L1CAM

Ono Pharmaceutical has inked a license agreement with LigaChem Biosciences (LCB) for LCB97, a pre-clinical antibody-drug conjugate (ADC) aimed at treating solid tumors. The Osaka-based company also announced a research collaboration and license agreement to generate new ADC candidates using LCB’s ConjuAll ADC platform. LCB97, which targets the L1 cell adhesion molecule (L1CAM), has shown strong anti-tumor effects in preclinical studies. Under the agreement, Ono secures exclusive global rights to develop, manufacture, and commercialize LCB97 for solid tumors. The deal includes upfront and milestone payments to LCB, potentially totaling up to $700 million, along with tiered royalties based on net sales. Additionally, the two companies will collaborate on developing further ADC candidates, giving Ono exclusive global rights to any new therapies targeting multiple solid tumors. With a market poised to reach over $13 billion by 2026, today’s ADCs may have finally earned their permanent place on the industry stage. In our three-part series, we cover the trajectory of cancer-fighting ADCs in the pharma industry, including the modality’s history, obstacles and success stories.

Presentation of in vitro studies of RM-0256, a novel anti-PD-L1 antibody conjugated to IR700, which comprises a dual mode of photoimmunotherapy: depletion of PD-L1 expressing tumor cells and depletion of PD-L1 expressing immunosuppressive cells In vivo studies of the treatment resulted in more effective tumor growth suppression compared to anti-PD-L1 antibody alone in an anti-PD-L1 sensitive mouse tumor model and tumor growth suppression compared to saline in an anti-PD-L1 resistant mouse tumor model A GLP toxicity study suggested that RM-0256 will be clinically well-tolerated SAN DIEGO, Sept. 19, 2024 /PRNewswire/ -- Rakuten Medical, Inc., a global biotechnology company developing and commercializing precision, cell-targeting therapies based on its proprietary Alluminox™ platform, today announces that the research results of the preclinical studies for PD-L1-targeted photoimmunotherapy were presented at the 83rd Annual Meeting of the Japanese Cancer Association (JCA2024) in Fukuoka, Japan on September 20, 2024 (JST). The key findings presented at JCA2024 Abstract Title: PD-L1 photoimmunotherapy kills immunosuppressive myeloid cells to activate local and systemic antitumor immunity Presenter: Amy H. Thorne, Ph.D. (Rakuten Medical, Inc.) Abstract Number: 30050 It has been observed in in vitro studies that this photoimmunotherapy has a dual mechanism of action (MoA): depletion of PD-L1 expressing tumor cells and depletion of PD-L1 expressing immunosuppressive cells such as tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). In addition to this dual MoA, the potential for systemic immune checkpoint inhibition was also observed. It has been observed in in vivo studies that the treatment resulted in more effective tumor growth suppression compared to anti-PD-L1 antibody alone in an anti-PD-L1 sensitive mouse tumor model and tumor growth suppression compared to saline control in an anti-PD-L1 resistant mouse tumor model. It has been observed in in vivo studies that the treatment affects the tumor microenvironment balance by depleting immunosuppressive tumor microenvironment cells and maintains checkpoint inhibition to enhance CD8+ T cell activation. RM-0256 was well-tolerated in a GLP toxicity study in which the drug was administered repeatedly to cynomolgus monkeys. Based on the preclinical study data, Rakuten Medical is currently considering new clinical development opportunities. About RM-0256 RM-0256 is a conjugate of a newly developed anti-PD-L1 antibody and IRDye®700DX (IR700), a light-activatable dye, that accumulates specifically on PD-L1-expressing cells. PD-L1 is a protein that inhibits the anti-cancer immune response by deactivating killer T cells, via binding to PD-1 which is abundantly expressed on the T cell surface1. PD-L1 is expressed in many solid tumors such as melanoma, lung, urothelial, gastrointestinal, gynecological, breast, and head and neck, among others, helping these tumors evade the immune system2. In addition to being present on tumor cells, PD-L1 is also expressed on suppressive immune cells within the tumor microenvironment such as tumor associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs)3. In preclinical studies, PD-L1-targeted photoimmunotherapy resulted in the necrosis of PD-L1 expressing target cells and activation of an anti-cancer immune response. Furthermore, RM-0256 was shown to inhibit the PD-L1:PD-1 interaction, and thus is expected to act systemically as an immune checkpoint inhibitor, further enhancing the anticancer immune response after PD-L1-targeted photoimmunotherapy. 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 its innovative 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 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. 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. References 1. Chunwan Lu, Priscilla S. Redd, Jeffrey R. Lee, Natasha Savage & Kebin Liu (2016) The expression profiles and regulation of PD-L1 in tumor-induced myeloid-derived suppressor cells, OncoImmunology, 5:12, DOI: 10.1080/2162402X.2016.1247135 2. Kythreotou A, Siddique A, Mauri FA, et al. PD-L1Journal of Clinical Pathology 2018;71:189-194. 3. Shklovskaya, E.; Rizos, H. Spatial and Temporal Changes in PD-L1 Expression in Cancer: The Role of Genetic Drivers, Tumor Microenvironment and Resistance to Therapy. Int. J. Mol. Sci. 2020, 21, 7139. 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

Head-to-Head Phase 3 Trial Compared to Pembrolizumab Initiated HONG KONG, Sept. 15, 2024 /PRNewswire/ -- At the 2024 European Society for Medical Oncology (ESMO) Conference, Akeso released the Phase 2 clinical results of its internally developed PD-1/VEGF bispecific antibody, ivonescimab, with or without ligufalimab (anti-CD47 antibody AK117) for the first-line treatment of PD-L1-positive (CPS≥1) recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) At the data cut-off date of March 19, 2024, results indicate that for HNSCC with a high need for rapid tumor reduction, the ivonescimab regimen has demonstrated clinically meaningful reduction in tumor size. When combined with ligufalimab, both tumor shrinkage and survival benefits demonstrated further improvement from ivonescimab alone. Both ivonescimab alone and the ivonescimab plus ligufalimab combination have achieved preliminary efficacy data that surpassed previously disclosed PD-1 studies. The objective response rate (ORR) for ivonescimab monotherapy group is 30%, while the ORR increases to 60% in ivonescimab plus ligufalimab group. The disease control rate (DCR) is 80% for ivonescimab monotherapy group improves to 90% with ligufalimab. As of the report time, the antitumor efficacy of the ivonescimab continues to be promising, with some patients showing an improvement from stable disease (SD) to partial response (PR). The ORR for ivonescimab monotherapy and the combination of ivonescimab plus ligufalimab was to 40% and 65%, respectively. The median progression-free survival (mPFS) for ivonescimab monotherapy group was 5.0 months, with the 6-month PFS rate not yet reached. For the combination with ligufalimab group, the mPFS was 7.1 months, with a 6-month PFS rate of 71.8%. The safety profile of the ivonescimab for first-line treatment of PD-L1-positive R/M HNSCC was manageable, with no treatment-related adverse events (TRAE) leading to drug discontinuation or death in both the ivonescimab monotherapy and the ivonescimab plus ligufalimab groups. Although programmed cell death protein 1 (PD-1) inhibitors combined with chemotherapy are approved as first-line treatments for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC), some patients exhibit poor responses to this approach, highlighting the need for new treatment strategies. Akeso has initiated a phase 3 clinical study comparing ivonescimab combined with ligufalimab versus pembrolizumab for the first-line treatment of PD-L1 positive R/M HNSCC. This study offers the potential to provide a new, highly effective immunotherapy option for these patients and may pave the way for the advancement of cancer immunotherapy 2.0. SOURCE Akeso, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED