Since its inception, the UK Cystic Fibrosis Infection Biorepository (UKCFIB) has made significant strides in accelerating drug and diagnostic discovery efforts for cystic fibrosis (CF) lung infections. By uniting eight CF centres and associated laboratories across the UK, the biorepository has streamlined access to samples and expertise, including novel sample types from people living with CF.
The biorepository has brought together collections from multiple centres, providing access to more than 34,000 samples, supported over 20 innovators, and fostered important collaborations. It has also supported the development of bespoke strain collections and panels, provided essential guidance to the sector, and reduced time-to-sample, accelerating development timelines.
With its globally accessible collection of enriched samples from CF and non-CF sources, the biorepository serves as a key resource, supporting innovators in developing new therapies and diagnostic tools to improve the lives of people living with CF and other chronic lung infections.
Now, as we look to the future, the biorepository remains committed to enabling access to high-quality samples, data, and collaborative expertise to support researchers in advancing innovation in CF and beyond.
Connie Takawira, Partnership Manager, CF AMR Syndicate
1 | Introduction
The UKCFIB is a UK-wide network of laboratories dedicated to improving access to high-quality, relevant clinical samples and connections within the CF community. It is a critical resource that is accelerating global innovation in CF and chronic lung infection research.
CF is an inherited, life-limiting and progressive disease, affecting an estimated 162,000 people globally. Disease-causing mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene cause the production of thick, sticky mucus, which accumulates in multiple organs. In the lungs, mucus buildup traps pathogens, making people with CF vulnerable to recurrent lung infections. Over time, these infections become increasingly difficult to treat due to antimicrobial resistance (AMR). Chronic infections lead to a gradual decline in lung function, which has a drastic impact on quality of life for both people living with CF and their loved ones.
The numbers of antibiotics that I’m able to take is so limited. Having new treatments would take away a lot of my fears around what my health is going to look like going forward.
Sarah, who has CF
Innovation is urgently needed to provide more options to those who live with drug-resistant CF-lung infections, but developing treatments and tools to tackle AMR in CF is challenging.
CF lung infections are incredibly complex. They comprise polymicrobial communities of bacteria, fungi, and viruses and constantly evolve in response to antimicrobial drugs.
In recent years, the introduction of CFTR modulator therapies has added extra complexity to the CF clinical landscape. While these therapies have been highly effective in reducing the frequency and severity of lung infections, not everyone can benefit from them, and their impact on lung infections and lung microbiology remains to be fully understood.
Clinical samples for research and development
To demonstrate their effectiveness and move through the development pipeline, new treatments should be tested using clinical isolates that represent the infections currently affecting people with CF. While lab-adapted strains are useful for preliminary studies, they often fail to predict treatment outcomes for pathogens in the CF lung, which adapt in response to the complex environment. CF lung pathogens form biofilms embedded in thick mucus, coexist with polymicrobial communities of other pathogens, and frequently enter slowgrowing or dormant states. All these factors influence their susceptibility to treatment.
The same principle applies to diagnostics. For novel tools to be accurate and relevant in today’s diverse landscape of CF infections, they must be able to measure infection across different biospecimens. Traditional diagnostics for CF infections relied heavily on sputum. However, sputum is now much harder to obtain due to the success of modulator therapies in specific CF populations. As a result, alternative biospecimens, such as blood and urine, are becoming increasingly important.
For decades, innovators have faced difficulties accessing clinically relevant CF samples. More specialised collections and diverse biospecimens (i.e., blood and urine) pose an even greater challenge, especially those from people with CF who use CFTR modulator therapies or from the same person over time.
Although people with CF and their care teams work hard to make clinical samples available to advance research, administrative processes for obtaining samples can often be lengthy and complicated. This makes it difficult for researchers to access the samples they need, when they need them.
These factors slow innovation and highlight an urgent need for improved sample access and knowledge sharing in CF.
The UKCFIB was launched by the CF AMR Syndicate in 2021 to help address these challenges.
The CF AMR Syndicate supports innovators in academia and industry who have a discovery that could lead to a new therapeutic or diagnostic for people with CF. Underpinned by the Syndicate’s managing partners, Cystic Fibrosis Trust, Medicines Discovery Catapult, and LifeArc, it provides the expertise, resources, and tools needed to take an idea from development to the clinic. In doing so, it helps to combat the growing threat of AMR and improves care for people with CF.
2 | About the biorepository network
With funding from Cystic Fibrosis Trust, Antabio, and the Cystic Fibrosis Foundation, the UKCFIB was established in August 2021 to improve access to high-quality, clinically relevant CF samples, data, and expertise. The aim was to help innovators accelerate the development of novel antimicrobials and diagnostics for CF-related and chronic lung infections.
How does it work?
The biorepository is a network of eight laboratories in the UK that collect and store respiratory samples of both CF and non-CF origin. Each lab is connected to a specialised centre that holds clinics for adults and children with CF, as well as people who live with other chronic lung infections, such as bronchiectasis. Some people who attend clinics kindly donate samples such as sputum, blood, and urine. Samples are processed and made available for researchers to access, along with associated data and clinical information that would otherwise not be readily available.
Sample contributions from people with chronic lung infections are crucial to ensure that antimicrobial treatments and diagnostic research remain relevant and effective.
Access to samples and support
Through the CF AMR Syndicate, innovators who require samples for research can be signposted to the relevant centre holding the samples they need. A standardised Material Transfer Agreement (MTA) is in place to expedite the time it takes from enquiry to sample receipt.
Researchers can access:
• Bacterial and fungal isolates* from donated samples, often with associated pathogen genetic information and clinical data**.
• Sputum (frozen or whole) with associated clinical data**.
• Multiple isolates taken from individuals over time, which helps researchers to study pathogen evolution.
• Antimicrobial susceptibility testing, including combination testing in different formats and models.
Queen’s University Belfast
University of Liverpool
University of Cardiff Public Health Wales
University of Exeter
Medicines Discovery Catapult
Nottingham University NHS University of Cambridge
Imperial College London
*Isolates are individual pathogen strains that have been separated from a larger sample. Available isolates include but are not limited to: Pseudomonas aeruginosa, nontuberculous mycobacteria (NTM), Burkholderia cepacia complex, Aspergillus fumigatus, and Scedosporium apiospermum.
**Data could include information on lung function, frequency of exacerbations, any co-infecting pathogens, and drug history.
The funding partners:
Locations of the eight UKCFIB laboratories in the UK, plus Medicines Discovery Catapult, the coordinating centre.
3 | Our Community
When researchers access the biorepository, they gain access to more than just samples. Through the CF AMR Syndicate, researchers can access a unique, focused, and coordinated community, as well as the expertise, resources, and tools needed to take an idea through development to the clinic.
More than just a source of samples, the biorepository is a catalyst for innovation in CF, and beyond.
Collaborations and partnerships
Across many therapeutic areas, siloed approaches in research and development continue to be a barrier to progress. Innovators with new technologies can accelerate development timelines and gain visibility, which are key factors that attract investment, by collaborating with experts and leaders in the field who can help answer critical questions more efficiently. In some cases, innovators who accessed the biorepository have been connected to partners with specific expertise, forming collaborations which have advanced projects forward.
The connections we made through the CF AMR Syndicate have been invaluable for advancing our novel technology. Learning from experienced leaders with high-quality expertise and access to cutting-edge research tools helped us better understand our technology and accelerate its development. We’ve since applied for grants and published papers with our collaborators, which have helped with our credibility in the field, and we now have long-term partners that we can rely on whenever we have questions.
Patrick Grossman, CEO, Invitris
Read more about the impact of the biorepository on Invitris’ novel technology on page 13.
Keeping people with CF at the heart of research
People living with CF are central to the work of the biorepository, and their support has been essential to its progress. Members of the community have played an active role on the governance and advisory board, helping to oversee the biorepository’s function and contributing to its strategic direction. Beyond governance, people living with CF have also participated in and contributed to knowledge exchange events organised by the biorepository. By sharing their lived experiences, priorities, and needs with researchers, they help ensure that new medicines and diagnostic tools are developed with their perspectives in mind.
Biorepository management team
A management team was established to oversee the operation and direction of the biorepository. The team comprised principal investigators from each of the centres in the network, as well as people with CF and their loved ones. An advisory committee, comprising key opinion leaders and stakeholders from the UK, Europe, and the US, including industrial researchers, biobanking professionals, and people with CF, provided additional operational and strategic guidance to maximise the resource’s impact.
The biorepository is a unique resource that empowers innovators to overcome critical translational barriers by providing access to highquality samples and expert guidance. We’re proud to connect innovators with the tools and resources they need to bring cutting-edge technologies closer to the clinic for the people who need them most.
Connie Takawira, Partnership Manager, CF AMR Syndicate
CF families can often feel extremely isolated, and at times it can be difficult for us to appreciate that there is an entire landscape of people, each with their own history of infections. For me, it was wonderful to experience this team with the joint goal of sharing samples – each of which represents a person in a clinic being asked for yet another cough swab, or sputum sample, or blood draw – with a community of researchers working to improve the lives of people with CF.
I was very impressed by the team’s focus on the practical details of their work, from legal agreements to sequencing the samples, as well as the respect and value placed on them. Ultimately, as a parent, it gave me hope that eventually something positive can come from a tough day in the hospital, and that the samples we share are in good hands.
Gillian Flovell, parent of a child with CF and member of the biorepository management team
4 | Our Impact
Since launch, the biorepository has been instrumental in reducing barriers to research and development in the CF AMR field. Its support has enabled the advancement and translation of various discovery projects, from small molecule therapeutics and bacteriophages to novel diagnostics, across both commercial and academic institutions. Innovators who have accessed the biorepository have gone on to secure millions of pounds in funding to scale their research.
Pie charts show the organisation type, location and therapeutic modality of each enquiry. Enquiries include direct and indirect requests for samples and scoping enquiries to learn about what is accessible via the biorepository.
Key achievements
Key achievements
Through a series of strategic achievements, the biorepository has established itself as a high-value resource that meets the evolving needs of researchers, clinicians, and the CF community.
Simplifying access to samples from people with CF
Organisation
Geography UK
The CF AMR Syndicate succeeded in bringing together eight distinct CF laboratories across the UK, virtually, through a single access point and with a single point of contact. This has enabled better visibility of, and easier access to, clinical samples that would have previously been extremely difficult and time-consuming to source. Streamlined access has facilitated faster research progress, enabling studies to advance more rapidly and attract new sources of funding.
Thanks to the strains we obtained from the biorepository, we were able to set up reporter assays to discover novel antibiotic and antifungal compounds that are effective against some of the world’s most deadly pathogens. Additional clinical isolates have been invaluable in validating our hit compounds and give further confidence in their downstream development. These compounds have been crucial in demonstrating that our discovery pipeline works, and we have since secured over £5 million in dilutive and non-dilutive funding.
Anne Grijzenhout, Chief of Staff, Bactobio
Small
Further details on the indirect enquiries made to individual centres are not comprehensive.
Enriching and enhancing samples to meet evolving research needs
Since the introduction of CFTR modulator therapies, expectorated (coughed) sputum is less available, and infections within the lungs of people with CF are becoming increasingly diverse. As a result, there is a growing need for updated collections of samples and data that are reflective of this diversity to improve the relevance and impact of research.
To address these needs, centres in the network were supported with grant funding from Cystic Fibrosis Trust and Cystic Fibrosis Foundation. This funding enabled them to enrich and enhance their collections.
Some of the funded projects included:
• Validating alternative sampling methods and sample types to support diagnostics development.
• Enriching collections with more genetic information.
• Increasing the efficiency of sample processing.
• Testing the feasibility of sputum collection by post for the early detection of Pseudomonas aeruginosa.
• Optimising methods to extend sample preservation.
• Building collections of contemporary circulating isolates alongside associated genetic sequence and metadata from people taking CFTR modulator therapies.
These projects addressed key gaps, strengthened collections, and broadened the samples and data available to support more robust research and development efforts.
Empowering innovators with expert guidance on strain selection
Researchers working in CF are expected to use panels of common CF pathogens to test the efficacy of their novel antimicrobials, but designing a CF pathogen strain panel is complex. The optimal approach varies depending on the pathogen being studied, and there is no one-sizefits-all solution. This was recognised as an area where researchers would benefit from clearer, more consistent guidance to advance their research.
In 2022, leading experts from centres in the biorepository network, alongside other leading collaborators, published a strain selection report which provides best practice guidance to the sector on selecting appropriate strains for robust efficacy testing. The report also highlights priorities for future enrichment of samples and data relevant to CF antimicrobial drug discovery.
Five core principles for strain selection
The strain selection guidance document outlines five core principles and questions that should be applied when designing a robust efficacy testing panel for CF pathogens. These include:
1 What are my criteria and how many strains do I need?
2 Does this cover all relevant resistance phenotypes?
3 Will this be representative of species and strain population diversity?
4 Does it account for clonal variation, strain evolution and any adaptation to CF lung infection?
5 Can I validate my data, and will it be reproducible? (i.e., are samples accessible within a public collection or from a single curated source)
Read the strain selection guidance document here >
Simplifying efficacy screening with a bespoke mini-panel
In addition to providing strain selection guidance, the biorepository and the CF AMR Syndicate have developed and made available a bespoke, first-triage, preclinical strain panel for robust efficacy screening. This pathogen panel comprises diverse CF clinical isolates and reference strains, simplifying the path for innovators to generate early, clinically relevant efficacy data. The mini-panel is now available to support studies through the UK Health Security Agency’s (UKHSA) Open Innovation in AMR platform.
To learn how to work with UKHSA to evaluate the efficacy of novel therapeutics or other interventions using this panel, please contact UKHSA at: amr.screening@ukhsa.gov.uk
Reducing time from enquiry to fulfilment through process optimisation
When the biorepository launched, each centre had its own MTA. This meant that agreements had to be negotiated across sites when samples were acquired from more than one centre, which delayed access.
In 2023, the biorepository network successfully implemented a standardised MTA and cost recovery model. This reduced administrative and legal workflows for sample release, which in extreme cases could have taken over seven months, to less than two weeks. It also improved transparency and accessibility for researchers. These changes have driven efficiencies for both the cost centre and the innovator, enabling critical research to progress more rapidly.
The overarching MTA removed the need for repeated negotiations and lengthy legal reviews with each individual innovator. This has reduced administrative burden and enabled us to share clinical isolates in a more timely manner to accelerate R&D. In fact, we have recently sorted an MTA with a company in just under two weeks!
Michael Tunney, Professor of Clinical Pharmacy, Queen’s
University Belfast
Stimulating
knowledge sharing through running cross-sector events
The biorepository has played a crucial role in facilitating cross-sector collaboration and networking through various workshops and events. These gatherings have provided a unique platform for collection centres, clinicians, researchers, regulators, and people with CF to come together and engage with other stakeholders, fostering meaningful dialogue and driving progress across the community.
Through these interactions, participants have been able to discuss critical issues facing the advancement of research in CF lung infections, including strain and isolate needs for preclinical testing and evolving needs for diagnostic development. Output reports from these events summarise key takeaways, actionable recommendations, opportunities, and areas for further research.
Speaking about a cross-collaborative PIPE-CF* and biorepository joint workshop in 2022, attendees said:
The workshop provided a forum for researchers, industry, policymakers, and others to share views and ideas, which provided a unique perspective on CF research. This is invaluable, as it contextualises the research being carried out and gives clarity to the direction CF research will take.
Tom Barton, PhD student, University of Dundee
The biggest takeaway from the event for me was the general feeling among attendees that there is a disconnect between researchers and clinicians, and people with CF. It is important that researchers connect with the CF community frequently to ensure that quality of life for the patients can be maintained while effective treatments are delivered.
Hollie Leighton, PhD student, University of Liverpool
Read the PIPE-CF and UKCFIB 2022 workshop report here >
Read the Virtual Symposium on Diagnostics Meeting Report here>
*PIPE-CF is a Strategic Research Centre, co-funded by Cystic Fibrosis Trust and Cystic Fibrosis Foundation, focused on establishing best practices for accurately testing the effectiveness of new antimicrobial therapies for CF lung infections.
Impact in numbers
8
9
3 centres across the UK united with a single access point
24
24 research projects from across Europe* supported between 2021-2025
funded projects to strengthen collections and practices across the network scientific papers or reports published to support the community**
3
>34,000
samples curated from diverse respiratory disease populations
>3,000
>3,000 isolates supplied to support research and development efforts
new samples and sample types generated, optimised, or enriched with data
*Companies were based in the UK, Germany, France, and Switzerland.
**Includes: A meeting report for the virtual symposium on diagnostics for lung infections and exacerbations, a report for a joint workshop with PIPE-CF on current needs and future priorities for preclinical testing of antimicrobials for CF lung infections, and a guidance document for selecting relevant bacterial strains for novel therapeutic testing.
Read the meeting report here >
Read the workshop report here >
Read the guidance document here >
Impact in action: Advancing bacteriophage therapy in CF case study
Invitris is a leading biotechnology company based in Germany that is focused on advancing research and development in life sciences and medical technology.
The company developed a groundbreaking technology, called Phactory, which can generate synthetic bacteriophages and other proteins to combat different diseases in just a single step.
Barriers to Development
Whilst Invitris has a robust and promising platform, gaining access to the bacterial isolates, data and expertise required to validate the antibacterial effects of the bacteriophages it produced was challenging. This was especially true for contemporary circulating strains of Pseudomonas aeruginosa.
Engaging with the biorepository
Invitris engaged with the biorepository in 2021 to access the isolates they needed to build their data package. Through the biorepository, Invitris accessed:
• 20 currently circulating and multidrug-resistant P aeruginosa isolates from people with CF.
• Expertise on suitable chronic in vivo and biofilm infection models, through facilitated introductions to relevant CF AMR Syndicate network members.
The path to success
With the support of connections in the CF AMR Syndicate network and subsequent collaborations, Invitris has won several awards and secured over £5m in funding, enabling the company to expand its team and open its own laboratories and offices.
Invitris is now developing an automated printer for its bacteriophage platform, a novel technology that could soon make personalised bacteriophage therapy for CF a reality. Personalised therapy offers the potential to improve treatment efficacy and reduce the likelihood of resistance developing, ultimately improving the standard of care for people with chronic and multidrug-resistant lung infections.
Finding relevant clinical isolates with phenotypic data is a major challenge for companies like ours working to develop new solutions for cystic fibrosis and other infections. The biorepository and its connections have been instrumental in enabling us to screen our phages efficiently and secure investment. Thanks to this support, we’re now only a few years away from the clinic, where we hope to make a real difference for people living with chronic lung infections.
Patrick Grossman, CEO, Invitris
5 | Get in touch
Innovation to tackle chronic lung infections is urgently needed. With multi-drug-resistant infections on the rise and treatment options declining, the need for new solutions has never been greater.
The UKCFIB is a globally accessible resource built to support innovation. If you are working on solutions for chronic lung infections, we invite you to connect with us and explore how we can support your work, whether that be through access to clinically relevant samples, collaborative opportunities, or resources and expertise.
Statement on funding
Special thanks to Antabio, Cystic Fibrosis Trust, and the Cystic Fibrosis Foundation whose funding helped to establish the biorepository network and address key barriers faced by researchers working in CF. The biorepository remains available to researchers globally and has now expanded to facilitate signposting to the European Bronchiectasis Registry (EMBARC) and the UKHSA.
About the CF AMR Syndicate
The CF AMR Syndicate supports innovators in academia and industry who have a discovery that could lead to a new therapeutic or diagnostic for people with CF. It provides access to a unique, focused and coordinated community and the expertise, resources and tools needed to take an idea through development to the clinic. Underpinned by Cystic Fibrosis Trust, Medicines Discovery Catapult and LifeArc, the Syndicate addresses the unmet lung health needs of people with cystic fibrosis and helps discoveries go further in tackling antimicrobial resistance in chronic lung infections.
To learn more about the CF AMR Syndicate and how to join the uniquely focused and coordinated network, visit: cfamr.org.uk/
Get in touch
To learn more about the biorepository network, visit: cfamr.org.uk/toolkit/uk-cf-infection-biorepository/ OR cfamr.org.uk/contact/
