COVID-19 Vaccines Under Clinical Development

Ad5-nCoV (Recombinant Novel Coronavirus Vaccine - Adenovirus Type 5 Vector)

Phase - II

Non- Replicating Viral Vector

CanSino Biologics Inc.

Hubei, China

Insitute of Biotechnology, Academy of Military Medical Sciences, PLA of China

1. Adverse reactions
   (Time frame: 0-14 days post vaccination)
2. Anti-S antibody IgG titer
   (Time frame: on day 28 post vaccination)
3. Anti-SARS-CoV-2 neutralizing antibody titer
   (Time frame: on day 28 post vaccination)

December 30, 2020

• On March 17, 2020, China approved the first clinical trial of the recombinant novel coronavirus vaccine jointly developed by Cansino and the Institute of Biotechnology; the trial will enroll 108 subjects at Tongji Hospital in Wuhan, China
• Ad5-nCov is a genetically engineered vaccine candidate with the replication-defective adenovirus type 5 as the vector to express SARS-CoV-2 spike protein; used Sartorius' Biostat STR single-use bioreactor system for the upstream preparation of the recombinant vaccine

• Occurrence of adverse reactions
  (Time frame: 0-14 days post vaccination)
• Anti SARS-CoV-2 S antibody response(ELISA)
  (Time frame: 28 days post vaccination)
• Neutralizing antibody response to SARS-CoV-2
  (Time frame: 28 days post vaccination)

January 31, 2021

ChAdOx1 nCoV-19

Phase - II

Non- Replicating Viral Vector

University of Oxford

Hampshire, United Kingdom

-NA-

1. Assess efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19 -
   • Number of virologically confirmed (PCR positive) symptomatic cases (6 months)
2. Assess the safety of the candidate vaccine ChAdOx1 nCoV -
   • Occurrence of serious adverse events (SAEs) (6 months)

May 2021

-NA-

mRNA-1273

Phase - II (IND Accepted)

LNP-encapsulated mRNA

National Institute of Allergy and Infectious Diseases (NIAID)

United States

Moderna

1. Frequency of:
   • solicited local reactogenicity adverse events (AEs) (Through 7 days post-vaccination)
   • any medically-attended adverse events (MAAEs) (Day 1 to Day 394)
   • new-onset chronic medical conditions (NOCMCs) (Day 1 to Day 394)

June 1, 2021

• As of April 17, BARDA's commitment of up to $483M would enable the company to ramp their supply if the vaccine candidate is successful in the clinic

INO-4800

Phase - I

DNA plasmid vaccine with electroporation

Inovio Pharmaceuticals

United States

Coalition for Epidemic Preparedness Innovations (CEPI)

1. Percentage of Participants with
   • Adverse Events (AEs) (Baseline up to Week 52)
   • Administration (Injection) Site Reactions (Day 0 up to Week 52)
   • Adverse Events of Special Interest (AESIs) (Baseline up to Week 52)
2. Change from Baseline in -
   • Antigen-Specific Binding Antibody Titers ((Baseline up to Week 52)
   • Antigen-Specific Interferon-Gamma (IFN-γ) Cellular Immune Response (Baseline up to Week 52)

April 2021

• As of April 16, the International Vaccine Institute said the Coalition for Epidemic Preparedness Innovations granted $6.9M to Inovio to work with the IVI and the Korea National Institute of Health in a phase I/II trial of INO-4800 in South Korea

BNT162a1
(BNT162a1, BNT162b1, BNT162b2, BNT162c2)

Phase - II

mRNA

Biontech SE

Pfizer

1. Percentage of participants reporting local reactions [ Time Frame: For 7 days after dose 1 and dose 2 ]
   • Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
2. Percentage of participants reporting systemic events (Time Frame: For 7 days after dose 1 and dose 2)
   • Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.

January 27, 2023

• Pfizer confirmed lead compound shows antiviral activity; as of April 9, clinical study could start in third quarter; as of April 23, Biontech announced German regulator approved phase I/II program
• The company will test four different candidates, two of which have nucleoside modified mRNA, one with a uridine containing mRNA and another with a self-amplifying mRNA construct
• All are lipid nanoparticle formulations and as of April 29, they completed dosing of 12 patients in first cohort of the COVID-19 prophylaxis study in Germany
• As of May 5, first participants dosed in phase I/II trial in U.S. Study is designed to determine safety, immunogenicity and optimal dose of four candidates; estimated enrollment is 7,600

Inactivated vaccine

Phase - I/II

Inactivated

Wuhan Institute of Biological Products

Hubei, China

Sinopharm

Incidence of adverse reactions/events
(Time Frame: 0-7 days after each dose of vaccination)

November 2021

-NA-

Inactivated vaccine

Phase - I/II

Inactivated

Beijing Institute of Biological Products

Hubei, China

Sinopharm

Incidence of adverse reactions/events
(Time Frame: 0-7 days after each dose of vaccination)

November 2021

-NA-

Inactivated SARS-CoV-2 vaccine

Phase - I/II

Inactivated + alum

Sinovac Research and Development

Hubei, China

-NA-

A. Clinical Trial Identifier - NCT04383574 -

1. Safety index-incidence of adverse reactions (Day 0-28 after each dose vaccination)
   • Incidence of adverse reactions after each dose vaccination
2. Immunogenicity index-seroconversion rates of neutralizing antibody (30th day after the second dose vaccination)
   • Neutralizing antibody assay will be performed using the micro-neutralization method. Seroconversion will be defined as a change from seronegative (<1:8) to seropositive (≥1:8), or ≥4 fold increase from baseline.

July 20, 2020

-NA-

B. Clinical Trial Identifier - NCT04352608

1. Safety indexes of adverse reactions (beginning of the vaccination to 28 days after the whole schedule vaccination)
   • Occurence of adverse reactions post vaccination
2. Immunogenicity indexes of neutralizing-antibody seroconversion rates for the emergency vaccination schedule (14th day after two doses of vaccination)
   • The seroconversion rates of neutralizing antibodies against 2019 novel coronavirus tested by micro-neutralization assay in serum
3. Immunogenicity indexes of neutralizing-antibody seroconversion rates for the routine vaccination schedule (28th day after two doses of vaccination)
   • The seroconversion rates of neutralizing antibodies against 2019 novel coronavirus tested by micro-neutralization assay in serum

August 13, 2020

-NA-

Pathogen-specific aAPC Vaccine

Phase - I

-NA-

Shenzhen Geno-Immune Medical Institute

Guangdong, China

Shenzhen Third People's Hospital; Shenzhen Second People's Hospital

1. Frequency of vaccine events
   (Time frame: Measured from Day 0 through Day 28)
2. Frequency of serious vaccine events
   (Time frame: Measured from Day 0 through Day 28)
3. Proportion of subjects with positive T cell response
   (Time frame: 14 and 28 days after randomization)

July 31, 2023

-NA-

Lentiviral Minigene Vaccine (LV-SMENP)

Phase - II

-NA-

Shenzhen Geno-Immune Medical Institute

Guangdong, China

Shenzhen Third People's Hospital; Shenzhen Second People's Hospital

1. Clinical improvement based on the 7-point scale
   (Time frame: 28 days after randomization)
2. Lower Murray lung injury score
   (Time frame: 7 days after randomization)

July 31, 2023

• A decline of 2 points on the 7-point scale from admission means better outcome. The 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death)
• Murray lung injury score decrease more than one point means better outcome. The Murray scoring system range from 0 to 4 according to the severity of the condition."

BCG Vaccine (Intradermal)

Phase - III

-NA-

Ain Shams University

Cairo, Non-US, Egypt

-NA-

1. Estimate the incidence of confirmed COVID-19 among the healthcare workers in isolation hospitals
   (Time frame: 9 months)
2. Evaluate the effectiveness of BCG vaccine in protecting the healthcare workers in isolation hospitals against the risk of COVID-19 infection
   (Time frame: 9 months)

October 1, 2020

-NA-

BCG Vaccine

Phase - III

-NA-

UMC Utrecht

Netherlands

Radboud University

Health Care Workers absenteeism (Maximum of 180 days)

October 25, 2020

-NA

Inactivated SARS-CoV-2 vaccine

Inactivated + alum

Sinovac Research and Development Co., Ltd.

Measles-Mumps-Rubella Vaccine (MV-COVID19)

Phase - III

-NA-

Kasr El Aini Hospital

Cairo, Egypt

-NA-

Number of participants with asymptomatic or mild COVID-19 disease defined as fever, plus at least one sign or symptom of respiratory disease including cough, runny/blocked nose, plus positive SARS-Cov-2 test (Time frame: Measured over the 6 months following randomization)

October 1, 2020

-NA-

BCG Vaccine

Phase - III

-NA-

Universidad de Antioquia

Antioquia, Colombia

-NA-

Incidence of COVID-19 cases confirmed or probable in the study population (From date of randomization to 360 day of the study)

June 2021

-NA-

BCG Vaccine

Phase - III

-NA-

Murdoch Childrens Research Institute

Australia

Royal Children's Hospital

1. Number of participants with COVID-19 disease defined as (Measured over the 6 months following randomisation) -
   • fever (using self-reported questionnaire), plus
   • at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus
   • positive SARS-Cov-2 test (PCR or serology)
2. Severe COVID-19 disease incidence -
   • Number of participants who were admitted to hospital or died (Time frame: Measured over the 6 months following randomisation)

October 30, 2020

-NA-

BCG Vaccine

Phase - IV

NA

Texas A&M University

United States

Baylor College of Medicine; M.D. Anderson Cancer Center; Cedars-Sinai Medical Center; Harvard University

1. Incidence of COVID 19 Infection
   (Time frame: 6 months)

May 2022

-NA-

CAR-NK Cells

Phase - II

-NA-

Chongqing Public Health Medical Center

Chongqing, China

Chongqing Sidemu Biotechnology Technology Co.,Ltd.

1. Clinical response
   • Efficacy of NKG2D-ACE2 CAR-NK cells in treating severe and critical 2019 new coronavirus (COVID-19) pneumonia
2. Side effects in the treatment group
   • Safety and tolerability of NKG2D-ACE2 CAR-NK cells in patients with severe and critical 2019 new coronavirus (COVID-19) pneumonia

May 31, 2020

-NA-