CyNRGY platform (RRx-001)
A new class of anti-cancer therapies with the potential to convert “treatment-resistant” tumors into “treatment sensitive” tumors
EpicentRx’s lead CyNRGY platform program, RRx-001, is among a portfolio of immunotherapeutic compounds that normalize the tumor microenvironment, activate the tumor associated macrophages (TAMs) of the innate immune system, and sensitize solid tumors to standard therapies in small cell lung cancer (SCLC), glioblastoma, colorectal cancer and additional cancers.
RRx-001 is a next generation, small molecule anticancer immunotherapeutic that downregulates the CD47/SIRPα axis and repolarizes TAMs and other immunosuppressive cells in the tumor microenvironment to an immunostimulatory phenotype. RRx-001 is designed to be used either as a monotherapy or in combination with chemotherapy, radiation therapy or immunotherapy.
RRx-001 has Orphan Drug designation from FDA for SCLC, neuroendocrine cancer and glioblastoma, and from EMA for SCLC.
CD47 and SIRPα as guideposts of RRx-001-mediated innate checkpoint activity in solid tumors
The search for immune-related biomarkers to prospectively identify responders to RRx-001 is ongoing. Based on tumor biopsies from RRx-001-treated patients enrolled in Phase II clinical trials, response appears to correlate with increased infiltration of TAMs, usually a poor prognostic indicator due to strong immunosuppression. However, in the case of RRx-001, an extensive macrophage infiltrate in biopsied preclinical and clinical lesions is suggestive of better clinical outcomes. Since the main underlying mechanism of RRx-001 activity is dual downregulation of the antiphagocytic, “do not eat” CD47/SIRPα checkpoint axis, high CD47/SIRPα expressing tumors are thought to serve as guideposts for the prediction and monitoring of antitumor activity. Correlation of RRx-001-mediated outcomes and response with a combination CD47 and SIRPα biomarker is under preclinical evaluation as well as clinical investigation in the Phase III REPLATINUM trial in SCLC.