New Preliminary Findings on Potential Response Indicator of Rakuten Medical's Alluminox Treatment from Phase 2 Window of Opportunity Study at SNMMI 2023

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Jun 30, 2023, 14:00 ET

- ¹⁸F-FDG PET/CT imaging 1 day after Alluminox treatment with ASP-1929 may serve as a potential indicator of treatment response
- The oral presentation was given by Dr. Lindenberg of NCI, NIH, which is collaborating with Rakuten Medical to conduct ASP-1929-103, the Company's very first study for operable cancer

SAN DIEGO, June 30, 2023 /PRNewswire/ -- Rakuten Medical, Inc., a global biotechnology company developing and commercializing precision, cell targeting therapies based on its proprietary Alluminox™ platform, today announced that new interim evaluation data from the ASP-1929-103 study has been presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2023 Annual Meeting held from June 24 to 27. ASP-1929-103 is a Phase 2, open-label, single-arm, window of opportunity study* of Alluminox treatment (photoimmunotherapy: PIT) using an antibody-dye conjugate ASP-1929 with fluorescence imaging (ClinicalTrials.gov Identifier: NCT05182866) in patients with operable primary or recurrent head and neck squamous cell carcinoma (HNSCC) or cutaneous squamous cell carcinoma (cuSCC).

The oral presentation was given by Liza Lindenberg, M.D., of the National Cancer Institute (NCI), which has a Cooperative Research and Development Agreement to conduct ASP-1929-103 study. ASP-1929-103 is the very first clinical trial of Alluminox treatment in operable cancer. As part of this trial, early time point (1 day) ¹⁸F-FDG PET/CT imaging was investigated as a potential response indicator of Alluminox treatment.

The preliminary, descriptive imaging analysis based on interim evaluation of 6 patients in ASP-1929-103 study presented during the meeting showed that ¹⁸F-FDG PET/CT imaging demonstrates a therapeutic response 1 day after Alluminox treatment using ASP-1929. PET/CT is an imaging modality for combined acquisition of positron emission tomography (PET) and computed tomography (CT) pictures. ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) is the radiotracer used for this PET study. Like glucose (sugar), ¹⁸F-FDG is taken up by cells, particularly rapidly dividing cells such as cancer cells. Following uptake, ¹⁸F-FDG accumulates in the cytoplasm rather than undergoing further metabolism which results in signal amplification from labeled cells.

Key findings presented at SNMMI 2023
"Early ¹⁸F-FDG Response after Near-Infrared Photoimmunotherapy for Head and Neck and Cutaneous Squamous Cell Carcinoma" (Abstract: P50) presented by Liza Lindenberg, M.D., Molecular Imaging Branch, NCI, NIH

- ¹⁸F FDG PET/CT demonstrates a therapeutic response 1 day after a single ASP-1929 PIT treatment
- Delayed ¹⁸F-FDG PET/CT imaging may decrease confounding inflammatory uptake on scans
- Pathologic tumor response may add complementary information to ¹⁸F-FDG PET/CT in PIT

Disclaimer: These early findings may change upon trial completion and final data analysis.

ASP-1929-103 study overview
ASP-1929-103 is a Phase 2, open-label, single-arm, window of opportunity study* of Alluminox treatment (PIT) using an anti-EGFR antibody-dye conjugate, ASP-1929 with fluorescence imaging in patients with operable primary or recurrent HNSCC or cuSCC. The study, sponsored by Rakuten Medical in collaboration with NCI and Shimadzu Corporation (Shimadzu), will enroll 22 patients in the US to evaluate the efficacy and safety of a single Alluminox treatment using ASP-1929 administered prior to standard of care surgical tumor resection. The feasibility of the Shimadzu fluorescence imaging system for real-time monitoring and recording of the fluorescence of the IRDye® 700DX portion of ASP-1929 will also be assessed.

* Window of opportunity study takes place in the period between a cancer diagnosis and the subsequent initiation of standard treatment, during which, the patient receives a non-standard drug or treatment of interest over a short period of time ^1.2.
^1.Aroldi F, Lord SR. Window of opportunity clinical trial designs to study cancer metabolism. Br J Cancer. 2020;122(1):45-51. doi:10.1038/s41416-019-0621-4.
^2.Schmitz S, Duhoux F, Machiels JP. Window of opportunity studies: Do they fulfil our expectations? Cancer Treat Rev. 2016 Feb;43:50-7. doi: 10.1016/j.ctrv.2015.12.005. Epub 2015 Dec 31. PMID: 26827692.

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 delivering our innovative treatments as quickly as possible to as many patients as possible all over the world. The company has offices in 6 countries, including the United States, where it is headquartered, Japan, the Netherlands, 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.

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. ASP-1929 received Fast Track designation from the U.S. Food and Drug Administration (FDA) in January 2018, and is currently under investigation in a global Phase 3 clinical trial for recurrent head and neck cancer. 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. Outside of Japan, ASP-1929 has 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.

SOURCE Rakuten Medical, Inc.