RE:RE:Durability, Durability, DurabilityUpon the following understanding of ONCY's pelareorep's mechanism of action, reovirus (pelareorep) reduces HIF-1α expression in hypoxic tumor fractions, contributing to the overall oncolytic effect by reducing transcription of HIF1α-responsive genes including VEGF and those responsible for maintaining cancer stem cell phenotypes.
HIF-1α is a strong inducer of CD39, CD38 and the A2Rs that are key mediators of extracellular adenosine signaling in the TME, thus reovirus-mediated elimination of hypoxic fractions can also effect changes in the adenosinergic environment. Adenosine signaling in the TME activates intracellular cyclic adenosine monophosphate and is associated with profound immune suppression.
As a result ONCY's reovirus (pelareorep's) inhibition of HIF-1α down-regulates adenosine signaling in the TME with the effect of converting an immunosuppressive TME into one that is conducive for the addition of PD-(L)1 immune checkpoint inhibition, such as Roche's Tecentriq or Merck KGaA/Pfizer's Bavencio, as several immediate examples, thus resulting in enhanced treatment efficacy and T-cell endurance verus T-cell exhaustion, leading to treatment durability.