First-in-Human Results of SynGEM Demonstrate that the RSV Vaccine Is Well-Tolerated and Capable of I

SynGEM a needle-free nasal spray vaccine against respiratory syncytial virus

*

SynGEM shown to be safe and immunogenic in healthy adults

*

SynGEM the first non-replicating intranasal RSV subunit vaccine to induce persistent antibody responses in humans

Groningen, the Netherlands, March 6, 2019 – Virtuvax B.V. and the trustee of biotech company Mucosis B.V., Mr. Holtz LLM today announce the results of a first-in-human study of the intranasal Respiratory Syncytial Virus (RSV) vaccine candidate, SynGEM. The study was executed by Imperial College London. Results of the study have been posted (in press) on the website of the American Journal of Respiratory and Critical Care Medicine (1). The vaccine was found to be safe and immunogenic in healthy adults.

“Virus-specific immunogenicity induced after SynGEM vaccination was demonstrated by systemic IgG+ and IgA+ responses in terms of antibody-secreting cells (ASCs)” indicated prof. Openshaw, professor of Experimental Medicine at Imperial College London. Professor Openshaw added that “SynGEM induced some RSV-specific mucosal IgA in most individuals, particularly in those with low pre-existing F-specific IgA titers. Indeed, higher doses of the vaccine induced prolonged IgA-producing ASC responses in some volunteers.” Prof. Openshaw further explained that “The publication includes in vitro data supporting the clinical observations, showing that SynGEM induces a dose-dependent antibody response associated with cytokine production from T-helper cells.”

Dr. Chiu, principal investigator of the clinical trial, commented: “Previously, we showed that antibodies induced by natural RSV infection were only short-lived and we hypothesized that RSV-induced immunomodulatory mechanisms impaired the antibody responses against the virus. In this study, SynGEM not only induced immune responses but also boosted long-term systemic RSV-specific antibodies for at least 6 months. Vaccination with the SynGEM RSV vaccine therefore was not associated with evidence of immune modulation, as seen after infection with live RSV.”

In another publication also in AJRCCM, senior author Prof. Louis Bont of University Medical Center Utrecht, The Netherlands commented on the SynGEM trial. Prof. Bont argued that in the absence of a correlate of protection to RSV, vaccine developers are working in the dark. In the case of SynGEM, preclinical data had shown protection against infection suggesting evidence of the vaccine providing protective immunity. However, despite the induction of broad immune responses, neutralizing antibodies were not detected in the clinical trial. In their comment, the authors suggested that testing of the SynGEM vaccine in a human challenge model might be a quick way to finally determine proof of concept of efficacy.

The investigators of Imperial College were surprised that no detectable neutralizing antibody responses were found, since extensive stability tests had shown stable binding of such antibodies by SynGEM. Openshaw said: “the system needs further optimization, but establishes proof of principal that the nasal vaccine approach can work. It was a shame that the programme was ended before the infection challenge component could be performed”. Trustee of Mucosis, Mr. Holtz, commented: “During the clinical trial, Mucosis was confronted with a sudden shortage of finances and the company had to apply for bankruptcy before the final results were known as published today. Since these long-term data have become available as of now, any further development of the vaccine may be taken forward by other companies interested in doing so.”

SynGEM is based on a unique pre-fusion version of the F subunit of RSV, shown to raise more potent serum neutralizing antibodies against RSV compared with the post-fusion F antigen approach others have used. The pre-fusion conformation (pre-F), which predominates on infectious virions, displays a distinct antigenic site (site Ø) preferentially targeted by the most potent neutralizing antibodies. Pre-clinical studies using SynGEM showed induction of high levels of both systemic and mucosal antibodies. Delivered via the mucous membranes in the nose, the vaccine candidate is also able to recruit antibodies produced in the mucosal linings of the body, with the potential to effectively stop the virus from entering the body via the mucosal pathways, where over 90% of pathogens enter the body. SynGEM is based on Mucosis’ patented Mimopath technology, which uses bacterium-like particles (BLP) derived from food-grade bacteria, to deliver the antigen in a more natural conformation and boost the body’s immune response to the virus.

RSV is a common contagious infection of the lungs and respiratory pathways, eliciting cold-like symptoms in adults. Whilst RSV infection is normally mild in healthy adults, the infection can lead to serious and sometimes fatal diseases such as pneumonia and bronchiolitis, most often in susceptible populations such as the young and elderly. Every year in the US, RSV infections lead to 57,527 hospitalizations of children under 5 year’s old (2)and are responsible for up to 200,000 deaths annually worldwide (3). The annual global burden of RSV illness is significant, with 33.8 million estimated new episodes of RSV-associated acute lower respiratory infection (ALRI) worldwide in children under 5, and over 3.4 million hospital admissions associated with severe RSV disease. Global mortality was estimated at 253,500 deaths in 2010.

The Wellcome Trust translational fund supported the clinical trial of SynGEM with a staged award of up to €3.44 million (£2.77 million).

Note for Editors About Mucosis

Mucosis B.V. (Mucosis) was a clinical-stage biotechnology company using a proprietary technology platform to develop next-generation needle-free human vaccines for infectious diseases. The investigational patient-friendly vaccines Mucosis developed, can be delivered via the nose or mouth to elicit a more natural immune response with a broader base of protection. Mucosis’s lead product SynGEM, a stabilized recombinant vaccine delivered intranasally to prevent respiratory syncytial virus (RSV) infection, entered human proof-of-concept studies in 2016.

Following an immediate shortage of capital, the District Court in Groningen, the Netherlands, declared bankruptcy of Mucosis on June 27, 2017 and appointed Mr. R.G. Holtz LLM as trustee. On behalf of the trustee, sale of the Mucosis assets is executed by the private company with limited liability Virtuvax B.V., Odijk, The Netherlands. Virtuvax B.V. provides strategic advice, technology and expertise for the development of vaccines. The company is headed by Ernst Soethout PhD and provides its services for vaccine development globally.

References

1. Ascough S, Vlachantoni I, Kalyan M, Haijema BJ, Wallin-Weber S, et al. Local and Systemic Immunity Against RSV Induced by a Novel Intranasal Vaccine: A Randomised, Double- Blind, Placebo-Controlled Trial. Am J Respir Crit Care Med. 2019 Feb 12. doi: 10.1164/rccm.201810-1921OC. [Epub ahead of print]

2. Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, et al. The burden of respiratory syncytial virus infection in young children. New Engl J Med. 2009;360(6):588-98.

3. Nair H., Nokes D., Gessner B., Dherani M., Madhi S., Singleton R., et al. (2010) Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet 375: 1173–1181

###

Media Enquiries: Virtuvax BV

Ernst Soethout PhD, managing director

Virtuvax BV

Odijk, the Netherlands

e-mail: e.soethout@virtuvax.nl

Tel : +31 6 2989 4729

Mr. Job Holtz LLM, trustee

Bout Advocaten – Bout Lawyers

Groningen, the Netherlands

e-mail: holtz@boutadvocaten.nl

Tel: +31 5 0314 0840