25 September 2020 - - China-based clinical-stage biotechnology company Clover Biopharmaceuticals has released positive preclinical data demonstrating that its protein-based COVID-19 S-Trimer vaccine candidate in combination with adjuvants from either GSK (London Stock Exchange: GSK) or Dynavax (NASDAQ: DVAX) induces a strong immune response and protection against SARS-CoV-2 in animal models, the company said.

The manuscript describing the results titled "S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates" has been submitted for peer review and can be accessed on an online preprint server at bioRxiv.

Clover's COVID-19 S-Trimer vaccine was developed by combining the trimeric SARS-CoV-2 spike (S)-protein with the company's proprietary Trimer-Tag technology.

In preclinical studies, adjuvanted S-Trimer induced strong humoral and Th1-biased cell-mediated immune responses in mice, rats and monkeys, with levels of neutralizing antibodies at or higher than levels observed in human convalescent sera.

Rhesus macaques that received the vaccine and were subsequently challenged with SARS-CoV-2 virus were protected against infection, as demonstrated by clinical observations (protection from body weight loss and increases in body temperature) and significant reduction in viral loads in lung tissues and swabs, with no signs of disease enhancement.

Strong immune responses and protection were observed when the S-Trimer was administered with either GSK's pandemic adjuvant system or Dynavax's CpG 1018 adjuvant plus alum.

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.

In June 2020, Clover announced the start of a Phase 1 clinical trial.

The trial is a randomized, observer-blind, placebo-controlled study to assess the safety, reactogenicity and immunogenicity of the adjuvanted COVID-19 S-Trimer vaccine at multiple dose levels.

The study has completed enrollment of 150 adult and elderly participants. Preliminary results show that the vaccine is likely to be safe and well-tolerated, with high levels of neutralizing antibodies observed.

Based on these preliminary results, an additional 200 participants will be enrolled in a Phase 1 dose-expansion study at the selected S-Trimer dose-level and adjuvanted with either GSK's pandemic adjuvant or Dynavax's advanced adjuvant CpG 1018 plus alum.

Clover intends to initiate a global Phase 2/3 vaccine efficacy study before the end of 2020. Detailed Phase 1 data will be made available in a peer-reviewed publication in the near future. The clinical trials and Clover's COVID-19 vaccine program are being supported by funding and collaboration with the Coalition for Epidemic Preparedness Innovations.

Clover Biopharmaceuticals is a global, clinical-stage, research-based biotechnology company focused on discovering, developing and commercialising transformative biologic therapies, with a focus on oncology and autoimmune diseases, as well as viral vaccines.

Having raised more than USD 200m in total capital since 2016, Clover is utilizing its proprietary Trimer-Tag technology platform to develop novel biologics targeting trimerization-dependent pathways.

Additionally, Clover is leveraging its in-house GMP biomanufacturing capabilities to support large-scale production of its biologic therapies.

Utilizing Clover's proprietary Trimer-Tag technology, S-Trimer is a trimeric SARS-CoV-2 spike (S)-protein subunit vaccine candidate.

Similar to other enveloped RNA viruses such as HIV, RSV and Influenza, SARS-CoV-2 is also an RNA virus that has a trimeric spike (S) protein on its viral envelope.

The trimeric S protein of SARS-CoV-2 is responsible for binding to host cell surface receptor ACE2 and subsequent viral entry, making it the primary target antigen for vaccine development.

S-Trimer resembles the native trimeric viral spike protein and is produced via a rapid mammalian cell-culture based expression system.

Trimer-Tag is an innovative drug development platform which 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.

Clover is using its Trimer-Tag technology with global IP position to develop recombinant trimerized fusion proteins that are able to effectively target these previously undruggable pathways.