Rakuten Medical Announces Initiation of Global Phase 3 Trial of ASP-1929 Photoimmunotherapy in Combination with Pembrolizumab for First-Line Recurrent Head and Neck Cancer

• First patient treated in the U.S.
• Initial enrollment planned for the U.S., Japan, and Taiwan, with further expansion to additional countries and regions

SAN DIEGO, Jan. 23, 2025 /PRNewswire/ -- Rakuten Medical, Inc., a global biotechnology company developing and commercializing precision, cell-targeting Alluminox™ platform-based photoimmunotherapy, today announced the initiation of its global multi-regional Phase 3 clinical trial evaluating ASP-1929 photoimmunotherapy in combination with anti-PD-1 (pembrolizumab) as a first-line therapy for recurrent head and neck squamous cell carcinoma (HNSCC) (Protocol number: ASP-1929-381 / Acronym: ECLIPSE* / ClinicalTrials.gov Identifier: NCT06699212). The first patient in this trial recently received a study treatment at the Avera Cancer Institute in Sioux Falls, South Dakota, USA. Alongside the U.S., patient enrollment is slated for sites in Japan and Taiwan, followed by additional countries and regions.

The ASP-1929-381 study is a multi-regional multi-center, randomized, open-label Phase 3 trial, designed to assess the efficacy and safety of ASP-1929 photoimmunotherapy in combination with pembrolizumab as a first-line treatment for locoregional recurrent HNSCC without distant metastases. Approximately 400 patients globally will be randomized to either an experimental arm receiving ASP-1929 photoimmunotherapy in combination with pembrolizumab, or a control arm receiving the current pembrolizumab-based standard of care (SOC), where patients may receive pembrolizumab alone or in combination with chemotherapy according to the physician's choice.

The primary endpoint is Overall Survival (OS), with key secondary endpoints including Complete Response Rate (CRR) and Overall Response Rate (ORR).

This study builds on data from an interim evaluation (data cut-off: August 31, 2023) of 19 patients enrolled in the HNSCC cohort of a prior Phase 1b/2 study (ASP-1929-181 study / ClinicalTrials.gov Identifier: NCT04305795). The data showed an estimated 24-month survival rate of 52.4%, with a median OS not yet reached, and a generally tolerated safety profile.

Head and neck cancer ranks as the 7^th most common cancer globally with over 90% classified as squamous cell carcinoma¹. More than 60% of HNSCC patients present with locally or regionally advanced disease (stage III or IV)¹. Of these, 15-40% will experience recurrence, facing a poor prognosis and a 5-year overall survival rate of less than 50%¹.

Dr. Kristen Coffroth, MD of Avera Medical Group Ear, Nose & Throat - Head and Neck Surgery, and one of the investigators for the ASP-1929-381 study at the Avera Cancer Institute, stated, "Photoimmunotherapy has a unique mode of action, which involves a biophysical disruption of targeted cells. Pembrolizumab has become a mainstay in systemic treatment for recurrent/metastatic HNSCC. This trial will evaluate whether the combination of ASP-1929 photoimmunotherapy with pembrolizumab can harness synergistic antitumor effects, which may shed new light on the treatment of locoregional recurrent HNSCC."

Dr. William Chad Spanos, MD, FACS of Avera Medical Group Ear, Nose & Throat - Head and Neck Surgery, and Principal Investigator for the ASP-1929-381 study at the Avera Cancer Institute, added, "I am impressed by the technology behind photoimmunotherapy, which offers a novel and targeted approach to cancer treatment. Combining this with pembrolizumab has the potential to expand first-line treatment options for patients with recurrent HNSCC. I am pleased to initiate this groundbreaking trial at our site and look forward to contributing to advancing care for patients facing this challenging disease."

Mickey Mikitani, Chief Executive Officer and Vice Chairman of the Board of Rakuten Medical, concluded, "The initiation of this global Phase 3 trial marks a significant milestone in our journey to contribute to the treatment and lives of patients with head and neck cancer and potentially others affected by cancer. With encouraging data from Phase 1b/2 study, we are optimistic about the potential of ASP-1929 photoimmunotherapy combined with pembrolizumab to improve treatment outcomes in recurrent head and neck cancer."

Disclaimer: Rakuten Medical's Alluminox™ platform-based photoimmunotherapy is investigational outside Japan.

* ECLIPSE: Eliminating Cancer with Laser Illumination and PhotoSEnsitizer

1. Chow LQM. Head and Neck Cancer. N Engl J Med. 2020;382(1):60-72. doi:10.1056/NEJMra1715715

About Rakuten Medical
Rakuten Medical, Inc. is a global biotechnology company developing and commercializing precision, cell-targeting Alluminox™ platform-based photoimmunotherapy, which, in pre-clinical studies, has been shown to induce rapid and selective cell killing. Rakuten Medical's photoimmunotherapy is currently investigational outside Japan. Rakuten Medical is committed to its mission to conquer cancer by developing its pioneering treatments as quickly as possible to as many patients as possible all over the world. The company has offices in 5 countries/regions, 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 Rakuten Medical's investigational technology platform that combines pharmaceuticals, medical devices, medical technology, and other peripheral technologies. Rakuten Medical is developing Alluminox platform-based photoimmunotherapy, which involves two key steps: 1) drug administration and 2) targeted illumination using medical devices. The drug component consists of a cell-targeting moiety conjugated to a light-activatable dye, such as IRDye^® 700DX (IR700), that selectively binds the surface of targeted cells, such as tumor cells. The device component consists of a light source that locally illuminates the targeted cells with red light (690nm) to transiently activate the drug. Rakuten Medical's 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 tumor cells and/or the removal of targeted immunosuppressive cells within the tumor microenvironment. Photoimmunotherapy was originally developed by Dr. Hisataka Kobayashi and team from the National Cancer Institute in the United States. Outside Japan, Rakuten Medical's Alluminox platform-based photoimmunotherapy is investigational.

About ASP-1929
Rakuten Medical's first pipeline drug developed on 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 receptor (EGFR), a cancer antigen expressed in multiple types of solid tumors, including head and neck, breast, lung, colorectal, prostate and pancreatic cancers. After binding to cancer cells, ASP-1929 is locally activated by illumination with red light (690 nm), emitted by a laser device system to produce a photochemical reaction. This reaction is believed to cause damage to the membrane of cancer cells, leading to selective necrosis of cancer cells. In Japan, ASP-1929 received marketing approval from the Japanese Ministry of Health, Labor, and Welfare for unresectable locally advanced or recurrent head and neck cancer in September 2020, under the Sakigake Designation System and the Conditional Early Approval System. ASP-1929 photoimmunotherapy in combination with pembrolizumab is currently under investigation in a global Phase 3 clinical trial as a first-line therapy for recurrent head and neck cancer. Outside Japan, ASP-1929 has not yet been approved for commercial use 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.

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