On January 30, 2023 Mickey Mikitani, Co-CEO of Rakuten Medical, Inc. reported a presentation to investors from around the world at the 41st Annual J.P. Morgan Healthcare Conference (JPM2023) on January 10, 2023, in San Francisco, California, U.S (Press release, Rakuten Medical, JAN 30, 2023, View Source;301734064.html [SID1234626652]). The presentation included an overview of Rakuten Medical’s third antibody-dye conjugate,"RM-0256," to potentially reach the clinic, an update on the pipeline as a whole including its second asset "RM-1995" which is already in the clinical stage, an overview of the commercial growth in Japan for the Alluminox treatment using its leading compound "ASP-1929", global expansion of the company leveraging the success in Japan, and key milestones for the next few years.

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RM-0256 – currently being evaluated in pre-clinical studies – is a conjugate of an anti-PD-L1 antibody and IRDye700DX (IR700), a light-activatable dye, that accumulates specifically on PD-L1-expressing cells. PD-L1 is a protein that inhibits the anti-cancer immune response by deactivating killer T cells, by binding to PD-1 which is abundantly expressed on the T cell surface.1 PD-L1 is expressed in many solid tumors such as melanoma, lung, urothelial, gastrointestinal, gynecological, breast, and head and neck, among others, helping these tumors evade the immune system.2 In addition to being present on tumor cells, PD-L1 is also expressed on suppressive immune cells within the tumor microenvironment such as tumor associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs).3 In pre-clinical studies, Alluminox therapy using RM-0256 has been observed to enable the accumulation of RM-0256 on PD-L1-expressing target cells followed by activation of the IR700 by illumination with 690nm non-thermal light, resulting in destruction of the target cells by its photochemical reaction. This reaction may lead to immunogenic cell death (ICD) and activation of an anti-cancer immune response. Furthermore, the anti-PD-L1 antibody itself comprising RM-0256 has been observed to inhibit the PD-L1:PD-1 interaction and may act systemically as an immune checkpoint inhibitor, further enhancing the anticancer immune response after light irradiation.

In Japan, commercial launch of ASP-1929 (brand name in Japan: Akalux) continues to accelerate. 230+ doctors at 100+ institutions have been certified to provide the novel treatment, leading to 200+ treatments being administered in the 2 years since launch. (*ASP-1929 is investigational outside of Japan.) Publications based on real world data in Japan, "Quality-of-Life Evaluation of Patients with Unresectable Locally Advanced or Locally Recurrent Head and Neck Carcinoma Treated with Head and Neck Photoimmunotherapy"4 and "Near-Infrared Photoimmunotherapy for Oropharyngeal Cancer,"5 indicated that the treatment using ASP-1929 achieved good disease control without decreasing the Quality of Life (QOL). (**ASP-1929 is investigational outside of Japan and these quality-of-life assessments are specific to the Japanese population studied.)

Leveraging on the data and knowledge that is being accumulated in Japan, Rakuten Medical is further pursuing global expansion. For India, where it has established a subsidiary in 2022, global phase III trial of ASP-1929 in locoregional recurrent head and neck squamous cell carcinoma (ASP-1929-301 / ClinicalTrials.gov Identifier: NCT03769506) is being prepared for initiation in the country. Subject to positive clinical trial results, ASP-1929 could be approved as early as 2025 in the U.S., Taiwan, India, and other countries. A number of pipeline milestones are expected in the next few years, including the initiation of RM-1995 and RM-0256 clinical trials and the progression of several clinical trials with ASP-1929.

Mickey started his J.P. Morgan presentation with the question "What kind of future would open up if we could kill only targeted cells?" and showcased the potential of Rakuten Medical’s investigational technology by saying "In the decade since I first encountered this therapy, which is completely different from existing treatments, we have been developing the technology at a tremendous pace. Our goal goes beyond establishing a position as a local treatment. Existing therapies have taken over a century to evolve and establish themselves as standards of care – we aim to achieve this same position for our technology on a much shorter timeline."

The slides and audio of Mickey’s presentation at JPM2023 are available for download at the following links.

Slides: View Source
Audio: View Source