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 128.9 million infections and 2.8 million deaths globally as of March 31, 2021.

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 by the SARS-CoV-2 virus. Leveraging Trimer-Tag™ platform, we developed SCB-2019, a recombinant SARS-CoV-2 fusion protein, that preserves the native trimeric structure of S-protein in the pre-fusion form, important for inducing antibodies against viral neutralization epitopes.

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

By combining SCB-2019 with Dynavax’s CpG 1018 advanced adjuvant and aluminum hydroxide (alum), we created a protein-based COVID-19 vaccine candidate, SCB-2019 (CpG 1018/Alum).

Clover is conducting SPECTRA, a global pivotal Phase 2/3 clinical trial evaluating the efficacy, safety, and immunogenicity of SCB-2019 (CpG 1018/Alum).
SARS-CoV-2 virus Spike (S) Protein
Viral Envelope
A stabilized trimeric antigen of the S-protein (S-Trimer™) developed by Trimer-Tag™

Supporting the global crisis response with innovative vaccine technology

Employing the Trimer-Tag™ technology platform, we have developed a 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 to elicit strong immune responses. These adjuvants such as CpG 1018 and aluminum hydroxide are used in FDA and EMA approved and commercialized vaccines. CpG 1018 and aluminum hydroxide 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 and a Phase 1 clinical 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.

    SCB-2019 (CpG 1018/Alum) is adjuvanted to elicit strong immune responses. Our Phase 1 clinical trial results, as published in The Lancet, demonstrated that SCB-2019 (CpG 1018/Alum) induced high neutralizing antibody titers and Th1-biased cell-mediated immune responses.

  • Potentially differentiated and favorable safety profile.

    In our Phase 1 clinical trial, SCB-2019 (CpG 1018/Alum) demonstrated a favorable safety profile with no serious vaccine-related adverse events and few moderate-to-severe local and systemic adverse events. 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).

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

    SCB-2019 (CpG 1018/Alum) is stable for at least two months at room temperature and is expected to be stable long term in refrigeration conditions. Because SCB-2019 (CpG 1018/Alum) can be stored at standard refrigeration temperatures or at room temperature, it 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.

  • Large-scale production capacity.

    We are potentially able to produce more than 1 billion doses of SCB-2019 annually at peak capacity at our commercial-scale manufacturing facility located in Changxing, Zhejiang province, China.

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

Based on positive results from preclinical study and a phase 1 trial, SCB-2019 (CpG 1018/Alum) is undergoing evaluation in 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 is expected to enroll over 22,000 adult and elderly participants across Latin America, Asia, Europe, and Africa. An interim analysis of the primary endpoint is expected in the middle of 2021. SCB-2019 (CpG 1018/Alum) could potentially become one of the first protein-based COVID-19 vaccines to be commercialized globally through the COVAX facility.

For more details about the trial, visit clinicaltrials.gov

Second-generation COVID-19 vaccine candidates

Multiple variants of the SARS-CoV-2 virus have emerged and are circulating globally, including but not limited to B.1.1.7, B.1.351 and P.1. New information about the characteristics of these variants is rapidly emerging and concerns regarding the effectiveness of currently authorized vaccines against these new strains have been raised. Clover is well-positioned to rapidly develop second-generation COVID-19 vaccine candidates to address the emerging variants of concern leveraging the Trimer-Tag™ technology platform.

In early 2021, we initiated the production of vaccine antigens against the three aforementioned variants of concern. We expect to make a candidate selection in 2021 and initiate clinical trials thereafter. The pre-clinical immunogenicity study in mice indicated that our monovalent B.1.351 vaccine could potentially be broadly protective against the currently circulating original strains and variants of concern. We continue to monitor the emerging strains and plan to initiate development of new vaccine candidates to target emerging variants of concern for the SARS-CoV-2 virus.

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 $328 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

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FAQs

  • What is the purpose of adjuvants in a vaccine?

    SCB-2019 (CpG 1018/Alum) is adjuvanted to elicit strong immune responses. These adjuvants such as CpG 1018 and aluminum hydroxide are used in FDA and EMA approved and commercialized vaccines. CpG 1018 and aluminum hydroxide 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.

  • What ages could be eligible for our COVID-19 vaccine candidate?

    SCB-2019 (CpG 1018/Alum) is currently being studied in individuals 18 years and older. Clover also plans to initiate additional clinical trials for SCB-2019 (CpG 1018/Alum) in subpopulations of COVID-19 vaccine addressable populations, including, but not limited to, immunocompromised patients and the pediatric population.

    We will explore our COVID-19 vaccine candidate in diverse age groups to evaluate the potential to help everyone at risk, and we are committed to developing and providing safe and effective COVID-19 vaccines for all communities in need.

  • Have there been any side effects with SCB-2019 (CpG 1018/Alum)?

    Side effects from vaccines are usually associated with the injection site (e.g., pain, redness, swelling) or are general systemic symptoms (e.g., fatigue, headache, myalgia). These side effects typically resolve within a few days after injection.

    Based on data from our preclinical studies and Phase 1 clinical trial, SCB-2019 (CpG 1018/Alum) appears to be well-tolerated with a favorable safety profile.

  • What does the Phase 1 data tell us?

    SCB-2019 (CpG 1018/Alum) has been shown to induce strong immune responses against the SARS-CoV-2 virus and demonstrated favorable safety and tolerability in adult and elderly subjects. No serious adverse events were reported.

  • What is the objective of SPECTRA, a global phase 2/3 study for SCB-2019 (CpG 1018/Alum)?

    SPECTRA, our global Phase 2/3 clinical trial, is evaluating the efficacy, safety and immunogenicity of SCB-2019 (CpG 1018/Alum). This study is a double-blind, randomized, controlled study of SCB-2019 (CpG 1018/Alum) in a two-dose regimen, given 21 days apart. This global efficacy study was initiated on March 24, 2021. The study is expected to enroll over 22,000 adult and elderly participants across Latin America, Asia, Europe, and Africa. An interim data readout on the primary endpoint is expected in the middle of 2021.

  • What steps are you taking to ensure the safety of SCB-2019 (CpG 1018/Alum)?

    Clover has a global management team with deep experience and capabilities in drug discovery, clinical operations, biomanufacturing, drug commercialization, and capital markets.

    As part of SPECTRA, we have formed an independent external Data and Safety Monitoring Board (DSMB). The DSMB will review clinical trial data on an ongoing basis to ensure the safety of trial participants and validity and integrity of data.

  • If the Phase 2/3 clinical trial is successful, how soon will SCB-2019 (CpG 1018/Alum) be available to the public?

    Pending positive results from the interim analysis on the primary endpoint in SPECTRA, we plan to submit conditional regulatory approval applications to the EMA, the NMPA, and the WHO in the second half of 2021. We will work closely with regulators around the world to ensure that, if approved, SCB-2019 (CpG 1018/Alum) is made available to all populations in need as soon as possible.

  • How many doses of SCB-2019 (CpG 1018/Alum) can be produced?

    Clover has an in-house, commercial-ready cGMP manufacturing facility in Changxing, Zhejiang province, China, and will potentially be able to produce more than 1 billion doses of SCB-2019 annually at peak capacity.

  • How stable is Clover’s SCB-2019 (CpG 1018/Alum) and what are the refrigeration requirements for storage and transport?

    SCB-2019 (CpG 1018/Alum) is stable for at least two months at room temperature and is expected to be stable long-term 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?

    The Coalition for Epidemic Preparedness Innovations (CEPI) and Clover are committed to ensuring equitable global access to SCB-2019 (CpG 1018/Alum) and will make SCB-2019 (CpG 1018/Alum) available for procurement and allocation through the COVAX Facility.

    The COVAX Facility is a global initiative which aims to procure and fairly distribute two billion doses of COVID-19 vaccines by the end of 2021, to help protect the most at-risk groups in all participating countries.