DENGUE & HUMAN VIRAL DISEASES

FUTURE ANTIVIRAL TREATMENT

Dengue Fever

Dengue is the most common mosquito-borne viral disease in the world. The global incidence of dengue has grown dramatically in recent decades and the disease is now endemic in more than 100 countries with an estimated economic burden as high as 39 billion USD worldwide. Till date, no therapeutic agents exist to treat dengue infections. The Sanofi Pasteur vaccine has limited efficacy over the 4 serotypes and is even less efficacious with the highly virulent serotype 2, which is prevalent in South East Asia. Additionally, the vaccine precludes children under 9 and adults over 45, age groups which happen to be particularly vulnerable to the disease. Also notable is the fact that the antiviral small molecule drug Celgosvir has failed to reduce viraemia and the fever burden in dengue patients during clinical phase 2 trials. The trial will be repeated using much higher doses, which raises concerns about potential adverse reactions.

RetroMAD1 for as a Therapeutic for Dengue and Other Viral Diseases

In vitro antiviral assays for RetroMAD1 has shown strong efficacy against all 4 dengue serotypes with more than 99% of viral reduction. RetroMAD1 has also demonstrated efficacy in an in vivo model of dengue (AG129 mice) with 50% survival in treated group where 100% death is the untreated control outcome. Based on the promising results observed through our molecular docking studies and enzyme substrate assay, the NS2B-NS3 protease (essential for viral replication) is proposed as one of the main targets for RetroMAD1. 2D gel electrophoresis revealed that RetroMAD1 affects the dengue virus life cycle by targeting viral entry, replication and translation, as major inhibitory down regulations were observed in the levels of the corresponding viral and host proteins.

RetroMAD1 is an orally delivered protein, and can be easily self-administered. It is also relatively stable in solution and does not require cold chain transport. Pharmacokinetic studies on non-human primates show that RetroMAD1 enters the blood within 30 minutes of ingestion and has a relatively high bioavailability of 39%. Both acute and sub-chronic studies conducted in several animal models indicated no signs of toxicity such as mortality, change in general behaviour, or pattern and histology of selected organs, even when extreme concentrations of RetroMAD1 were administered. Studies have also shown that RetroMAD1 is only very weakly immunogenic.

We propose the following applications of RetroMAD1 for dengue:
i. Early treatment of symptomatic dengue patients
ii. Halting dengue transmission by asymptomatic/pre-symptomatic dengue patients
iii. Prevention of dengue infection by prophylactic treatment


Besides dengue, RetroMAD1 also shows activity against a wide range of human viruses, including Ebola virus and Zika virus.

Pre-clinical development of RetroMAD1 is currently underway, with the aim of starting first-in-human trials in 2018. We welcome potential investors interested in our technology platform as well as scientific collaborators to get in touch with our team.

Please contact Thamil Vaani (thamil.vaani{at}biovalence.com.my) or Tiffany Coney Ung (tiffany.ung{at}biovalence.com.my).