Computer-aided drug design
antivirals engage the patient’s own immunity to naturally defend against viral infection without the emergence of drug resistance
Evrys Bio broad-spectrum antivirals are based on the discovery that certain human proteins, called sirtuins, normally defend the human (host) cell from being invaded by many different virus-types. Sirtuins regulate the metabolism of the host cell. When a virus infects the host cell, the virus redirects the metabolic machinery of its host to support production of virus DNA and proteins. By modulating sirtuin activity, Evrys Bio drugs restore metabolism that favors the host cell and enhances host defense-mechanisms while eliminating productive conditions for virus propagation. Since host-mediated metabolism is essential to provide the necessary building blocks for the virus, the virus cannot evolve resistance mutations around Evrys Bio drugs.
Three features differentiate Evrys Bio sirtuin-targeted antivirals from currently marketed direct-acting antivirals that target a virus protein: (1) a high barrier to viral resistance, (2) effective against a variety of different virus-types, and (3) therapeutic utility in multiple areas of significant unmet medical need.
Evrys Bio drugs were initially identified in a screen for drug-like chemicals demonstrating modulatory effects on the enzyme activity of any of the seven human sirtuins 1-7. Sirtuins are evolutionarily conserved enzymes that modify other proteins through de-acylation; Evrys Bio founders demonstrated sirtuins are also evolutionarily conserved viral restriction factors (view publication). Sirtuin modulators are drug-like chemicals that increase or decrease the ability of sirtuins to modify downstream proteins. To optimize sirtuin drugs for antiviral use in the clinic, Evrys Bio leverages our world-class expertise in both sirtuin and virus biology starting with structural information about all seven sirtuins and computer-aided drug-design to model the desired drug selectivity, with the desired sirtuin interaction(s), to be validated through X-ray crystallography. Evrys Bio proprietary and drug-like candidates are first validated as antivirals in virus growth assays in primary cells and then in cross-species animal models against diverse viruses spanning enveloped and non-enveloped DNA and RNA viruses. In the clinic, reduction of viremia in patients will provide a predictive disease-modifying biomarker to facilitate early clinical development. Thus, the Evrys Bio sirtuin-based antiviral-platform benefits from the validation of sirtuin-based drugs in viral assays in culture, in animals, and in the clinic, tracking the desired disease-modifying effect to inhibit virus growth through the entire drug-development process.
Virus- growth assays
Proof of Concept in man
Evrys Bio products will have the potential to transform the practice of medicine by offering treatment options that target a broad-spectrum of viral infections responsible for an entire infectious disease condition, such as respiratory infections. Current virus-targeted therapies, such as influenza antivirals, are only effective against the targeted virus, i.e. influenza A or influenza B, and exclude other respiratory viral infections presenting with similar symptoms, such as respiratory syncytial virus (RSV), SARS virus, and others. In the case of respiratory infections, in a typical season, influenza only accounts for ~20% of such infections referred to by physicians as influenza-like illness. Evrys Bio is developing a portfolio of first-in-class, broad-spectrum antivirals, that can be safely administered without the problem of virally-acquired resistance. The goal is one therapy to target and cure each infectious disease condition. In addition to a pan-respiratory infections antiviral, Evrys Bio has active programs targeting multiple (opportunistic) infections endangering transplant patients and their graft organs; a liver infections antiviral targeting HBV, HCV and HCMV; and a brain-penetrant antiviral to treat viral encephalitis.