RE:RE:RE:RE:ONCY May 09, 2024 Earnings CallTranscript ONCY's Bracelet-1 Phase 2 metastatic breast cancer study included patients with metastatic estrogen receptor– or progesterone receptor–positive/HER2-negative breast cancer who progressed on at least 1 hormone-based therapy with a CDK4/6 inhibitor.
A 2022 study highlighted cross-talk between unfolded protein response (UPR) signaling and RNA-mediated PRR activation (stimulates innate immunity and adaptive immunity) as a means of enhancing anti-cancer efficacy with potential pro-immunogenic consequences.
During hypoxic conditions, cells undergo critical adaptive responses that include the up-regulation of hypoxia-inducible proteins (HIFs) and the induction of the unfolded protein response (UPR). ONCY's pelareorep down-regulates HIF-1α levels and in so doing remodels the tumor microenvironment (TME) for sequential immune checkpoint inhibition.
This has implications for future clinical development of PRR agonists and oncolytic viruses, and broadens the therapeutic remit (reversed mirror training) of CDK4/6 inhibitors to include roles as both ER stress and dsRNA PRR sensitizers.
https://www.biorxiv.org/content/10.1101/2022.09.28.508679v1.full