COVAX-19 (GC004) / Flinders University, Vaxine, GeneCure Biotechnologies, Medytox, CinnaGen - LARVOL DELTA

A Phase 3b/4 Randomised Trial of 3 Doses of Protein-based Covid-19 Vaccine (SpikoGen) (clinicaltrials.gov) - P3 | N=39 | Completed | Sponsor: Vaxine Pty Ltd | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease

Booster Study of SpikoGen COVID-19 Vaccine (clinicaltrials.gov) - P3 | N=81 | Completed | Sponsor: Vaxine Pty Ltd | Active, not recruiting ➔ Completed | N=150 ➔ 81 | Trial completion date: Oct 2024 ➔ Sep 2025

Enrollment change • Trial completion • Trial completion date • Infectious Disease • Novel Coronavirus Disease

Immunogenicity and safety study of a single dose of SpikoGen® vaccine as a heterologous or homologous intramuscular booster following a primary course of mRNA, adenoviral vector or recombinant protein COVID-19 vaccine in ambulatory adults. (PubMed, Vaccine) - P3 | "A single SpikoGen® booster was well tolerated and stimulated cross- antibody responses against Omicron variants, regardless of the primary vaccine course received. With SARS-CoV-2 variants continuing to evolve, ongoing research is needed into optimum booster strategies."

Journal • Infectious Disease • Novel Coronavirus Disease • Pediatrics • Respiratory Diseases

Evaluation of anti-SARS-CoV-2 RBD antibody response after booster dose of SpikoGen® in individuals with two previous doses of Sinopharm and its association with HLA-DR and -DQ alleles. (PubMed, Hum Immunol) - "In conclusion, our study showed that the booster dose of SpikoGen® can elicit a robust anti-RBD antibody response which was positively associated with DRB1*14 allele."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • HLA-DQB1 • HLA-DRB1

Effect of SpikoGen subunit vaccine administration during pregnancy on fetal development of rats. (PubMed, Clin Exp Vaccine Res) - "Also, there was no difference in the overall skeletal opacity and density between the control and treatment groups. The results of this study indicated no negative impacts of the vaccine administration during pregnancy on developing of fetuses in rats."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Effects of age and gender on immunogenicity and reactogenicity of SpikoGen recombinant spike protein vaccine: a post-hoc analysis. (PubMed, Sci Rep) - "Overall, SpikoGen® exhibited positive immunogenicity and low reactogenicity, indicating that a low incidence of adverse events does not equate to poor immunogenicity. SpikoGen® remains a promising protein-based vaccine platform for COVID-19 protection."

Journal • Retrospective data • Fatigue • Infectious Disease • Musculoskeletal Pain • Novel Coronavirus Disease • Pain

Post-Hoc Analysis of Potential Correlates of Protection of a Recombinant SARS-CoV-2 Spike Protein Extracellular Domain Vaccine Formulated with Advax-CpG55.2-Adjuvant. (PubMed, Int J Mol Sci) - "SpikoGen® further reduced the risk of re-infection (OR 0.29) in baseline seropositive (previously infected) as well as baseline seronegative participants. This indicates that while SpikoGen vaccine is protective in seronegative individuals, those with hybrid immunity have the most robust protection."

Clinical • Journal • Retrospective data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Australian Phase 2b Study to Assess Effect of Dose Interval on Spikogen Covid-19 Vaccine (clinicaltrials.gov) - P2/3 | N=200 | Active, not recruiting | Sponsor: Vaxine Pty Ltd | Trial completion date: Jun 2024 ➔ Oct 2024

Trial completion date • Infectious Disease • Novel Coronavirus Disease

A Phase 3b/4 Randomised Trial of 3 Doses of Protein-based Covid-19 Vaccine (SpikoGen) (clinicaltrials.gov) - P3 | N=39 | Active, not recruiting | Sponsor: Vaxine Pty Ltd | Trial completion date: Jun 2024 ➔ Oct 2024

Trial completion date • Infectious Disease • Novel Coronavirus Disease

Booster Study of SpikoGen COVID-19 Vaccine (clinicaltrials.gov) - P3 | N=150 | Active, not recruiting | Sponsor: Vaxine Pty Ltd | Trial completion date: Jun 2024 ➔ Oct 2024

Trial completion date • Infectious Disease • Novel Coronavirus Disease

The immunologic outcomes and adverse events of COVID-19 vaccine booster dose in immunosuppressed people: A systematic review. (PubMed, Prev Med Rep) - "This study examines the efficacy and safety of three COVID-19 booster vaccines including mRNA-based vaccines (BNT162b2 (BioNTech/Pfizer) and/or mRNA-1273 (Moderna)), Non-Replicating Viral-Vector vaccines (ChAdOx1 nCoV-19 vaccine (AstraZeneca) and/or Ad26...This systematic review highlights preliminary evidence supporting the immunologic outcomes and safety of COVID-19 vaccine boosters in enhancing immune responses against SARS-CoV-2. However, further research is needed to determine optimal timing intervals between primary vaccination series and boosters while considering global equity issues and variant-specific considerations."

Adverse events • Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Clinical development of SpikoGen®, an Advax-CpG55.2 adjuvanted recombinant spike protein vaccine. (PubMed, Hum Vaccin Immunother) - "Eight million doses of SpikoGen® have been delivered, and a next-generation booster version is currently in development. This highlights the benefits of adjuvanted protein-based approaches which should not overlook when vaccine platforms are being selected for future pandemics."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Pediatrics • Respiratory Diseases

Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is a cellular receptor for delta inulin adjuvant. (PubMed, Immunol Cell Biol) - "Together, these results identify DC-SIGN as a putative receptor for Advax. Given the known immunomodulatory role of DC-SIGN, the findings described here have implications for the use of Advax adjuvants in humans and inform future mechanistic studies."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • ICAM3

Australian Phase 2b Study to Assess Effect of Dose Interval on Spikogen Covid-19 Vaccine (clinicaltrials.gov) - P2/3 | N=200 | Active, not recruiting | Sponsor: Vaxine Pty Ltd | Trial completion date: Feb 2024 ➔ Jun 2024 | Phase classification: P2b ➔ P2/3

Phase classification • Trial completion date • Infectious Disease • Novel Coronavirus Disease

A Phase 3b/4 Randomised Trial of 3 Doses of Protein-based Covid-19 Vaccine (SpikoGen) (clinicaltrials.gov) - P3 | N=39 | Active, not recruiting | Sponsor: Vaxine Pty Ltd | Phase classification: P3b/4 ➔ P3 | Trial completion date: Dec 2023 ➔ Jun 2024 | Trial primary completion date: Aug 2023 ➔ Dec 2023

Phase classification • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Comparative Immunogenicity and Neutralization Potency of Four Approved COVID-19 Vaccines in BALB/c Mice. (PubMed, Iran J Immunol) - "Our results indicate significant immunogenicity and neutralization efficacy induced by PastoCovac Plus and Sinopharm, but not by Noora and SpikoGen. This suggests the need for additional comparative assessment of the potency and efficacy of these four vaccines in vaccinated subjects."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Comparative immunogenicity and safety of SpikoGen®, a recombinant SARS-CoV-2 spike protein vaccine in children and young adults: An immuno-bridging clinical trial. (PubMed, Int Immunopharmacol) - "SpikoGen® vaccine was shown to be safe, well tolerated and immunogenic in children as young as 5 years of age, with non-inferior responses to those seen in adults. The Iranian FDA authorisation of SpikoGen® vaccine is now extended down to 5 years of age."

Journal • Fatigue • Infectious Disease • Novel Coronavirus Disease • Pain • Respiratory Diseases

Advax-CpG55.2-adjuvanted monovalent or trivalent SARS-CoV-2 recombinant spike protein vaccine protects hamsters against heterologous infection with Beta or Delta variants. (PubMed, Vaccine) - "Overall, the study results confirmed that the current SpikoGen® vaccine based on Wuhan spike protein was still able to protect against clinical disease caused by either the Beta or Delta virus variants but suggested additional protection may be obtained by combining it with extra variant spike proteins to make a multivalent formulation. This study highlights the complexity of optimizing vaccine protection against multiple SARS-CoV-2 variants and stresses the need to continue to pursue new and improved COVID-19 vaccines able to provide robust, long-lasting, and broadly cross-protective immunity against constantly evolving SARS-CoV-2 variants."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Vaccination is the most effective and best way to avoid the disease of COVID-19. (PubMed, Immun Inflamm Dis) - "Among the vaccines that stimulate the host's immune system with the help of DNA are: undergoing Phase 2/3 trials including INO-4800 (International Vaccine Institute; Inovio Pharmaceuticals), Symvivo, Canada-COVID19 (AnGes, Inc.); GX-19 (Genexine, Inc.). BNT162b2 and mRNA-1273 vaccines were made by BioNTech/Pfizer/Fosun Pharma group and Moderna/NIAID group, respectively, which are considered as types of RNA vaccines...Among the inactive viral vaccines, the following can be mentioned: CoronaVac (Sinovac) WIBP vaccine (Wuhan Institute of Biological Products, Sinopharm), BBIBPCorV (Beijing Institute of Biological Products, Sinopharm), BBV152/Covaxin (Bharat Biotech, ICMR, National Institute of Virology) And among the protein-based/subunit vaccines, the following can be counted: NVX-CoV2373: (Novavax); SCB-2019 vaccine (Clover Biopharmaceuticals AUS Pty Ltd.); Covax-19 (GeneCure Biotechnologies; Vaxine Pty Ltd.) mRNA vaccines, viral vector vaccines, and protein..."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Developmental and reproductive safety of Advax-CpG55.2™ adjuvanted COVID-19 and influenza vaccines in mice. (PubMed, Vaccine) - "No evidence of antigen interference was observed when SpikoGen® vaccine was mixed and co-administered with influenza hemagglutinin vaccine to pregnant dams. Together with the strong safety profile of SpikoGen® vaccine seen in adults and children in human trials, this DART study data supports the safety of Advax-CpG55.2 adjuvanted COVID-19 and influenza vaccine in women of childbearing potential including during pregnancy."

Journal • Preclinical • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases

Immunogenicity and Safety of a Booster Dose of the SpikoGen Vaccine in Kidney Transplant Recipients After Two Doses of Sinopharm Vaccine (clinicaltrials.gov) - P=N/A | N=43 | Completed | Sponsor: Cinnagen | Recruiting ➔ Completed | N=100 ➔ 43

Enrollment change • Trial completion • Infectious Disease • Novel Coronavirus Disease • Transplantation

A Phase 3b/4 Randomised Trial of 3 Doses of Protein-based Covid-19 Vaccine (SpikoGen) (clinicaltrials.gov) - P3b/4 | N=39 | Active, not recruiting | Sponsor: Vaxine Pty Ltd | Recruiting ➔ Active, not recruiting | N=400 ➔ 39

Enrollment change • Enrollment closed • Infectious Disease • Novel Coronavirus Disease

Spikogen Booster Study (clinicaltrials.gov) - P3 | N=150 | Active, not recruiting | Sponsor: Vaxine Pty Ltd | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2023 ➔ Jun 2024 | Trial primary completion date: Apr 2023 ➔ Dec 2023

Enrollment closed • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Ability of SpikoGen®, an Advax-CpG adjuvanted recombinant spike protein vaccine, to induce cross-neutralising antibodies against SARS-CoV-2 variants. (PubMed, Immunology) - "This resulted in high neutralisation including against the Omicron variants. This data supports ongoing use of SpikoGen® vaccine for protection against recent SARS-CoV-2 Omicron variants."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Australian Phase 2b Study to Assess Effect of Dose Interval on Spikogen Covid-19 Vaccine (clinicaltrials.gov) - P2b | N=200 | Active, not recruiting | Sponsor: Vaxine Pty Ltd | Trial completion date: Mar 2023 ➔ Feb 2024 | Trial primary completion date: Oct 2022 ➔ Feb 2023

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease