Championing breakthrough treatments
TrippBio focuses on developing new and innovative therapies with low risk and high efficacy to treat serious viral pathogens like COVID-19, influenza, RSV, measles, Dengue, and Zika. Our pipeline includes PanCytoVir™ and related analogs.
Mechanism of antiviral action
Viral replication inhibitor
As viruses rely on host proteins, targeting these host proteins to inhibit viral replication may prevent drug resistance, leading to a broad-spectrum therapeutic approach, given how viruses exploit common cellular pathways.
Studies exploring RNAi screenings of human type II A549 cells infected with A/WSN/33 and other flu strains revealed key host genes needed for flu replication. One of the host genes identified was the organic anion transporter-3 gene (OAT3)—a member of the solute carrier (SLC) superfamily. Transfection of A549 cells with siRNA targeting the OAT3/SLC22A8 gene silenced flu replication.
As OAT3 is important for flu replication, a drug that inhibits OAT3 should be effective as an antiviral drug for flu. Studies showed that PanCytoVir™—a classical clinical inhibitor of OAT1 and OAT3—reduces OAT3 mRNA and protein levels, and probenecid treatment in vitro and in vivo reduced flu lung titers in a murine model.
Potential anti-inflammatory benefits
PanCytoVir™ can modulate the expression of ACE2, and targets the pannexin-1 gene, PANX1. PANX1 is an ATP release channel that facilitates the communication between T cells to inhibit the severity of airway inflammation. PANX1 limits airway inflammation driven by type-2 CD4+ T-cell inflammatory responses, and PanCytoVir™ is an inhibitor of PANX1 that mediates the activation of caspase-1 and release of IL-1β induced by P2X7 receptor activation.
P2X7R is expressed in macrophages and other immune cells, and is an ion channel gated by high concentrations of extracellular ATP, i.e., concentrations known to be present at sites of inflammation.
Measles is a highly contagious, serious disease caused by a virus. Before the introduction of a measles vaccine in 1963 and widespread vaccination, major epidemics occurred approximately every 2-3 years and measles caused an estimated 2.6 million deaths each year. Measles is still common in many developing countries – particularly in parts of Africa and Asia. The overwhelming majority (more than 95%) of measles deaths occur in countries with low per capita incomes and weak health infrastructures.
We are a strong contender in the fight against the COVID-19 pandemic, researching the efficacy of the existing drug PanCytoVir™ in treating symptoms and infection of the SARS-CoV-2 virus.
Influenza type A viruses are categorized based on the combinations of two different proteins: the hemagglutinin (H) and the neuraminidase (N), located on the surface of the virus. The currently circulating type A viruses are H1N1 and H3N2 subtypes.
PanCytoVir™ has demonstrated potent in vitro and in vivo activity against the influenza virus. Given the in vitro potency, in vivo efficacy, favorable pharmacokinetic profile, and safety record, TD-214 is being evaluated as a treatment option for patients infected with influenza.
Currently, for RSV there is no vaccine available, and therapeutic treatments are very limited. Nearly 60%-70% of the children below the age of one have been infected with RSV and 2%–3% of these infections result in hospitalization.
Preclinical studies have shown that PanCytoVir™ has no detectable cytotoxicity for patients, yet inhibits virus replication in a dose-dependent fashion at nanomolar-to-micromolar concentrations.
Dengue is a mosquito-borne viral disease that is prone to pandemics. The last 50 years have seen a 30-fold increase in incidence and geographic spread.
The global incidence of dengue fever has gone up drastically. The number of dengue cases reported to WHO in the last two decades has increased eightfold, from 505,430 cases in 2000 to 2.4 million in 2010 and to 5.2 million in 2019. Even the reported deaths between the period 2000 to 2015 have increased from 960 to 4032.
The largest outbreak of Zika was in 2015-2016 and affected a total of 71 countries and territories, mainly in the Americas, with additional cases also reported in Singapore and the Pacific Islands.
In 2017, the disease resurfaced in parts of India, with three cases reported in May, 2017. South-East Asia, Thailand and Singapore recorded more than 400 cases of Zika infection, and 19 of the 27 countries in the Western-Pacific region had confirmed cases, making it the worst affected region after the Americas.