Dengue

Dengue – a mosquito-borne tropical disease

Dengue virus is spread by the Aedes aegypti mosquito. It is flavivirus that is a rapidly growing health problem in tropical and sub-tropical countries of the World. There are four antigenically distinct dengue virus serotypes (DENV-1 to -4). Following infection with all four serotypes, individuals may have asymptomatic disease to debilitating dengue fever, to the more severe dengue hemorrhagic fever or the highly dangerous dengue shock syndrome encompassing the shock from vascular leakage, internal hemorrhage and organ dysfunction which can leading to death.

Geographical Spread of Dengue

  1. WHO, dengue guidelines for drug treatment, prevention and control, WHO/HTM/NTD/DEN/2009.1
  2. European Center for Disease Prevention and Control, Dengue Fever Fect Sheet for Professionals.

Dengue Disease Progression

1. Day 1-7 from Infection

Headache, pain behind the eyes, loss of appetite, vomiting, fever, nausea, muscle/joint pain, rash.

2. Day 7-10 from infection

Bed rest, unable to work/attend school

3. 4-6 weeks from infection

Major fatigue and tiredness

4. Early diagnosis and effective treatment

Early diagnosis and effective treatment started as soon as possible after infection can substantially reduce mortality, morbidity and the cost burden of Dengue.

Dengue Prevalence and Mortality

The World Health Organization estimates on the annual incidence of individuals infected by dengue are found below. As of today, there is no effective treatment of acute dengue infection. Thus, there is every reason to believe there is a huge opportunity to make an impact on morbidity and mortality with an effective point of care treatment.

The annual cost of dengue is also very substantial and estimated in 2015 to be in excess of US$ 9 Billion. Driving these costs are the direct costs attributed to patient care and as well as indirect costs associated with lost productivity, lost wages etc. In addition, the vast majority of individuals touched by dengue are in low/middle income countries where often healthcare is provided on a self-pay basis and there are limited or non-existent sickness benefits.

Dengue infection has a substantial impact on the individuals well-being and ability to work – with an average of almost 4 days in hospital for those requiring hospitalisation

GEN-Y Biologics and Dengue Management

  • Highly sensitive and serotype-specific Point-of-Care test.
  • Rapid turn-around with results in 15 minutes.
  • Ideal for in-field, out-patient and hospital diagnosis as well as epidemiological monitoring of dengue outbreaks.
  • Initial serotype 1 therapeutic for treatment of Dengue (~50% WW infections).
  • Followed by serotype 2-3-4 therapeutic.
  • Followed by Tetravalent treatment.
  • Development of the tetravalent mAb combination therapeutic for prophylaxis.
  • Tetravalent to be employed for travellers to endemic areas (tourists, armed services, other agencies) and for potential use in outbreak scenarios.

GEN-Y Biologics and Dengue Management

  • Highly sensitive and serotype-specific Point-of-Care test.
  • Rapid turn-around with results in xx minutes.
  • Ideal for in-field, out-patient and hospital diagnosis and epidemilogical monitoring of Dengue outbreaks.
  • Fully human therapeutic mAb for treatment of Dengue infection.
  • Initial GMP material therapeutic prepared for the treatment of Dengue serotype 1 (~50% WW infections).
  • Treatments for Dengue serotype 2-3-4 available in 2 Year.
  • Tetravalent treatment available in 3 years.
  • Development of the travalent mAb combination therapeutic for prophylaxis.
  • Tetravalent to be employed for travellers to endemic areas (tourist, amed services, other agencies) and for potential use in outbreak scenarios.

Dengue Point of Care Diagnostic

Managing Dengue – A rapid, accurate test will allow swift, effective treatment

The ability to have an impact on dengue will be driven by the ability to make a rapid, accurate diagnosis of the dengue serotype with which the individual has been infected. Once the serotype has been identified, the appropriate future mAb dengue treatment can be administered to neutralise the dengue.

Antibody-Dependent Enhancement - Why knowing your Dengue infection serotype is important

People who are infected a subsequent time with a different type of the dengue virus may experience something called “antibody-dependent enhancement” (ADE) in which the body’s immune response actually makes the clinical symptoms of dengue worse and increases a person’s risk of developing severe dengue.

Model of antibody-dependent enhancement of dengue infection

Antibody (Ab)-dependent enhancement of infection occurs when preexisting antibodies present in the body from a primary (first) dengue virus (DENV) infection bind to an infecting DENV particle during a subsequent infection with a different dengue serotype. The antibodies from the primary infection cannot neutralize the virus. Instead, the Ab–virus complex attaches to receptors called Fcγ receptors (FcγR) on circulating monocytes. The antibodies help the virus infect monocytes more efficiently. The outcome is an increase in the overall replication of the virus and a higher risk of severe dengue.

Dengue Treatment – A novel human antibody treatment to stop dengue in its tracks in infected patients

GEN-Y has the ambition and the tools to make a major impact in the treatment of dengue infection – the type of impact that will reduce the period of sickness of symptomatic dengue, save lives and reduce the cost of the disease for patients and other stakeholders

Through use of state-of-the-art technology and a unique antibody discovery platform, GEN-Y has isolated 4 monoclonal antibodies (mAb) that have the potential to achieve our ambition

Preclinical studies employing the serotype-1 mAb, that represents around 50% of worldwide dengue infections, gives reason to be confident that a new paradigm in dengue treatment may be just round the corner

The findings below from established preclinical models demonstrate the potential speed and efficacy of the treatment

Rapid Virus Neutralisation in Dengue in Serotype-1 Infected Human Blood

Blood infected with dengue serotype-1 virus is treated with the serotype-1 mAb at various dose levels. The impact on viremia is measured at 6hours following administration of the mAb.

The viral load is substantially and highly statistically significantly reduced at 1μg and 3μg doses.

Dengue Virus Neutralisation in Preclinical Animal Dengue Model

Mice were injected with the Dengue virus (serotype-1) at the start of experimentation. Mice that developed viraemia and dengue-like symptoms were treated with 1 dose of dengue serotype 1 mAb.

These data indicate that the 10μg dose completely neutralised the dengue virus rapidly without any rebound.

Implications of these data

These studies and others provide a strong rationale for the efficacy of the mAb dengue treatment. As the mAb have been isolated from convalescent dengue patients, this also gives reassurance that the risk of side-effects will be low.