CD63

KANAZAWA, Japan, April 3, 2025 /PRNewswire/ -- Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, demonstrates a novel approach for nanoscopic profiling of small extracellular vesicles (sEVs) using high-speed atomic force microscopy (HS-AFM) videography. This pioneering method provides an unprecedented level of detail in characterizing sEV subpopulations, offering new insights into their biological roles and potential applications in disease diagnostics. Extracellular vesicles (EVs), including exosomes and microvesicles, play a crucial role in intercellular communication by transferring biomolecules such as proteins, lipids, and RNA. These tiny vesicles act as molecular couriers, shuttling messages between cells to regulate immune responses, tissue repair, and even disease progression. Despite their significance, the accurate characterization of these nanoscale vesicles remains a major challenge due to their small size and heterogeneity. Existing techniques, such as nanoparticle tracking analysis (NTA) and flow cytometry, lack the resolution to provide precise structural and compositional information at the single-vesicle level. In this study, led by Keesiang Lim and Richard W. Wong, the team utilized HS-AFM to visualize the nanotopology of sEVs derived from HEK293T cells under physiological conditions. Their findings revealed distinct sEV subpopulations enriched with specific exosome markers, such as CD63 and CD81. Notably, they observed that sEVs smaller than 100 nm exhibited greater membrane rigidity and higher co-localization with exosomal markers compared to larger vesicles, which showed significant height fluctuations. "Our study represents a major advancement in extracellular vesicle research," says Wong. "By leveraging HS-AFM videography, we can now directly observe the dynamic interactions of surface markers on individual sEVs, paving the way for the development of high-precision EV-based biomarkers." This nanoscopic immunophenotyping approach has the potential to revolutionize early disease detection, particularly in cancer diagnostics, where exosome-based biomarkers are gaining attention. Additionally, the method could contribute to advancements in targeted drug delivery and regenerative medicine by enabling more precise characterization of therapeutic EVs. Glossary Molecular Couriers: Small extracellular vesicles (sEVs) that transport biomolecules between cells, facilitating intercellular communication. High-Speed Atomic Force Microscopy (HS-AFM): A high-resolution imaging technique that enables real-time visualization of nanoscale structures and dynamic biological processes. Nanotopology: The study of surface structures and nanoscale features of biological entities, such as extracellular vesicles, under physiological conditions. Immunophenotyping: The process of identifying specific biomolecular markers on cell-derived vesicles using antibodies to differentiate subpopulations. Reference Muhammad Isman Sandira, Keesiang Lim, Takeshi Yoshida, Elma Sakinatus Sajidah, Shinnosuke Narimatsu, Reon Imakawa, Kota Yoshimura, Goro Nishide, Yujia Qiu, Azuma Taoka, Masaharu Hazawa, Toshio Ando, Rikinari Hanayama, Richard W Wong, Nanoscopic Profiling of Small Extracellular Vesicles via High-Speed Atomic Force Microscopy (HS-AFM) Videography, Journal of Extracellular Vesicles March 2025 DOI: 10.1002/jev2.70050 URL: Funding The research was supported by the World Premier International Research Center Initiative (WPI) of MEXT, Japan, along with funding from JST SPRING, MEXT/JSPS KAKENHI, JST CREST, Hokuriku Bank, Takeda Science Foundation, and Shimadzu Science Foundation. Contact Kimie Nishimura (Ms) Project Planning and Outreach, NanoLSI Administration Office Nano Life Science Institute, Kanazawa University Email: [email protected] Kakuma-machi, Kanazawa 920-1192, Japan About Nano Life Science Institute (WPI-NanoLSI), Kanazawa University Understanding nanoscale mechanisms of life phenomena by exploring "uncharted nano-realms". Cells are the basic units of almost all life forms. We are developing nanoprobe technologies that allow direct imaging, analysis, and manipulation of the behavior and dynamics of important macromolecules in living organisms, such as proteins and nucleic acids, at the surface and interior of cells. We aim at acquiring a fundamental understanding of the various life phenomena at the nanoscale. About the World Premier International Research Center Initiative (WPI) The WPI program was launched in 2007 by Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT) to foster globally visible research centers boasting the highest standards and outstanding research environments. Numbering more than a dozen and operating at institutions throughout the country, these centers are given a high degree of autonomy, allowing them to engage in innovative modes of management and research. The program is administered by the Japan Society for the Promotion of Science (JSPS). See the latest research news from the centers at the WPI News Portal: Main WPI program site: About Kanazawa University As the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 17 schools offering courses in subjects that include medicine, computer engineering, and humanities. The University is located on the coast of the Sea of Japan in Kanazawa – a city rich in history and culture. The city of Kanazawa has a highly respected intellectual profile since the time of the fiefdom (1598-1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 10,200 students including 600 from overseas. SOURCE Kanazawa University WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

SAN DIEGO, SHANGHAI and SYDNEY, April 28, 2023 /PRNewswire/ -- Inmagene Biopharmaceuticals ("Inmagene") today announced positive topline results from a Phase 1 study evaluating IMG-004 in healthy participants. IMG-004 is a potent, non-covalent, reversible, and brain permeable third-generation Bruton's tyrosine kinase (BTK) inhibitor. Inmagene is developing the drug candidate to potentially treat immunological diseases. The study was a single ascending dose design with dose levels of 30 mg to 600 mg. The objectives of the study were to evaluate the safety, pharmacokinetic, and pharmacokinetic effects of IMG-004 in healthy participants. A total of 40 participants were randomized in the study, with 30 participants receiving IMG-004 and 10 receiving placebo. Additional details can be found at clinicaltrials.gov, using identifier NCT05349097. IMG-004 was well tolerated, with no dose-limiting or serious adverse events. It was rapidly absorbed following the oral administration with peak concentrations occurring around 2 hours post-treatment and was eliminated with a terminal half-life ranging from 26 to 37 hours. In an ex vivo basophil CD63 activation assay, IMG-004 showed robust and dose-dependent target engagement. A maximum (approximately 95%) inhibition of basophil activation was observed at a dose level as low as 100 mg, up to 600 mg. Sustained inhibition (80-90%) of basophil activation was observed at 100mg up to 600mg, for at least 72 hours post-treatment. "BTK remains an attractive target for autoimmune diseases but many BTK inhibitors have been limited by serious safety risks due to their molecular features," commented Dr. Yufang Lu, Chief Medical Officer of Inmagene. "Designed specifically as a non-covalent, reversible, and brain permeable BTK inhibitor, IMG-004 has demonstrated a longer half-life and pharmacodynamic effect than most leading BTK inhibitors. It presents the best-in-class potential as a therapeutic candidate for autoimmune diseases." Dr. Michael Shi, Head of R&D and Chief Medical Officer of HUTCHMED commended, "Autoimmune diseases are often chronic, requiring long-term care and monitoring. We understand and value the desire for safety, convenience and quality of life for this group of patients. Our teams are committed to the discovery and development of novel treatment options to address the high unmet medical needs." About IMG-004 Designed specifically for inflammatory and autoimmune diseases that usually require long-term treatment, IMG-004 is potent, highly selective and brain permeable. It was originally discovered by HUTCHMED, with Inmagene assuming the development responsibility at the candidate stage. Inmagene has an exclusive option to in-license IMG-004's global rights for the treatment of immunological diseases. About Inmagene Inmagene is a global clinical-stage biotechnology company focused on developing novel therapeutics for immunology-related diseases. Inmagene's most advanced drug candidate is IMG-020 (izokibep), which has successfully met the protocol endpoints in global Phase 2 studies for both psoriasis and psoriatic arthritis (PsA). It has received the IND approval from China's Center for Drug Evaluation (CDE) for Phase 3 studies in plaque psoriasis. In addition, IMG-007, a monoclonal antibody (mAb) against OX40 with a silenced antibody-dependent cell-mediated cytotoxicity (ADCC) function, is entering two global Phase 2 clinical trials. IMG-004 is in Phase 1 development. Moreover, IMG-008, a long-acting mAb against IL-36 receptor (IL-36R), has been cleared by the FDA via an IND-application for Phase 1 clinical development. Believing in "Borderless Innovation", the Inmagene team strives to integrate efficient resources worldwide to develop novel therapeutics for global patients. Based on its proprietary QuadraTek® platform, Inmagene creates and develops several novel drug candidates with global rights. Inmagene also in-licenses drug candidates and, together with its partners, carries out global development activities, including global multi-center clinical trials. Inmagene has formed strategic partnerships with multiple partners, such as HUTCHMED and Affibody AB, to develop highly innovative drug candidates. For more information, please visit: About HUTCHMED HUTCHMED is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has more than 4,600 personnel across all its companies, at the center of which is a team of about 1,700 in oncology/immunology. Since inception it has advanced 12 cancer drug candidates from in-house discovery into clinical studies around the world, with its first three oncology drugs now approved and marketed in China. For more information, please visit: –med.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect Inmagene's and/or HUTCHMED's current expectations regarding future events, including expectations regarding the therapeutic potential of IMG-004 for the treatment of patients with immunological diseases, the further clinical development of IMG-004, expectations as to whether clinical studies of IMG-004 would meet their primary or secondary endpoints, and expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding IMG-004's potential to successfully advance in clinical studies and to eventually gain approvals in any jurisdiction, the safety profile of IMG-004, the timing of these events, and the impact of the COVID-19 pandemic on general economic, regulatory and political conditions. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of various risks applicable to HUTCHMED, see HUTCHMED's filings with the U.S. Securities and Exchange Commission, on AIM and with The Stock Exchange of Hong Kong Limited. Neither Inmagene nor HUTCHMED undertakes to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise. SOURCE Inmagene

Malignant melanoma is a relatively aggressive type of skin cancer. When detected early, it is usually treatable by surgical resection only, but metastases develop often spreading to distant areas. Currently, tumor thickness and the presence of ulceration are some of the known prognostic factors used as indicators of malignant melanoma. Therefore, the discovery of valuable markers to assess the malignant potential of melanoma more accurately may be necessary to develop appropriate treatments. Cross talk between cancer cells and surrounding stromal cells is believed to orchestrate cancer progression through a variety of mechanisms. Cancer-associated fibroblasts (CAFs) - key factors in the tumor microenvironment - in particular have been implicated in cancer cell progression. It has also been reported that the exosomes, a type of small vesicles, produced by CAFs play an important role in cancer progression. A research group led by Naho Fujii, M.D., and Professor Hisashi Motomura from Osaka Metropolitan University Graduate School of Medicine investigated the effect of CAF-derived exosomes on the growth of malignant melanoma cells. The group found that the transmembrane proteins CD9 and CD63 were mainly present on CAF-derived exosomes, and that among the exosomes, the CD9-positive ones inhibited the growth of malignant melanoma cells. "As a plastic surgeon, usually I provide surgical treatment for skin cancer, but I have wanted to study other treatment methods for a long time," explained Fujii, M.D. "This study suggests that CD9-positive exosomes inhibit the growth of malignant melanoma, so CD9-positive exosomes may be a useful marker to evaluate the malignant grade of melanoma. We expect further research will lead to the development of new treatments in that line." Fujii N, Yashiro M, Hatano T, Fujikawa H, Motomura H. CD9-positive Exosomes Derived from Cancer-associated Fibroblasts Might Inhibit the Proliferation of Malignant Melanoma Cells. Anticancer Res. 2023 Jan;43(1):25-33. doi: 10.21873/anticanres.16130