Myeloid Tumor

▎药明康德内容团队报道 10月29日，中国国家药监局药品审评中心（CDE）官网公示，正大天晴申报的1类新药TQB3909片获批两项新的临床试验默示许可，拟联合化疗用于急性淋巴细胞白血病（ALL）患者的治疗。根据中国生物制药官方新闻稿介绍，这是其自主研发的一款BCL-2抑制剂。 截图来源：CDE官网 BCL-2家族蛋白可以通过阻止线粒体外膜通透化（MOMP），从而抑制肿瘤细胞凋亡，其过表达与癌症的耐药性的形成密切相关。通过抑制BCL-2与促凋亡蛋白（如BAK）的结合，抑制BCL-2依赖性肿瘤的生长，可以发挥抗肿瘤的作用。 TQB3909是一款BCL-2抑制剂。在2024年欧洲肿瘤内科学会（ESMO）年会上，研究人员以口头报告的形式首次公布了TQB3909的1期临床研究结果。该1期临床研究共纳入69例患者接受TQB3909治疗，其中34例复发或难治性非霍奇金淋巴瘤（R/R NHL）、18例慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（R/R CLL/SLL），以及17例急性白血病（AML）。 研究数据表明，TQB3909治疗R/R CLL/SLL患者总体缓解率（ORR）为88.9%，完全缓解/完全缓解伴不完全血液学恢复（CR/CRi）为44.4%；对BTK抑制剂耐药的R/R CLL/SLL患者的ORR为83.3%，CR/CRi为41.7%。 根据中国药物临床试验登记与信息公示平台官网，有近十项TQB3909相关的临床研究正在开展，其中联合JAK抑制剂TQ05105片用于治疗中高危骨髓纤维化、联合阿扎胞苷治疗髓系恶性肿瘤、单药治疗复发或难治性CLL/SLL、单药治疗复发或难治性套细胞淋巴瘤（MCL）等均已经进入1/2期临床研究阶段。 本次TQB3909获批新的临床研究，意味着该产品的临床研发迎来新的进展。 参考资料： [1]中国生物制药1类新药BCL-2抑制剂获批临床. Retrieved Oct 29, 2024. From https://mp.weixin.qq.com/s/W5930qwA-zPJlafIft_V8g 本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈。转发授权及其他合作需求，请联系wuxi_media@wuxiapptec.com。 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

BETHESDA, Md., Oct. 23, 2024 /PRNewswire/ -- The National Institutes of Health (NIH) has launched a proof-of-concept precision medicine clinical trial to test new treatment combinations targeting specific genetic changes in the cancer cells of people with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The trial, funded by NIH's National Cancer Institute (NCI), aims to accelerate the discovery of more tailored treatments for these aggressive cancers of the blood and bone marrow. Continue Reading The precision medicine trial aims to match patients to treatments based on the genetics of their cancer. Credit: National Human Genome Research Institute "NCI is uniquely positioned to conduct this type of study, which is one of a series of NCI precision medicine trials that are helping pave the way for more personalized treatment of cancer," said W. Kimryn Rathmell, M.D., Ph.D., director of NCI. "By making these trials available to patients in communities around the country, we bring cutting edge science to people where they live and ensure that what we learn from our study participants can benefit patients like them in the future." "AML and MDS are a heterogeneous group of cancers that can progress very quickly. Treatment advances depend in part on the ability to rapidly identify which subtype of cancer each patient has so that treatments can be tested for their specific cancer," said Richard F. Little, M.D., of NCI's Division of Cancer Treatment and Diagnosis. Dr. Little is the NCI coordinator for the trial, known as the Myeloid Malignancies Molecular Analysis for Therapy Choice (myeloMATCH). "The goal of myeloMATCH is to test combinations of drugs to treat the disease in a highly targeted way and to be able to start treatment quickly after diagnosis." Initially, people enrolled in the trial with newly diagnosed AML or MDS will undergo rapid genetic testing of their tumor samples. Based on the molecular characteristics of their tumors, they will be matched to a substudy testing a treatment appropriate for the specific genetic changes and characteristics associated with their disease, if one is available, or to standard treatment if an appropriate substudy is not available. If the initial treatment works to reduce a patient's disease, they will undergo further genetic testing to match them to a subsequent substudy testing a treatment that is appropriate for the specific genetic changes associated with their remaining disease. As the amount of a patient's disease decreases, study investigators will use increasingly sensitive tools, such as biomarker assays, to identify appropriate treatments for any remaining cancer cells. The myeloMATCH trial aims to enroll several thousand people within the first few years, with new substudies rolled out over time. Blood and bone marrow samples collected from participants during the course of the trial will be used to develop and refine the assays, as well as understand what genetic changes might be associated with the development of resistance to a treatment. myeloMATCH is being conducted by the National Clinical Trials Network, with the participation of the NCI Community Oncology Research Program (NCORP). Initial substudies will be led by the SWOG Cancer Research Network, the Alliance for Clinical Trials in Oncology, the ECOG-ACRIN Cancer Research Group, and the Canadian Cancer Trials Group. The Frederick National Laboratory for Cancer Research, Fred Hutch Cancer Center, and Children's Hospital Los Angeles will provide clinical laboratory support for the substudies. myeloMATCH is one of three next-generation precision medicine trials that NCI has under way. ComboMATCH is testing the effectiveness of treating adults and children who have relapsed solid tumors with new drug combinations that target specific tumor alterations. ImmunoMATCH has launched a pilot study to determine whether prospective characterization of the immune status of a tumor can be used to improve the response to targeted immunotherapy treatments, with plans to expand to larger studies in the future. All three trials are successors to NCI-MATCH, NCI's groundbreaking precision medicine clinical trial, which showed that people with advanced cancer may benefit from genomic sequencing to help plan their treatment. "When President Biden and the First Lady re-ignited the Cancer Moonshot, they set two clear goals: To prevent more than 4 million cancer deaths by 2047 and to improve the experience of people who are touched by cancer," said Danielle Carnival, deputy assistant to the President for the Cancer Moonshot. "To achieve that goal, the U.S. government is working to expand access to innovative trials like this one, bring targeted new treatments to patients, and, ultimately, save lives." Learn more about myeloMATCH and the substudies that are currently open. About the National Cancer Institute (NCI): NCI leads the National Cancer Program and NIH's efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI website at or call NCI's contact center, the Cancer Information Service, at 1-800-4-CANCER (1-800-422-6237). About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih.gov. SOURCE NATIONAL CANCER INSTITUTE WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Ten presentations at ESGCT 2024 detail the therapeutic potential and applicability of the company’s platform in rare neurometabolic diseases and beyond Nature manuscript highlights clinical results supporting long-term durability and safety profile of genetically corrected hematopoietic stem and progenitor cells Research letter detailing results from the world’s first prospective, population-based newborn study for metachromatic leukodystrophy recently published in the New England Journal of Medicine LONDON and BOSTON, Oct. 23, 2024 (GLOBE NEWSWIRE) -- Orchard Therapeutics, recently acquired by Kyowa Kirin with the goal of accelerating the delivery of new gene therapies to patients around the globe, today announced multiple data presentations and publications highlighting the transformative potential of HSC gene therapy and newborn screening. Ten presentations (three oral and seven posters) from across its hematopoietic stem cell (HSC) gene therapy portfolio will be featured at the European Society of Gene and Cell Therapy (ESGCT) 31st Annual Congress taking place October 22-25, 2024, in Rome, Italy. Featured data include several accepted abstracts and encore presentations detailing clinical, biochemical and other functional outcomes from across the company’s commercial- and clinical-stage neurometabolic portfolio in metachromatic leukodystrophy (MLD), the Hurler subtype of mucopolysaccharidosis type I (MPS-IH), and mucopolysaccharidosis type IIIA (MPS-IIIA), also known as Sanfilippo syndrome type A. Pertaining to earlier-stage pipeline programs, company researchers will also highlight the potential of the platform beyond rare neurometabolic conditions, including: An oral presentation of preclinical proof-of-concept data showing the therapeutic potential of OTL-104 for NOD2-deficient Crohn’s disease, a severe and treatment-refractory form of the condition;A poster presentation outlining the potential of HSC gene therapy as a mechanism to deliver therapeutic antibodies across the blood-brain-barrier and into the central nervous system; andAnother poster presentation detailing the feasibility of utilizing HSC gene therapy to provide stable and targeted immunotherapy for autoimmune disorders through the ability of HSCs to differentiate into T regulatory (Treg) cells engineered to express chimeric antigen receptors (CAR). This approach combines the durability of HSC gene therapy with the suppressive activity of autoantigen-specific CAR-Treg cells. Details of the oral presentations are as follows (all times in CEST): Title: Stem cell gene therapy for Childhood Dementias – a Sanfilippo storyDate/Time: Wednesday, October 23 at 9:00 a.m.Presenter: Brian Bigger#INV20 Title: Haematopoietic stem cell gene therapy as a treatment for NOD2-deficient severe Crohn’s DiseaseDate/Time: Thursday, October 24 at 10:45 a.m.Presenter: Piv Sagoo#OR064 Title: Lentiviral haematopoietic stem cell gene therapy (atidarsagene autotemcel) for late juvenile Metachromatic leukodystrophy (MLD)Date/Time: Friday, October 25 at 12:00 p.m.Presenter: Valeria Calbi#OR099 Details of the poster presentations are as follows (all times in CEST): Title: Lentiviral ex vivo autologous HSC gene therapy as a tool to deliver therapeutic antibodies beyond the blood brain barrierDate/Time: Tuesday, October 22 from 7:30 to 9:00 p.m.Presenter: Chiara Recchi#P0309 Title: HSC-derived CAR-Treg gene therapy: a novel approach for the treatment of multiple sclerosisDate/Time: Tuesday, October 22 from 7:30 to 9:00 p.m.Presenter: Lily Du#P0293 Title: Biological properties and clonality of engineered hematopoietic stem/progenitor cells persisting long-term after gene therapyDate/Time: Wednesday, October 23 from 1:30 to 3:00 p.m.Presenter: Pamela Quaranta#P0412 Title: Atidarsagene autotemcel (autologous hematopoietic stem cell gene therapy) preserves cognition, language, and speech and slows brain demyelination and atrophy in early-onset metachromatic leukodystrophy Date/Time: Thursday, October 24 from 6:00 to 7:30 p.m.Presenter: Valeria Calbi#P0880 Title: Unveiling myeloid-mediated enzymatic correction of ARSA-deficient neural cells in hematopoietic stem cell gene therapy for Metachromatic LeukodystrophyDate/Time: Thursday, October 24 from 6:00 to 7:30 p.m.Presenter: Vasco Meneghini#P0898 Title: Hematopoietic Stem Cell Gene Therapy for Hurler Syndrome (OTL-203): interim skeletal, neurological and systemic outcomes Date/Time: Thursday, October 24 from 6:00 to 7:30 p.m.Presenter: Valeria Calbi#P0886 Title: Hematopoietic stem cell-based gene therapy in Mucopolysaccharidosis type I Hurler (OTL-203): focus on skeletal damage and cross-correction mechanismsDate/Time: Thursday, October 24 from 6:00 to 7:30 p.m.Presenter: Ludovica Santi#P1016 Nature manuscript elucidates sustained long-term reconstitution and lineage commitment of genetically corrected HSPCs In a paper published online today in Nature, titled “Long-term lineage commitment is modulated by the underlying disease in hematopoietic stem cell gene therapy patients,” researchers from the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) detail clinical results elucidating the long-term reconstitution, lineage commitment and the incidence of somatic mutations of genetically corrected hematopoietic stem and progenitor cells (HSPCs). In the study, researchers examined and compared hematopoietic reconstitution in 53 patients treated with Orchard’s current and former HSC gene therapy programs for three genetic diseases, including MLD (n=29), Wiskott-Aldrich syndrome (WAS; n=15), and β-thalassemia (β-Thal; n=9) with up to 8 years of follow-up (median 4 years), using vector integration sites as a surrogate of clonal identity. Based on the analysis, all patients had a polyclonal repertoire consistent with other lentiviral-based HSC gene therapy studies and previously reported clinical results. Importantly, no somatic mutations known to drive clonal hematopoiesis or myeloid cancer were found in any patient from the MLD cohort and no increase of somatic mutations was observed over time. Program-specific differences in the clonal complexity of the various lineages and the incidence of somatic mutations suggest an impact of the underlying disease biology on hematopoietic reconstitution. These findings add to the compendium of evidence supporting the long-term durability and safety profile of Orchard’s HSC gene therapy portfolio. Results from the world’s first prospective, population-based NBS study for MLD published in NEJM A research letter detailing results from the world’s first prospective, population-based newborn screening (NBS) study for MLD was published in the September 18, 2024, issue of the New England Journal of Medicine (NEJM). The aim of the study, which was conducted in Hannover, Germany, was to evaluate the technical feasibility of MLD NBS and to develop and implement a comprehensive care pathway to provide prompt confirmatory diagnostics, clinical assessment, subtype prediction, clinical follow-up, and treatment. Dried blood spot samples from the first 109,259 newborns were tested in a three tier, high-throughput screen based on increased sulfatide levels, reduced ARSA enzyme activity and ARSA gene sequencing. Three newborns were identified as screen positive and were confirmed to have MLD and referred for pre-symptomatic treatment. The screening algorithm and comprehensive clinical care pathway represents a novel diagnostic and treatment paradigm for MLD, with the potential to significantly alter clinical practice by reducing morbidity and mortality in children with MLD by enabling pre-symptomatic treatment. About Orchard TherapeuticsOrchard Therapeutics, a Kyowa Kirin company, is a global gene therapy leader focused on ending the devastation caused by genetic and other severe diseases by discovering, developing, and commercializing new treatments that tap into the curative potential of hematopoietic stem cell (HSC) gene therapy. In this approach, a patient’s own blood stem cells are genetically modified outside of the body and then reinserted, with the goal of correcting the underlying cause of disease with a single treatment. Founded in 2015, Orchard’s roots go back to some of the first research and clinical developments involving HSC gene therapy. Our team has played a central role in the evolution of this technology from a promising scientific idea to a potentially life-transforming reality. Today, Orchard is advancing a pipeline of HSC gene therapies designed to address serious diseases where the burden is immense for patients, families and society and current treatment options are limited or do not exist. For more information, please visit www.orchard-tx.com. About Kyowa KirinKyowa Kirin aims to discover and deliver novel medicines and treatments with life-changing value. As a Japan-based Global Specialty Pharmaceutical Company, we have invested in drug discovery and biotechnology innovation for more than 70 years and are currently working to engineer the next generation of antibodies and cell and gene therapies with the potential to help patients with high unmet medical needs, such as bone & mineral, intractable hematological diseases/hemato oncology, and rare diseases. A shared commitment to our values, to sustainable growth, and to making people smile unites us across the globe. You can learn more about the business of Kyowa Kirin at www.kyowakirin.com.