Lotte Holdings Healthcare & Biopharmaceutical CVC Invests in Rakuten Medical, Inc.

LOTTE Holdings Co., Ltd. (Tokyo, Representative Director, President & CEO: Motohiro Tamatsuka, hereinafter "Lotte Holdings") has made an investment in Rakuten Medical, Inc. (hereinafter "Rakuten Medical") through its Healthcare & Biopharmaceutical Corporate Venture Capital (hereinafter "HB-CVC"). This marks the eighth investment by HB-CVC.

Rakuten Medical, established in 2010, is a global biotechnology company headquartered in San Diego, California, USA. It is advancing the development and commercialization of photoimmunotherapy (*1) based on its proprietary technology platform, "Auminox® Platform."

Currently, a global Phase III clinical trial is underway for its lead investigational drug, "ASP-1929," to evaluate the efficacy of combination therapy with the immune checkpoint inhibitor pembrolizumab (*3) as a first-line treatment (*2) for recurrent head and neck cancer. This trial aims to generate key data for a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA), scheduled for 2028. Patient enrollment is ongoing in the U.S., Japan, Taiwan, and Ukraine, with Poland also planned for future implementation.

In addition to head and neck cancer, the company is actively expanding its pipeline through in-house development and investigator-initiated trials. With support from the Japanese government, a Phase I clinical trial for a new investigational drug, "RM-0256," using photoimmunotherapy for solid tumors, is scheduled to begin in the second quarter of 2026. Furthermore, investigator-initiated trials for photoimmunotherapy using ASP-1929 for esophageal cancer and gynecological cancers are also underway. "ASP-1929" has already received manufacturing and marketing approval in Japan for head and neck cancer, and the company is accelerating the establishment of a system to support global expansion by strengthening its commercial foundation.

This investment by HB-CVC will contribute to further strengthening the business foundation for Rakuten Medical's ongoing clinical and commercial activities. In parallel with this investment, Lotte Biologics (Headquarters: Seoul, Korea), a global CDMO (Contract Development and Manufacturing Organization) jointly funded by the Japanese and Korean Lotte Groups, signed a manufacturing services agreement with Rakuten Medical at the J.P. Morgan Healthcare Conference in January 2026. Under this agreement, Lotte Biologics will undertake the manufacturing of some of Rakuten Medical's products at its GMP (*4) compliant Syracuse, New York facility, supporting Rakuten Medical's global clinical development and future commercial supply.

The Lotte Group aims to support the development of Rakuten Medical's innovative cancer treatment technology through its advanced biopharmaceutical manufacturing capabilities, contributing to the treatment of patients worldwide.

■ Comment from Dr. Baek Jun, Head of Healthcare & Biopharmaceutical CVC Business, Lotte Holdings

This investment demonstrates our strong confidence in the significant potential of Rakuten Medical's "Auminox® Platform," as well as its steady progress in achieving regulatory approval milestones in the U.S. and its global expansion. We are confident that concrete business synergies will emerge between the two companies, accelerating development and scale-up, as Lotte Biologics will undertake biopharmaceutical manufacturing at its advanced GMP-compliant facilities. We are proud to support Rakuten Medical's innovation in advancing cancer treatment as precision medicine, backed by the comprehensive strength of the Lotte Group.

*1 Photoimmunotherapy: A treatment method that combines drugs and light, where light-activated drugs selectively destroy cancer cells.

*2 First-line treatment: The initial standard treatment for cancers that are difficult to surgically remove.

*3 Immune checkpoint inhibitor pembrolizumab: A drug that enhances immune function to attack cancer.

*4 GMP (Good Manufacturing Practice): Standards for manufacturing control and quality control of pharmaceuticals, etc.

About LOTTE Holdings Co., Ltd.

◆Company Name	LOTTE Holdings Co., Ltd.
◆Head Office Location	3-20-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023
◆Representative	Motohiro Tamatsuka
◆URL	https://lotte-hd.com/
◆CVC URL	https://lotte-hd.com/business/lifescience/bio-cvc/

In addition to its core confectionery and ice cream businesses, the company operates businesses such as professional baseball team management, real estate, finance, CVC, hotels, healthcare, and content IP. Going forward, we will boldly challenge ourselves to create new businesses by combining business seeds from Japan and Korea, in addition to further innovation in the food business.

The Lotte Group began its business in 1948 in Japan (Tokyo) with the manufacturing and sales of chewing gum. Currently, with headquarters functions in Japan and Korea, it operates businesses in approximately 35 countries and regions worldwide, including food, distribution, finance, biopharmaceuticals, healthcare, data centers, hotels/resorts, entertainment, and construction. We uphold "Lifetime Value Creator" as our group-wide vision, aiming to continuously provide value throughout people's life cycles.

About Lotte Biologics

Lotte Biologics was established in 2022 with its headquarters in Seoul, Korea, with a mission to provide medicines that contribute to a healthier world. At its Syracuse Bio Campus in New York, USA, it offers high-quality GMP manufacturing services for drug substances. This facility has a total production capacity of 40,000 liters with eight 5,000-liter stainless steel bioreactors. The campus also houses analytical QC testing labs and warehouse facilities approved by over 62 regulatory authorities worldwide. Furthermore, Lotte Biologics is expanding into new specialized areas through antibody-drug conjugate (ADC) conjugation technology services. It has invested over $100 million in ADC modalities with both drug substance manufacturing and conjugation capabilities, providing end-to-end services from drug substance manufacturing to conjugation. Looking ahead, Lotte Biologics is advancing the construction of an advanced bioplant at its Songdo Bio Campus in Korea. The first plant has already broken ground and is scheduled to begin operations in 2027. The facility will be equipped with eight 15,000-liter stainless steel bioreactors for commercial production and multiple 2,000-liter single-use bioreactors for clinical applications. These will form a manufacturing hub boasting a total bioreactor capacity exceeding 120,000 liters.

For more details, please visit https://www.lottebiologics.com.

About Rakuten Medical
Rakuten Medical is a global biotechnology company developing and commercializing new therapies for cancer and other diseases, combining drugs and light, based on its technology platform called Auminox® Platform. Non-clinical studies (undisclosed data) of drugs and medical devices developed based on this platform have confirmed selective necrosis of specific cells. Rakuten Medical aims to achieve its mission of "Conquering Cancer." by delivering its innovative therapies to as many patients as possible worldwide, as quickly as possible. In addition to its headquarters in the U.S., it has bases in five countries/regions worldwide: Japan, Taiwan, Switzerland, and India. Rakuten Medical Japan is the Japanese subsidiary of Rakuten Medical, Inc. (U.S. corporation). For more information, please visit https://rakuten-med.com/jp/.

About Auminox® Platform

The Auminox® Platform is the name of a therapeutic technology platform based on cancer photoimmunotherapy developed by Dr. Hisataka Kobayashi and others at the U.S. National Cancer Institute. This platform is a comprehensive technology base that utilizes pharmaceuticals, medical devices, medical technologies, and other related technologies, and Rakuten Medical is developing products and therapies based on it. Treatment using this platform consists of two stages: "drug administration" and "light irradiation." The drug is a complex composed of a photosensitizer (a substance that reacts to light) and a carrier (a component that selectively accumulates in specific cells). After administering the drug and allowing it to selectively accumulate in specific cells, those cells are irradiated with specific light using a dedicated laser irradiation system, which activates the photosensitizer, leading to the necrosis or elimination of specific cells through biochemical and physical processes.

About ASP-1929

ASP-1929 (generic name: cetuximab sarotalocan sodium), the first drug developed by Rakuten Medical based on the Auminox® Platform, is an antibody-photosensitizer conjugate in which the anti-EGFR antibody cetuximab is bound to the photosensitizer dye IRDye® 700DX. It has been confirmed to specifically accumulate in cells expressing epidermal growth factor receptor (EGFR). EGFR is known to be expressed in various types of solid cancers, including head and neck cancer, breast cancer, lung cancer, colorectal cancer, prostate cancer, and pancreatic cancer. After ASP-1929 accumulates in target cancer cells, irradiation with 690 nm wavelength laser light using a dedicated laser irradiation system locally excites ASP-1929, causing a photochemical reaction. This is believed to selectively cause necrosis of cancer cells with damaged cell membranes. In Japan, it was designated as a target product for the Sakigake (Pioneering) Designation System and applied under the Conditional Early Approval System, receiving manufacturing and marketing approval from the Ministry of Health, Labour and Welfare in September 2020 for "unresectable locally advanced or locally recurrent head and neck cancer." It has not received manufacturing and marketing approval from regulatory authorities outside Japan. Furthermore, an international Phase III clinical trial is being conducted to evaluate the efficacy and safety of Auminox treatment (photoimmunotherapy) using this drug in combination with the anti-PD-1 antibody drug pembrolizumab as a first-line treatment for recurrent head and neck squamous cell carcinoma.