Clinical Trial Landscape and Phase 3 COVID-19 Vaccine Update

Clinical Trial Landscape and Phase 3 COVID-19 Vaccine Update Emily Coates, PhD Larisa Strom, Colorado School of Public Health Colorado Vaccine Equity Taskforce: Training on COVID-19 Vaccine Development November 20, 2020 Outline

• Overview of U.S. federal health agencies • Clinical trial phases and regulations of vaccines • Vaccine safety and efficacy standards • U.S. government’s COVID-19 vaccine strategy • Phase 3 COVID-19 vaccine candidates in the U.S. • Strategies for vaccine distribution following FDA Emergency Use Authorization (EUA)/Biological License Application Approval Overview of the Department of Health and Human Services (HHS) • Founded in 1953 as a department within the Department of Health, Education, and Welfare; reorganized as single entity in 1980 • Mission statement: “to enhance the health and well-being of all Americans, by providing for effective health and human services and by fostering sound, sustained advances in the sciences underlying medicine, public health, and social services” • Comprised of 11 operating divisions, including the Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC) and National Institutes of Health (NIH) • HHS total budget authority for fiscal year 2020: 1,292,523 (in millions) • FDA: $5,900; CDC: $6,767; NIH: $41,680 • Workforce: 84,505 employees (2018) • Mission: “to protect the public health by ensuring the safety, efficacy, and security of human Food and Drug and veterinary drugs, biological Administration products, and medical devices” • Regulates vaccine clinical trials, (FDA) licenses vaccines, and monitors vaccine safety after licensure • Workforce: 18,555 employees • Mission: “to protect America from health, safety and security threats, Centers for Disease both foreign and in the U.S.” • Promotes immunization at the Control and country, regional, and global Prevention (CDC) levels by providing evidence-based strategies to control and eliminate vaccine-preventable diseases • Workforce: 10,796 employees • Mission: “to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability” National Institutes • Comprised of 27 institutes including the National of Health (NIH) Institute of Allergy and Infectious Diseases (NIAID) • Within NIAID, the Vaccine Research Center (VRC) “conducts research that facilitates the development of effective vaccines for human disease” • Workforce: 18,668 employees Other Divisions within HHS

• Administration for Children and Families (ACF) • Administration for Community Living (ACL) • Agency for Healthcare Research and Quality (AHRQ) • Agency for Toxic Substances and Disease Registry (ATSDR) • Centers for Medicare & Medicaid Services (CMS) • Health Resources and Services Administration (HRSA) • Indian Health Service (IHS) • Substance Abuse and Mental Health Services Administration (SAMHSA) Outline

Clinical Trial Operations and Recruitment Questions How does NIH recruit for clinical trials?

• Advertising in public places such as transit, radio, newspapers, bulletins • How are communities of color engaged/selected for VRC trials? • Advertisements on radio stations catering to urban or Spanish-speaking populations • Informed consent documents in Spanish to facilitate trial participation in that underrepresented ethnic group • Community outreach to college campuses, including community colleges Is there a minimum threshold of minority population inclusion that must be met in a clinical trial?

• While there is no minimum threshold, the FDA strongly encourages that participants from diverse populations are included in all phases of vaccine development to ensure that vaccines are safe and effective in all affected populations • Vaccine safety and efficacy assessments, particularly in late phase clinical trials, should include an adequate representation of populations most impacted by COVID-19, specifically racial and ethnic minority groups Are community advisory boards a requirement for clinical trials?

• Although not required, community advisory boards can be utilized to provide feedback or raise concerns during the protocol development stage • Institutional Review Boards (IRBs) are required and designated under FDA regulations to review and monitor biomedical research involving human subjects • Human subjects research: research that uses, studies, or analyzes information or biospecimens through intervention or interaction with subject; or research that uses, studies, analyzes, or generates identifiable private information or biospecimens • IRBs have authority to approve, require modifications to, or disapprove research FDA Emergency Use Authorizations (EUA) What is an FDA Emergency Use Authorization?

• EUA allows the use of unapproved medical products to diagnose, treat, or prevent serious or life-threatening diseases in response to a declared public health emergency for which there are no adequate, approved, and available treatments • Introduced in 2004 as a measure against weapons of mass destruction • Criteria for issuing an EUA: • The known and potential benefits of the product outweigh the product’s known and potential risks • Sufficient data on product’s safety profile • Proof of worthwhile efficacy • Cannot be granted outside of a declared emergency • EUAs have previously been granted to products for anthrax, Ebola, Enterovirus, Zika, H1N1 influenza, MERS • EUA has only been granted for one vaccine, Anthrax Vaccine Adsorbed (AVA) in 2005, for individuals ages 18-65 at heightened risk of anthrax exposure Why now? FDA October 2020 Emergency Use Authorization for Vaccines to Prevent COVID-19: • FDA recommends EUA if data from phase 3 studies supports a positive benefit-risk assessment • Efficacy standard for approving EUA for COVID-19 vaccine: >=50% disease reduction in treatment vs placebo groups • A median of 2 months of safety follow-up data is required before companies can apply for EUA • Following Authorization: • Not subject to usual informed consent requirements, but recipients are provided a fact sheet detailing the product, its potential risks and benefits, and have the option to refuse the product • To minimize risk of EUA interfering with long-term safety and efficacy assessments, it is essential that data is still gathered on the vaccine even after the EUA Outline

What criteria are used to deem a vaccine “safe”?

• Pre-clinical studies to assess safety • In vitro and in vivo testing help define immunogenicity and safety profile • Animal models help identify vaccine-related safety risks and assist in selecting an appropriate dose, regimen, and administration route • Clinical trials • Safety is monitored for a 2-month median follow-up after full vaccination regimen to allow for detecting any potential AEs • FDA usually requires 6 or more months of safety follow-up for serious or other medically attended AEs before approving the licensure of a vaccine • Data and Safety Monitoring Boards (DSMBs) • Independent group of experts who oversee clinical trials and whose roles include: • Periodical review and evaluation of participant safety, study conduct and progress, and efficacy (if necessary) • Ability to make recommendations regarding trial continuation, modification, or termination When is a DSMB required?

• A DSMB is required for: • All Phase 3 trials* • High-risk Phase 2 trials • Multi-site and randomized Phase 2 trials* • May be required for Phase 1 or 2 trials if trial is blinded, first-in-man, includes high-risk populations, or involves high-risk interventions • A DSMB is not generally required (but may still be recommended) for: • Single-center, open-label Phase 1 and 2 trials • Multi-site, high-risk Phase 1 trials with clear guidelines and criteria for halting the trial if unexpected side effects occur *Excludes certain low-risk nutritional or behavioral studies where participants should only experience mild side effects Assessing Long-term Safety after Licensure

• As with all licensed vaccines, the vaccine’s safety profile will continue to be monitored post-licensure in order to facilitate detecting any rare AEs in the general population and populations underrepresented in pre-licensure trials • Phase IV trials may be conducted to continue assessing vaccine safety profile after licensure • Pharmacovigilance plan for COVID-19: 24-month post-licensure monitoring between CDC and FDA to determine vaccine’s performance in real-life scenarios to monitor efficacy and rare adverse events not found in pre-licensure trials • Post-licensure monitoring systems: • Vaccine Adverse Event Reporting System (VAERS) • Vaccine Safety Datalink (VSD) • Post-Licensure Rapid Immunization Safety Monitoring (PRISM) • Clinical Immunization Safety Assessment Project (CISA) Vaccine Adverse Event Reporting System (VAERS)

• Co-managed by CDC and FDA • National early warning system that detects unexpected AE reporting patterns that may indicate potential safety concerns in licensed vaccines • Collects and analyzes reports of AEs after an individual receives a vaccine • Anyone can report an AE; healthcare providers are required to report certain AEs and vaccine manufacturers are required to report all AEs • Public datasets available at https://vaers.hhs.gov/data/datasets.html Additional Systems that Monitor Safety Post-Licensure

• Vaccine Safety Datalink (VSD) • Collaboration between CDC and 9 health care organizations across U.S. • Conducts safety studies on vaccines based on concerns raised in medical literature and concerns reported to VAERS • Post-Licensure Rapid Immunization Safety Monitoring (PRISM) • Developed by FDA to utilize electronic health information • Utilizes data form a network of U.S. healthcare organizations • Allows scientists to access vaccine safety data in >190 million individuals • Clinical Immunization Safety Assessment (CISA) • Collaboration between CDC and 7 medical research centers across U.S. • Conducts research to identify prevention strategies for AEs after immunization Vaccine Efficacy

• Vaccine Efficacy endpoints are based on weighing the potential benefits against the potential risks and therefore vary based on: • The pathogen • Transmission dynamics • Consequences of infection • Examples • Mosquirix malaria vaccine: ~30% efficacy • Seasonal influenza vaccine: 45% efficacy (averaged across past decade) • MMR: 97% efficacy • HPV vaccine: nearly 100% efficacy What should our expectation of efficacy be for a COVID-19 vaccine?

FDA June 2020 Development and Licensure of Vaccine to Prevent COVID-19: • An efficacious COVID-19 vaccine should reduce at least one of the following: • Rate of confirmed infection • Severity of disease • Duration of infection • Primary efficacy endpoint should be >= 50% with lower bound of CI around efficacy endpoint of >30% • It is strongly encouraged that vaccine candidates demonstrate efficacy in the following populations: • Racial and ethnic minorities • Elderly individuals and individuals with medical comorbidities • Pregnant women and women of childbearing potential who are not actively avoiding pregnancy How common is it for trials to be halted due to adverse reactions?

• Halts in clinical trials are not uncommon, particularly in late-stage trials with large populations that contain high-risk participants • Pauses in trials are conducted to ensure the safety of trial participants • DSMB will likely recommend trial to be paused if any unexpected AE occurs • Before unpausing a trial, it must be determined: • If the AE occurred in a vaccine or placebo recipient • If the AE was directly related to or caused by the vaccine

Have vaccines been recalled after being released to market?

• 1955 Cutter Incident • One company, Cutter Laboratories, produced a polio vaccine contaminated with live poliovirus • 70,000 children developed muscle weakness, 164 developed permanent paralysis; 10 fatalities • Vaccine was recalled immediately following reported cases • Vaccine recalls in recent years • Usually precautionary and voluntarily by the manufacturer during quality testing (due to public perception) • Recalls occur even when no AEs have been reported • If any safety concerns arise, FDA will recall vaccine immediately Outline

How is the vaccine development process for COVID-19 being fast-tracked while still meeting safety standards?

• FDA’s June 2020 Development and Licensure of Vaccine to Prevent COVID-19: “The general safety evaluation of COVID-19 vaccines, including the size of the safety database to support vaccine licensure, should be no different than for other preventive vaccines for infectious diseases. Safety assessments throughout clinical development should include: ” • Solicited local and systemic adverse events for 7+ days following each administration in an adequate number of participants in order to characterize reactogenicity • Unsolicited AEs in all participants for 21-28+ days following each administration • Serious and other medically attended AEs in all participants for 6+ months after completion of all vaccine administrations • All pregnancies should be monitored for pregnancy outcomes in participants for which date of conception is prior to administration or within 30 days of administration U.S. Government’s Accelerated Plan: Operation Warp Speed (OWS)

• Coordination between Department of Defense, several divisions within the HHS (FDA, CDC, NIH, BARDA), and the private sector • Goal: to accelerate Covid-19 vaccine development, manufacturing, and distribution while maintaining safety and efficacy standards • Typical vaccine development timelines take approximately 73 months; OWS’s proposed accelerated timeline is approximately 14 months • Traditional timeline steps are not eliminated but instead occur simultaneously • May have financial risks but will not increase product safety risk • Aims to have hundreds of millions of vaccine doses available and deployed to the public by mid-2021 OWS Criteria for Vaccine Candidates

• Robust preclinical or early-stage clinical trial data to support the potential of clinical safety and efficacy • Based on vaccine-platform technologies that permit fast and effective manufacturing, as well as safe and effective vaccine • mRNA, replication-effective live-vector, recombinant-subunit adjuvanted protein platform, attenuated replicating live-vector • Demonstration of industrial process scalability, yields, and consistency in order to reliably produce over 100 million dose by mid-2021 • Due to advances in vaccine technology, and lessons learn from rapid responses to recent Ebola and Zika outbreaks, ph 1 clinical testing for vaccine candidates began in March 2020 and ph 3 in July OWS Purchase Agreements

• OWS has provided over $10 billion in funding to companies including: • Moderna • $955 million for design and testing • Advance purchase agreement of $1.53 billion for 100 million doses (with option to acquire 400 million additional doses) • Pfizer • Did not receive financial support from OWS for design or testing of vaccine • Advance purchase agreement of $1.95 billion for 100 million doses (with option to acquire 500 million additional doses) • AstraZeneca • $486 million for design and testing • Advance purchase agreement of $1.2 billion for 300 million doses (with option to acquire 100 million additional doses) • Janssen • $456 million for design and testing • Advance purchase agreement of >$1 billion for 100 million doses (with option to acquire 200 million additional doses) Outline

Source: New York Times Ongoing Phase 3 COVID-19 Vaccine Trials in the U.S. ModernaTX, Inc. Pfizer/BioNTech AstraZeneca/Oxford Janssen /NIAID University Pharmaceuticals (Johnson & Johnson)

Vaccine Type mRNA mRNA Adenovirus vector (ChAdOx1) Adenovirus vector (Adenovirus 26) Trial sample size 30,000 (1:1) 43,998 (1:1) 40,051 (2:1) 60,000 (1:1) (vaccine:placebo) Status Enrollment completed Enrollment completed Enrolling Enrolling Number of administrations 2 (28 days apart) 2 (21 days apart) 2 (28 days apart) 1

Efficacy Target per protocol 60% (30%) 60% (30%) ≥50% (30%) 60% (30%) (low 95% CI Efficacy)

Target number of cases 151 164 150 154

Cases required for interim 53 32 75 • 6 cases in participants ≥60 efficacy analysis by DSMB years • ≥20 moderate to severe cases • ≥5 cases meeting primary endpoint of severe cases

CT.gov registration number NCT04470427 NCT04368728 NCT04516746 NCT04505722

*defined as meeting primary endpoint Ongoing Phase 3 COVID-19 Vaccine Trials in the U.S: Results To-Date

Minority Inclusion in Phase 3 COVID-19 Trials

• Moderna/NIAID vaccine • 11,000 participants from racially diverse backgrounds • 63% white, 20% Hispanic/Latinx, 10% black, 4% Asian, 3% other race • Pfizer/BioNTech vaccine • 42% of global participants from racially diverse backgrounds • 30% of U.S. participants from racially diverse backgrounds • No publicly available demographic data for AstraZeneca or Janssen vaccines Demographic Data for Pfizer and Moderna Phase 3 Trials

Pfizer Phase 3 demographic data Moderna Phase 3 demographic data Pfizer Efficacy Results • November 9th announcement • Preliminary results suggested vaccine to have >90% efficacy 7 days following second administration (4 weeks after first administration) • Results reported after 94 confirmed COVID-19 cases • November 18th update • 95% efficacy after 170 confirmed cases reported • 8 cases in vaccine group vs. 162 cases in placebo group • 9/10 severe cases were in placebo group • Consistent efficacy results across age, race and ethnicity groups; 94% efficacious in older adults • No significant Grade 3 AEs reported • Most common severe AE was fatigue in 3.7% after 2nd dose • Headache reported in 2% after 2nd dose • Fewer AEs and of milder severity reported in older adults • 2 months of median follow-up safety data completed; EUA application in coming days • If EUA is granted: • Up to 50 million doses could be available by end of 2020 • 12.5 million Americans could receive both vaccinations by end of year • Up to 1.3 billion doses for global distribution by end of 2021 Moderna Preliminary Results: November 16th

• Company reported 94.5% efficacy 2 weeks following second administration (6 weeks after first administration) • Primary endpoint: 95 confirmed cases of COVID-19 • 5 cases observed in treatment group vs 90 in placebo group • 15/95 cases were participants ages 65+ • 20/95 cases were participants from diverse communities (12 Hispanic/Latinx, 4 black/African American, 3 Asian, 1 multiracial) • Secondary endpoint: 11 severe cases observed, all in placebo group • No significant safety concerns reported by DSMB • Majority of AEs were of mild or moderate severity • Grade 3 (severe) AEs included: • After first administration: pain at injection site (2.7%) • After second administration: fatigue (9.7%), myalgia (8.9%), arthralgia (5.2%), headache (4.5%), pain (4.1%), redness at injection site (2.0%) • Majority of events resolved shortly after • By 2nd half of November, will reach 2 months of collected safety data needed for EUA application • If EUA is granted: • Up to 20 million doses could be available by end of 2020 • 10 million Americans could receive both vaccinations by end of year • 500 million to 1 billion doses for global distribution by end of 2021 Outline

• OWS Partnerships • CDC executed existing contract with McKesson Corporation (who distributed the H1N1 vaccine in 2009-2010) to aid in distribution • Partnership with CVS and Walgreens to deliver vaccine to vulnerable populations in long-term care facilities • Strategy to ensure equitable coverage and access to every American • Continue engagement with state, tribal, territorial and local partners, other stakeholders, and the public in order to communicate public health information and promote confidence and uptake in the vaccine • Distribute vaccines immediately upon EUA/BLA grant, using a transparently developed, phased allocation methodology • Delivery of vaccine to sites with goal of no upfront cost to providers and no out-of-pocket cost to recipients • Ensuring that administration sites have capabilities to store, handle, and administer vaccines • Commitment to ensure that rural and hard-to-reach populations receive the vaccine • Ensure safe administration and availability of administration supplies • Monitor vaccination program data through an information technology (IT) system to support and track distribution, administration, and other necessary data OWS Phased Distribution Approach

Potentially limited supply of available vaccine doses Plan: focus initial efforts on reaching the critical populations (most vulnerable and at-risk populations). Phase 1 Ensure vaccination locations selected can reach populations, manage cold chain requirements, and meet reporting requirements for vaccine supply and uptake

Large number of vaccine doses available Plan: focus on ensuring access to vaccine for members of Phase 1 critical populations who were not yet Phase 2 vaccinated as well as for the general population; expand provider network

Sufficient supply of vaccine doses for entire population Plan: Focus on ensuring equitable vaccination access across the entire population. Monitor vaccine Phase 3 uptake and coverage; reassess strategy to increase uptake in populations or communities with low coverage

Source: US DHHS OWS Vaccine Implementation

Source: US DHHS Storage Requirements for Vaccine Candidates

• Pfizer • Specially designed, temperature-controlled thermal shippers utilizing dry ice can temporarily store product for 15 days at temperatures of -70°C±10°C (-94±50°F) • Moderna • 30-day stability at standard refrigerator temperatures of 2-8°C (36-46°F) • 6-month stability for shipping and long-term storage at standard freezer temperatures of -20°C (-4°F)

How is the federal government working to address hesitancy around the vaccine once publicly available? • Vaccine hesitancy named one of ”Ten threats to global health in 2019” by World Health Organization • Vaccination is one of the most cost-effective ways to prevent disease, preventing 2-3 million deaths per year • An additional 1.5 million deaths could be prevented if global immunization coverage improves • Reasons for not vaccinating are complex and include complacency, inconvenient access, and lack of confidence • Recommendations for facilitating COVID-19 vaccine uptake should include: • Public transparency about the benefits and risks of the vaccine • Ensuring equitable allocation and distribution • Developing approaches to administer vaccines in safe, familiar, and easily accessible locations for vulnerable populations

“The federal government is procuring hundreds of millions of doses of safe and eﬀective vaccines, and has contracted with McKesson for purposes of vaccine distribution, such that no American will be charged for either the COVID-19 vaccine or its distribution. Various plans, supported by the CARES Act and the Families First Coronavirus Response Act, are under development with the objective of ensuring no one will be charged any out–of-pocket expenses for the administration of the vaccine either. The objective is to ensure no one desiring vaccination will face an economic barrier to receiving one.” In Summary:

• Clinical trials are regulated by the FDA with rigorous monitoring and safety requirements in place • The FDA has pre-defined criteria for EUA due to the public health risks of the pandemic • Vaccine monitoring occurs even after FDA approval • Four vaccine candidates have advanced to Phase 3 testing for COVID-19 in the U.S. • While the process has been accelerated, these candidates are subject to same rigorous safety requirements as all other vaccines on the typical development timeline • Preliminary Phase 3 efficacy results in mRNA candidates are promising, more results expected soon Additional Resources • HHS resources • OWS factsheet: https://www.hhs.gov/coronavirus/explaining-operation-warp-speed/index.html • OWS distribution plan: https://media.defense.gov/2020/Sep/16/2002498509/-1/-1/1/OPERATION_WARP_SPEED_STRATEGY_FOR_D ISTRIBUTING_COVID19_VACCINE.PDF • FDA Guidance for COVID-19 vaccines: https://www.fda.gov/media/139638/download • FDA EUA Guidance for COVID-19 vaccines: https://www.fda.gov/media/142749/download • CDC COVID-19 Vaccination interim operations playbook: https://media.defense.gov/2020/Sep/16/2002498510/-1/-1/1/COVID19_VACCINATION_PROGRAM_PLAYBO OK.PDF • Phase 3 COVID-19 vaccine candidates trial information • Moderna: https://clinicaltrials.gov/ct2/show/NCT04470427 • Pfizer: https://clinicaltrials.gov/ct2/show/NCT04368728 • AstraZeneca: https://clinicaltrials.gov/ct2/show/NCT04516746 • Janssen: https://clinicaltrials.gov/ct2/show/NCT04505722 References by Section • Overview of U.S. federal health agencies • Overview of HHS: https://www.hhs.gov/about/strategic-plan/introduction/index.html • Organization of HHS: https://www.hhs.gov/about/agencies/orgchart/index.html • Overview of FDA: https://www.fda.gov/about-fda/what-we-do • Overview of CDC: https://www.cdc.gov/about/organization/mission.htm • Overview of NIH: https://www.nih.gov/about-nih/what-we-do/mission-goals • Overview of VRC: https://www.niaid.nih.gov/about/vrc • CDC global immunization resources: https://www.cdc.gov/globalhealth/immunization/default.htm • Clinical trial phases and regulations of vaccines • Stages of vaccine development: https://www.cnn.com/world/live-news/coronavirus-pandemic-09-09-20-intl/h_7e15241d0236761f277b43f9fc5 04bec • FDA recommendations of minority inclusion in vaccine clinical trials: https://www.fda.gov/media/139638/download • Role of Institutional Review Boards: https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/institutional-review-boards-irbs-an d-protection-human-subjects-clinical-trials • FDA EUA guidelines: https://www.fda.gov/media/142749/download References by Section • Vaccine safety and efficacy standards • Overview of the vaccine safety process: https://www.cdc.gov/vaccinesafety/ensuringsafety/history/index.html • Ensuring vaccine safety: https://www.fda.gov/files/vaccines,%20blood%20&%20biologics/published/Ensuring-the-Safety-of-Vaccines-in-the-United- States.pdf • Data and safety monitoring: https://grants.nih.gov/policy/humansubjects/policies-and-regulations/data-safety.htm • Safety and efficacy endpoints for COVID-19 vaccine candidates: https://www.fda.gov/media/139638/download • Vaccine post-licensure monitoring: https://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/index.html • VAERS Public dataset: https://vaers.hhs.gov/data/datasets.html • Mosquirix vaccine efficacy: https://www.who.int/news-room/q-a-detail/malaria-vaccine-implementation-programme • Efficacy by vaccine: https://www.cdc.gov/vaccines/vpd/vaccines-diseases.html • Vaccine recalls: https://www.cdc.gov/vaccinesafety/concerns/recalls.html • FDA recall alerts: https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/enforcement-reports • U.S. government’s COVID-19 vaccine strategy • Overview of OWS: https://www.hhs.gov/coronavirus/explaining-operation-warp-speed/index.html • COVID-19 vaccination program interim playbook: https://media.defense.gov/2020/Sep/16/2002498510/-1/-1/1/COVID19_VACCINATION_PROGRAM_PLAYBOOK.PDF References by Section

• Phase 3 COVID-19 vaccine candidates in the U.S. • Global COVID-19 vaccine tracker: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html?referringSource=articleShare • Moderna Phase 3 trial information: https://clinicaltrials.gov/ct2/show/NCT04470427 • Pfizer Phase 3 trial information: https://clinicaltrials.gov/ct2/show/NCT04368728 • AstraZeneca Phase 3 trial information: https://clinicaltrials.gov/ct2/show/NCT04516746 • Janssen Phase 3 trial information: https://clinicaltrials.gov/ct2/show/NCT04505722 • Moderna Phase 3 demographic data: https://www.modernatx.com/sites/default/files/content_documents/2020-COVE-Study-Enrollment-Completion-10.22.20.pdf • Pfizer Phase 3 demographic data: https://www.pfizer.com/science/coronavirus/vaccine • Moderna press releases: https://investors.modernatx.com/news-releases • Pfizer press releases: https://www.pfizer.com/news • Strategies for vaccine distribution following EUA • OWS COVID-19 vaccine distribution strategy: https://media.defense.gov/2020/Sep/16/2002498509/-1/-1/1/OPERATION_WARP_SPEED_STRATEGY_FOR_DISTRIBUTING_COVID19_VACCINE.PDF • COVID-19 vaccination program interim playbook: https://media.defense.gov/2020/Sep/16/2002498510/-1/-1/1/COVID19_VACCINATION_PROGRAM_PLAYBOOK.PDF • Pfizer COVID-19 vaccine storage requirements: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine • Moderna COVID-19 vaccine storage requirements: https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-longer-shelf-life-its-covid-19-vaccine • https://www.who.int/vietnam/news/feature-stories/detail/ten-threats-to-global-health-in-2019 • WHO 2019 threats to global health: https://www.who.int/vietnam/news/feature-stories/detail/ten-threats-to-global-health-in-2019