Rakuten Medical Presented PD-L1 Photoimmunotherapy Preclinical Results at 2024 JCA Meeting

Rakuten Medical, Inc., a global biotechnology firm, recently unveiled promising preclinical research findings for RM-0256, an innovative anti-PD-L1 antibody conjugated to the dye IR700, at the 83rd Annual Meeting of the Japanese Cancer Association (JCA2024) in Fukuoka, Japan. This novel photoimmunotherapy showcases a dual mechanism: targeting and depleting PD-L1 expressing tumor cells and immunosuppressive cells within the tumor microenvironment.

Key findings presented by Amy H. Thorne, Ph.D., revealed that in vitro studies indicated this photoimmunotherapy could effectively deplete tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). This dual mechanism of action highlights the therapy's potential for systemic immune checkpoint inhibition by disrupting the PD-L1:PD-1 interaction, which deactivates killer T cells.

In vivo studies further demonstrated RM-0256's efficacy. In an anti-PD-L1 sensitive mouse tumor model, the therapy led to more substantial tumor growth suppression compared to treatment with an anti-PD-L1 antibody alone. Similarly, in an anti-PD-L1 resistant mouse tumor model, RM-0256 exhibited significant tumor growth inhibition relative to saline controls. This enhanced suppression is attributed to the therapy’s impact on the tumor microenvironment, where it depletes immunosuppressive cells, fostering an environment conducive to CD8+ T cell activation.

Safety data from a GLP toxicity study indicated that RM-0256 is well-tolerated in cynomolgus monkeys, supporting its potential for clinical application. Building on these encouraging results, Rakuten Medical is exploring further clinical development opportunities for RM-0256.

RM-0256 operates by utilizing a newly developed anti-PD-L1 antibody conjugated with IRDye®700DX (IR700). This dye accumulates specifically on PD-L1 expressing cells, which are known to inhibit anti-cancer immune responses by binding to PD-1 on T cells. PD-L1 is prevalent in a variety of solid tumors, including melanoma, lung, urothelial, gastrointestinal, gynecological, breast, and head and neck cancers. It also appears on suppressive immune cells within the tumor microenvironment, such as TAMs and MDSCs. The preclinical studies demonstrated that RM-0256 not only causes the necrosis of PD-L1 expressing cells but also activates a broader anti-cancer immune response.

Rakuten Medical, Inc. is striving to combat cancer through its proprietary Alluminox™ platform, which integrates targeted drugs with light-activated components to induce rapid and selective cell killing. The Alluminox platform, still under investigation outside Japan, has shown potential in preclinical studies to cause both local and systemic immune activation through the targeted destruction of cancer cells and immunosuppressive cells in the tumor microenvironment.

The promising preclinical findings for RM-0256 strengthen Rakuten Medical's resolve to advance its development into clinical stages and eventually offer new hope for cancer patients worldwide. The company's mission is to deliver innovative treatments rapidly and broadly, leveraging its presence in the United States, Japan, Taiwan, Switzerland, and India to address the global cancer burden.