Clover COVID-19 (SCB-2019) Vaccine Description
Clover Pharmaceutical COVID-19 vaccine (SCB-2019) is a trimeric SARS-CoV-2 spike (S)-protein subunit vaccine candidate developed by Clover Pharmaceuticals by combining the trimeric SARS-CoV-2 spike (S)-protein with the company’s proprietary Trimer-Tag© technology.
The COVID-19 S-Trimer vaccine SCB-2019 (CpG 1018/Alum) resembles the native trimeric viral spike protein produced via a rapid mammalian cell-culture-based expression system.
Trimer-Tag is an innovative drug development platform that allows the production of novel, covalently-trimerized fusion proteins. Many major disease targets are trimerization-dependent such as the tumor necrosis factor superfamily (involved in extrinsic apoptosis, immune co-stimulation, and inflammation) as well as enveloped RNA virus antigens responsible for entry into host cells. Thus, Trimer-Tag may be an important platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses, stated an article published by the journal Nature in March 2021.
In Phase 1 clinical trial, Clover’s COVID-19 vaccine-induced levels of neutralizing antibodies were higher than in people previously infected with SARS-CoV-2. In addition, strong Th1-biased cell-mediated immune responses were observed.
On February 1, 2021, Dr. Ralf Clemens, Chairman of the Scientific Advisory Board for Clover’s COVID-19 Vaccine Program, commented in a press release, “This phase 1 dose-finding and adjuvant justification study demonstrated the potential of Clover’s adjuvanted vaccine candidates to bring added value to the global portfolio of COVID-19 vaccines. In addition, in both adult and elderly subjects, the vaccine candidates were safe. They elicited cellular immune responses and high neutralizing antibody titers with a favorable ratio of neutralizing/binding antibodies. These findings give confidence that Clover’s COVID-19 vaccine candidates are suitable for further clinical development.”
China-based Clover Biopharmaceuticals's protein-based COVID-19 S-Trimer vaccine candidate combined with adjuvants from GSK or Dynavax induces a strong immune response and protection against SARS-CoV-2 in animal models.
Clover is currently advancing SPECTRA, a global pivotal Phase 2/3 clinical trial evaluating the efficacy, safety, and immunogenicity of SCB-2019 (CpG 1018/Alum), and expects interim data for vaccine efficacy around the middle of 2021. Pending positive interim data, Clover plans to submit conditional regulatory approval applications to the EMA, the NMPA, and the WHO in the second half of 2021 and plans to commence product launch by the end of 2021.
SCB-2019 - DrugBank Accession Number: DB15805
Clover COVID-19 Vaccine (SCB-2019) History
Preclinical data have shown Clover’s protein-based adjuvanted COVID-19 vaccine candidate, S-Trimer, induces a strong neutralizing immune response in animals and protects nonhuman primates from a SARS-CoV-2 challenge. And strong immune response and protection were observed with adjuvant systems from GSK and Dynavax. These positive preclinical data supported the decision to progress adjuvanted vaccine candidates using both adjuvants into Clover’s ongoing Phase 1 clinical study of S-Trimer in healthy adult and elderly participants, said the company on September 25, 2020.
On November 3, 2020, CEPI extended its partnership with Clover Biopharmaceuticals to fund the COVID-19 vaccine candidate through global Phase 2/3 study to licensure. As a result, CEPI’s total investment in Clover’s S-Trimer vaccine candidate will be up to $328 million, including previously announced commitments of $69.5 million, which have funded preclinical studies and Phase 1 clinical trials.
On December 4, 2020, Clover announced the Phase 1 trial was a randomized, observer-blind, placebo-controlled study to assess the safety, reactogenicity, and immunogenicity of the adjuvanted COVID-19 S-Trimer vaccine candidates formulated with different antigen levels. No serious adverse events related to the vaccine candidates studied were reported. The majority of adverse events were mild and transient. S-Trimer is adjuvanted with GSK’s pandemic adjuvant system-induced neutralizing antibody titers (seroconversion) in 100% of participants at the selected 9 µg S-Trimer dose in both adult and elderly groups, with geometric mean titers (GMT) greater than 1:1,800. In addition, CpG-1018/alum-adjuvanted S-Trimer induced neutralizing antibodies in 100% of adult participants at the selected 30 µg S-Trimer dose with GMT greater than 1:1,000 seroconversion was observed in 88% (7 out of 8) in the elderly. Strong Th1 cell-mediated immune responses were also observed for the vaccine candidates with either adjuvant.
The new CEPI funding announced on November 4, 2020, will also enable additional clinical studies in special populations, such as people with autoimmune conditions, immunocompromised individuals, pregnant women, and children. In parallel to the clinical development process, the program will continue scaling up the manufacturing process to potentially enable the production of more than one billion vaccine doses annually and build up vaccine inventory, which – if the vaccine is proven to be safe and effective - could be deployed rapidly upon licensure.
“SPECTRA (phase2/3 study) is the result of unprecedented cross-border collaboration across four continents, and we extend our deepest gratitude to all of the participants, the investigators, and our partners for their ongoing support in achieving this momentous event,” stated Joshua Liang, CEO of Clover Biopharmaceuticals, on July 6, 2021. SPECTRA is a double-blind, randomized, controlled study of SCB-2019 (CpG 1018/Alum) administered in a two-dose regimen, 21 days apart. 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. Given the geographic diversity of SPECTRA, Clover expects to announce a robust dataset in Q3 2021.
Joshua Liang is the co-inventor of the COVID-19 S-Trimer vaccine. Clover Biopharmaceuticals is a global clinical-stage biotechnology company based in Chengdu, China, focused on discovering and developing transformative biologic therapies and vaccines.
Clover COVID-19 Vaccine (SCB-2019) Indication
COVID-19 S-Trimer (SCB-2019) is indicated to prevent SARS-CoV-2 infection, which causes COVID-19 disease. The adolescent (ages 12-18) subgroup in the SPECTRA clinical trial has also initiated enrollment and will complete enrollment in 2021.
Clover COVID-19 Vaccine (SCB-2019) Storage Requirements
Preliminary results from stability studies have demonstrated that S-Trimer is stable at 2-8o C for at least 6-months (longer-term stability studies are ongoing) and stable at room temperature and 40o C for at least one month, in line with the adjuvants tested. Thus, Clover’s COVID-19 vaccine candidates' ability to be stored in standard refrigeration temperatures makes them suitable for broad global distribution based on current results.
Clover COVID-19 Vaccine (SCB-2019) News
July 6, 2021 - Clover announced the completion of targeted enrollment of adult and elderly participants in SPECTRA, a global pivotal Phase 2/3 clinical trial evaluating the efficacy, safety, and immunogenicity of SCB-2019 (CpG 1018/Alum), Clover’s COVID-19 vaccine candidate. The adolescent (ages 12-18) subgroup in SPECTRA has also initiated enrollment and will complete enrollment in Q3 2021.
July 1, 2021 - This blog takes a closer look at CEPI’s collaboration with Clover, some of the additional CEPI programs it leverages, and the potential advantages of Clover’s innovative vaccine technology, which could strengthen global efforts to end the acute phase of this devastating pandemic.
June 30, 2021 - Clover Biopharmaceuticals announced an advance purchase agreement with Gavi, the Vaccine Alliance, to provide up to 414 million doses of its protein-based COVID-19 vaccine candidate for procurement through the COVAX Facility.
June 30, 2021 - Clover Biopharmaceuticals and Dynavax Technologies Corporation announced the execution of a commercial supply agreement of Dynavax’s CpG 1018TM advanced adjuvant for use in Clover’s protein-based COVID-19 vaccine candidate, SCB-2019 (CpG 1018/Alum). The commercial supply agreement extends to the end of 2022. The agreement includes doses for delivery in 2021, which were manufactured under the previously announced funding agreement between Coalition for Epidemic Preparedness Innovations and Dynavax.
March 24, 2021 - Clover Biopharmaceuticals and Dynavax Technologies Corporation announced the first participants had been dosed in Clover’s SPECTRA trial (Study Evaluating Protective-Efficacy and Safety of Clover’s Trimeric Recombinant Protein-based and Adjuvanted COVID-19 Vaccine), a global Phase 2/3 clinical trial evaluating the efficacy, safety, and immunogenicity of Clover’s protein-based S-Trimer COVID-19 vaccine candidate adjuvanted with Dynavax’s CpG 1018 plus alum.
March 1, 2021 - Nature study: S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates. Our data demonstrate that S-Trimer adjuvanted with either AS03 or CpG 1018 plus alum can induce robust humoral and cellular immune responses in various animal species and protective immunity against SARS-CoV-2 infection in nonhuman primates, with no signs of disease enhancement. Collectively, these results support the advancement of adjuvanted S-Trimer through human clinical studies to further demonstrate safety, immunogenicity, and vaccine efficacy.
February 23, 2021 - Clover Biopharmaceuticals announced the completion of an oversubscribed $230 million Series C financing. This financing round brings Clover’s total capital raised in the last 12 months to over $400 million. The proceeds will support the continued development and expansion of Clover’s pipeline of protein-based vaccines and biologic cancer therapies utilizing its innovative and proprietary Trimer-Tag© technology platform. Clover expects to initiate a global Phase 2/3 efficacy trial for SCB-2019 (S-Trimer), its COVID-19 vaccine candidate, in the first half of 2021 and has initiated production planning for potentially hundreds of millions of vaccine doses in 2021.
February 8, 2021 - The Lancet Study: S-Trimer (SCB-2019) Protein Subunit Vaccine for COVID-19. The SCB-2019 vaccine formulated with either AS03 or CpG/Alum adjuvants was well tolerated and elicited robust humoral and cellular immune responses against SARS-CoV-2.
February 1, 2021 - Clover Biopharmaceuticals Announces Publication of Phase 1 Clinical Trial Data for its Adjuvanted COVID-19 Vaccine Candidates in The Lancet. Clover plans to initiate a global Phase 2/3 study to evaluate the S-Trimer COVID-19 vaccine candidate's safety and efficacy adjuvanted with Dynavax’s advanced adjuvant CpG 1018 plus alum within the next few months. The Coalition for Epidemic Preparedness Innovations (CEPI) has committed to funding Clover’s S-Trimer COVID-19 vaccine candidate through licensure with a total investment of up to$328 million, a portion of which will support the global Phase 2/3 study.
January 29, 2021 - The Lancet study: Safety and immunogenicity of S-Trimer (SCB-2019), a protein subunit vaccine candidate for COVID-19 in healthy adults: a phase 1, randomized, double-blind, placebo-controlled trial. The SCB-2019 vaccine, comprising S-Trimer protein formulated with either AS03 or CpG/Alum adjuvants, elicited robust humoral and cellular immune responses against SARS-CoV-2, with high viral neutralizing activity. In addition, both adjuvanted vaccine formulations were well-tolerated and are suitable for further clinical development.
December 4, 2020 - Clover Biopharmaceuticals announced positive clinical data from its Phase 1 trial demonstrating that its protein-based COVID-19 S-Trimer vaccine candidates in combination with adjuvants from either GSK or Dynavax induce strong immune responses, including neutralizing antibodies and cell-mediated immunity, as well as favorable safety and tolerability profiles in 150 adult and elderly participants.
November 3, 2020 - The Coalition for Epidemic Preparedness Innovations announced that it would fund the development of the protein-based S-Trimer COVID-19 vaccine candidate by China-based Sichuan Clover Biopharmaceuticals, Inc. through a global pivotal Phase 2/3 efficacy clinical trial and to licensure in China and globally if the vaccine is proven to be safe and effective.
September 25, 2020 - Clover Biopharmaceuticals Announces Positive Preclinical Data and Updates on Phase 1 Study for its Adjuvanted S-Trimer COVID-19 Vaccine Candidate.
September 24, 2020 - Study: S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates. 'Trimer-Tag may be an important new platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.'
July 8, 2020 - The Coalition for Epidemic Preparedness Innovations announced the expansion of its partnership with Sichuan Clover Biopharmaceuticals, Inc. to rapidly advance Clover's development and manufacture protein-based COVID-19 S-Trimer vaccine candidate, which is based on Clover’s proprietary Trimer-Tag© vaccine technology platform.
June 19, 2020 - Clover Biopharmaceuticals announced that the first participants had been dosed in Phase 1 first-in-human study evaluating the company’s COVID-19 S-Trimer subunit vaccine candidate (SCB-2019), which is based on Clover’s proprietary Trimer-Tag vaccine technology platform.
S-Trimer COVID-19 Vaccine (SCB-2019) Clinical Trials
Clinical Trial NCT04405908: SCB-2019 as COVID-19 Vaccine - The Phase 1 trial was a randomized, observer-blind, placebo-controlled study to assess the safety, reactogenicity, and immunogenicity of the adjuvanted COVID-19 S-Trimer vaccine candidates formulated with different antigen levels. No serious adverse events related to the vaccine candidates studied were reported. The majority of adverse events were mild and transient. S-Trimer is adjuvanted with GSK’s pandemic adjuvant system-induced neutralizing antibody titers (seroconversion) in 100% of participants at the selected 9 µg S-Trimer dose in both adult and elderly groups, with geometric mean titers (GMT) greater than 1:1,800. CpG-1018/alum-adjuvanted S-Trimer induced neutralizing antibodies in 100% of adult participants at the selected 30 µg S-Trimer dose with GMT greater than 1:1,000, and seroconversion was observed in 88% (7 out of 8) in the elderly. Strong Th1 cell-mediated immune responses were also observed for the vaccine candidates with either adjuvant.