Rakuten Medical has announced that its third drug candidate, RM-0256, has been selected for funding by the Japan Agency for Medical Research and Development (AMED) under its Support Program for Orphan Drug prior to the Designation. The AMED grant will support clinical development of this novel photoimmunotherapy for treating unresectable, advanced, or recurrent malignant epithelial tumors.
RM-0256 represents a significant advancement in cancer immunotherapy, combining a proprietary anti-PD-L1 monoclonal antibody with IRDye®700DX (IR700), a light-activatable dye for which Rakuten Medical holds exclusive global manufacturing and supply rights. This innovative approach targets Programmed Cell Death Ligand 1 (PD-L1), a key immune checkpoint protein that enables tumors to evade immune detection by binding to PD-1 receptors on activated T cells.
Triple Mechanism of Action
Pre-clinical studies have revealed that PD-L1-targeted photoimmunotherapy operates through three complementary mechanisms of action. The therapy directly depletes PD-L1-expressing tumor cells through necrosis, activates anti-tumor immunity by eliminating PD-L1-expressing immunosuppressive cells, and provides checkpoint blockade by inhibiting PD-L1/PD-1 interaction, potentially enhancing systemic immune responses.
PD-L1 is widely expressed across various solid tumors, including melanoma, ocular melanoma, lung, urothelial, gastrointestinal, gynecological, breast, and head and neck cancers. The protein is also found on immunosuppressive cells within the tumor microenvironment, such as tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs).
Addressing Unmet Medical Need
In Japan, malignant epithelial tumors affect approximately 22,000 individuals annually. Current treatment approaches for unresectable advanced or recurrent cases rely primarily on systemic therapies, including chemotherapy and immune checkpoint inhibitors. However, patients who develop resistance to these treatments face severely limited therapeutic options, highlighting the critical need for novel approaches.
The Alluminox™ platform underlying RM-0256 combines pharmaceuticals with medical devices through a two-step process: drug administration followed by targeted illumination using red light at 690nm wavelength. This targeted illumination transiently activates the drug, leading to rapid and selective necrosis of targeted cells through a biophysical process that compromises membrane integrity.
Platform Technology and Development
Rakuten Medical's pre-clinical data demonstrate that the Alluminox platform activation results in local and systemic innate and adaptive immune activation due to immunogenic cell death of targeted tumor cells and removal of immunosuppressive cells within the tumor microenvironment. The photoimmunotherapy technology was originally developed by Dr. Hisataka Kobayashi and his team at the National Cancer Institute in the United States.
With AMED funding support, Rakuten Medical is accelerating development of RM-0256 as a multimodal cancer therapy designed to induce both local and systemic anti-tumor effects. The company, headquartered in the United States with offices across five countries including Japan, Taiwan, Switzerland, and India, continues its mission to develop pioneering cancer treatments for global patient populations.
The therapy remains investigational outside Japan, with ongoing clinical development supported by this strategic funding partnership with AMED's orphan drug development program.
