LA JOLLA, Calif.--(BUSINESS WIRE)--EpicentRx, Inc., a clinical cancer immunotherapy company targeting both sides of the immune system to deliver cancer treatments with minimal toxicity, today announced that the U.S. Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for AIM-001, an oncolytic adenovirus that is enhanced with a TGF-β (beta) trap transgene. With a Phase 3 trial of its lead program CD47 antagonist RRx-001 for the treatment of small cell lung cancer (SCLC) already in progress, AIM-001 is EpicentRx’s second program to move into clinical testing.
Cancer cells overexpress TGF-β, an immunosuppressive protein, to circumvent or thwart immune surveillance and cancer immunotherapy. The effect of AIM-001 is potentially three-fold: 1) it lyses and kills tumor cells, thus releasing signals to activate T-cell responses, 2) it overexpresses TGF-β trap transgene, neutralizing TGF-β and reprograming the tumor microenvironment from immunosuppressive to immunostimulatory, and 3) since TGF-β is a master regulator of fibrosis, the TGF-β trap may reduce the fibrotic stroma and enable better penetration of anticancer therapies.
"The clearance of our IND is a major milestone for EpicentRx and the first of many oncolytic adenoviruses that are planned for development," said Tony R. Reid, M.D., Ph.D., Chief Scientific Officer of EpicentRx. “Since overexpression of TGF-β is common in many different cancers and an underlying mechanism of chemo- and immunoresistance, we generated this TGF-β trap virus to concomitantly lyse tumor cells and neutralize TGF-β,” Dr. Reid said.
EpicentRx anticipates that AIM-001 will not only demonstrate single agent activity but also ‘turn up the heat on cold tumors’ and, in combination with both chemotherapy and immune checkpoint therapies, yield synergistic anti-tumor responses. EpicentRx plans to begin clinical trials with AIM-001 this year.
“AIM-001 was designed to trigger in situ vaccination and to turn the injected tumor into a nidus for antigen recognition by the immune system and generation of a potent adaptive T cell response against distant tumors,” stated Christopher Larson, M.D., Ph.D., head of the EpicentRx viral program.
In addition to AIM-001, EpicentRx has developed additional IP-protected oncolytic adenoviruses with the capacity to accommodate multiple transgenes and has potential applicability to a broad range of disease targets, including those that have been considered "undruggable."
As part of its broader effort to ‘release the immunosuppressive brakes’ and turn immunologically cold tumors hot, EpicentRx’s lead program RRx-001 stimulates macrophage-mediated phagocytosis and converts “treatment-resistant” tumors into “treatment-sensitive” tumors. The candidate has been evaluated in multiple clinical studies, including the ongoing Phase 3 REPLATINUM trial for the treatment of SCLC.
Having closed its $35 million series D round last year, the company is poised to complete the Phase 3 REPLATINUM trial with RRx-001 and advance its diverse oncolytic adenoviral portfolio including AIM-001.
About EpicentRx, Inc.
EpicentRx is a patient-driven oncology company developing new mechanisms of immunotherapy that work across diverse patient populations and tumor types with minimal toxicity, enabling the best-possible quality of life during treatment. Through two distinct technology platforms, each targeting a different half of the immune system, the company is developing drug candidates designed to act alone or in combination with other medicines to outsmart cancer. EpicentRx’s lead program is among a portfolio of novel drugs, derived from a class of molecules called dinitroazetidines, that downregulates CD47 – SIRPα to alter the tumor microenvironment and optimize immune response, and has been tested in several clinical trials including an ongoing Phase 3 study in small cell lung cancer. The company is also advancing multiple programs through its smart virus platform, including personalized cancer vaccines that are designed to target both chemotherapy and immune resistant tumors. For more information, please visit www.epicentrx.com and follow EpicentRx on Twitter and LinkedIn.