Mucosis BV, a Dutch company developing mucosal vaccines that can be applied needle-free via the nose or mouth, is rapidly advancing toward clinical studies that could pave the way for the arrival of broad-based and durable protection from respiratory syncytial virus (RSV).

The small company, based in Groningen, the Netherlands, is already manufacturing supplies of its lead vaccine candidate, a stabilized prefusion F protein recombinant vaccine to prevent RSV infection, to support a toxicity study. Next, it plans to submit an investigational medicinal product dossier to the UK health authorities at year-end with the intention of starting a phase I trial of the vaccine, called Syngem, early in 2016.

The first spin-off of Biomade Technology Foundation, a Groningen research institute dedicated to developing and exploiting molecular nanotechnologies, Mucosis completed a €3 million (US$4 million) series A round in September 2007. Since then, it has received funding from the nonprofit PATH and, in April 2014, added a €5 million funding and equity investment from China's Changchun BCHT Biotechnology Co. in return for a license to the RSV candidate and its platform technology. In addition, its roster of current investors includes Biogeneration Ventures, Medsciences Capital, NV NOM and Utrecht Holdings.

While targeting influenza at first, Mucosis generated positive proof-of-concept data in its first human trial in 2011. However, given how crowded the influenza vaccine field is, CEO Thomas Johnston looked for another area to apply the technology. Eventually finding what he told BioWorld Today is a "blue ocean" opportunity in RSV, which takes a significant toll on both the young and the elderly, he refocused the company on the virus.

RSV is one of the principal causes of acute lower respiratory disease, including bronchiolitis and pneumonia, in infants and children all over the world and one of the leading causes of death from acute lower respiratory infection in children, according to a survey of epidemiology literature by Thomson Reuters Cortellis. While healthy children usually recover within a week or two after suffering mild, cold-like symptoms, between 100,000 to 126,000 babies younger than 1 year are hospitalized due to RSV infection each year, according to the Centers for Disease Control and Prevention.

In large part because infection does not produce life-long immunity, the virus is now recognized as an important pathogen in adults as well as children. But the matter of how RSV, a virus that is relatively immutable, manages to infect people again and again – even those with circulating antibodies to the virus – has long gone unanswered, Peter Openshaw, director of the Centre for Respiratory Infection at the National Heart and Lung Institute at Imperial College, London, told BioWorld Today.

To explore the problem and determine the factors that would best predict whether people once infected with RSV would become infected again, Openshaw – also a member of Mucosis' scientific advisory board – embarked on a study that closely tracked experimental infection in adult volunteers. The results, published in the March 2, 2015, edition of the American Journal of Respiratory and Critical Care Medicine, found that virus-specific immunoglobulin (IgA) memory B-cell responses are "remarkably absent after RSV infection, possibly explaining susceptibility to re-infection" and suggesting that vaccines able to induce durable RSV-specific IgA responses may be more protective than those generating systemic antibodies alone.

The team further determined that a serum-neutralizing antibody, once thought of as the best correlate of protection against RSV, is bested by levels of virus-specific nasal immunoglobulin, suggesting that induction of a local immune response in the nasal tissue may hold advantages as an approach to tackling the virus. Though not discounting live virus vaccines, which he suggested could gain traction with modifications, Openshaw said that "this gives us pretty good evidence that an antigen that is presented by the nasal mucosa in the way that Mucosis does would be a natural way forward in terms of trying to develop protective vaccines, because it could potentially induce exactly the sort of responses we see with local nasal IgA that ought to be protective."

Kees Leenhouts, Mucosis' co-founder and chief scientific officer, invented the company's Mimopath platform. After working the first half of his career on bacteria used in foods such as cheese, he developed a particle that could be used to present vaccine antigens to build up a first line of defense. "The idea is to have these 'soldiers' at the border in order to protect against pathogens coming in," and not just in the bloodstream once the pathogen has already entered the body, he told BioWorld Today.

Given RSV's estimated $38.1 billion economic burden in the U.S. and three biggest European markets, developing a widely used vaccine could be a windfall for the first company to provide it. RBC Capital Markets analyst Michael Yee predicted that a successful broad-based vaccine could be a $1 billion product. Because of the potential prize, Mucosis is in good company.

Medimmune LLC's Synagis (palivizumab), an injectable monoclonal antibody against the RSV F glycoprotein, is already on the market. While its focus is the protection of infants at high risk for severe lung disease from RSV, even with that niche it hit nearly $1.1 billion in 2013 sales. But with the American Academy of Pediatrics issuing guidelines in July 2014 that called on doctors to limit its use, consensus forecasts for the drug fell to $697 million this year, according to Thomson Reuters Cortellis.

In the pipeline, Johnston's former employer, Novavax Inc. is also working to gain approval for its FDA fast-tracked late-stage RSV F-Protein nanoparticle vaccine candidate, preparing for the potential initiation of phase III trials with a $175 million public offering, announced Tuesday. Johnson & Johnson's is chasing the prize through its $1.75 billion acquisition of Alios Biopharma Inc. at the end of September 2014. Gilead Sciences Inc. is working on oral fusion inhibitor GS-5806 and Glaxosmithkline plc has an active development program in the space, too. (See BioWorld Today, Sept. 25, 2013, and June 9, 2014, and Oct. 1, 2014.)

Given all the big-name players, Johnston admitted that the competitive landscape is challenging. But if all goes well with the planned phase I, Mucosis could be initiating a phase IIa challenge study in 2017 that could potentially uncover advantages for its novel approach. If successful, programs for other pathogens in which mucosal delivery might boost compliance among the shot-shy, even potentially human papillomavirus infection, could come next, the company said.