BIA Antibody Taskforce: setting up a consortium at pace in times of crisis

Eric Johnsson, former Policy and Public Affairs Manager at the BIA, tells the story of how a world-leading consortium was set up at the start of the pandemic and completed the fastest antibody discovery process ever run in the UK.

In March 2020, as the UK and the rest of Europe were in strict lockdown and COVID-19 hospital admissions were sharply rising, a group of experts across the UK came together under the BIA umbrella with the aim to do something that’s never been done before – set up a consortium of biotech companies, academia and charities to identify, develop and start dosing patients with neutralising antibodies in less than nine months to protect at-risk groups and avoid a new UK lockdown.

The consortium achieved its aims of discovering a developable pair of novel, potent antibodies to SARS-CoV-2 within seven months. At this stage there was a national change in emphasis to vaccination and efforts were paused until the necessary investment could be secured to enable the further development and clinical trials. Nonetheless, the Taskforce achieved many critical milestones and will leave behind an important legacy.

As the BIA lead on the Antibody Taskforce, in this blog I reflect on the key achievements of the group and the lessons learned from setting up a consortium, at pace, in times of crisis.

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Image: Biotech companies, academia and charities came together to form the BIA Antibody Taskforce.

Needed: Ventilators, vaccines – and antibodies

In the first wave of COVID-19 infections, there was an urgent need for ventilators and the development of safe and effective vaccines. At this stage, the BIA had already established a Vaccine Manufacturing Taskforce to support the manufacturing and scale up efforts for early vaccine candidates, including what later became the Oxford/AstraZeneca vaccine. However, the BIA community also recognised that even if a successful vaccine were to be developed (which in March 2020 was far from certain), there would be a strong need for effective antibody therapies to protect at risk groups and treat seriously ill patients.

A small group was rapidly formed under the leadership of Jane Osbourn, CSO at Alchemab and former BIA Chair, Paul Kellam, VP Infectious Diseases and Vaccines at Kymab, and Paul Varley, VP Biopharmaceutical Development at Kymab, to map out the UK’s antibody capabilities, explore what a BIA antibodies workstream could contribute to the global fight against the pandemic, and how it could be achieved. Early on, the group predicted that if they decided to push ahead, it would be a 24/7 endeavor and only have a tiny chance of succeeding.

A call for help

At a BIA webinar in March 2020, Jane announced that a BIA workstream on COVID-19 antibodies was being formed. Jane explained that the urgent need and importance required a culture of putting commercial considerations to one side. She highlighted that “there is a huge willingness to support by providing expertise, ideas and capabilities, not just from BIA members but from the broader life sciences community in the UK”.

At that webinar, my email was provided as the contact for which people could reach out. Soon, my inbox was flooded with offers of help from across the UK’s biotech community. It was amazing to see the willingness of companies large and small, academic groups and charities to help in any way possible.

Collaboration, fast

A core team was soon established in the form of a Steering Committee to provide governance and scientific oversight of the Taskforce. In addition to Jane and the two Pauls, it consisted of Deirdre Flaherty, VP Programme Management at Abcam; John McCafferty, CSO at IONTAS; Simon Henderson, Director of Toxicology and Non-clinical Safety at Kymab; Gavin Screaton, Head of Medicine at Oxford University; and me from the BIA. Members were added to the Steering Committee throughout the project to ensure the right expertise was available at the right points in time. For example, Christian Schneider, Director of the National Institute for Biological Standards and Control (NIBSC) (now Interim CSO at MHRA), was part of the Steering Committee at the start of the project and made valuable contributions to help it get off the ground.

Given the incredibly ambitious timeline, the only way the project had even a small chance of succeeding was through parallel working streams: one on the antibody discovery and identification, and the other on manufacturing. The workload in each team was phased to avoid redundancy. Both teams also worked with each other closely to ensure that the manufacturing could quickly start once promising antibodies had been identified.

Both workstreams were up and running extremely quickly. At this stage, there were no legal agreements – not even a non-disclosure agreement (NDA) – and crucially, there was no funding. None of that stopped the Taskforce members though, as the focus was purely on innovative and fast problem-solving.

Another key condition for the success of the project was an ongoing and open dialogue with regulators. For example, to meet the target of starting human trials within nine months, the antibodies used in the trials had to be manufactured much more rapidly than normal. Through open discussions with the MHRA, the manufacturing workstream could share their early thinking of how to rapidly manufacture antibodies without compromising safety, and receive ongoing feedback. This strong engagement from the MHRA enabled the project to progress at a much quicker rate than otherwise possible.

No funding? No problem… right now

As the Taskforce was pushing ahead with its work, the question around funding was becoming increasingly important. While the antibody discovery process was well underway, this is a relatively inexpensive process (but by no means insignificant when undertaken without commercial prospects) compared to the manufacturing for large-scale clinical trials. For the Taskforce’s antibodies to ultimately make a difference by reaching patients, we needed to secure sizable funding.

Despite engagement with potential funders, including the Government’s Vaccine Taskforce and the Therapeutics Taskforce, we were unable to secure funding for the manufacturing of large-scale trials. This meant that our aim of starting first in human trials by December 2020 would not be possible. While disappointing, the work of the discovery team to identify promising antibodies was going very well, so this temporary setback was no reason to stop.

Novel antibody candidates identified in record time

In October, the Taskforce announced that it had reached a major milestone – the identification of differentiated antibody combinations that would be taken forward for further development as an antibody cocktail.

The team had developed an accelerated and rigorous approach to create a pool of over 600 novel candidates and identified a set of antibodies with the greatest potential in record time. Rather than taking the industry standard 18 months for antibody discovery, the Taskforce did it in less than seven. In doing so, we not only had promising antibodies that had the potential to make a difference in the fight against COVID-19, but we had also established an accelerated pathway that can be applied in future pandemics.

This video created by the Taskforce explains what antibodies are and their role in beating COVID-19.

Meanwhile, the manufacturing workstream was developing plans for how the antibody candidates could be developed at even greater speed using transient manufacturing, which has the potential to go from gene to product in just two-three months. They secured funding from UKRI to run a feasibility project, which is currently on track to demonstrate proof of principle.

Mutation and evolution

The Taskforce knew that there was a risk that the virus would mutate, which was one of the reasons why a cocktail of two different antibodies was going to be taken forward. However, despite best efforts, the emergence of new variants in December 2020 meant that the novel antibodies previously identified would no longer be as effective.

While a second national lockdown was a fact, the vaccine rollout provided some light on the horizon. Rather than continuing with the plans to take the antibody candidates into the clinic, the Taskforce scaled down its activity and assessed the best way forward. There is a vital role for COVID-19 antibody-based therapies to play worldwide, and the Taskforce, like the virus itself, is now evolving, details of which will come in due course.

Legacy

While no longer active, the BIA Antibody Taskforce leaves an important legacy behind.

Through the rapid antibody discovery process, many lessons were learnt in how to run a consortium approach to drive drug discovery forward. Through the process, many companies in the Taskforce also made valuable scientific advances, some of which were recently published in Frontiers in Immunology.

The Taskforce demonstrated that revolutionary advancements in antibody manufacturing and regulatory approaches can be applied in pandemics and times of crises – and hopefully, in drug development generally. Antibody manufacturing technology and development will also play a key part in the Government’s considerations on how to scale-up the UK’s medicines manufacturing capacity.

Finally, the collaborative foundations established by the Taskforce remain. These are being currently leveraged to fight this pandemic and could act as a blueprint for the next health emergency. Next time, a consortium can be set up even faster. 

Final thought

The BIA Antibody Taskforce was ultimately all about people. They came together at speed in an open and collaborative way, contributed their expertise and resources, and worked tirelessly to do their part to find a solution to COVID-19. The BIA and I are proud to have worked alongside these experts across the UK who are committed to making a difference.