Rakuten Medical Taiwan Announces Commencing a Phase 2 Clinical Trial for Head and Neck Squamous Cell Carcinoma Photoimmunotherapy based on the Alluminox™ platform at 5 Leading Medical Centers and the Enrollment of First Patient

TAIPEI, Taiwan, June 21, 2022 /PRNewswire/ -- Rakuten Medical Taiwan, Inc. today announced that their ASP-1929 Photoimmunotherapy Phase 2 clinical trial (ClinicalTrials.gov Identifier: NCT05265013) has enrolled and treated its first patient. This trial is using ASP-1929 photoimmunotherapy based on the Alluminox™ platform in combination with anti-PD1 therapy in head and neck squamous cell carcinoma to measure patient's Objective Response Rate (ORR). The trial will be conducted in 3 medical centers in North Taiwan and 2 medical centers in Central Taiwan.

According to official cancer registration report, head and neck cancer ranks third in male cancer incidence and fourth in male cancer mortality in Taiwan, with an annual incremental of about 10,000 patients. Majority¹ of the patients are males between the ages of 40 and 60. Local recurrence or metastasis is one of the leading causes of death in head and neck cancer patients², and nearly one-half of recurrent or metastatic patients survive for less than one year³. After receiving treatment, about 40% of patients will still face in situ or local recurrence⁴.

Dr. Chun Wei Huang from Department of Otorhinolaryngology, Head and Neck Surgery of China Medical University Hospital, who participated in the trial, explained: "Currently patients have limited treatment options after recurrence. When surgery, chemotherapy combined with targeted therapy, radiotherapy, etc. fail to show obvious efficacy in treating head and neck cancer, not only the patients but the medical teams are disappointed. Patients are also prone to losing confidence for further treatment. In addition to this phase II clinical trial, Taiwan is also expected to join more clinical trials. The introduction of more clinical trials presents not only new chances for patients, but also new possibilities for head and neck cancer treatment."

"ASP-1929 has been conditionally approved by the MHLW in Japan and we are establishing more clinical evidence to help cancer patients around the world. The investment of this Phase 2 trial reiterates our long-term commitment in developing Taiwan as the foothold to Asia expansion. The enrollment of first patient also demonstrates the robust momentum and tight-knit collaboration of Rakuten Medical around the globe. We look forward to providing patients with impactful new treatment options as soon as possible," said Mickey Mikitani, Co-CEO of Rakuten Medical, Inc.

Reference
[1] Health Promotion Administration, Ministry of Health and Welfare, 2019 Cancer Registration Report
[2] A Novel CXCR4-Targeted Diphtheria Toxin Nanoparticle Inhibits Invasion and Metastatic Dissemination in a Head and Neck Squamous Cell Carcinoma Mouse Model. Pharmaceutics. 2022 Apr 18;14(4):887. doi:10.3390/pharmaceutics14040887
[3] Argiris A, Harrington KJ, Tahara M, Schulten J, Chomette P, Ferreira Castro A, Licitra L. Evidence-Based Treatment Options in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck. Front Oncol. 2017 May 9;7:72. doi: 10.3389/fonc.2017.00072.
[4] Daniela Alterio, Giulia Marvaso, Annamaria Ferrari, Stefania Volpe, Roberto Orecchia, Barbara Alicja Jereczek-Fossa (2019.) Modern radiotherapy for head and neck cancer

About Rakuten Medical, Inc.
Rakuten Medical, Inc. is a global biotechnology company developing and commercializing precision, cell targeting investigational therapies on its Alluminox™ platform, which, in pre-clinical studies have been shown to induce rapid and selective cell killing and tumor necrosis. Outside of Japan, Alluminox therapies have not yet been approved as safe or effective by any regulatory authority. The company's first investigational drug developed on the Alluminox™ platform, ASP-1929, has achieved Fast Track designation from the FDA and Sakigake Designation from the Japanese Ministry of Health, Labour, and Welfare, and is currently the subject of a global phase 3 clinical trial for recurrent head and neck cancer. Rakuten Medical is committed to its mission to conquer cancer by delivering our innovative treatments as quickly and safely as possible to as many patients all over the world as possible. The company has offices in 5 countries, including the United States, where it is headquartered, Japan, the Netherlands, Taiwan and Switzerland. For more information, visit www.rakuten-med.com.

About Alluminox™ platform
The Alluminox™ platform is an investigational 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 non-thermal 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 Alluminox may also result in local and systemic innate and adaptive immune activation due to immunogenic cell death of the targeted cells and/or the removal of immunosuppressive elements within the microenvironment. Outside of Japan, Alluminox therapies have not yet been approved as safe or effective by any regulatory authority.

About ASP-1929
Since 2013, Rakuten Medical, Inc. has been using an exclusively licensed antibody complex to develop new cancer therapies based on its Alluminox™ technology platform. Rakuten Medical's first pipeline drug developed using its Alluminox platform is ASP-1929, an antibody-dye conjugate comprised of the antibody cetuximab and IRDye® 700DX, a light activatable dye. ASP-1929 binds to epidermal growth factor receptors (EGFR), a cancer antigen expressed in multiple types of solid tumors, including head and neck, cutaneous, esophageal, lung, colon and pancreatic cancers. After binding to cancer cells, ASP-1929 is locally activated by non-thermal red light (690 nm) illumination emitted by a laser device system. Pre-clinical data indicates that Alluminox technology induces a biophysical process that compromises cell membrane integrity, leading to cancer cell death and tumor necrosis. ASP-1929 received conditional early approval from the Japanese Ministry of Health, Labor, and Welfare in September 2020, and is currently under investigation in a global phase 3 clinical trial for recurrent head and neck cancer. Rakuten Medical, Inc. is moving forward with product development by conducting clinical trials of monotherapy and combination therapy with other drugs. Outside of Japan, ASP-1929 and the laser device system 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 ASP-1929, the Alluminox™ platform and IRDye® 700DX, as well as other regulatory and marketing authorization efforts, the potential benefits, efficacy, and safety of ASP-1929 and other 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 ASP-1929, 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 ASP-1929, 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 ASP-1929, 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.

SOURCE Rakuten Medical, Inc.