COVID-19 Vaccine Technology

COVID-19 Vaccine Technology

COVID-19 is a global pandemic caused by infections due to the SARS-CoV-2 virus. There has been a steady increase in the cumulative cases of COVID-19 worldwide since March 2020, when WHO declared COVID-19 a pandemic. Due to its high transmissibility, the COVID-19 pandemic has resulted in over 460 million infections and over 6 million deaths globally as of March 2022.

SARS-CoV-2, the RNA virus that causes COVID-19, has a trimeric spike (S) protein on its viral envelope that is responsible for binding to the host cell surface receptor, ACE2, and subsequent viral entry, making it the primary target antigen for vaccine development.

Vaccines against COVID-19 that elicit protective immune responses are crucial to the prevention and mitigation of infection caused by the SARS-CoV-2 virus. Leveraging Trimer-Tag™ technology platform, we developed the SCB-2019 antigen and combined it with Dynavax’s CpG 1018 advanced adjuvant and aluminum hydroxide (alum), to create our protein-based COVID-19 vaccine candidate. SCB-2019 (CpG 1018/Alum), our COVID-19 vaccine candidate, is a recombinant SARS-CoV-2 fusion protein that preserves the native trimeric structure of the S-protein in the prefusion conformation form, which is important for eliciting protective immunity against the SARS-CoV-2 virus.

Our COVID-19 vaccine candidate: SCB-2019 (CpG 1018/Alum)

In September 2021, Clover announced that SPECTRA, a global pivotal Phase 2/3 clinical trial evaluating the efficacy, safety, and immunogenicity of SCB-2019 (CpG 1018/Alum) met the primary and secondary efficacy endpoints.

We plan to submit conditional regulatory approval applications to the EMA, the NMPA and the WHO in the near term.
SARS-CoV-2 virus Spike (S) Protein
Viral Envelope
A stabilized trimeric antigen of the S-protein (S-Trimer™) developed by Trimer-Tag™

Responding to the global crisis with innovative vaccine technology

By employing the Trimer-Tag™ technology platform, we developed the SCB-2019 antigen, a stabilized trimeric form of the S-protein (S-Trimer™) based on the original strain of SARS-CoV-2.

SCB-2019 (CpG 1018/Alum) is adjuvanted with CpG 1018 and Alum to elicit strong immune responses. Both adjuvants are proven technologies currently used in FDA- and EMA-approved and commercialized vaccines. These two adjuvants are produced at scale under cGMP conditions and have significant safety databases in clinical and post-marketing studies.

The use of adjuvants is also of particular importance in a pandemic since it may reduce the amount of antigen required per dose, allowing more vaccine doses to be produced quickly.

In pre-clinical studies, a Phase 1 clinical trial and global Phase 2/3 SPECTRA Trial, SCB-2019 (CpG 1018/Alum) demonstrated the following advantages, making it a promising COVID-19 vaccine candidate:

  • Strong immune responses potentially leading to protective immunity.

    In SPECTRA, SCB-2019 (CpG 1018/Alum) demonstrated 100% efficacy against severe COVID-19, 100% efficacy against hospitalizations due to COVID-19, and 83.7% efficacy against moderate-to-severe COVID-19 cases caused by any strain of SARS-CoV-2. SCB-2019 (CpG 1018/Alum) was also the first COVID-19 vaccine candidate to demonstrate significantly reduced risk of COVID-19 in previously infected individuals. As published in The Lancet, in a Phase 1 clinical trial SCB-2019 (CpG 1018/Alum) induced high neutralizing antibody titers and Th1-biased cell-mediated immune responses, implying a balanced immune response. Neutralizing antibodies can prevent viruses from interacting with host cells and are part of humoral immunity. Virus specific CD4+ T-cell immune responses were detected in patients who recovered from COVID-19, which were mainly associated with Th1 cytokines, suggesting that strong Th1-biased cell-mediated immune responses are likely to contribute to vaccine efficacy.

  • Potentially differentiated and favorable safety profile.

    SCB-2019 (CpG 1018/Alum) demonstrated a favorable safety profile in SPECTRA, with no significant differences in systemic solicited adverse events or severe/serious adverse events compared to placebo. Moreover, in the Phase 1 clinical trial, SCB-2019 (CpG 1018/Alum) demonstrated weak or no Th2- and Th17- cellular immune responses, which are risk factors for vaccine associated enhanced respiratory disease (VAERD). Adjuvanted protein-based vaccines for a wide range of viruses have been approved and commercialized prior to the COVID-19 pandemic, unlike some other vaccine development platforms, such as mRNA, adenovirus, and DNA.

  • Highly stable and well-suited for global storage and distribution.

    Based on our ongoing stability studies, SCB-2019 (CpG 1018/Alum) is expected to be stable under standard refrigeration (2-8°C) storage and transportation conditions. As such, SCB-2019 (CpG 1018/Alum) is a potentially preferable and a more cost-effective solution for global distribution by leveraging existing and conventional infrastructure, a necessity when transporting to remote and low-resource regions.

  • Well-characterized manufacturing processes at our in-house commercial-ready facility with large-scale production capacity.

    We are potentially able to produce more than one billion doses of SCB-2019 annually at peak capacity at our commercial-scale manufacturing facility located in Changxing, Zhejiang province, China. This facility is certified by a QP within the European Union (EU), a requirement to achieve EU current Good Manufacturing Practices (cGMP) standards. The manufacturing process for SCB-2019 is well-characterized and similar to that of other recombinant proteins. We are following these cGMP standards at our Changxing manufacturing facility to ensure a high level of quality control, allowing us to quickly scale up for mass vaccination. Moreover, we believe SCB-2019 (CpG 1018/Alum) could be a cost-effective vaccine product given the high productivity of the manufacturing process.

SPECTRA, a Global Phase 2/3 Clinical Trial for SCB-2019 (CpG 1018/Alum)

In September 2021, SCB-2019 (CpG 1018/Alum) achieved the primary efficacy endpoint and secondary efficacy endpoints in SPECTRA. Based on the SPECTRA results, SCB-2019 (CpG 1018/Alum) demonstrated 100% efficacy against severe COVID-19, 100% efficacy against hospitalizations due to COVID-19, and 84% efficacy against moderate-to-severe COVID-19 caused by any strain of SARS-CoV-2 in SPECTRA. Against the Delta variant, SCB-2019 (CpG 1018/Alum) demonstrated 79% efficacy against COVID-19 of any severity in SPECTRA. SCB-2019 (CpG 1018/Alum) also had a favorable safety profile in SPECTRA with no significant differences in systemic solicited adverse events or severe/serious adverse events compared to placebo. Moreover, SCB-2019 (CpG 1018/Alum) was the first COVID-19 vaccine candidate to demonstrate a significantly reduced risk of COVID-19 in previously infected individuals.

We subsequently plan to submit conditional regulatory approval applications to the NMPA, the EMA and the WHO in the near-term. SPECTRA, our global, pivotal Phase 2/3 clinical trial for vaccine efficacy, safety, and immunogenicity. SPECTRA is a double-blind, randomized, controlled study of SCB-2019 (CpG 1018/Alum) in a two-dose regimen, given 21 days apart. SPECTRA commenced in March 2021 and enrolled over 30,000 adult and elderly participants across Latin America, Asia, Europe, and Africa.

For more details about the trial, visit clinicaltrials.gov

Advancing our COVID-19 Development Platform

SCB-2019 (CpG 1018/Alum)

We plan to submit conditional regulatory approval applications to the NMPA, the EMA, and the WHO in the near-term. We also intend to supply additional SCB-2019 (CpG 1018/Alum) post conditional approval via bilateral negotiations and supply arrangements with global governments.

Clover has also expanded the SPECTRA clinical trial to evaluate adolescents and we plan to initiate a trial for the pediatric population.

Clover and investigators are conducting multiple clinical trials exploring SCB-2019 (CpG 1018/Alum) as a heterologous booster, which is the administration of a different COVID-19 vaccine technology from the primary vaccination, and as a homologous booster following primary vaccination with SCB-2019 (CpG 1018/Alum).

Developing our second-generation COVID-19 vaccines

Multiple variants of the SARS-CoV-2 virus have emerged and are circulating globally. Given the error-prone nature of RNA virus replication, more variants will inevitably emerge as the virus is transmitted.

We are leveraging the proprietary Trimer-Tag™ technology platform to develop candidates that have the potential to expand the breadth of vaccine-induced neutralizing antibodies to address the existing and potential new variant strains of the SARS-CoV-2 virus. We have advanced SCB-2020s (CAS-1), a second-generation, potentially broadly protective COVID-19 vaccine candidate based on the chimeric Beta variant and the prototype trimeric SARS-CoV-2 S-protein, into a Phase 1 clinical trial. CAS-1 is Clover’s proprietary oil-in-water emulsion-based adjuvant system developed in-house. We also continue to develop our bivalent COVID-19 vaccine candidate, which combines the trimeric spike antigen from the original SARS-CoV-2 strain and the Omicron variant.

Fostering collaboration for worldwide vaccine access

Clover understands the need for equitable distribution and access to COVID-19 vaccines. To support this global effort, we have partnered with and are fully funded by the Coalition for Epidemic Preparedness Innovations (CEPI). CEPI has agreed to provide Clover with up to $397.4 million in grant funding to support the development of SCB-2019 (CpG 1018/Alum), procurement, and allocation through the COVAX Facility to help protect at-risk populations in participating countries.

Key Milestones

2020
2021

January 2020

Announced a plan to develop SCB-2019 as a COVID-19 vaccine candidate

February 2020

Achieved initial S-Trimer™ antigen expression for SCB-2019

March 2020

Entered into a collaboration with Dynavax

April 2020

Announcement of CEPI partnership

June 2020

First participants dosed with adjuvanted COVID-19 vaccine candidates in a Phase 1 clinical trial

September 2020

Announced positive, preclinical adjuvanted COVID-19 vaccine candidate data and the formation of a Global SAB

November 2020

Additional Funding from CEPI totaling $328 million

December 2020

Announced positive clinical data from a Phase 1 clinical trial evaluating the adjuvanted COVID-19 vaccine candidates

February 2021

Publication of the Phase 1 clinical trial data for our adjuvanted COVID-19 vaccine candidates in The Lancet

Clover and Dynavax announce plans for a global Phase 2/3 efficacy trial

March 2021

Initiation and first participants dosed in SPECTRA, a Global Phase 2/3 Clinical Trial for Adjuvanted COVID-19 Vaccine Candidate

May 2021

Announced Positive Preclinical Data for Second-Generation Protein-Based COVID-19 Vaccine Candidate Demonstrating Broad Neutralization Against Variants of Concern

June 2021

SPECTRA Global enrollment surpassed 29,000 adult and elderly participants resulting in one of the most ethnically diverse COVID-19 clinical trials conducted to date, including over 45% of participants from Asia, 45% from Latin America and the remainder from Europe and Africa

Sep 2021

Announced that Clover’s adjuvanted protein-based COVID-19 vaccine candidate, SCB-2019 (CpG 1018/Alum) achieved the primary efficacy endpoint and secondary efficacy endpoints in SPECTRA, a global pivotal Phase 2/3 clinical trial.

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FAQs

  • What were the key takeaways from SPECTRA, a global phase 2/3 study for SCB-2019 (CpG 1018/Alum)?

    SPECTRA, our global Phase 2/3 clinical trial, evaluated the efficacy, safety and immunogenicity of SCB-2019 (CpG 1018/Alum). This study was a double-blind, randomized, controlled study of SCB-2019 (CpG 1018/Alum) in a two-dose regimen, given 21 days apart.

    SPECTRA met the primary and secondary efficacy endpoints in September 2021, demonstrating 100% efficacy against severe COVID-19, 100% efficacy against hospitalizations due to COVID-19, and 84% efficacy against moderate-to-severe COVID-19 caused by any strain of SARS-CoV-2 in SPECTRA. Against the globally dominant Delta variant, SCB-2019 (CpG 1018/Alum) demonstrated 79% efficacy against COVID-19 of any severity in SPECTRA. SCB-2019 (CpG 1018/Alum) also had a favorable safety profile in SPECTRA with no significant differences in systemic solicited adverse events or severe/serious adverse events compared to placebo. Moreover, SCB-2019 (CpG 1018/Alum) was the first COVID-19 vaccine candidate to demonstrate a significantly reduced risk of COVID-19 in previously infected individuals.

  • How is Clover’s SCB-2019 (CpG 1018/Alum) COVID-19 Vaccine candidate stored?

    SCB-2019 (CpG 1018/Alum) is stable for at least two months at room temperature and is expected to be stable for approximately 12 months in refrigeration conditions. The ability to store SCB-2019 (CpG 1018/Alum) in standard refrigeration temperatures or room temperature makes it a potentially preferable and a more cost-effective solution for global distribution, leveraging existing and conventional infrastructure, a necessity when transporting to remote and low-resource regions.

  • How will Clover’s SCB-2019 (CpG 1018/Alum) be distributed globally?

    Clover’s COVID-19 vaccine candidate, if approved, will be available for procurement and allocation through the COVAX Facility, a global initiative established by WHO, GAVI, and CEPI.

    Clover may also consider commercializing SCB-2019 (CpG 1018/Alum) post conditional approval via bilateral negotiations and supply arrangements with global governments.