Cetuximab Sarotalocan Sodium (Genetical Recombination)

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 7th 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 Photo SEnsitizer 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 . 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. Contact Us SOURCE Rakuten Medical, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

近日（1月22日），乐普生物宣布与ArriVent BioPharm达成全球独家许可协议，据协议，乐普生物将其ADC管线MRG007的除大中华以外地区开发、制造和商业化的全球独家权益授予ArriVent，为此，乐普生物将获得ArriVent总计4700万美元的一次性首付款和近期里程碑付款，最高达11.6亿美元的开发、注册和销售等里程碑付款，以及基于大中华区以外地区净销售额的分级特许权使用费。 这是乐普生物继CMG901之后，第二款实现对外授权的ADC管线，MRG007是一款针对消化道癌的ADC，具体靶点未披露，目前尚处于临床前阶段，公司预计IND申请计划在今年上半年提交，初步的临床开发重点是结直肠癌、胰腺癌及其他消化道恶性肿瘤。 产品管线 乐普生物目前有7条ADC管线在研，部分ADC管线来自于其2018年7月收购的上海美雅珂生物。最快的管线已经到上市申报阶段。在适应症开发上，主要集中于实体瘤，开发了EGFR、HER2、TF、GPC3等靶点ADC。 乐普生物的ADC偶联技术上取得了Synaffix的授权，美雅珂于2019年引进了从荷兰Synaffix公司引进了两项ADC专利技术GlycoConnect™和 HydraSpace™，GlycoConnect™是一种偶联技术，能够利用天然糖基化位点实现定点偶联。而 HydraSpace™是一种高极性化的连接子技术，这些技术能够直接应用于任何现有抗体，无需进行任何额外的蛋白质设计，且与所有类别的ADC的毒素兼容。 在此基础上，乐普生物自己持续优化、进行迭代，并建立了新一代ADC技术平台Hi-TOPi，Hi-TOPi的平台其设计特点包括：Linker在血液循环中高度稳定，在肿瘤细胞中高效释放毒素。Payload为新型TOP1抑制剂，具有更高的活性，因其并非Pgp的底物，具有克服耐药性的潜力。 从公司的ADC管线临床进展来看，已经来到了收获期阶段，大部分的ADC管线都推到了临床中后期阶段，并且EGFR、TF、GPC3这些靶点ADC赛道相对不是非常拥挤。 MRG003是目前全球进展最快的EGFR ADC，已提交用于治疗复发性/转移性鼻咽癌(R/MNPC)的新药上市申请，有望成为国内首个批准上市的EGFR-ADC。目前MRG003针对头颈鳞癌（HNSCC）的III 期临床正在进行中。MRG003所处的EGFR ADC赛道竞争格局较好，全球范围内目前仅有一款EGFR ADC获批上市，为日本厚生省批准的光敏ADC产品ASP-1929，用于二线头颈鳞癌治疗。 CMG901的进度也很快，进入到临床Ⅲ期。这款ADC最早实现了海外授权，2023年2月，乐普生物将CMG901的全球权益授权给阿斯利康，后者支付6300万美元预付款、11.25亿美元里程碑付款以及一定比例的销售分成。 MRG004目前推进到临床Ⅱ阶段，是进展最快的国产TF-ADC，基于Synaffix ADC定点偶联平台技术开发。 相对来说，作为一款靶向HER2的ADC，MRG002面临的竞争形势较为激烈。不过，乐普生物选择了较为差异化的适应症——肝转移乳腺癌。根据在第47届圣安东尼奥乳腺癌研讨会（SABCS）上报告的II期临床结果显示，MRG002在该一群体中取得了60.8%的客观缓解率（ORR）和9.4个月的缓解持续时间（DoR）。 总结 乐普生物在创新药方面铺设较广，在抗体、ADC、双特异性抗体、溶瘤病毒等多种形式的药物上都有涉足，ADC这块已经算是迈入了收获期，今年有望迎来首款上市产品，MG901和MRG002也都已经进入临床III期阶段，或许公司也会很快也会启动上市申报。