- Findings in the clinic and preclinical study presented at India's largest medical conference for head and neck cancer
Rakuten Medical, Inc., a global biotechnology company developing and commercializing precision, cell targeting therapies based on its proprietary Alluminox™ platform, is pleased to announce that there were three invited presentations on the Alluminox treatment (photoimmunotherapy) at the 23rd National Conference of Foundation for Head and Neck Oncology (FHNO 2023) held in Daman, India, on December 22-24, 2023. These presentations were delivered by two physicians who have extensive clinical experience in Alluminox treatment in Japan and track record of research for further development of this therapy.
* Rakuten Medical’s EGFR-targeted therapy based on Alluminox™ platform is investigational outside of Japan and not approved in India for commercial use. All other therapies based on the platform are investigational globally.
Three invited presentations on Alluminox treatment at FHNO 2023
Title: Photoimmunotherapy for Lower Gingival Cancer
Presenter: Daisuke Nishikawa, MD, PhD, Department of Head and Neck Surgery, Aichi Cancer Center, Japan
Session: INVITED VIDEOS
Time & Date: 8:00 – 9:00 am, December 22, 2023 (5 mins for his presentation)
This video presentation shared the concepts of patient selection and treatment procedures such as needle puncture and light illumination in the commercial setting in Japan. The treatment for a patient with lower gingival cancer and a history of radiotherapy was shared in the video. Management of the patient’s adverse events such as postoperative edema and the time course of a fistula that occurred with tumor shrinkage were also presented.
Title: Photoimmunotherapy for Recurrent Head and Neck Cancers – Japanese experience
Presenter: Daisuke Nishikawa, MD, PhD, Department of Head and Neck Surgery, Aichi Cancer Center, Japan
Session: RECURRENT & METASTATIC DZ
Time & Date: 3:00 – 4:30 pm, December 22, 2023 (15 mins for his presentation)
This presentation included case reports, clinical outcomes and safety of the Alluminox treatment in the commercial setting in Japan, as well as the results of translational research on immune response. In 26 treatments administered to 15 patients at the Aichi Cancer Center from January 2021 to December 2023, generally good responses were observed. Release of damage-associated molecular patterns (DAMPs) and production of chemokines, which suggest an immune response, were observed in post-treatment peripheral blood samples from 7 treatments given to 5 patients at the Center, potentially suggesting induction of immunogenic cell death with this treatment1. In Japan, this treatment is currently positioned as the last line of locoregional treatment for recurrent head and neck cancer, and is being conducted with special consideration for adverse events such as pain, edema, fistula, and photosensitivity.
Title: Near-infrared Photoimmunotherapy: Translational research and clinical application
Presenter: Ryuhei Okada, MD, PhD, Department of Head and Neck Surgery, Tokyo Medical and Dental University Hospital
Session: DR SUDHIR BAHADUR SCIENCE SYMPOSIUM
Time & Date: 8:30 – 9:30 am, December 24, 2023 (15 mins for his presentation)
In a case report of a patient with hypopharyngeal carcinoma treated with this EGFR-targeted therapy in the commercial setting in Japan, tumor shrinkage was observed during the course of 4 treatments, and disease control was achieved with this treatment alone for one year prior to progressive disease. Preclinical studies conducted to further improve treatment outcomes were also presented. In a mouse study of tumor cell-targeted photoimmunotherapy (PIT) in combination with anti-PD-1, the combination group showed statistically significant reduction of tumor growth and prolonged survival compared to the control or monotherapy groups.2 In a preclinical study of PIT targeting CD25, local depletion of Tregs in the tumor microenvironment resulted in rapid activation of effector cells, suggesting immune activation and abscopal effect.3 In other preclinical studies, PIT targeting CTLA4 showed anti-tumor effects by locally eliminating Tregs in the tumor microenvironment,4 and PIT targeting both EGFR and CD25 demonstrated statistically significant tumor growth inhibition compared to the control or monotherapy groups5.
Dr. Nishikawa’s presentation
Dr. Okada’s presentation
Dr. Nishikawa
Dr. Okada (left)
Alluminox treatment Using ASP-1929: Approved in Japan and investigational globally
A drug “Akalux® IV Infusion 250 mg” (development code: ASP-1929) and a device “BioBlade® Laser System”, both of which were developed based on Rakuten Medical's Alluminox™ platform, received the world-first marketing and to-date only approval in Japan for unresectable locally advanced or recurrent head and neck cancer in September 2020. Since commercial launch in January 2021, more than 400 treatments have been provided in Japan (as of December 2023).
Alluminox treatment using ASP-1929 is currently being evaluated in a global Phase 3 clinical trial (ASP-1929-301 study / ClinicalTrials.gov Identifier: NCT03769506, CTRI Number: CTRI/2023/05/052728) for locoregional, recurrent head and neck squamous cell carcinoma (HNSCC) in countries and regions including the United States, India and Taiwan. The first patient in India enrolled in ASP-1929-301 study received study treatment in August 2023. For more details, please see our press release.
Rajesh A Kantharia, M.D., Organizing Chairman of FHNO 2023 and principal investigator of the ASP-1929-301 study at Kailash Cancer Hospital and Research Center, stated “We are pleased to have both physicians at FHNO 2023 to share their experiences in Japan with this novel therapy with prestigious healthcare professionals working on head and neck cancer across India. Head and neck cancer, which afflicts a large number of the Indian population, is one of the biggest medical challenges in our country. Photoimmunotherapy is being developed as highly selective for targets such as tumor cells, and it is also being studied extensively in both monotherapy and combination therapy, thus I see great potential in this continually evolving investigational technology. In ASP-1929-301 study in India, we have started treating enrolled patients. We hope that this investigational therapy will contribute to the improvement of head and neck cancer care in India.”
Dr. Kantharia
1. Ishihara H, Nishikawa D, Muraoka D, et al. Changes in serum DAMPs and cytokines/chemokines during near-infrared photoimmunotherapy for patients with head and neck cancer. Cancer Med. 2023; 00: 1-6. doi:10.1002/cam4.6863
2. Nagaya T, Friedman J, Maruoka Y, et al. Host Immunity Following Near-Infrared Photoimmunotherapy Is Enhanced with PD-1 Checkpoint Blockade to Eradicate Established Antigenic Tumors. Cancer Immunol Res. 2019;7(3):401-413. doi:10.1158/2326-6066.CIR-18-0546
3. Sato K, Sato N, Xu B, et al. Spatially selective depletion of tumor-associated regulatory T cells with near-infrared photoimmunotherapy. Sci Transl Med. 2016;8(352):352ra110. doi:10.1126/scitranslmed.aaf6843
4. Okada R, Kato T, Furusawa A, et al. Local Depletion of Immune Checkpoint Ligand CTLA4 Expressing Cells in Tumor Beds Enhances Antitumor Host Immunity. Adv Ther (Weinh). 2021;4(5):2000269. doi:10.1002/adtp.202000269
5. Okada R, Furusawa A, Vermeer DW, et al. Near-infrared photoimmunotherapy targeting human-EGFR in a mouse tumor model simulating current and future clinical trials. EBioMedicine. 2021;67:103345. doi:10.1016/j.ebiom.2021.103345
About Rakuten Medical, Inc.
Rakuten Medical, Inc. is a global biotechnology company developing and commercializing precision, cell targeting therapies based on its proprietary Alluminox™ platform, which, in pre-clinical studies, has been shown to induce rapid and selective cell killing and tumor necrosis. Alluminox therapies have not yet been approved outside of Japan. Rakuten Medical is committed to its mission to conquer cancer by developing our innovative treatments as quickly as possible for patients all over the world. The company has offices in 5 countries, including the United States, where it is headquartered, Japan, Taiwan, Switzerland and India. For more information, visit www.rakuten-med.com.
About Alluminox™ platform
The Alluminox™ platform is an investigational technology platform based on a cancer therapy called photoimmunotherapy, which was developed by Dr. Hisataka Kobayashi and team from the National Cancer Institute in the United States. Rakuten Medical is developing the Alluminox platform as a technology consisting of a drug, device, and other related components. The drug component of the platform consists of a targeting moiety conjugated with one or more dyes leading to selective cell surface binding. The device component consists of a light source that locally illuminates the targeted cells with light to transiently activate the drug. Pre-clinical data have shown that this activation elicits rapid and selective necrosis of targeted cells through a biophysical process that compromises the membrane integrity of the targeted cells. Therapies developed on the Alluminox platform may also result in local and systemic innate and adaptive immune activation due to immunogenic cell death of the targeted cancer cells and/or the removal of targeted immunosuppressive cells within the tumor microenvironment. Outside of Japan, Alluminox therapies have not yet been approved by any regulatory authority.
Forward Looking Statements
This press release contains forward looking statements that correspond to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements include various risks, uncertainties, and assumptions that may cause Rakuten Medical’s business plans and results to differ from the anticipated results and expectations expressed in these statements. These “forward looking statements” contain information about the status and development of our products, including the Alluminox™ platform, as well as other regulatory and marketing authorization efforts, the potential benefits, efficacy, and safety of therapies created using the Alluminox platform, and the status of regulatory filings. The approval and commercial success of the product may not be achieved. Forward looking statements relate to the potential benefits, efficacy, and safety of our therapies, and the status of regulatory filings. Such statements may include words such as “expect,” “believe,” “hope,” “estimate,” “looks as though,” “anticipate,” “intend,” “may,” “suggest,” “plan,” “strategy,” “will,” and “do”, and are based on our current beliefs. In addition, this press release uses terms such as “important,” “notable,” and “abnormal” to express opinions about clinical trial data. Ongoing clinical trial studies include various risks and uncertainties, in particular, problems that arise during the manufacturing stage of our therapies, the occurrence of adverse safety events, situations in failure to demonstrate therapeutic benefits, and other various risks and uncertainties, both reasonable and unreasonable. For this reason, actual results, including regulatory approvals and uncertainties in the commercialization process of our therapies, may differ from published information. Except to the extent required by applicable law, we undertake no obligation to publicly update this or any other forward-looking statement, whether because of new information, future developments or events, changes in assumptions, changes in the factors affecting forward-looking statements. If one or more forward-looking statement(s) is updated, no inference should be drawn that additional updates will be made to those or other forward-looking statements.
