Candidate: S-Trimer (SCB-2019)

Category: VAX

Type: Protein-based COVID-19 vaccine based on Clover’s Trimer-Tag© vaccine technology platform, and containing Dynavax’s proprietary toll-like receptor 9 (TLR9) agonist adjuvant CpG 1018

2022 Status: Studies Show Immune Response vs. Omicron—Clover said March 17 that positive clinical results from several studies evaluating SCB-2019 showed durable, high efficacy after primary vaccination and robust immune response against Omicron as a booster. The results, Clover said, provided strong evidence for use of SCB-2019 for primary vaccination and as a universal COVID-19 booster candidate.

Clover cited in part a follow-up analysis of 26,400 participants in the Phase II/III SPECTRA trial (NCT04672395), showed that a two-dose series of SCB-2019 provided high and durable protection in individuals at five months after the second dose. Efficacy was maintained at 100% against severe COVID-19 and 95% against hospitalizations associated with COVID-19 at five months after the second dose in the primary vaccination setting.

Clover also cited data from lab studies showing:

  • A heterologous booster dose of SCB-2019 in individuals previously receiving two doses of AstraZeneca’s COVID-19 vaccine induced approximately 2-fold higher levels of neutralizing antibodies against Omicron when compared to individuals receiving three doses of AstraZeneca’s vaccine.
  • A single dose of SCB-2019 in individuals previously infected with SARS-CoV-2 induced approximately 4-fold higher levels of neutralizing antibodies against the Omicron variant when compared to individuals receiving three doses of AstraZeneca’s COVID-19 vaccine, in a non-head-to-head trial.
  • A homologous booster dose of SCB-2019 in individuals previously receiving two doses of SCB-2019 primary vaccination induced unspecified “multi-fold” higher levels of neutralizing antibodies against the Omicron variant when compared to individuals receiving three doses of AstraZeneca’s COVID-19 vaccine, in a non-head-to-head trial. Also, a homologous booster dose appeared to induce a robust and rapid immune response against prototype strain and Omicron variant that exceed levels after the primary immunization series, Clover said.

Clover said it is advancing SCB-2019 as a universal COVID-19 booster vaccine candidate to potentially enable its use as a booster dose, regardless of the vaccine technology used for the primary vaccination or previous SARS-CoV-2 infection history.

2021 Status: Next-gen vaccine aces preclinical study—Researchers from Clover posted a preprint in bioRxiv on May 17 showing positive preclinical data from its second-generation, protein-based COVID-19 vaccine candidate, a modified B.1.351 Spike (S)-Trimer (B.1.351 S-Trimer) that showed broad neutralization against the original SARS-CoV-2 strain and variants of concern, specifically the South African variant (B.1.351), Brazil variant (P.1), and UK variant (B.1.1.7).

As the SARS-CoV-2 virus mutates and additional data emerges, we are prepared to innovate and develop next-generation COVID-19 vaccines,” Clover CEO Joshua Liang said. “The continued global rollout of highly-effective first-generation COVID-19 vaccines is paramount to controlling the current pandemic and supports the rapid development of our first-generation COVID-19 vaccine candidate SCB-2019,” which he said was now under study in a pivotal Phase II/III clinical trial.

Clover and Dynavax said March 24 that the first participants had been dosed in Clover’s global Phase II/III SPECTRA trial (NCT04672395), designed to assess the efficacy, safety and immunogenicity of  Clover’s S-Trimer COVID-19 vaccine candidate adjuvanted with Dynavax’s CpG 1018 plus alum. The double-blind, randomized, controlled study is administering the adjuvanted S-Trimer COVID-19 vaccine candidate in a two-dose regimen, given 21 days apart. The study is expected to enroll over 22,000 adult and elderly participants at multiple sites across Latin America, Asia, Europe and Africa, Clover and Dynavax said.

An interim analysis of the primary endpoint is expected in mid-2021, depending on trial enrollment and occurrence of COVID-19 cases in the study, according to the companies. SPECTRA is fully funded by the Coalition for Epidemic Preparedness Innovations (CEPI). Through this collaboration, hundreds of millions of adjuvanted S-Trimer vaccine doses will potentially be made available for procurement and allocation through the COVAX Facility to protect the most at-risk populations in participating countries.Clover said February 22 it expects to initiate a global Phase II/III efficacy trial for SCB-2019 (S-Trimer) in the first half of 2021 and has initiated production planning for potentially hundreds of millions of vaccine doses in 2021.

Clover disclosed its plans for the SPECTRA trial and plans to produce potentially hundreds of millions of doses in 2021 on February 22, in a company announcement that it completed an oversubscribed $230 million Series C financing, whose proceeds are intended in part to support continued development and expansion of Clover’s pipeline of protein-based vaccines and biologic cancer therapies. The financing round brings Clover’s total capital raised in the last 12 months to over $400 million (over RMB 2.5 billion). The Series C round was co-led by GL Ventures and Temasek, with participation from Oceanpine Capital, OrbiMed and existing investor Delos Capital.

Clover said it has also initiated development of additional vaccine programs including multivalent SARS-CoV-2 (covering multiple variants), rabies and influenza.

2020 Status: Dynavax said August 13 it was awarded a $3.4 million grant from the Bill & Melinda Gates Foundation toward scaling up production batch size to allow for increased capacity of Dynavax’s CpG 1018 advanced adjuvant. That effort will support capacity of up to 750 million adjuvant doses annually, which can be further increased if needed, according to the company.

In June, Dynavax said the first participants had been dosed in a Phase I clinical trial (NCT04405908) designed to assess Clover Biopharmaceuticals’ COVID-19 vaccine candidate containing the Company’s CpG 1018 adjuvant.

The randomized, double blind, placebo controlled, first-in-human study will evaluate the safety, reactogenicity, and immunogenicity of SCB-2019 at multiple dose levels, administered as 2 intramuscular injections in approximately 90 adult healthy subjects 18-54 years of age and approximately 60 elderly healthy subjects 55 to 75 years of age. The trial and Clover’s COVID-19 vaccine program are being supported by funding and collaboration with the Coalition for Epidemic Preparedness Innovations (CEPI).

The Phase I study will evaluate SCB-2019 alone, SCB-2019 with Dynavax’s CpG 1018 adjuvant combined with alum, and SCB-2019 in combination with a different adjuvant. The collaboration has been expanded to include clinical supply of CpG 1018 to Clover, based on preclinical results that showed the ability of CpG 1018-adjuvanted SCB-2019 to elicit neutralizing antibodies in multiple animal species. Preliminary safety and immunogenicity results of the study are expected in August.

Dynavax told analysts and investors May 19 that it expects that one or more of its collaboration partners “will commence a Phase I clinical trial of a potential COVID-19 vaccine as soon as July 2020,” according to a regulatory filing. regulatory filing.

Dynavax and Clover on March 24 said they launched a research collaboration to develop a vaccine candidate to prevent COVID-19. Clover agreed to advance the evaluation of COVID-19 S-Trimer in preclinical studies. The companies said Clover could rapidly scale-up and produce large-quantities of a new coronavirus vaccine since it has one of the largest in-house, commercial-scale cGMP biomanufacturing capabilities in China.

Clover said it applied its patented Trimer-Tag© technology to design the viral spike (S)-protein construct and complete its gene synthesis once the genomic DNA sequence of SARS-CoV-2 became public in late January.


COVID-19: 300 Candidates and Counting

To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:

FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.

DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data

KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.

TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.

GEN has also tagged the most common treatment types:

● ANTIVIRAL
● VAX
● ANTIBODY
● RNA