains may be relevant to particular research questions, none of the models used could accurately replicate all aspects of the disease, particularly the molecular changes seen in the brain resulting in the formation of plaques and tangles as seen in Alzheimer’s cases. Gréta also created a scoring system to assess the potential reproducibility of each study using criteria from the ARRIVE guidelines for reporting animal research. Ensuring animal studies are reported thoroughly and accurately is important for assessing the value of the research and the outcomes.

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Sharing information

Sharing information is a core element of our work at FRAME in our mission to replace the need for animal experiments in medical and scientific research, education, and testing.

This year, despite the global pandemic, we have continued to share information with key audiences who all have parts to play in helping us achieve our mission. We have also strengthened our resources to increase our capacity and enable us to do this more effectively moving forward.

Our goal was to disseminate information on non-animal research methods, how to find and use them, raise awareness of initiatives, issues and regulatory changes, and share training and funding opportunities within the scientific community at all levels.

This year we achieved this through:

• Sharing information with the public to raise awareness of our work in replacing animals in research and show donors how their gifts are being used to bring change. We shared local and global initiatives and relevant campaigns that increase voices pushing for a move to non-animal research methods, to educate and provide more insight and context to animal and non-animal research issues and how we can path the way to change.

• Sharing information with future scientists, regulators, and decision makers to raise awareness of modern non-animal technologies, the 3Rs, research ethics, good experimental deign and increase knowledge of the regulatory framework for using animals in research, how to find and use alternatives and areas for improvement within the current system.

• Launching a new website . Following the appointment of FRAME CEO Celean Camp, FRAME started to evolve a new strategy and plan to ensure we had the correct people and infrastructure in place to facilitate the sharing of information with our audiences effectively and efficiently. As part of this, a project to create a new website began in summer 2020, with the aim of making information and resources more accessible to everyone. The website launched in February 2021.

• Researching and publishing a report on attitudes to animal testing . We commissioned a global survey with the aim of increasing understanding of public awareness and attitudes to animal research and gather insights that would inform FRAME’s future messaging. The report: ‘Fact or Fiction: Mapping perceptions of animal testing’ was published on the FRAME website in June 2020.

Amongst its findings, the survey revealed that:

• 93% of the general public think more needs to be done to replace and reduce the use of animals in testing and research

• 52% of people think stopping the use of animals in all types of research and testing could happen immediately.

• 42% of people see greater funding of alternatives as the most important factor in helping to end the use of animals in testing and research.

• 75% of survey respondents see the pharmaceutical industry as the biggest user of animals for research and testing.

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Sharing information

• The findings of the research were cited later in 2021 in an open letter to the ECHA (European Chemicals Agency) in response to its decision calling for animal tests on chemicals for cosmetics use, and signed by over 400 companies and organisations from the cosmetics industry. The report was also referenced in global news coverage of the campaign, including articles in The Guardian, Elle, Harper’s Bazaar, and Business Telegraph.

• Developing our partnership with the University of Nottingham. Throughout 2020 and 2021 we have continued our partnership with the University of Nottingham and explored opportunities for expanding this in the future. We work closely with colleagues in the Centre of Applied Bioethics where we support the post of Research Fellow Dr Michelle Hudson-Shore to continue her work on joint projects such as the FRAME Training School in Experimental Design and other training provisions. We also continue to fund the FRAME Laboratory annually and maintain close links with Dr Andrew Bennett, the Director and supervisor of the PhD students and their lab projects.

• Delivering a virtual Training School. FRAME has held annual Training Schools in experimental design and statistical analysis of biomedical and bioscience experiments since 2008. These training courses are now held in collaboration with the University of Nottingham. Historically, these courses have been face-toface, but the pandemic meant that the 2020 Training School due to take place at the Moredun Research Institute had to be postponed. Following overwhelming support and interest in an online event, FRAME shifted the approach to deliver the training virtually in April 2021.

• Publishing Alternatives to Laboratory Animals (ATLA). We continued to publish our peer-reviewed, scientific journal ATLA in partnership with SAGE Publishing. In May 2020, Professor Judith Madden of Liverpool John Moores University was appointed as ATLA’s new Editor-in-Chief. In January 2021, Esther Haugabrooks (Physicians Committee for Responsible Medicine, Washington DC, USA), Helena Kandarova (Slovak Academy of Sciences, Bratislava, Slovakia), Winfried Neuhaus (Austrian Institute of Technology, Vienna, Austria) and Alicia Paini (European Commission, Joint Research Centre, Ispra, Italy) all joined ATLA as Associate Editors.

There were around 30,000 full text downloads from the SAGE/ATLA platform this year. The most frequently downloaded paper from the April 2020–2021 ATLA issues was a comprehensive review of in silico tools as alternatives to animal testing.

Authors of papers in the April 2020–2021 ATLA issues were from various countries, including India, the Philippines, Turkey, Egypt, the Netherlands, and the Czech Republic, amongst others. Papers featured a wide range of subjects, such as the environmental toxicity testing of hospital wastewater using in vitro methods; intestinal organoids; an evaluation of blood–brain barrier models; a lung inflammation model; and a critique of the use of animal models in psychiatric disorders.

Four Virtual Special Collections were launched in March 2021. These covered education and training resources; in silico tools; serum-free approaches; and biobanking. The aim is to create a platform of collated papers on these specific topics on the ATLA website. This will represent a valuable resource of information for a wide and varied audience, including research scientists, educators, policy makers and regulators.

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9

Creating change

FRAME promotes the use of non-animal methods through activities such as campaigning, funding and the publication of research, and through our educational work and resources. We promote robust scientific methods and available non-animal techniques and their benefits, to the current scientific community and scientists of the future.

Through our own research, FRAME is continually investigating and developing new methods at the forefront of science. We also collaborate with other organisations, industry, and laboratories across a wide range of biological and medical fields to help advance science and bring change.

Our goal was to promote uptake of non-animal methods, ensure that barriers to adoption are reduced, and engage in constructive challenge around the inherent problems of animal models.

This year we achieved this through:

• Supporting Home Office working groups. FRAME has a history of advising the UK government in the development of policy around the use of animals in science and the implementation of alternative methods. To this end, we remain a member of the Animal Welfare stakeholder group and attend meetings held by the ASRU (Animals in Science Regulation Unit) - the Home Office unit responsible for regulating the operation of the Animals (Scientific Procedures) Act 1986 (ASPA). As a result of this association, at the start of 2021, FRAME was asked to contribute to the ‘Future Capability Working Group’ set up by the Animals in Science Committee (ASC). The Animals in Science Committee (ASC) is a non-executive, non-departmental public body established under the requirements of ASPA to provide independent expert advice to ministers on matters relating to the welfare of species protected under the Act and their use in scientific procedures. FRAME completed and submitted two horizon scanning documents on key issues we felt would potentially impact the use of animals in research in the future. One summarised key concerns around GA (genetically altered) animal use in research, and the other the need to prioritise non-animal methods more robustly. We also took part in the follow-up workshops in 2021 alongside other invited attendees.

• Facilitating volunteering opportunities. Volunteers are key to the work of many charities, contributing to fundraising, events, and administrative tasks. Due to the nature of FRAME’s mission, it is essential that we stay abreast of changes in regulation, policy, training, funding and advances in research in order to share and signpost relevant content and news to the right audiences, as well as informing our own work. Following on from volunteering enquiries from people with the skills to help support these aspects of our work, FRAME took on a volunteer to support ongoing projects at the end of 2020 and an PhD intern at the beginning of 2021. The opportunity to engage with scientists and future policymakers early in their career and support the development of their knowledge and skillset is something we are passionate about. In the next few years, we aim to build our volunteer network and capacity to offer similar opportunities.

Jessie Hellier joined FRAME in November 2020 as a volunteer which successfully led to the full-time role of policy and projects intern. As a volunteer, Jessie supported our work around the 30[th] anniversary of the FRAME Lab and helped us to reconnect with our alumni around the world.

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• In February 2021, FRAME welcomed Margarita Kalamara, Molecular Microbiology PhD student at the University of Dundee, as an intern as part of the Professional Internship for PhD Students (PIPS) scheme, funded by the Biotechnology and Biological Sciences Research Council’s (BBSRC) through the East of England Bioscience (EASTBIO) Doctoral Training Partnership. The scheme provides students with the opportunity to carry out a work placement unrelated to their doctoral research during their PhD, to help early career researchers understand the context of their research and allow them to explore the range of opportunities in which they can apply their PhD skills and training after they graduate.

At FRAME, Margarita carried out a project reviewing the provision of experimental design and 3Rs training on PhD courses at universities across the UK, with the aim of identifying where improvements can be made and how FRAME can influence change.

Margarita's final report highlights large variety in mandatory and optional training provision between universities and institutions.

Commenting on the opportunity, Margarita said: “Being able to work as part of a charity that does such important work has been fantastic. Not only have I learnt about the field of researching and promoting alternatives to animal methods, but I have also experienced what it is like to work in the third sector. Having the chance to explore alternative careers to academia and learn about my areas of interest in the context of a Professional Internship is a great privilege and I am very grateful to EASTBIO and everyone at FRAME for all their support.”

• Sustaining supporter and external communications. We continued to disseminate key news, views and updates via the new FRAME website and social media platforms including Facebook, Twitter, Instagram, and LinkedIn. Articles covered key areas of concern and interest for FRAME such as the use of GA animals, accelerating the uptake of alternatives, the impact of the COVID-19 pandemic on animal research and ongoing research projects in the FRAME Laboratory including diabetes and breast cancer. We also increased our email communication to subscribers, with e-shot updates issued twice a month.

In 2020, FRAME was approached by HelpFilm – a charity that provides free professional animations for non-profit organisations. Together, we produced an animation summarising our key mission to replace animal research and how we are trying to get there. The animation is available to view on ‘The Issue' page of our website.

In total, 35 news articles and blogs were uploaded to the FRAME website, and two issues of our print newsletter, FRAME News, were sent out to subscribers.

In October 2020, FRAME’s thought leadership article, ‘Human models for human drug development’ was published in Drug Discovery World – one of the leading sources of drug discovery and development news. The article questions why the outdated practice of using animals has not yet been sufficiently challenged, discusses the need for a shift in ‘replacement’ thinking, and explores what needs to be done to make responsible, reproducible, human-relevant approaches a first choice for research teams across industry and academia, as well as the part industry insiders can play.

• Recruiting new expertise to FRAME’s Board of Trustees. In June 2020, we appointed Dr Carol Treasure, founder and CEO of specialist animal-free contract testing laboratory, XCellR8, to our Board of Trustees. The appointment of Dr Lesley Gilmour, the Named Training and Competency Officer (NTCO) at the University of Glasgow, closely followed. The Board provides strategic direction and governance and works alongside the FRAME team that is led by CEO Celean Camp.

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Building resilience

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Change in investment values - £182,982
£24,645
£51,675
£0
£24,857 £209,700
Total income:
£35,417 Total expenditure:
£480,110
£310,256
£343,516
£217,420
£66,118
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We know that the effects of the COVID-19 pandemic have been far-reaching and have caused financial challenges and hardship for many. We’re extremely grateful to those who have continued to support us this year, and in particular our generous legacy donors who have helped sustain us for more than 50 years.

We rely entirely on donations and gifts to carry out our work, and appreciate each and every donation we receive.

This year, we have made a number of key investments to ensure that FRAME is a sustainable and resilient organisation with sufficient skills, support and income to continue its work in the long term.

These include:

• Appointing FRAME’s first Fundraising Manager – Catriona Sinclair joined FRAME as Fundraising Manager in January 2021 to build on our engagement and outreach work and strengthen relationships with stakeholders. Catriona is responsible for generating income for charitable activities and keeping in regular contact with the charity’s donors and supporters, as well as connecting individuals, businesses, and other organisations with FRAME’s work.

• Launching a new website – In 2020, the appointment of Celean Camp as CEO, along with the onset of the pandemic, provided the ideal opportunity for us to review FRAME’s marketing strategy and identify new opportunities and ways to engage with our target audiences. It was quickly identified that our existing website didn’t provide the necessary functionality to allow FRAME to grow and adapt to new pressures and challenges. Working with marketing and PR agency V Formation and digital agency Frogspark, we developed a new website with the aim of effectively engaging, educating, and facilitating the conversation around animal testing and alternatives. Since the website’s launch in February 2021, we’ve seen an increase in traffic and engagement, with the number of website visitors increasing and users spending more time on the site.

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Looking to the future

As we look ambitiously to the future, we are focused on increasing the sustainability of FRAME by diversifying our income streams, to reduce our reliance on legacies.

We will continue to strengthen our leading partnership with the University of Nottingham, including sustaining our annual grant to the FRAME Laboratory to support staff and students in their research work using human-relevant, non-animal methods. By doing this, we are able to increase the global reach and impact of our work, creating real, tangible change by reducing the number of animals used in medical and scientific research.

In addition to funding laboratory work, we will be expanding our current education and outreach efforts through the provision of educational resources for secondary schools. We also aim to conduct key research projects to uncover the underlying issues that are blocking the adoption of non-animal methods within scientific and medical research, including a survey of researchers working in academia and industry.

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Thank you

We would like to say a huge thank you to all our collaborators, donors, partners, and supporters. Without you we could not have achieved what we have this year, and we would not be able to continue working towards our goal to replace animals in scientific and medical research and testing.

FRAME is extremely grateful to the following people and organisations for their support:

• University of Nottingham

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FRAME Annual Report 2020-21

Fund for the Replacement of Animals in Medical Experiments www.frame.org.uk Registered charity number: 1176266

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FRAME, Cawley House, 149-155 Canal Street, Nottingham, NG1 7HR UK

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REGISTERED COMPANY NUMBER: 1176266 (England and Wales) REGisfERED CHARITY NUMBER: 1176266 Report of th• Trustees and Unaudlted Flnanclal Statements for the Year Ended 31 Marth 2021 THE FUND FOR THE REPLACEMENT OF ANIMALS IN MEDICAL EXPEIUME14TS (FRAME) CIO aayton & Brewill Chartered Accountants Cawley House 149-155 Canal Street Nottin9ham Nottinghamshl NGI 7HR

THE FUND FOR THE REPLACEMENT OF ANIMALS IN MEDICAL EXPERIMENTS (FRAME) CIO Cont•nts of th• Flnandal Ststements for the year end¢d 31 March 2021 P•qe R•port of th• Truste Znd•p•nd•nt Examln•r'• Report Statement of Plnandal Actlvltl•s 8•lance Sh••t C•8h Flow Stat•ment Not•• to the Ca*h Flow Ststement Not•J to th• Flnandal 5tatem•nts 9 to 18 Deta11￿ Stat•ment of Flnanclal Actlvltl 19 to 20

THE FUND FOR THE REPLACEMENT QF ANIMALS IN MEDICAL EXPERZMENT5 (FRAME) CIO Report of the Trustees for the year ended 31 Mar¢h 2021 The trustees who are also dlrectors of the tharity for the purposes of the Companles Act 2006, present their report with the financial statements of the charity for the year ended 31 March 2021. The trustees have adopted the provisions of Atcountlng and Reportlng by Charities: Statement of Recommended Practice applicable to charities preparing thelr accounts in attordance with the Financlal Reportlng Standard applicable in the UK and Republlc of Ireland IFRS 1021 (effective l January 2019). 08JECTIVES AND AcfivTrIes Objectlves and alm• The charltable objecknves of FKIME, as stèted in the 1969 Trust Deed. are: To promote the menral and moral Improvement of manklnd by worknng to relieve the sufferlng to anlmals when being used to assess adverse human reathons In medlcal, blolo9lcal. pharmaceutical ond other assoclated researches. To promote or asslst in the prov151on ol research Into acceptable new technlques and substitut8s for the use of anlmals In such medlcal, biological, phorynaceutical ond other assodated researches and promote the publicatSon Jnd dlssemlnatlon of the results such ￿search conducted by and in aSs￿latIOn with thè Charlty and to hlghllght and comment on such researth condurted by others. The charlty's fundamental alm Is to promote the embeddln9 of the 3Rs (Rauctlon, Reflnement and Replacement) in blomedlcal research and development. FRAME achleves Sts objectives through laboratory-based and olTice-based research Into non-anlmal r￿earch methods that enable safety testlng of chemlcals present in cosmetlcs, foodstufts, household products and pham)aceuticals. FRAME also is Involved In the valldation and ￿gUlatOry acceptance of these methods, that can also be used to study and understand human diseases and thelr treatment. The research. based largely In the FRAME ￿ternItjveS Lat)oratory {FAL) based In the Unlverslty of Nottlngham Medlcal School generates publScations In peer-revlewed scienUftc Journals and presentatlons at sclentyflc meetings. The Charlty publlshes Its own peer-￿vIeV￿d sdentlfic Joumal AT￿ (Alternatlves to Laboratory Animals). FRAME'S websltes, press releases and sodal media 4re the porta15 through whlch FRAME dlssemlnates It ctivitles and provldes èdvl¢e, consultancy and news servlces to industry, govemment, academia, and others interested In the fidd of athrnatives to Jnlmal testing. FRAME'S tralnlng schools offer trèinlng to research scientisvs expert •dvlce on experfmentsl design and 5tatlstlcal analysls to those undertakln9 animal procedures, In order to mlnlmlse the numbers of anlmals used and to maximlse the value of thelr studles. Slgnlflcant actlvltl Enclosed within published rep)rt. STRATEGIC REPORT STRu¢fuRE, GOVERNANCE A14D MANAGEME14T Governing document The charfty Is controlled by its 9ovemlng document, a deed of trust, and constitutes a Ilmlted., corDpanyi limited by guarantee, as defined by the Companies Art 2006. Recrultment and appolntment of new trustees The management of the CIO is the responslbillty of The Trustees who are elected under the tem)s of the trust deed. Trustees are elerted on the recommendation of fellow tnjstees and there must be at least four trustees at any one tlme, but no more than six. OryanlsatSon)I structur• The CIO is governed by Its knust deed. The Trustee5 exerdse ultimate control over The Fund for the Replacement of Animals In in Medical Experiments. work and activitles ensuring Its financlal and le9al responsibllities are property fulfilled. All Trustees give their Ume voluntarfty and ￿Ceive no direci financial or other benefits from the CIO. Page I

THE FUND FOR THE REPLAceMENY OF ANIMALS IN MEDICAL EXPERXMENTS {FRAME) CIO Report of the Tvustees for the Year•Thd￿ 31 March 2021 STRUCTURE, GOVERNANCE AND MANAGEMENT Indurtion Jnd tralning of new trust¢e$ The inductlon and training of trustees Is viewed as an ongolng process and ￿levant tralning opportunltles are brought to the attentlon of the board as requlred. Newly recruited trustees are offered an induction and training designe(l around thelr existing knowledge of The Fund for the Replacement of Animals in Medlcal Experfments and thelr role. Rl¥k management The trustees have a duty to Identfy and re￿e￿ the rlsks to whith the chartty Is exposed and to ensure ppropdate controls are In place lo provide reasonable assurance a9alnst fraud and error. REFEREPICE AND ADMINISTRATIVE DETAILS R¢g1St¢r￿ Compjny numhr 1176266 IEngland and Woles) R•9l¥tered Charlty number 1176266 R•gl*t•rod offl¢• Cawley House 149-155 Canal Street Nottlngham Nottlnghamshlre NGI 7HR Trustee• Professor D A Kendall (reslgned 30.9.2021) A Cadogan G Thomson Ireslgned 30.6.2021) M Newman {reslgned 30,6.2021) Dr C Treasure Chalr {appolnted 22.7.2020) Dr A Petrle {appolnted 27.1.2021} Dr L Gllmour (appolnted 22.7.2020) Ind¢p•nd•nt Ex•mln•r N F South FCA Clayton & Brewlll Chartered Accountants Cawley House 149-155 Canal Street Nottlngham Nottlnghamshlre NGI 7HR Soll¢ltorn Actons Sollcilors 20 Regents Street Nottlngham NGI 5BQ Bankers B?rclays Bank pk Nottingham Hlgh Street Branch PO Box 18 Nottlngham NGI 6FF Page 2

OF AN114ALS 114 MEDICAL EXPEIUMEMTS (FRAME) CIO forth• y••r •nd•d 31 M•rth 2021 Tha thirtty ao wored m th• 13th Oectsnbtr 2017 and was d¢xm•rt fty the to 30th June 20￿, On 30 2019. the trjnts d all iknds WKI aSXKlatd heid by unt￿￿rp(X0￿e￿l dwrki, Tl e¢s (rf Fund fr the Rep￿teM￿ (l Anlm•L8 Sn Mtsytil Expertrnerts (Chartty numbtr.. 259464) to the IrL¢Yrpyatrd tharfty, The FUNJ fw the Rep￿Cerne￿i of knlma15 In Mollcal Werfmtsits ao (tharlty Number. 1176266) Js port cltr fiThwl wmm•it ivfftn the tvrtl p•rtle& thLs 41 tt4rltai4e artfve5 th• crmi￿rnI partles J strnr• by order af the b)ard ¢1 tr￿t￿, •rxt 51gn&l on the boord¥ behalf by: the dlr•Ity5, on og•n- TriA

Independent Examlner's Report to the Trustees of THE FUND FOR THE REPLACEMENT OF ANIMAIS IN MEDICAL EXPERIMENTS (FRAME) CIO Independent examlner'$ report to the trust••s of THE FUND FOR THE REPLACEMEMf OF ANIMALS IN MEDICAL EXPERIMENTS {FRAMe) cro ('the Company,) I report to the charity trustees on my examlnatlon of the accounts of the Company for the year ended 31 March 2021. Responslblllties and basis of report As the tharity's trustees of the Company (and also its directors ft)r the purposes of company law) you are responsible for the preparation of the accounts in accordance wlth the ￿qu1￿MentS of the Companies Art 20061'the 2006 Art,). Having satisfied myself that the accounts of the Company are not requlred to be audited under Part 16 of the 2006 Art and are eliglble for Independent examination, I ￿pOrt in respect of my examlnatlon of yovr charlty's accounts as carded out under section 145 of the Charities Art 2011 I'the 2011 Act,). In carying out my examlnatlon I have followed the Directions given by the Charlty Cornmisslon under sertlon 145(5) Ibl of the 2011 Att. Independent oxamln•r's *tst•fflent Slnce your charity's gross Income exceeded £250,000 your examlner must be a member gf a Ilsted body. I can ¢onflrm that l am qualifled to undertake the examlnatlon because l am a reg1ste￿d member of FCA whlch Is one of the Ilstsd bodles. I have completed my examlnatlon. I conflrm that no matters have come to my attentlon In ,coynectlon wlth the exjmlnauon glvlng MÈ cause to belleve: accountSng records were not kept In respect of the Company as requlred by 5ertlon 386 of the 2006 Art: or the a¢counts do not accord wlth those records; or the accounts do not comply wlth the accountyng requlrements of settion 396 of the 2006 Act other than any requlrement that the accounts give a true and falr vlew which Is not a matter consldered as pèrt of an independent examination: or the accounts have not been prepbred in acwdance wlth the methods and prfnclples of the Statement of Recommended Practke lor accountin9 and reporting by charities (applicable to tharlti'es preparlng thelr accounts In attordance with the Thnanclal Reporting Standard applicable In the UK and Republlc of Ireland IFRS 102)). I have no concems and have come across no other rnatters In connecdon with the examlnatlon to which attentlon should be drawn In this report In order to enable a proper understJnding of the accounts to be ached. N F South FCA Clayton & Brewlll Chartered Accountants Cawley House 149-155 Canal Street Nottingham Noitlnghamshlre NGI 7HR Page 4

THE FVt4D FOR THE REPLACEMENT OF ANIMALS IN MEDICAL ExPE￿mENTs (FRAME) CIO statement of Financlal Attlvlile5 for tha year ended 31 March 2021 2021 Total funds 2020 Total funds Unrestricted funds Restricted funds Endowment funds Notes INCOME AND ENDOWMENTS FROM Donatlons and legacles 378.933 378.933 613,371 Other trading artlvltles Investment income 25.694 50,626 76,320 24.857 27,614 33,152 24,857 Total 404,627 50,626 24.857 480,110 674,137 EXPENDITURE 014 Rallng funds 66.118 66.118 65,705 Charltable actlvlti Untestrtct Grant ternatlve Research Publlcatlons Managemenl & Admln 19,287 5,000 202,700 19,287 5,000 202,700 16,582 200,000 28,788 213,783 157,099 3S,268 7,766 200,133 Total 450.204 35.268 7.766 493,238 524,858 Nel galnsl(losses) on investments 182,982 182,982 {130,291) NEr INCOME/(EXPENDITURE) 145.577) 15.358 200,073 169,854 18,988 Trnnsfer• between fund• 17 1,358 (1,358) Nrt mov•m•nt In funds (44.219) 14.000 200.073 169,854 18,988 RECONCILIATION OF FUNDS Tot41 lunds brought forward 575,559 78.966 848,272 1.502,797 1,483,809 TOTAL FUNDS CARIUED FORWARD 531,340 92.966 1,048.345 1,672,651 1,502,797 The notes form part of these f(nanaal Statements Page 5

EXPEIUMEKfs (FRAME) ao 31 M•rth 2021 )a 2020 Totsl fvnts fLffjds 14 32,813 92,966 ¥048,345 1,174.124 945,271 DEbtrMs Cbsh Jt l)ank and kn h•nd 15 74,462 603.438 74,462 603M38 24,394 4569,652 6T1,9 677,9 694,046 Awnts due 16 (179,373) (179,373) (136.520) 498,$27 498,527 557,S26 531.340 92,966 1,048,315 1,671651 1,502,797 NEf AS$E 531,340 92,966 1,048.345 1,6n,651 1.502,797 AINCffj 17 531,340 92.966 Z,0¢8,345 575,559 78,966 848,272 thywmtrt fvnds YOTAL FU14C4 1,672,651 1,502,797 The chJrltsblB Iwipary 15 ffjtIUed to ¢¥¢mp￿• fyom ll￿111 477 rf tre Cl￿wIeS kt 21 tho ywr 31 Mtrth 2021. Th¢ meml>trs hthp rKt rtquk¢d oxnpany to 1)i•ln an a￿1￿ rf Ils finandal 5t•tements tr the y¢ar •nded 31 March 2021 In acc¢Ydano Tnlth 476 c¢the Crynp•nles £t 2LX)6. The trustees Kknowlèjge thelr rEsp￿1￿1￿ ft (a) C￿t￿l¥￿ that chamtrblt c(¥npwry keeps that c(xnpty Settt6 386 and 387 dthe Companies Art 2006 arKI (b) prewlNJ fi￿ndal stottyT￿ glve a true fJlr the stjte Jffalr5 rf the charltèble as at the erKI cl wch ftmntsal year ar•J of ts Surplus for eJch flnandal ￿ar In aoJxd•nce wlth ￿u$r￿￿$ rf Secttsts 394 Ind 395 whlth r*,Ivy t￿npty wlth the reoulremerts Ctynpanfes Act 2(K6 relatlrYJ to fl￿ndal statwnents, 9) far as awknble trj the rhrltslJl• LThlPJry. and were on tts ty:

THE FUND FOR THE REPLACEMENT OF ANIMALS IN MEDICAL EXPERIMENTS IFRAME) CIO Cash Flow Statement for the year ended 31 March 2021 2021 2020 Notes Cash floTJVS from operating actlvltl•s Cash generated from operations (37.434) 168,957 Net cash {used In)Iprovlded by opernting artovlties (37,434) 168,957 Cash flows from Invertlng artlvltl Pvrchase of fixed asset investments Sale of flxed asset Investmenrs (1,013,275) 967,404 {493,9S5) 484,872 Net cash used In Investlng artlvltles (45,871) 19,0831 Cash Ilow• from flnanclng •thltl Income attributable to endowment Expendlture attrlbutable to endowment 24.857 (7,7661 44,151 110,4951 Net cash provlded by ftnanclrig actlvities 17.091 33,656 Change In <a$h and cash equlval•nts In the r•portlng perlod Cash and cash equlv4lonts at the beqlnnlng of the reportlng perfod (66,2141 193,530 669.652 476,122 Ca•h and ¢ash equlval•nts •t th• end of the r•portlng p•rlod 603,438 669,652 The notes form part of these financlal statements Page 7

THE FUND FOR THE REPLACEMENT OF ANIMALS IN MEDICAL Expe￿MENTs (FRAME) CIO Notes to tho Cash Flow Statement for th• year ended 31 March 2021 RECONCILIAllON OF NEf INCOME TO NET CASH FLOW FROM OPERATING ACTivrriES 2021 2020 Net In¢)m¢ for the reporting p•rlod (as the Ststement of Flnanclal A¢tivltl¢#) Adjustments for: Depreclatlon charyes IGaSnl/losse5 on Investments Income attributable to endowment Expendlture attributsble to endowrnent {Increase)Idecrease In debtors Increase In creditors 169,854 18,988 230 130.291 (44.151) 10,49S 41,135 11,969 (182,982) 124,8571 7,766 (50,068) 42,8S3 N•t ¢•h (u•4d In)/pro¥lded by op•r•llons (37,434) 168,957 ANALYSIS OF CHANGes IN NET FUNDS At 1.4.20 Cash flow At31.3.21 N•t cash Cash at bank ond In hand 669,652 (66,214) 603,438 669,652 166,2141 603,438 Total 669,652 166,2141 603,438 The notes fomi part of these finandal statements Page 8

THE FUND FOR THE REPLACEMEKr OF ANIMALS EN MEDICAL EXPERIMENTS (FRAME) CIO Notes to the Flnancial Statements for the ye•r endèd 31 March 2021 ACCOUNTING POLICIES Basls of preparlng the flnanclal st¥tem•nts The flnancial statements of the tharitable company. which is a public benefit entity unéer FRS 102, have been prepared In accordance wfth the Charfties SORP (FRS 102) 'Accounting and Reportlng by Charlues: Statement of Recommended Practice applicable to thjrities preparlng thelr accounts In attordance wlth the Flnandal Reportlng Standard appllcoble In the UK and Republ1¢ of Ireland IFRS 1021 {effectlve l January 2019),, Ananclal Reporting Standard 102 The Flnancial Reportlng Standard applicable In the UK and Republic of I￿land, and the Companies Act 2006. The financlal statements have been prepared Lbnder the hlstorScal cost convention, with the exceptlon of Investments which Jre induded at market value. as modified by the revaluatlon of ￿rtain assets. InMm• All Income Is recognlsed In the Ststement of Flnandal Activrties once the cha￿ty has entitlement to the funds. It Is probable that the Income wlll be recelved and the amount can be measured reliably. Exp•ndltur• Uabilities are recognlsed as e¥penditvre as soon as there Is a legal or constrnctlve obllgatlon commlttlng the cha￿ty to that expendlture, ￿ Is probable that a transfer of econom5c benents wlll be requlred In settlement and ttbe amount of the obllgatlon can be measured rellably. Expendlture Is accountesy for on an accruals basis and has been dassified under headlngs that a99￿gate all cost related to the category. Where costs cannot be d1￿ctlY att￿buted to particular headings they have been allocated to activitles on a basls con515tent wlth the use of resources. Grants offered subject to condlttons whlch have not been met at the year end date are noted as commltment but not accrued 45 expendlture. TaThglbl• fixed JHets Depreclatlon Is provlded at the followlng annual rates In order to write off each asset over Its estlfflated useful Ilfe. Computer equlpment 33% on cost T•x•tlon The charfty Is exempt from corporètlon tax on Its thadtsbk artlvitle5. Fund ac¢ountlng Unrestricted funds can be used In accordance wlth the charltable objectlves at the dlscretlon of the trustees. Restrl¢ted funds tan only be used for parttcular restrlrte(1 purposes withln the objects of the charity. Restrictlons arlse when spedfled by the donor or when fijnds are raised for partlcular re5trfcted purposes, Further explanatlon of the nature and purpose of eath fund Is Included in the notes to th'è flnanclal statements. P•nsloTr costs and other post-retlrement bantflts The charitable company operates a defined contributlon pension scheme. Contributions payable to the charttable company's penslon scheme are charyed to the Statement of Financial Actlvlties In the period to whith they relate. Page 9 contlnued...

THE FUND FOR THE REPLACE14ENT OF ANIMALS IN MEDICAL EXPERIMEPITS (FRAME) CIO Notqs to the Flnanclal Statements - contlnued forth¢ year ended 31 March 2021 CIUTICAL AccourirING JUDGEMENTS AND KEY SOURCES OF ESTIMATIQN UNCERTAINTY Although the CIO does generate Income from tradino and invesbment artlvltles, the majority of its income Is from donations and legaaes. It 15 the￿fOre rellant on the the contlnued support of onors. There is no reason to suggest thèt this would change in the future, but the variable nature of donations wlll have an lrnpact of the level of future artlvltles that the CIO is able to carry out, DONATIONS AND LEGACIES 2021 Total funds 2020 Total funds Vnrestrlrted ReS￿rted funds fvnds Endowrnent funds Donatlons Glft ald Legades 33,688 1,729 343,516 33,688 1,729 343,516 56,471 1,554 555,346 378,933 378.933 613,371 OTHER TRADING ACTivrriES 2021 Total ftjnds 2020 Total funds Unrestrlcted funds Restrfcted funds endowment nds Fundralslng Publlcatlons 24.64S 1,049 24,645 51,675 26,947 67 50,620 25.694 50,626 76,320 27,614 INVESTMENT INCOME 2021 Total funds 2020 Totsl funds un￿$t￿Cted funds RestrJrte(I funds Endowment funds Investment income 24,857 24,857 33,152 RAISING FUNDS Ralslng donatlons and leg•cl 2021 Total funds 2020 Total funds Unrestrfcted funds Re5tMcted funds Endowment funds Travel and subslsten AdvertisSng Subscriptions Prlntlng Staff tralnlng and development Sundry 65 62,441 2,154 901 6S 62,441 2,154 901 405 57,210 2.973 1,547 557 557 3,006 564 66.118 66,118 65,705 Page 10 continued...

THE FUND FOR THE REPLACEMENT OF ANIMALS IN MEDICAL EXPERIMENTS (FRAME) CIO Notes to the Fln•n¢l)1 Ststements - contlnued for th• year ended 31 March 2021 CHARITABLE AcrJvtrIES COSTS Grant funding of actlvltles (see note 9) Dlrect Costs {5ee note 8} Totals Untestrlrt Grant ternatlve Research Management & Admin 17.287 2,000 5,000 202,700 19.287 5,000 202,700 200,133 200,133 217.420 209,700 427,120 DIRECT cosrs op CHARrrABLE AcfiviTIES 2021 2020 Staff costs Trustees, expenses PTlntln9 Postage 142,042 92,898 947 30,317 631 352 68 2.153 3,900 2,673 1.875 412 81 695 495 Statlonery sun￿￿e$ Travel and 5ubslstence Subscrlptlons Icr rnalntenance Tralning School consultancv Legal and professlonal fees Research and (flsseminatlon Telephone Rates Insurance Repairs Foreign exchange galnlloss VAT Attountsnq fees Independent examinatlon fees Bad debt wrlte off ATLA fees Depreciauon 538 2,923 15,300 8,195 1,251 649 18,526 419 980 463 3,002 532 {1,593) 20,243 27,118 6,760 20,000 2,805 31 21,128 14,700 4,300 230 217,420 255,474 GRANTS PAYABLE 2021 2020 Untestrjrt Grant ternatlve Research 2,000 5,000 202,700 (12.903) 16,582 200.000 209,700 203,679 Page 11 continued...

THE FVND FOR THE REPLACEME14T OF AN114ALS IN MEDICAL EXPERIMEKfs (FIiAME} CIO Notes to the Financlal Ststements- contlnued for the year endad 31 M•rth 2021 GRA14TS PAYABLE- wntlnu•d The total grants paid to institutlons during the year was a5 follows.. 2021 2020 Vnlversity of Nottingham BrLtnel UnSverslty Unlverslty of Cardlff Univtr%ty of Cambridge 202,000 214,790 1,792 5,000 2,700 209,700 216,582 10. NET It4COME/{EXPENDITURE) Net in¢omel{expendltu￿) is Stated after charylngl{ttedlUng): 2021 2020 Depreclatlon - owned assets 230 11. TRUSTEES. REMUNERATION AND BENeFIYS There We￿ no trustee5' rernunerjtlon or other beneflts for the year ended 31 March 2021 nor for the year ended 31 March 2020. Trurt¢••' •xpen••# There were no trustees, expenses during the year (2020: E947). 12. STAFF cosrs 2021 2020 Wage5 and salarles Social secu￿tY ¢osts other penslon ¢05ts 100,957 22,630 18,455 55,471 21,574 15,853 142,042 92,898 The average monthly number of ern￿OYeeS durirvj the year was ès follows.. 2021 2020 Charltable acuvltles No employees recelved emoluments in excess of £60.000. Page 12 contSnued.

THE FUND FOR THE REPLACEMENT OF ANIMALS IN MEDICAL EXPERIMEf4TS (FRAME) CZO Notes to the Flnanclal 5t•tsments- continued for the y￿r ended 31 March 2021 13. TANGIBLE FIXED ASSETS Computer equlpment cosr At l April 2020 and 31 March 2021 28,578 DEPRECIATION At l Aprll 2020 and 31 March 2021 28,578 NET BOOK VALUE At 31 March 2021 At 31 March 2020 14. PIXED ASSEr INVESTMENTS Losted Investments MARKET VALUE At i Aprtl 2020 Additions Disposals Revaluatlons 945,271 1,013,275 1783,4221 11,0001 At 31 March 2021 1,174,124 Nrr BOOK VALUE At 31 Marth 2021 1,174, 124 At 31 March 2020 945,271 There were no Investment assets outside the UK. Cost or valuatlon Jt 31 March 2021 Is represented by: U5ted Investments Valuatlon In 2021 Cost 40,389 1,133,735 1,174,124 Flxed asset investments are ￿presented by quoted investrnents ItSted on a ￿cOgnised stock exchange. Market value at 31 March 2021 was É1,174,12512020: £945,272). Historfcal cost at 31 Marth 2021 wa5 £1,133,735 {2020: £990,004) At 31 March 2021 the charlty's finanoal a55ets were held and managed by HSBC Premier Dlscretlonary Management. The full value of the portfollo managed by HSBC is £1,198,823 whlch includes a £24,698 cash balance. Page 13 continued...

THE FUND FOR THE REPLACEMENT OF ANIMALS IN MEDICAL EXPEIUMENTS {FRAME) CIO Notes to the Flnanclal Statsments- contlnued for the year ended 31 Marth 2021 15. DEBTORS: AMOUNTS FALL114G DUE WITH114 ONE YEAR 2021 2020 Trade debtors VAT Prepayments and accrued income 14.000 26 60,436 15,200 2,913 6,281 74,462 24,394 16. CREDrroRS: AMOUNTS FALUNG DUE wrrHIN ONE YEAR 2021 2020 Trade (￿dItO Sodal securlty and other tsxes Other credltors Accruals and deferred Income 111,945 4,532 8,200 54,696 57,929 2,689 7S,902 179.373 136,520 17. MOVEMENT IN FUNDS Net movement In funds rransfers between hjnds At 1.4.20 31.3.21 Unie8trlcted fund* General fund Tralning School Fund 543.989 31,570 (45,577) 1,358 499,770 31,570 575.559 (45,577) 1.358 531,340 Re•trlcted fund• Alternatlve Researth Fund ATLA Fund Do9s Prolert Fund Educatlon Fund PILAS Fund 13.523 2,925 20,299 (805) 43,024 (11,474) 26,832 11,474 112,8321 13,523 16,925 20,299 (8051 43,024 78,966 15,358 11,358) 91966 Endowrnent funds FRAME Bill Annelt Annual Lertu Fund FRAME Endowment Fund 50,000 798,272 50,000 998,345 200,073 848.272 200.073 1,048,345 TOTAL FUNI>S 1.502,797 169.854 1.672,651 Page 14 continued...

THE AIND FOR THE REPLACEMENT OF ANIMALS IN MEDICAL EXPERIMEi*fs (FRAME) CIO Notes to the Financlal Ststements - continued for tha year ended 31 March 2021 17. MOVEMENT IN FVNOS - eontinyed Net movement in funds. induded In the above are as folh)ws'. Incoming resources Resources expended Gains and losses Movement n fijnds Unr••trlthd fund• General fvnd 404.627 {450,204} (45,5771 Restrlrted funds Alternatlve Researth Fund ATLA Fund (Ll.475) 123.793) {11,474) 26,832 50,625 50,626 Endowment fund• FRAME Endowfflent Fund {35,268) 15.358 24,857 17.766) 182,982 200.073 TOTAL FUNDS 480,110 (493,238) 182,982 169,854 Comp•r•tlv•s lor mov•ment In lunds Net movement in fvnds At 31.3.20 At 1.4,19 Vnrestrlct•d fund• General fund Tralnlng School Fund 414,545 29,221 129.444 2,349 543,989 31,570 443,766 131.793 R•strlrted fund• Alternatlve Research Fund ATLA Fund Dogs Prolett Fund Education Fund PILAS Fund 575.559 815 18,764 20,299 1,145 43,114 12,708 (15.839) 13,523 2,925 20,299 18051 43,024 11,9501 (901 84,137 (5,171) 7&966 Endowmant fund¥ FRAME 8111 Annett Annual Lecture Fund FRAME Endowment Fund 50,000 905,906 50,000 798,272 (107,6341 955.906 (107,6341 848,272 TOTAL FUNDS 1,483,809 18,988 1,502,797 Page 15 continued...

THE FUND FOR THE REPLACEMENT OF ANIMALS IN NEDICAL EXPERIMENTS IFRAME) CZO Notes to the Flnancial Statements- continued for the year ended 31 March 2021 17. MOVEMENT III FUNDS- continued Comparative net movement in lunds, Induded In the above are as follows.. Incomln9 Resources expended Garn5 and losses Movement in funds Unr¢*trfcted funds Genernl fund Trainlng School Fund 612.392 2.936 {482,948) (587) 129,444 2,349 615,328 (483,535) 131,793 Rostrlrted funds Alternatlve Research Fund ATLA Fund Edueatlon Fund PIW Fund 12.708 12.949 12,708 (15,839} (1,9501 (901 (28,7881 (1.950) 190) 25,657 (30.8281 Endowment funds FKAME Endowment Fund (5,171) 33.152 (10.495) (130,291) (107,634) TOTAL FUNDS 674,137 (524,8581 (130,291) 18,988 A current year 12 months and prtor year 12 months comblned posltlon Is as follows: Net movement in funds Transfers between funds At 31.3.21 At 1.4.19 Unrestrfrted fund• General fund Trainlng School Fund 414,545 29,221 83,867 2,349 1,358 499,770 31,570 443,766 86,216 R•8trlrted luftd• Alternat￿t Research Fund ATLA Fund Dogs Projert Fund Educatlon Fund PILAS Fund 1,358 531,340 815 18,764 20.299 1,14S 43,114 1,234 10,993 11,474 112,8321 13.523 16,925 20,299 IB051 43,024 {1,950) (90) 84,137 10.187 Endowment FRAME Bill Annett Annual Lerture Fund FRAME Endowment Fund {1,358) 92,966 50,000 905.906 50,000 998,345 92,439 955,906 92,439 1,048,345 TOTAL FUNDS 1.483.809 188,842 1,672,651 Page 16 contlnued...

THE FUt40 FOR THE REPLACEMEKr OF ANIMALS IN MEDICAL EXPERIMENTS (FRAME) ao Notes to the Finanaal Statements - continued for the year ended 31 March 2021 17. MOVEMENT IN FUNDS- continued A current year 12 months and prfor year 12 months comblned net movement In funds, Induded In the above are as follows: Incoming Resources expended Galn5 and losses Movement In funds Unrestrlrted fund• General fund Tralnln9 School Fund 1,017,019 2,936 (933,152) {5871 83,867 2,349 1,019.955 {933,739) 86,216 R¢strlrted funds Alternatlve Research Fund ATLA Fund EducatSon Fund PILAS Fund 12.709 63.574 (11.475) <52,581} {1,950} (901 1,234 10,993 (1,9501 1901 76,283 {66,0961 10,187 Endowment fund• FRAME Endowment Fund 58.009 (18,261) 52.691 TOTAL FUNDS 1,154,247 (1,018.096) 52,691 196,842 Unrestricted Fund¥ The General fund covers the ordlnary day-to-day expendlture of the ¢h•rlty. The General fund Is able to benefft from the transfer of investment Income earned by the Endowrnent fund for any year, so as long as the transfer of such Income does not rèsult In the Unrestrtcted fund either maklng a surplu5, or a larger surplus, in the year In whkh the transfer Is mède. The Tralning School lund Is a Designated fvnd for the tharltable purpose of runnlng tralning courses In furtherance of FRAME'5 charttable acyvltles. Any 5urplu5es generated are relnvested in future courses. Re*tTlrted Pund• The Alternatlves Research fvnd is made up of donations given for the purpose of supporbng. . the sclentlflc research work carrled out or commlssioned by FRAME. The ATLA fund Is made up of donations given for the purpose of suppordng the publlcatlon of FRAME'S sclentlflc loumal Alternadves to Laborntory Anlmals. The Do9s Project ftind is made up of donations glven for the purpose of research into the use of dogs in medical expedments. The HLAS fvnd exlsts to promote actlve dlscusslon of dlfferent perspethves In the use of laboratory animals in medical experiments. Endowment Funds During the year ended 31 Mèrch 1989 the charlty established the FRAME Endowment Trust. The objectlve of this lund was to enable the charity to finance long temi research expendlture by investment income from the Endowment fvnd. rather than relylng largely on current year Income, Part of the fijnd's capltal has prevIou￿Y been used to purchase Russel & Burch House in oréer to reduce the chadty's regular expendlture. Since Its creatlon, the Endowment fund has benefitted, periodically. from the transfer of surplus unrestrfrted operations fund incorne. Such transfers have been made solely at the trustees, dlscretlon who have ￿tained the right to release these funds bad( to the General fvnd if required. Page 17 continued...

THE FUND FOR THE REPLACEMENT OF ANIMALS IN MEDICAL EXPERIMEpifs (FRAME) CIO Not•s to th• financlal Statements - continued for the year ended 31 14arch 2021 17. MOVEMENT IN FUNDS- continue The charlty has applled for and been granted perniissTron by the Charity Commlsslon to utilise the Endowment fund to assist with the cash flow of the d￿rity when requlred. The FRAME &ll Anrhett Annual lettu￿ Endowment Fund constitutes a non-expendable financ5al reserve, the Interest on which Is use(1 to contribute towards the charfty'5 Cost of holdlng the 5111 Annett Lerture (formerly the FRAME Annual Lecbjrel held for the flr5t tlme In September 1999, 18. CAprrAL COMMITMENTS 2021 2020 Contrarted but not provlded for In the flnanclèl statements 19. RELATED PARTY DISCLOSURES Durlng the year, the trustees declared that they had no potential confllcts of Inte￿5t. Page 18

ThE FUND FOR THE REPLACEMENT OF ANIMALS IN MEDICAL EXPERIMENTS (FRAME) CIO D•talled Statemerrt of financlal Artlvltl¢s for the year ended 31 March 2021 2021 2020 114COME AND ENDOWMENTS Donatlons and 1•9a¢i•* Donations Glft ald Legacles 33,688 1.729 343.516 56,471 1,554 555,346 378,933 613,371 Other tradlng actlvltles Fundralsing Publlcatlons 24.645 51,675 26,947 667 76.320 27,614 Investment Income Investment Income 24,857 33,152 Total Incomlng Msoure 480, 110 674,137 EXPENDITURE Ral•lng donatSon• and l•gacl Travel and subslstencè Advertlslng Subscriptlons Prfntin9 Staff tralnlng and development Sundry 65 62,441 2,154 901 557 405 57,210 2,973 I,S47 3,006 564 66,118 65,705 Ch•rftable actlvftlgl Trustees, expenses Wages Soclal securfty Penslons Prir)Ung Postage 947 55,471 21,574 15,853 30,317 631 352 68 2,153 3,900 2,673 1,640 11,L38 18,526 419 980 463 3,002 532 170,639 100,957 22,630 L8.455 1,875 412 81 695 495 StatSonery Sundrles Travel and subslstence Subscrlptions Icr malntenance Training School consultancy Legal and professronal fees esearch and dlssemlnatlon Telephone Rates Insurance Repairs Carried forward 538 2,923 15,300 8,195 1,251 649 2,805 31 177,292 Thls page does not forni part of the statutory financial statements Page 19

THE FUND FOR THE REPLACEMENT OF ANIMALS IN MEDICAL EXPe￿mENTs (FRAME) CIO Detalled Statement of Flnantial Artivities for the year ended 31 March 2021 2021 2020 Charitable artlvltl Brought forward Forelgn exchange gain/loss VAT Accountsnry fees Independent examlnatlon fees Bad debt wrfte off ATU fees Computer equlpment Grants to instStulion5 177,292 170,639 {1.593) 20,243 27,118 6,760 20,000 12,077 230 203,679 21,128 14,700 4,300 209.700 427,120 459,IS3 Totsl resources expended 493,238 524.858 N•t (expendltur¢)/ln¢ome befor• g•ln$ and losses (13.128) 149,279 Reall•ed rKognl$ed galns and 1088e• Realised galnslllosses) on fixed asset Investments 182,982 {130,29 11 Nrt In￿ffle 169,854 18,988 Thls page does not fomi part of the ststutory finanual statements Page 20