Press Releases:
Monday, 16 August 2021
Excivion announces results of an international collaboration evaluating the utility of its novel point-of-care dengue and Zika antibody tests
CAMBRIDGE UK – Excivion Ltd (www.excivion.com), a biotechnology company developing novel vaccines based on its proprietary glycan-cloaking molecular design and adjuvant platforms, today announces the publication of a peer-reviewed article in Frontiers in Immunology (Echegaray et al. July 23, 2021, doi: 10.3389/fimmu.2021.703887) which demonstrates the unique performance advantages and versatility of its novel antigen and device design innovations embodied in the form of lateral flow antibody tests for dengue and Zika.
Dengue is a pandemic disease affecting at least 120 tropical countries and, increasingly, subtropical countries – a trend that is likely to increase with global warming. Dengue is responsible for fever and haemorrhagic disease. An estimated 105 million dengue infections occur each year, resulting in 500,000 hospitalisations and 44,000 deaths. There is no specific treatment for severe dengue, only supportive care such as IV fluids or blood transfusion. Although vaccines have been developed against dengue, the first of these (DengvaxiaÒ) is recommended only for people who have previously been infected with dengue, or in highly endemic territories where prior infection may be assumed. This is because the vaccine can prime for severe dengue in dengue-naïve subjects, which is highly undesirable. Recently it was also demonstrated (Katzelnick et al PMID 32855339) that Zika infection (like dengue infection) can prime for severe dengue and, so far, the priming effect of prior Zika vaccination on the risks of dengue vaccination (helpful or otherwise) is not known. These are compelling reasons for the development of improved point-of-care antibody tests (as advocated by WHO) that may inform vaccination practice with dengue (and Zika) vaccines. Currently there is no licensed Zika vaccine.
“We set out to develop novel antibody diagnostic tests for prior dengue and Zika based on our proprietary glycan-cloaked envelope proteins from dengue and Zika, which deliver improved specificity by concealing the highly cross-reactive fusion loop. The concept borrows from the immune stealth aspect of HIV’s ‘spike’ protein gp120, where its abundant glycans form a molecular capsule that thwarts antibody recognition. The same stealth principle is exploited by COVID. Here we applied this concept in a localised way to the fusion loop of the envelope proteins, ‘borrowing a leaf’ from HIV, one might say by planting the fusion loop with glycans. However, we were disappointed with the sensitivity of existing test architectures and, felt compelled to invent a more sensitive test architecture befitting the sensitivity needs of detection of historic dengue. These twin innovations, that is the glycan cloaking and the test architecture, were key to the successful development of the superior test. Previously, lateral flow antibody tests had been designed to diagnose ongoing dengue and Zika infections, at which time antibody levels are high. The new tests allow the detection of legacy concentrations of antibodies indicative of prior infection, which are a lot lower. This is important for the use of vaccines, by identifying subjects who are safely eligible to receive them.” Said Peter Laing CEO of Excivion and inventor of the patents.
Excivion’s granted patents in Europe and the USA (Granted European Patent No. EP3458471B1, Granted US Patent No. 11,028,133 B2) provide composition of matter coverage for glycan-cloaked flavivirus antigens covering all positions in the fusion loop which is 100% conserved across all major human flavivirus pathogens (Zika, dengue 1-4, Japanese encephalitis virus and yellow fever virus). These patents cover the diagnostic as well as the vaccine utility of the antigens. In addition, Excivion has a pending patent (in the US and elsewhere) on the novel lateral-flow test architecture for flaviviruses generally, which features a number of innovations over and above the use of hyperglycosylated antigens. These include: the arrest of antigen in the test via an appended tag via an immobilised anti-tag antibody (avoiding competition with antibodies against flaviviruses present in the sample that would otherwise attenuate signal); also the disposition of antigens in the fluid phase of the running test which optimises the conditions for antigen interaction with antibodies of the sample; and the inclusion of off-target antigens lacking a suitable tag, in order to eliminate false positives due to cross-reactivity at sites outside the fusion loop. The knowhow of the novel test architecture has been licensed to Coronex Ltd for COVID lateral-flow tests where it confers the same advantages as for dengue and Zika serology.
“The evaluation of the tests was conducted in collaboration with the groups of Dr. Leah Katzelnick of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, Dr. Eva Harris and Dr. Josefina Coloma of Berkeley School of Public Health, Dr. Shuenn-Jue Wu of the Naval Medical Research Center in Maryland, and Dr. Phil Cooper of St George’s in the UK. While their involvement does not imply any endorsement of the tests, their formidable expertise was key to conducting an effective evaluation, and working out how best to use the tests. The evaluation involved the use of well-characterised panels of PCR-proven cases of dengue and Zika, including studies of endemic populations of Nicaragua and Ecuador. The Excivion dengue lateral flow tests allow an unprecedented degree of sensitivity and specificity. The dengue lateral flow test was as sensitive as five commercial dengue antibody ELISAs, some of which make no distinction between Zika and dengue, but moreover was highly specific for dengue, versus its closest relative, Zika. The Zika lateral-flow test was likewise highly specific and sensitive (>98% and >93% respectively) for Zika antibodies, allowing reliable identification of prior Zika. At Excivion we believe that the novel antigens and test architecture are a game changer, particularly because the antigens can also be used in laboratory tests as well as point-of-care tests for detection of ongoing or historic dengue and Zika, and we are now seeking manufacturing collaborators and licensing partners for our patents world-wide.”
Excivion’s work on flavivirus diagnostics is funded by the Department of Health and Social Care as part of the UK Vaccine Network (UKVN), a UK Aid programme to develop vaccines for diseases with epidemic potential in low and middle-income countries (LMICs). The funding is delivered by Innovate UK under its SBRI programme via contracts 972224 and 971509. The views expressed in this release and in the article in Frontiers in Immunology are those of the authors and not necessarily those of Innovate UK or DHSC.
About Innovate UK
Innovate UK is the UK’s Innovation agency. It works with people, companies and partner organisations to find and drive the science and technology innovations that will grow the UK economy. www.innovateuk.gov.uk
Contact:
Peter Laing PhD, CEO, Excivion Ltd
+44 7572 816418
Monday, 13 July 2020
Excivion announces collaboration with Centre for Process Innovation (CPI) to optimise and scale up production of safe and effective Zika vaccine
Excivion Ltd, Cambridge, UK, today announced a partnership with CPI to optimise the manufacture of Excivion’s novel Zika vaccine antigen candidate, Zika-HX, an integral component of any future vaccine formulation. Excivion’s technology could help to prevent future pandemics of deadly viruses by avoiding the adverse immune responses common in current vaccine candidates for Zika and related viruses.
Zika is a member of the Flavivirus genus that includes dengue, yellow fever and tick-borne encephalitis. In the case of dengue virus, infection with one serotype may result in the generation of antibodies that can increase disease severity following infection with a second serotype. This process is known as antibody dependent enhancement (ADE). There is a significant risk that the vaccines in development to protect against flaviviruses may sometimes cause ADE and actually worsen the effects of the disease they are designed to prevent. Excivion’s flavivirus vaccine platform involves glycan-cloaking of the fusion-loop of the virus envelope protein, conferring protection while avoiding the generation of fusion-loop antibodies that cause ADE. For its proprietary Zika virus vaccine Excivion is applying a DrosophilaS2 insect cell-based protein production system, ExpreS2, from ExpreS2ion Biotechnologies ApS, Horsholm, Denmark, thereby obtaining high quality recombinant ZIKV protein for the ongoing development project.
Excivion have partnered with CPI to draw upon the company’s extensive experience in the optimisation and scale-up of biologics manufacturing processes. Over the next four months, CPI will proceed through a four-stage development programme including technology transfer, characterisation and upstream and downstream process development. Using its expertise and advanced technology housed at the National Biologics Manufacturing Centre, Darlington, CPI will work to characterise the structure of the purified Zika-HX antigen. A scalable downstream purification method for the required product forms will be optimised. The work on upstream processing will assess whether it is possible to control the oligomerisation state of the Zika-HX antigen within the existing bioprocess to maximise yield. CPI will have access to the initial bioprocessing data developed at ExpreS2ion.
Peter Laing, CEO at Excivion Ltd, said: “Throughout modern history, vaccines have proven to be the most cost-effective solution to disease prevention, however challenging manufacturing problems and the risk of ADE prevents more vaccines entering the market. I am pleased that ExpreS2ion’s production system has documented the initial bioprocessing needed to proceed as planned. Our partnership with CPI will enable us to optimise the purification of Zika-HX and proceed faster with its development into a vaccine.”
Lucy Foley, Director of Biologics at CPI, said: “Excivion’s flavivirus vaccine platform has the potential to produce safe and effective vaccines for viruses that represent some of the world’s greatest pandemic risks. We are looking forward to contributing to the Zika-HX project with our expertise in biologic manufacturing, helping Excivion to efficiently produce pure active antigens.”
The research is delivered by the Future Vaccine Manufacturing Research Hub (FVMRH) at Imperial College London. The FVMRH is committed towards researching innovative and more cost-effective vaccines for populations in lower and middle-income countries (LMICs). The hub’s goal is to improve the way vaccines are manufactured, stabilised and stored in partnership with vaccine manufacturers in Italy, India, Vietnam, Bangladesh, Uganda and China, as well as translational research partners comprising of the National Institute for Biological Standards and Control (NIBSC), CPI and NHS Blood and Transplant.
Notes to the Editor
About Excivion
Excivion is a UK-based biotechnology company developing solutions to the present and emerging healthcare needs of society that are sustainable and affordable by healthcare systems in the face of competing priorities imposed by an ageing population and the emergence of pandemic diseases. Vaccines, historically, have proven the most cost-effective solution to disease prevention, but also have a formidable potential to treat diseases once they have arisen. Excivion is in the vanguard of a new pharmaceutical model for this changing world in which vaccines feature globally in both disease-prevention and in the treatment of chronic diseases. Excivion’s work on the Zika vaccine is fundedby the Department of Health and Social Care as part of the UK Vaccine Network (UKVN), a UK Aid programme to develop vaccines for diseases with epidemic potential in low and middle-income countries (LMICs). The funding is delivered by Innovate UK under its SBRI programme.
About CPI
CPI is an independent technology innovation centre and a founding member of the UK Government’s High Value Manufacturing Catapult. Founded in 2004, CPI applies its years of experience across a broad range of industries to ensure that every great invention gets the best opportunity to become a successfully marketed product.
CPI’s integrated approach provides its partners with a unique combination of assets, expertise and skills to drive successful innovation. With a deep understanding of innovation processes and funding, outstanding technical expertise and industry-relevant assets, CPI enables products and process to be quickly and cost-effectively brought to market. By employing bright minds from both academia and industry, CPI helps create a bespoke team that will provide the right support, helping you to navigate the route to commercialisation while reducing risk along the way.
We form connections throughout the supply chain, bringing together investors, government organisations and academic institutions to facilitate the necessary partnerships for effective innovation. This increases productivity across industries and supports the development of next-generation manufacturing, highly-skilled jobs and economic growth for the UK.
About Innovate UK
Innovate UK is the UK’s Innovation agency. It works with people, companies and partner organisations to find and drive the science and technology innovations that will grow the UK economy. www.innovateuk.gov.uk
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Excivion Presents at Seventeenth UK Hepacivirus and Flavivirus Meeting - 17th-19th May 2019
Excivion Ltd. Announces the development of a novel point-of-care diagnostic to
facilitate the safe use of dengue vaccines in the field
- Excivion has developed an unique proprietary diagnostic to identify
dengue-naive subjects who should be spared dengue vaccination -
CAMBRIDGE, UK – (May 17, 2019) – Excivion Ltd (www.excivion.com) “Excivion”, a developer of novel vaccines for the prevention of emerging pandemic infectious diseases, today announced that it has developed a point-of-care diagnostic test with performance characteristics suitable, once licensed, to identify subjects who are dengue-naive and who should be spared dengue vaccination, in order to avoid the risk of priming for severe dengue. The current practice, required by the FDA, is that a laboratory-based test should be used for this purpose. However, the logistics of a laboratory-based test complicate the process of screening and there is general agreement that point-of-care is a better solution for the purpose
(Luo et al PMID: 30664935, https://www.who.int/immunization/diseases/dengue/q_and_a_dengue_vaccine_dengvaxia_use/en/).
Commenting on the new development, Peter Laing, CEO of Excivion, said, "There are a number of point-of-care tests in existence for historic dengue, but these have limited sensitivity and have been hampered by the emergence of Zika as a pandemic disease - the tests being generally not capable of reliably distinguishing prior Zika from dengue. In this instance we re-invented the point-of-care dengue test from the ground up, making it more sensitive and specific than licensed point-of-care tests, and better in these respects than many lab-based tests. We also made the test 'scaleable' to be manufacturable in the millions. In order to scientifically validate the test we made extensive use of plaque neutralisation assay which is the current 'gold standard', albeit requiring culture of live virus. The next step for us is to achieve licensing of the test as a companion diagnostic for dengue vaccines. We are currently seeking partners and philanthropic funding to bring this about. We further anticipate that Zika vaccines in development may require the use of the test as a companion diagnostic, in order to avoid priming for severe dengue in dengue-naive subjects."
The diagnostic has a number of proprietary innovations and exploits Excivion's unique glycan-cloaking technology which places an 'invisibility cloak' over the major cross-reactive site of the dengue and Zika antigens, such that cross-reactive antibodies (that would otherwise result in mis-diagnosis) can not be detected in the test which is highly specific for dengue antibodies. The compositions of matter and novel test architecture are protected by two PCT stage patent applications, the first of which (on the cloaked antigens), having entered the National Phase, is now pending in thirteen territories world-wide. Both of these applications have received very favourable PCT examination reports.
Peter Laing went on to say "The generous support and validation of the UK Government who are funding this work via a contract under the Small Business Research Initiative (SBRI) from the UK’s innovation agency, Innovate UK is gratefully acknowledged. Without their help we would never have been able to develop the test.”
About Excivion
Excivion is a UK-based biotechnology company developing solutions to the present and emerging healthcare needs of society that are sustainable and affordable by healthcare systems in the face of competing priorities imposed by an ageing population and the emergence of pandemic diseases. Excivion is producing novel vaccines that can be used to prevent emerging pandemic infectious diseases and to prevent and treat chronic diseases of ageing. Vaccines, historically, have proven the most cost-effective solution to disease prevention, but also have a formidable potential to treat diseases once they have arisen. Excivion is in the vanguard of a new pharmaceutical model for this changing world in which vaccines feature globally in both disease-prevention and in the treatment of chronic diseases.
About Innovate UK
Innovate UK is the UK’s Innovation agency. It works with people, companies and partner organisations to find and drive the science and technology innovations that will grow the UK economy. www.innovateuk.gov.uk
Forward-Looking Statements
This press release contains "forward-looking statements," as that term is defined under the Private Securities Litigation Reform Act of 1995 (PSLRA), which statements may be identified by words such as "expects," "plans," "projects," "will," "may," "anticipates," "believes," "should," "intends," "estimates," and other words of similar meaning, including statements regarding expected benefits of NGS cancer panels, the ability to accurately determine the heritable factors increasing the risk of cancer, permitting tailored treatment, screening and prevention of cancer in patients, as well as other non-historical statements about our expectations, beliefs or intentions regarding our business, technologies and products, financial condition, strategies or prospects. Many factors could cause our actual activities or results to differ materially from the activities and results anticipated in forward-looking statements. These factors include those described in our filings with the Securities and Exchange Commission, as well as the risks inherent in funding, developing and obtaining regulatory approvals of new, commercially-viable and competitive products and treatments. In addition, forward-looking statements may also be adversely affected by general market factors, competitive product development, product availability, federal and state regulations and legislation, the regulatory process for new products and indications, manufacturing issues that may arise, patent positions and litigation, among other factors. The forward-looking statements contained in this press release speak only as of the date the statements were made, and we do not undertake any obligation to update forward-looking statements. We intend that all forward-looking statements be subject to the safe-harbor provisions of the PSLRA.
Source: Excivion Ltd.
