Vaccine Task Force – Kate Bingham Gene Therapy Fixer

1. VACCINE TASK FORCE – KATE BINGHAM

2. 1Status of COVID-19 As of 19 March 2020, COVID-19 is no longer considered to be a high consequence infectious disease (HCID) in the UK. The 4 nations public health HCID group made an interim recommendation in January 2020 to classifyCOVID-19 as an HCID. This was based on consideration of the UK HCID criteria about the virus and the diseasewith information available during the early stages of the outbreak. Now that more is known about COVID-19, the public health bodies in the UK have reviewed the most up to date information about COVID-19 against the UK HCID criteria. They have determined that several features have now changed; in particular, more information is available about mortality rates (low overall), and there is now greater clinical awareness and a specific and sensitive laboratory test, the availability of which continues to increase. The Advisory Committee on Dangerous Pathogens (ACDP) is also of the opinion that COVID-19 should no longer be classified as an HCID. 1https://www.gov.uk/guidance/high-consequence-infectious-diseases-hcid

3. Vaccine Taskforce Aims Last updated 6 April 2020 Objective: The UK must be in a position to vaccinate the right proportion of the populationas soon as possible after a vaccine is available. To the extent it is complementary to that primary objective, we must ensure longer-term UK vaccine capabilityand capacity for clinical and industrial benefit. We need to support manufacturing facilities that reflect the latest developments in vaccine technologies focusing on newer technologies, including mRNA and viral vector approaches, rather than the traditional processusually taken that relies on large infrastructure and is very complex. We also need to act fast to make the most of emerging vaccine possibilities – notably(RETRACTED), which is already in phase one studies and looking to ramp up shortly to phase two, as well as two domestic vaccines, one close to clinical trial from Oxford (chimpadenovirus) and one at an earlier stage in Imperial (self-amplifying mRNA). Given the likely high failure rate, the manufacturing technology we put in place in the short, medium and long term must be capable of supporting whatever technology (cell culture or chemical synthesis)produce an eventual ‘winner’. What is the taskforce for? Currently there is work going on across government but it is not sufficiently coordinated. The taskforce will bring together government, industry, academics, funding agencies, regulators, logistics and finance to make rapid decisions to put the UK in a position to accelerate vaccine development and vaccinate the right proportion of the populationas soon as possible after a vaccineis available. Supportthe two leading UK academic groups at present (Oxford and Imperial) to allow them to progress to scale up as quickly and effectively as possible. Scope entire vaccines landscape and make connections with key companies (offering UKscience support and facilities) to ensure we can access vaccines wherever they emerge. Prepare the UK to offer itself as an expert clinical testing site, proactively approaching companies such as (RETRACTED) which are at the forefront of vaccine development. 2. Prepare the UK to offer itself as possible manufacturing site: 2.1 Secure(RETRACTED) as the company furthest forward on developing a vaccine, to develop a manufacturing base in the UK:

4. Professor Johnathan Van Tam (VTF) Deputy Medical Chief Officer, GSK Beechams, Roche, WHO, NERVTAG Chris Whitty (SAGE) Chief Medical Officer Tedros (WHO/UNITED NATIONS) Kate Bingham Biochemist and Venture Capitalist – The Vaccine Task Force Sir Patrick Vallance (SAGE/VTF) Chief Scientific Adviser

5. Press release: Government launches Vaccine Taskforce to combat coronavirus, April 17, 2020 Rapid development and production of a coronavirus vaccine will be driven by a new government-led Vaccine Taskforce, Business Secretary AlokSharma announced today (Friday 17 April). The taskforce, led by Chief Scientific Adviser Sir Patrick Vallance and Deputy Chief Medical Officer Professor Jonathan van Tam, will support efforts to rapidly develop a coronavirus vaccine as soon as possible by providing industry and research institutions with the resources and support needed. 21 new research projects combating coronavirus will receive government funding from a £14 million pot investmentto rapidly progress treatmentsand vaccines. This follows the government’s £250 million pledge to develop a vaccine, the biggest donation by any country, to the international programme to develop a coronavirus vaccine under the Coalition for Epidemic Preparedness Innovations(CEPI), putting the UK at the forefront of international efforts to fight the virus Representatives from government, academia and industry are coming togetherto form the taskforce. Members will include government Life Sciences Champion Sir John Bell, as well as AstraZeneca, and the Wellcome Trust. The taskforce is also working closely with the Bioindustry Association, which has set up an industry-led group, to accelerate vaccine development and manufacturing. One new project led by the University of Oxford will trial an anti-malarial drug believed to have anti-inflammatory properties to determine whether it could diminish the effects of COVID-19 on people in high risk groups. GP surgeries across the UK have been invited to take part in this ground-breaking trial This follows an initial £10.5 million allocated to 6 promising coronavirus projects in March 2of which are enabling pre-clinical and clinical vaccine trials Other projects receiving vital government funding from this new pot include: Imperial College London testing a vaccineagainst coronavirusthataims for the body to produce more protective antibodies Public Health Englandstudying how COVID-19 can be transmitted from person-to-person by determining how long it can survive in the air and on different materials found in hospitalsand households like fabric, plastics, metalsand ceramics

6. The UK hasalong-term commitment to vaccines investment and is the largest funder to Gavi, the global vaccine alliance. Gavi will play a key rolein making any new coronavirus vaccine available and affordable to the world’s poorest countries, which will help to slow the global spread of the disease and protect the British public from a deadly second wave of the disease. Altogether 27 research projectshave received a share of a £25 million investment. This follows a government research call to accelerate coronavirus studies and support the UK’s world-class scientists and researchers to further the development of vaccinesand treatments, as well as improve diagnosis and understanding of the disease. This announcement is part of a £25 million research response, which was announced in February. The first round of projects were announced on 23 Marchand the second round of projects announced today. The funding is being managed by UK Research & Innovation (UKRI) and the Department of Health and Social Care through the National Institute for Health Research (NIHR). PCR Tests introduced Spring-Summer, 2020 “Flatten the curve” March 19, 2020 (Spring Equinox March 21, 2020) Declared a Non-HCID WINTER SPRING SUMMER AUTUMN (Note: Do please read the other SAGE minutes on Face masks, asymptomatic transmission, Childrenandclosing schoolsto get more context to why these key decisions were being made and the funding involved all for the sake of a seasonal, common cold pathogen and the augmentation of a new network of laboratories and initiatives were set up as foundation stones or ‘4 Pillars’ to build upon)

7. SAGE January 22, 2020 SAGE convenes for 1st time Civil Contingencies Committee Cabinet Office Briefing Room A January 30, 2020 WHO Declared Pandemic Public Health Emergency of International Concern (PHEIC). Sir Patrick Vallance Chief Science Advisor February 2020 – March 18, 2020 SAGE, advised by SPI-M on Face masks, children and schools, pets and transmission and asymptomatic children/adolescents March 2, 2020 £10.5 million 6 promising coronavirusprojects March 6, 2020 £5 million JIREP Joint Initiative on Research in Epidemic Preparedness March 19, 2020 Declared a Non-HCID by Advisory Committee on Dangerous Pathogens (ACDP) March 23, 2020 “Lockdown” £25 million investment – 27 projects March 27, 2020 D614G (November) Commission on Human Medicines ACE-i and ARBsmight worsen COVID-19 infection Joint Committee on Vaccination and Immunisation [JCVI] April 1-2, 2020 UNCOVEREvidenceon Childrenand Transmission CEPI £250 million SPI-M April 6-17, 2020 Vaccine Task Force The Vaccine Taskforce Chief Scientific Adviser Sir Patrick Vallance Deputy Chief Medical Officer Professor Jonathan van Tam, Government Life Sciences Champion Sir John Bell, as well as AstraZeneca, and the Wellcome Trust. May 1, 2020 – UNCOVERMeta-analysis and reviewconcerning “Lockdown” May 27, 2020 – UNCOVERMeta-analysis Reviews on Facemasks/Face coverings May 29, 2020 UK Research & Innovation (UKRI Scientific Advisory Group for Emergencies (SAGE) publish minutes from meetings1 to 34 Chief Executive, Professor Sir Mark Walport 21 Research Projects £14 million Oxford will trial an anti-malarial drug May 31, 2020 [1] “Will the advice from Sagealways be right? No. Will the science change as we learn more? Of course, and we learn from scientists across the world. But the evidence we present to ministers will always be based on a careful analysis of the science available at the time, in line with both the Nolan principlesand the Civil Service Code.” WHO R&D Blueprint UNICEF Health Emergencies Preparedness Initiative (HEPI) August 15, 2020 - UNCOVER Summary of Indoor Transmission [1] https://www.gov.uk/government/speeches/chief-scientific-advisers-sunday-telegraph-article-31-may-2020

8. DFID-Wellcome Joint Initiative on Epidemic Preparedness Call for Proposal The UK Department for International Development (DFID) and Wellcomeare pleased to announce the launch of the first call for proposals under the Joint Initiative on Epidemic Preparedness. Background Focus of the Joint Initiative on Research and Epidemic Preparedness The £25M Joint Initiative will combine Wellcome’s funding interests across science, humanities and social science, product developmentand global policy, together with DFID’s global expertise and in-country links. DFID and Wellcome Trust have a strong history of supporting research that aims to improve global health. Outcomes and remit The objective of this call is to support the most suitable proposal(s) to generate new innovative and systematic ways to conduct social science researchin contexts of epidemic preparedness and response. Award-holdersare expected to closely work with stakeholders such as WHO and UNICEFat all three levels (national, regional, and headquarters) The expected outcomes are: - Co-developed standardised social science research protocols for diseases such as those listed in the WHO R&D Blueprint. The final number of protocolsto be developed should be determined by the applicant - Integration of standardised social science research protocols in future epidemic control activities - A research framework that can be incorporated in current and future training programmes designedfor social scientists engaged in epidemic response research The *R&D Blueprint aims to fast-track the availability of effective tests, vaccinesand medicines that can be used to save lives and avert large-scale crises. It identifies a list of priority diseases that pose a public health risk because of theirepidemic potential and for which there are either insufficient countermeasures or none at all. Established in 2015, the UNICEF Health Emergencies Preparedness Initiative(HEPI) has an operational presence in over 190 countries. The programme is a cross-sectoral initiative that coordinates operations to control endemic and epidemic diseases with significant public health impact on children,familiesand societies. *WHO Health Emergencies Programme Established in 2016

9. January 22, 2020 SAGEconvenes for 1st time January 30, 2020 WHO Declared Pandemic Public Health Emergency of International Concern (PHEIC). £500 million to COVAX WHO R&D Blueprint HEPI (Health Emergencies Preparedness Initiative) CEPI £250 million (£388 million) 21 Research Projects £14 million Pot Investment Oxford will trial an anti-malarial drug Civil Contingencies Committee Cabinet Office Briefing Room A SAGE SAGE Professor Tom Evans (ACDP, PHE) (Chair) letter dated March 13, 2020 SPI-M Chris Whitty Chief Medical Officer Sir Patrick Vallance Chief Science Advisor March 19, 2020 Jeremy Farrar (Director) £25M Joint Initiative Declared a Non-HCID by (ACDP) Advisory Committee on Dangerous Pathogens JIREP Joint Initiative on Research in Epidemic Preparedness £20 million March 23, 2020 “Lockdown” Altogether, 27 research projects (announced the same day March 23)have received a share of a £25 million investment Joint Committee on Vaccination and Immunisation [JCVI] COG-UK created in April 2020 £20 million funding fromDHSC, administered byUK Research and Innovation (UKRI), Wellcome Sanger Institute NadhimZahawi Vaccines minister April 6-17, 2020 Vaccine Task Force Kate Bingham appointed The Vaccine Taskforce Chief Scientific Adviser Sir Patrick Vallance Deputy Chief Medical Officer Professor Jonathan van Tam, Government Life Sciences Champion Sir John Bell, as well as AstraZeneca, and the Wellcome Trust. May 17, 2020 £84 million of new government funding funding includes £65.5 million for the vaccine being developed at the University of Oxford and £18.5 million for Imperial College London, as coronavirus vaccine trials accelerate May 29, 2020 UNICEF Health Emergencies Preparedness Initiative (HEPI) Scientific Advisory Group for Emergencies (SAGE) publish minutes from meetings1 to 34 Prof. Johnathan Van Tam DMCO, GSK Beechams, Roche, WHO, NERVTAG June 2020 UK will also host the upcoming global pledging conference for Gavi, the Vaccine Alliance.

10. 1As a starting point, the list of diseases outlined by the WHO Pandemic and Epidemic Departmentand those reported in the WHO Disease Outbreak News during the past five yearswere considered. The diseases were organized according to mode of transmission, and various factors were analysed, including impact on children and pregnant women, severity of morbidity and mortality, epidemic and pandemic potential, and wider socioeconomic impact. UNICEF is also working with WHO and other partners to drive research and development (R&D), including availability of vaccines, diagnostics and therapies. NOTE: Italicizeddiseases are those with pre-existing UNICEF global programs. 1https://programme.worldwaterweek.org/Content/ProposalResources/PDF/2017/pdf-2017-7105-1-HEPI%20Overview%20(March%202017).pdf – March 2017

11. You may request support for: • Costs to engage with the European Commission International Network of Social Sciences Research Centres and any other relevant networks such as GOARN, ALERRT, ISARIC, and Social Science in Humanitarian Action platform. Review of applications Applications will be considered by an Expert Advisory Panel specifically formed to support the DFID-Wellcome Joint Initiative on Epidemic Preparedness. Additional scientific experts will be invited to provide written comments if the funders and/or panel chair deem this necessary. DFIDandWellcome’s decision will be final and will not be open to appeal. Applications will be submittedtoandprocessed by Wellcome on behalf of theJoint Initiative.

12. January 30, 2020 WHO Declared Pandemic Public Health Emergency of International Concern (PHEIC). £250 million March 3, 2020 – Alexander De Pfieffel Johnson Handshaking with patients in a Coronavirus Hospital March 16-18, 2020 SAGE/Vallanceadvise‘lockdown’ (see SAGE minutes) March 2, 2020 £10.5 million March 19, 2020 6 promising coronavirusprojects Declared a Non-HCID March 6, 2020 £5 million March 23 2020 “Lockdown”, “MustStay at Home” – Schools Closed JIREP Joint Initiative on Research in Epidemic Preparedness March 26, 2020 The Health Protection (Coronavirus, Restrictions) (England) Regulations 2020 introduced There is no official definition of what a ‘lockdown’ is WHO R&D Blueprint UNICEF Health Emergencies Preparedness Initiative (HEPI) March 27 Alexander De Pfieffel Johnson & Matt Hancock test positive Chief Medical Adviser tested positive April 3, 2020 1st Nightingale Hospital opened The Vaccine Taskforce April 6, 2020 (see Slide 9) Alexander De Pfieffel Johnson taken to St Thomas’s Hospital. ReleasedApril 12, 2020 Chief Scientific Adviser Sir Patrick Vallance Deputy Chief Medical Officer Professor Jonathan van Tam, Government Life Sciences Champion Sir John Bell, as well as AstraZeneca, and the Wellcome Trust. April 17, 2020 1To ensure compliance with the Government’s instruction to stay at home, we will immediately: Close all shops selling non-essential goods,​ including clothing and electronic stores and other premises including libraries, playgrounds and outdoor gyms, and places of worship; We will stop all gatherings of more than two people in public – excluding people you live with; and we’ll stop all social events​, including weddings, baptismsand other ceremonies, but excluding funerals. No Prime Minister wants to enact measures like this. I know the damage that this disruption is doing and will do to people’s lives UK Research & Innovation (UKRI) Chief Executive, Professor Sir Mark Walport 21 Research Projects £14 million Oxford will trial an anti-malarial drug June 15, 2020 Non-essential shops could reopen July 4, 2020 Restaurants, pubs and hairdressers to reopen 1https://www.gov.uk/government/speeches/pm-address-to-the-nation-on-coronavirus-23-march-2020

13. Inside the Race to Develop a COVID-19 vaccine – Kate Bingham, Chair of VTF October 21, 2020 (22 page PDF) Department for Business, Energy & Industrial Strategy Development of vaccines against COVID-19 is uncertain COVID-19 has traits which are not yet understood • People disproportionately affected • Immune response variable • No vaccine was approved for use against SARS-CoV-1 Viruses mutate, e.g. flu • Herd immunity may never be possible The most advanced clinical vaccine modalities have never been approved by regulators: • Adeno viral vaccines (e.g. Oxford) and mRNA vaccines (e.g. BioNtech, Moderna) • No long term experience or safety data Goals of UK Vaccine Taskforce Vaccinate the appropriate UK population against COVID19 as soon as practicable to restore UK’s economic growth Short term: to reduce mortality Ultimately: to buildsterilising populationimmunity  60 million doses

14. VALNEVA VLA2001(UK-SCOTLAND/FRANCE) – Inactivated Whole Virus Vaccine PFIZER/BIONTECH BTN162b2 (US/GERMANY) – mRNA GSK/SANOFI PASTEUR (UK/FRANCE) – Adjuvanted Protein JANSSEN /J&J Ad26-CoV2-S –(US/BELGIUM) - Adenovirus Type 26 NOVAVAX NYX-CoV2373(US) - Adjuvanted OXFORD/ASTRAZENECA (UK) ChAd0X1/AZD-1222– Adenovirus Type 26 UK contribution to international vaccine supply Global leadership to get vaccines to shared equitably • Up to £500m for COVAX: multilateral arrangement for vaccine procurement open to all countries • UK role in shaping the facility and encouraging countries to join • Support to COVAX team to share learning • Funding and delivery of professional vaccine trials • UKco-funding Janssen 2-dose vaccine trial to demonstrate long term immunity • UK funding of Recovery Trialdelivering definitive results on efficacy, or lack of, COVID19 therapeutics including neutralising antibodies 1 1Inside the Race to Develop a COVID-19 vaccine – Kate Bingham, Chair of VTF, October 21, 2020

15. [1[ https://www.cogconsortium.uk/news_item/reflections-on-the-achievements-of-cog-uk/ [1] “Population genetic analyses indicatethat D614Gconfers increased transmission fitness, but there was no evidence that patients infected with the Spike 614G variant had higher COVID-19 mortality or clinical severity” [1] How do we link SARS-CoV-2 sample data with other information? Each sample submitted to COG-UK is given a new, unique identifier. This consists of a COG-UK site code and a string of letters and numbers — something like COG-4A996. This COG-UK ID is used to link samples, sequences and the associated data together across the consortium. Labs carrying out tests provide COG-UK with data about when and where the sample was collected as well as basic, non-identifying information about the personwho took the test: COG-UK was established in April 2020 supported by £20 million funding from the COVID-19 rapid-research-response “fightingfund” from Her Majesty’s Treasury (established by Professor Chris Whitty and Sir Patrick Vallance), and administered by the National Institute for Health Research (NIHR), UK Research and Innovation (UKRI), and the Wellcome Sanger Institute. The consortium was also backed by the Department of Health and Social Care’sTesting Innovation Fund on 16 November 2020 All of this data is combined with the viral sequences in COG-UK’s central database, called MRC-CLIMB (the Cloud Infrastructure for Microbial Bioinformatics) funded by the UK’s Medical Research Council)..

16. 2020 National Pathology Exchange [NPEx] PCR result from the lab is matched to the sample barcode VACCINE TASK FORCE CREATION Laboratory Information Management System April 2020 LIMS Kate Bingham (biochemist) AppointedTsar VTF (2021: Managing Director of SV Health Investors) NHSBusinessServices Authority(BSA) May 4, 2020 – Fact sheet for Healthcare Providers EUROIMMUNAnti-SARS-CoV-2 ELISA (IgG) PCR Barcode matched to NHS number and GP record It is unknown how long IgG antibodies toSARS-CoV-2will remain present in the body after infection and if they confer immunity to infection. LIGHTHOUSE LABS Test Swab May 12 , 2020 – Press release SARS-CoV-2 Testing From EUROIMMUN IgG antibody test ELISA SARS-CoV-2 Testing From EUROIMMUN PCR July 23, 2020 Additional £100 million to Cell and Gene Therapy Catapult Manufacturing Innovation Centre NHS DIGITAL July 20, 2020 ARTICNETWORK Wellcome UK makes binding agreement for the Pfizer/BioNTech vaccine andValneva Local Authorities August 3 ,2020 UK teams up with Wockhardt for ‘fill and finish’ services at Wrexham, North Wales, UK to produce AstraZeneca/Oxford ADZ1222 PCR August 5 ,2020 UK and Valnevato invest in coronavirus vaccine manufacturing, Livingston, West Lothian, Scotland September 2020 Alok Sharma Phase 3 trials for NOVAVAX NYX-CoV2373vaccinein the U.K. Concluded January 2021 – 60 million doses JCVI Joint Committee on Vaccination and Immunisation NadhimZahawi Vaccinesminister VACCINE TASK FORCE CHM November 16 MRHA Government secures 5 million doses of Moderna vaccine (available Spring 2021) Commission on Human Medicines MODERNA mRNA-1273 7 different developers and has secured 355 million vaccine doses MRHA PFIZER BIONTECH December 2, 2020 Pfizer TN162b2 approved SAGE 2021 SPI-M-O

17. (Note: It is ironic that very early on, these people were advised not to treat this outbreak like InfluenzabecauseSARS-CoV-2 ‘behaves differently’, yet, here we are (in September and October, 2020) and the entire simulated model is based on influenza pandemic planning)

18. ADZ1222/ChAd01X BTN162b2 mRNA-1273 Ad26-CoV2-S NVX-CoV2373 CoronaVac

19. Authorised& Rolled out Newly authorised Not ready Still in early stages NOVAVAX (US) – 3,030,000,000/1,236,000,000 OXFORD/ASTRAZENECA (UK) ChAd0X1/AZD-1222 – 2,892,013,000/2,603,800,000 GSK/SANOFI PASTEUR (UK/FRANCE) – 1,600,000,000/532,000,000 PFIZER/BIONTECH BTN162b2 (US/GERMANY) – 1,800,000,000/1,060,000,000 CUREVAC – 1,100,000,000/225,000,000 JANSSEN /J&J–(US/BELGIUM) – 1,100,000,000/1,068,000,000 MODERNA -950,000,000/760,500,000 SINOVAC – 750,,000,000/310,000,000 VALNEVA VLA2001 with Dynavax Technologies CpG1018 adjuvant (UK-SCOTLAND /FRANCE) – 160,000,000/100,000,000 ARCTURUS – 100,000,000/4,000,000