Reach - a non-regulatory announcement

AIM: FIPP

29 November 2021

Frontier IP Group Plc

("Frontier IP" or the "Group")

Portfolio news - The Vaccine Group announces significant milestone in development of next generation COVID-19 vaccine

Frontier IP, a specialist in commercialising intellectual property, notes the following announcement that portfolio company The Vaccine Group ("TVG" or the "Company") has achieved a significant milestone in the development of its next generation COVID-19 vaccine for use in humans. Frontier IP holds a 17 per cent equity stake in the Company.

Neil Crabb, Frontier IP Chief Executive Officer, said: "The first generation of COVID-19 vaccines have had a fantastic impact. However, COVID-19 is not going to disappear, so there is a need for a new generation of vaccines. There is a growing body of evidence to show that stimulating a T cell response confers longer-lasting immunity than other approaches and also offers the potential to provide protection against current and future variants of the disease."

Jeremy Salt, Chief Executive of The Vaccine Group, said: "These very strong trial results show that a COVID-19 vaccine based on our novel herpesvirus platform could prove to be extremely effective in mitigating the long-term impact of the disease.  We are clearly excited about the potential for the vaccine."

Simon Graham, Group Leader at The Pirbright Institute, said: "Given the emerging data that strongly suggest an important role for cellular immunity in controlling SARS-CoV-2 infection, these are particularly promising results."

The Vaccine Group statement begins:

The Vaccine Group announces significant milestone in development of next generation

COVID-19 vaccine

·    Trial data show strong T cell responses to SARS-CoV-2, as well as the more divergent SARS-CoV-1, demonstrating potential for broad immunity against current and future variants of the causal agent of COVID-19 

·    Vaccination is not blunted by pre-existing immunity against the vaccine platform allowing for repeated use as a 'booster' after initial vaccination

The Vaccine Group ("TVG" or the "Company") today announces the results of pre-clinical trials in pigs for a SARS-CoV-2 vaccine candidate for use in humans based on its novel herpesvirus-based vaccine platform technology.

The results show that a strong T cell response is stimulated by a single immunisation, which is further boosted by a subsequent immunisation with the identical vaccine after a four-week interval. The trials were run in collaboration with The Pirbright Institute, England.

Laboratory analysis of immune responses to the vaccine confirmed T cell responses in all animals. Further analysis showed both SARS-CoV-2-specific gamma interferon producing CD4⁺ helper T cells and CD8⁺ cytotoxic T cells (CTLs) against SARS-CoV-2 were induced.

The vaccine has been developed to direct T cell immune responses against three SARS-CoV-2 proteins. The potential for such a T cell-focused vaccine approach has been highlighted following recent reports of substantial T cell-based immune memory in SARS-CoV-2 convalescent patients* and a correlation of immunological control with the prevalence of CTLs**.

CTLs are an important part of the body's defence system because they destroy cells infected by the virus. This means they remove infected cells swiftly, before the virus can replicate. Most vaccines either on the market or under development are aimed at attacking the virus directly once it has already replicated and been released from the infected cell by stimulating an antibody response against the spike protein on the surface of the virus. However, antibodies are more sensitive to evasion by virus mutation.

In vitro stimulation of lymphocytes isolated from peripheral blood samples after vaccination showed reactivity against peptides from both SARS-CoV-2, the causal agent of the COVID-19 pandemic, and also the SARS-CoV-1 virus isolated from the 2003 SARS outbreak.

These data underline the ability of this vaccine to stimulate broad coronavirus immune responses which would be expected to be beneficial in controlling infection with current circulating SARS-CoV-2 viruses (e.g., Delta) as well as future variants of the virus.

Pathogen targets of T cell-based immunity are known to vary less than antibody targets, therefore this result is in line with this vaccine strategy.

Following early discussions with the UK's MHRA, TVG is seeking immediate funding to move the vaccine candidate to a full Proof-of-Concept stage before Phase I trials in humans can be undertaken.

The vaccine candidate is based upon TVG's herpesvirus vector system, which allows for repeated reimmunization and booster doses to be used without decreasing efficacy.

Jeremy Salt, Chief Executive of The Vaccine Group, said: "These very strong trial results show that a COVID-19 vaccine based on our novel herpesvirus platform could prove to be extremely effective in mitigating the long-term impact of the disease.  We are clearly excited about the potential for the vaccine."

Simon Graham, Group Leader at The Pirbright Institute, said: "Given the emerging data that strongly suggest an important role for cellular immunity in controlling SARS-CoV-2 infection, these are particularly promising results."

* Le Bert,et al 2020 https://www.nature.com/articles/s41586-020-2550-z;

* Grifoni et al, 2020 https://www.cell.com/action/showPdf?pii=S0092-8674%2820%2930610-3

** Swadling, L., Diniz, M.O., Schmidt, N.M. et al. Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2. Nature (2021). https://doi.org/10.1038/s41586-021-04186-8

** Luo et al. 2020. https://pubmed.ncbi.nlm.nih.gov/32544099/

The Vaccine Group statement ends

ENQUIRIES

About T cells and SARS-CoV-2

The structural proteins spike (S), membrane protein (M) and nucleocapsid (N) are core building blocks of coronaviruses, including SARS-CoV-1 and SARS-CoV-2.

·    Spike (S) protein, is on the surface of the virus and is responsible for the distinctive crown-like structure. S protein is required for infection of a cell by binding to the ACE2 receptor on the cell surface.

·    Membrane (M) protein, which spans the membrane of the virus, plays a major role in assembly of the virus particle.

·    Nucleocapsid (N) protein, is found inside the virus and has many functions from helping copy and package the genetic information of the virus through to also being involved in virion assembly.

The body's active defence when attacked by a pathogen, such as the SARS-CoV-2 virus, is governed by two types of adaptive immune response (cell-mediated and antibody-mediated) through two white blood cell lineages: the mononuclear/macrophages and lymphocytes (both B and T cells).

Lymphocytes circulate in the body until they are activated by contact with a specific piece of protein of a pathogen, which is called an antigen. They bind the antigen (in this case from SARS-CoV-2) presented by mononuclear/monocytes acting as antigen presenting cells via their surface proteins.  In the case of B cells this is antibody.

The antigen presenting cell internalises the virus and then expresses short peptide sequences of the viral proteins through a molecule called MHC Class II. A helper CD4+ T cell then binds on to the MHC Class II molecule, which triggers the transformation of the B cell into plasma cells and memory B cells.

Plasma cells mass manufacture antibodies to the virus, which then circulate in the blood and tissues. However, these antibodies are tailor made to combat very specific regions present in the original infecting virus.  In the case of the SARS-CoV-2 virus, this is most usually against targets on the Spike protein. This means the antibodies might not be effective against a coronavirus with a mutated spike protein. And because Spike proteins are the main contact point between a coronavirus and cells in the body, mutations in this region can have a significant impact on efficiency of cellular entry.

Memory B cells are a reserve: they remember the virus and so can respond quickly if the body is reinfected.

Most Covid-19 vaccines either on the market currently or under development aim to stimulate a B cell-derived serum antibody response to SARS-CoV-2 virus through inclusion of only the Spike proteins itself or its gene.

CD8+ cytotoxic T cells (CTLs) attack infected cells directly, rather than the free virus. When a cell is infected, the virus starts to replicate by producing its proteins including nucleocapsid (N), membrane (M) and spike proteins (S). The infected cells express peptides, short sequences of the proteins, on their surface via a molecule called MHC Class I.

The CTL recognises infected cells because of the presence of the MHC Class I molecule presenting viral peptides. It binds on to the infected cell and kills it before the virus can be released. Importantly, for SARS-CoV-2, T cells target all of the three proteins N, M and S.  The generation of the immediate effector T cells are accompanied by the production of long-lived memory T cells.

The T cell targets on nucleocapsid and membrane proteins mutate much more slowly than the Spike protein antibody targets, and they are more similar between SARS-CoV-1 and SARS-CoV-2 viruses.

This gives rise to the expectation that a vaccine stimulating a T cell response to both viruses will be in a strong position to combat any variants of the SARS-CoV-2 virus.

ABOUT THE VACCINE GROUP

The Vaccine Group, a spin out from the University of Plymouth, is developing vaccines based on benign forms of herpesviruses. These are a group of viruses found in all animals, including humans.

The Company is targeting two main areas: zoonotic diseases, which jump from animals to humans, and economically damaging diseases in livestock. The COVID-19 vaccine is the first of the company's vaccines being developed for humans.

The Company and its international partners have so far been backed by more than £9 million in grant funding from the US, UK and Chinese governments. The US government is funding development of Ebola and Lassa fever virus vaccines. The company has also signed its first commercial agreement to develop vaccines for Porcine Respiratory and Reproductive Virus Syndrome with ECO Animal Health Group plc.

Other projects underway include developing a vaccine against Streptococcus suis, a disease in pigs which can be fatal in humans and can only currently be treated with large doses of antibiotics.

For more information: www.thevaccinegroup.com 

ABOUT THE PIRBRIGHT INSTITUTE

The Pirbright Institute is a world leading centre of excellence in research and surveillance of virus diseases of farm animals and viruses that spread from animals to humans. Based in the UK and receiving strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC) part of UK Research and Innovation (UKRI), the Institute works to enhance capability to contain, control and eliminate these economically and medically important diseases through highly innovative fundamental and applied bioscience.

The Institute is an independent company, limited by guarantee and a registered charity, governed by a Board of non-executive Trustee Directors.

With an annual income of £37 million from grants and commercial activity, and a total of £43.7 million strategic investment from BBSRC UKRI during 2021-2022, the Institute contributes to global food security and health, improving quality of life for animals and people.

For more information about The Pirbright Institute see: www.pirbright.ac.uk

ABOUT FRONTIER IP

Frontier IP unites science and commerce by identifying strong intellectual property and accelerating its development through a range of commercialisation services. A critical part of the Group's work is involving relevant industry partners at an early stage of development to ensure technology meets real world demands and needs.

The Group looks to build and grow a portfolio of equity stakes and licence income by taking an active involvement in spin-out companies, including support for fund raising and collaboration with relevant industry partners at an early stage of development.

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