Cheat Sheet: COVID-19 pipeline

Primary sponsor(s) Description Platform Funders Status Considerations Read more

Pfizer / BioNTech Comirnaty mRNA ($500M) Ph. I/II ongoing: 456/ Efficacy: Interim analysis shows that the candidate was safe and well-tolerated with New York Times mRNA that encodes for USG ($1.9M) Ph. II planned: 960/ an efficacy rate of 95%. SARS-CoV-2 spike protein. Warp Speed Finalist Ph. II/III ongoing: 44K US +5 Manufacturing/delivery: mRNA are relatively easy to scale and Authorization: EUA in EU, US, +9; WHO manufacture. Emergency Validation Platform history: No previous mRNA vaccines licensed for use. Approval: Bahrain, , ,

Moderna mRNA-1273 mRNA USG ($2.48B) Ph. I ongoing: 155/US Efficacy: Interim analysis shows that the candidate was safe and well-tolerated Moderna Synthetic messenger RNA CEPI/GAVI (Undisclosed) Ph. II/III ongoing: 3000 (12 to 17 years)/ US with an efficacy rate of 94.5%. Statement that encodes for SARS- Warp Speed Finalist Ph. III ongoing: 30,000/US Manufacturing/delivery: mRNA vaccines are relatively easy to scale and CoV-2 spike protein. COVAX Portfolio Authorization: EUA in , EU, manufacture (potential for 1B doses by 2022); likely to require two doses, but a AVAC Israel, US third may be necessary. Webinar Approval: Switzerland Platform history: No previous mRNA vaccines licensed for use.

U. of Oxford AZD1222 Viral USG ($1.2B) Ph. II ongoing: 300 vols (6-17 years)/ UK Efficacy: Ph. III interim analysis shows vaccine was safe and well-tolerated, efficacy Science AstraZeneca Chimpanzee Adeno vector vector CEPI/GAVI ($750M) Ph. II/II ongoing: 12,390/UK; 1700/ averaged 70.4% (62 - 90% depending on dose); <25% efficacy against mild to expressing SARS-CoV-2 EU ($923M) Ph. III ongoing: 40K /US+; 10K/ moderate illness in . spike protein. Warp Speed* Finalist Authorization: EUA in Argentina, India, UK Manufacturing/delivery: Adeno vector vaccines can be manufactured quickly and COVAX** Portfolio Approval: None at scale (capacity to produce 2B doses has been secured). Platform history: Vaccine utilizing the Ad26 platform (Ad26.ZEBOV) has been approved for use against Virus Disease.

Sinopharm / Beijing BBIBP-CorV x 2 Whole No Funding Disclosed Ph. I/II: ongoing: 640/China Efficacy:Ph. III interim analysis showed an effficacy of 86%. Cell Institute of Biologic inactivated Ph III ongoing: 45K/UAE. Bahrain, Jordan, Manufacturing/delivery: Inactivated vaccines may require booster doses; GEN Products / Egypt; 3K/Argentina; 6K/Peru relatively shelf-stable compared to other platforms. Wuhan Authorization: EUA in Egypt Platform history: Numerous whole inactivated vaccines, including , Hep A Institute Approval: Bahrain, China, UAE and rabies.

Gamaleya Research Sputnik V Viral Ministry of Health- Ph. I complete: 38/Russia; 38/Russia Efficacy:Ph. III analysis shows vaccine was safe and well-tolerated; efficacy averaged Sputnik V Institute Combination Ad5 and vector Ph. II/III planned: 1600/ India 91.4% and >90% in individuals over 60. Ad26 vector expressing Ph. III ongoing: 40K/Russia Manufacturing/delivery: Adeno vector vaccines can be manufactured quickly and at the SARS-CoV-2 spike Ph. III planned: 100/Belarus;1000/UAE; scale (Russia has orders for 1.2 billion doses from 50 countries). glycoprotein 2000/ Venezuela Platform history: Vaccine utilizing the Ad26 platform (Ad26.ZEBOV) has been Authorization: EUA in Argentina; Early/ approved for use against Ebola Virus Disease. limited use in Belarus, Russia Approval: None

J&J JNJ-78436735 Viral J&J investment (~$500M) Ph. I and I/II ongoing: 250/; 1045/ Efficacy: Initial results show that the vaccine has an efficacy of 72% in the US, Nature Ad26 vector expressing vector USG ($1.45B) Belgium, US 64 percent in South Africa and 61% in Latin America. SARS-CoV-2 spike protein. Warp Speed Finalist Ph. II ongoing: 550/Germany, , Manufacturing/delivery: Product does not need to be stored at subzero temperatures, and it may require just a single dose. Ph. III ongoing: 30K (2 dose)/, Platform history: Utilizes the same technology used to make its , Germany, RSA+6; 60K(1 dose)/Argentina, which was granted European regulatory approval in May 2020. Brazil, Chile+7 Authorization: Bahrain, US Continued on page 2

The COVID-19 vaccine pipeline ‘Cheat Sheet’ reflects front-runner candidates along with products with significant investments from the USG, CEPI and the ACT-A COVAX pillar.

Cold Chain Considerations Doses Emergency Use Authorization: A regulatory mechanism to facilitate the availability and use of unapproved Refrigeration (2-8O C) Freezer (-20 C) Deep Freeze (-70 C) Anticipated number of doses medical products, including vaccines, during public health emergencies.

Last updated March 5, 2021 avac.org 1 Primary sponsor(s) Description Platform Funders Status Considerations Read more

Novavax NVX-COV2373 Protein CEPI ($388M) Ph. I ongoing: 130/ Efficacy: Interim analysis shows that the candidate had an efficacy of nearly 90% Novavax Full-length recombinant Subunit USG ($1.6B) Ph. II ongoing: 2900/ RSA in the UK, but only 50% in South Africa against the variant B.1.351. statement SARS-CoV-2 glycoprotein Warp Speed Finalist Ph. III ongoing: 15,000/ UK; 30K/US, Manufacturing/delivery: GMP production initiated with capacity for large-scale nanopartical vaccine COVAX Portfolio Mexico manufacturing (est. 1B doses by end of 2021). adjuvanted with Matrix M. Platform history: The same nanoparticle platform succeeded in a Ph. III trial for NanoFlu, an for older adults.

Sinovac Biotech CoronaVac Whole No Funding Disclosed Ph. I/II ongoing: 1166/China Efficacy:Varying reports of efficacy reported, ranging from just over 50 percent in medRxiv inactivated Ph III ongoing: 8K/Brazil, 1600/ Indonesia, Brazil to 91 percent in Turkey. Pharmaceutical 4K/Bangladesh, 13K/Turkey, 1K/China Manufacturing/delivery: Inactivated vaccines may require booster doses; relatively Technology Authorization: EUA for limited use in China shelf-stable compared to other platforms. Approval: China Platform history: Numerous whole inactivated vaccines, including polio , Hep A, and rabies.

Bharat Biotech/ Whole No funding disclosed Ph. I/II ongoing: 755/ India Immunogenicity: Ph. I/II trial data showed the vaccine was safe and triggered an medRxiv Indian Council of inactivated Ph. III ongoing: 25.8K/ India antibody response. Medical Research Authorization: EUA in India; still pending Manufacturing/delivery: Inactivated vaccines may require booster doses; relatively final Ph. III efficacy data shelf-stable compared to other platforms. Covaxin is stable at room temperature for Approval: None atleast a week. Platform history: Numerous whole inactivated vaccines, including polio, Hep A and rabies.

CanSino Biologics Viral No funding disclosed. Ph. I complete: 108/China Immunogenicity: Ph. I participants developed binding antibodies, neutralizing Lancet Ad5 vector expressing vector Ph. II ongoing: 508/China antibodies and T-cell responses; potential for pre-existing immunity against Ad5. FiercePharma SARS-CoV-2 spike Ph.III ongoing: 40K/ Argentina, Chile, Manufacturing/delivery: TBC. glycoprotein. Mexico, Pakistan, Saudi Arabia Platform history: Vaccine utilizing the Ad26 platform (Ad26.ZEBOV) has been Authorization: EUA in Mexico, Pakistan. approved for use against Ebola Virus Disease. Limited use in Chinese military as a “specially needed drug” Approval: None

Inovio INO-4800 DNA CEPI ($17.2M) Ph. I ongoing: 40/US Immunogenicity: Preliminary Ph. I data shows antibody and cellular immune Inovio Ph. 1 DNA plasmid vaccine with BMGF ($5M) Ph. II/III ongoing: 160/S Korea responses. Statement electroporation. USG ($83M) 6K/US Manufacturing/delivery: INO-4800 is stable at room temperature for more than a COVAX Portfolio year and is not required to be frozen in transport or storage. Platform history: No licensed DNA vaccines for use in humans.

CureVac CVnCoV mRNA CEPI ($8.3M) Ph. I ongoing: 284/Belgium, Germany Immunogenicity: TBC. CureVac mRNA vaccine that EU ($$421M) Ph. II ongoing: 691/Panama, Peru Manufacturing/delivery: mRNA vaccines are relatively easy to scale and statement encodes for the spike USG. (Undisclosed) Ph. II/III ongoing: 36,500/ Germany manufacture. protein formulated with COVAX Portfolio Ph. III ongoing: 2520/ Germany Platform history: No previously licensed mRNA vaccines. lipid nanoparticles.

(TBC)

Imperial College Synthetic self-amplifying Self- UK ($50.7M) Ph. I/II ongoing: 300/UK Immunogenicity: TBC. New York Times RNA producing SARS- amplifying Philanthropies ($6.2M) Ph. III planned: 6000/UK Manufacturing/delivery: Imperial College created a special-purpose company to CoV-2 spike protein. RNA sell the vaccine (VacEquity) at lowest possible cost in UK and LMICs. PRODUCT BEING REFORMULATED TO Platform history: No licensed self-amplifying RNA vaccines. (TBC) ADDRESS VARIANTS

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Last updated March 5, 2021 avac.org 2 Primary sponsor(s) Description Platform Funders Status Considerations Read more

Sanofi / GSK DNA from the surface Subunit USG ($2.1B) Ph. I/II ongoing: 440/US Immunogenicity: Interim results showed insufficient response in older adults; Sanofi Statement protein of the SARS-CoV-2 Warp Speed Finalist Ph. III planned: 30K/ Sanofi refining antigen concentration to address. virus is inserted into insect US+ (Delayed) Manufacturing/delivery: The adjuvant system is designed to boost the immune cells, which express antigen response and allow less to be used per dose. GSK will manufacture 1B doses of its that is then purified and adjuvant system in 2021. combined with GSK’s Platform history: Same platform as vaccine candidates for Influenza, SARS-CoV pandemic AS03 adjuvant. (FDA approve).

Clover BIoPharma / GSK SCB-2019 Subunit CEPI ($3.5M) Ph. I ongoing: 150/Australia Immunogenicity: In preclinical studies, adjuvanted SCB-2019 induced neutralising Press release A trimeric subunit spike Ph. II/III planned antibodies in animals. protein developed by China- Manufacturing/delivery: The adjuvant system is designed to boost the immune based Clover, delivered response and allow less to be used per dose, potentially allowing more doses to be alongside an adjuvant. supplied. GSK will manufacture 1B doses of its adjuvant system in 2021. Platform history: TBC. (TBC)

Refresher on vaccine platforms

Platform About Licensed products Learn more Inactivated vaccines consist of the whole virus, which has been killed with heat or chemicals so that it can’t cause illness. Polio Inactivated viral vaccines Inactivated In general, inactivated virus vaccines do not provide as strong of an immune response as live attenuated vaccines, so additional doses may be needed. Live attenuated vaccines are made up of whole viruses that have been weakened in a lab (usually through culturing). MMR Live attenuaed vaccines: historical Live attenuated They tend to elicit a stronger immune response than inactivated vaccines. Varicella successes and current challenges TB Subunit vaccines introduce a fragment or portion of the virus into the body. This fragment is enough to be recognized Pertussis Subunit Vaccines Subunit by the immune response and stimulate immunity. HPV Hep. B Viral vector vaccines insert a gene for a viral protein into another, harmless virus (replicating or non-replicating). Ebola What are viral vector vaccines? Viral vector This harmless virus then delivers the viral protein to the vaccine recipient, which triggers an immune response. Veterinary vaccines • Replicating viral vectors are able to produce copies of the viral protein, potentially triggering an enhanced immune response. RNA vaccines work by introducing an mRNA sequence (the molecule that tells cells what to build) coded for a disease- None An introduction to RNA vaccines mRNA specific antigen. Once this antigen is reproduced within the body, it is recognized and triggers an immune response.

DNA-based vaccines work by inserting synthetic DNA of viral gene(s) into small DNA molecules called plasmids. None WHO: About DNA vaccines DNA Cells take in the DNA plasmids and follow their instructions to build viral proteins, which are recognized by the immune system, and prepare it to respond to disease exposure.

*Operation Warp Speed: US government body responsible for strategic approach, coordination and resource allocation for COVID-19 vaccines **COVAX: The vaccine pillar of ACT-A, the global collaboration to accelerate development, production and equitable access to new diagnostics, therapeutics and vaccines. COVAX is led by GAVI, CEPI and WHO.

About AVAC. AVAC is a non-profit organization that uses education, policy analysis, advocacy and a network of global collaborations to accelerate the ethical development and global delivery of new HIV prevention options as part of a comprehensive response to the pandemic. For more information, visit www.avac.org.

Last updated March 5, 2021 Cheat Sheet: COVID-19 vaccine pipeline 3