The Atriva Approach
The Atriva Approach
Atriva Therapeutics pursues a new approach
By combining antiviral and anti-inflammatory activity in one tablet, Atriva Therapeutics pursues a new approach to develop treatments for viral infections. With its unique, broadly active and efficacious mode of action based on MEK inhibition, Atriva is spearheading current drug innovation in areas of high unmet medical need, such as COVID-19 and influenza.
The company’s lead drug candidate zapnometinib targets the intracellular Raf/MEK/ERK signaling pathway. This pathway is central for replication of many RNA viruses, such as the influenza virus, Hantavirus or respiratory syncytial virus (RSV) and also SARS-CoV-2, the virus that causes COVID-19. In influenza virus infected cells, the interaction of zapnometinib with MEK (MAPK/ERK kinase) prevents export of the viral genome protein complexes (ribonucleoprotein, RNP) from the nucleus to the cytoplasm, thus blocking the formation of functional new viral particles. This ultimately reduces the viral load in the body.
Figure: Antiviral activity of zapnometinib: intracellular MEK inhibition.
In addition, zapnometinib has the potential to modulate the pro-inflammatory cytokine response of the body, avoiding overshooting cytokine response that can be caused by such viral infections. MEK inhibition can inhibit the gene expression of some of the cytokines involved, like TNF-α, IL-1ß, IP-10, IL-8, MCP-1 and MIP-1a, and thus mitigate the overactive inflammatory response in the lungs of patients who are severely ill with influenza or COVID-19.
Figure: Viral replication and cytokine storm. Zapnometinib addresses these effects, which often lead to severe progression of respiratory viral infections.
Research & Development
The company’s lead drug candidate is the MEK inhibitor zapnometinib. The small molecule, which can be administered orally (tablet), is under advanced clinical development in two severe respiratory viral diseases: COVID-19 and influenza, two disease areas with urgent need for effective therapeutics.
Preclinical studies have proven the antiviral efficacy of zapnometinib against various strains of influenza virus, hantavirus and respiratory syncytial virus (RSV). These promising data led to a Phase I clinical study with 70 healthy volunteers, which was successfully conducted in 2019 and demonstrated excellent safety and tolerability of zapnometinib (NCT04385420). In addition, pharmacokinetics exposure and determination of MEK inhibition were verified and confirmed the maintenance of clinically relevant blood levels. This supports the intended once-daily regime for the ongoing Phase II clinical development.
Discover the ongoing clinical trials in COVID-19 and influenza.
The company’s lead drug candidate is the MEK inhibitor zapnometinib. The small molecule, which can be administered orally, is under advanced clinical development in two severe respiratory viral infections: the newly discovered COVID-19 and influenza, two disease areas with an urgent need for effective therapeutics.
As a first-in-class concept for severe respiratory viral infections, including SARS-CoV-2 and influenza virus, that use the Raf/MEK/ERK signalling pathway, zapnometinib is also studied in haemorrhagic viral infections, such as hantavirus, and provides a strong platform portfolio.