Cabazitaxel Acetone

近日，中国药物临床试验登记与信息公示平台官网公示，默沙东（MSD）和Orion公司共同登记了两项MK-5684片针对转移性前列腺癌的国际多中心（含中国）3期临床研究。公开资料显示，MK-5684片是默沙东和Orion公司合作开发的一款口服非类固醇CYP11A1抑制剂。 前列腺癌是常见的男性癌症之一。前列腺癌细胞的生长具有雄激素依赖性，故患者最初对雄激素剥夺治疗（ADT）敏感，而经持续ADT后仍然发生疾病进展的患者会发展为转移性去势抵抗性前列腺癌（mCRPC），这类患者的肿瘤已扩散至前列腺以外。研究表明，类固醇激素是驱动前列腺癌的关键因素之一，细胞色素P450 11A1（CYP11A1）是类固醇合成过程中的重要限速酶，靶向CYP11A1提供了抑制类固醇激素生产的有效手段。 MK-5684（又称ODM-208）是Orion公司发现和开发的一款潜在“first-in-class”CYP11A1特异性口服非类固醇抑制剂，被开发用于治疗前列腺癌等激素依赖性的癌症。通过抑制CYP11A1酶的活性，MK-5684可以抑制所有类固醇激素和可能激活雄激素受体（AR）信号通路的激素前体的产生。这与AR配体结合域（LBD）激活体细胞点突变的患者尤其相关，而体细胞点突变正是mCRPC对激素治疗的抵抗机制之一。 2022年7月，默沙东宣布和Orion公司达成全球研发合作协议，共同开发后者的在研疗法ODM-208和其它靶向CYP11A1的药物。双方将共同开发和商业化ODM-208，Orion公司将获得2.9亿美元前期付款。 本次默沙东和Orion公司在中国启动的两项临床研究分别为：一项随机、开放性、3期研究，旨在既往使用1种新型内分泌治疗（NHA）期间或之后发生疾病进展的mCRPC患者中比较MK-5684与可选择的醋酸阿比特龙或恩扎卢胺的疗效；另一项为随机、开放性3期研究，旨在既往接受过NHA和紫杉烷类化疗的mCRPC患者中比较MK-5684与可选择的醋酸阿比特龙或恩扎卢胺的疗效。 根据2024年1月发表在2024年美国临床肿瘤学会泌尿生殖系统肿瘤研讨会（ASCO GU）上的数据，MK-5684在伴有或不伴有AR-LBD突变的mCRPC患者中的2期临床研究取得积极结果。研究共纳入66例AR-LBD突变阳性和68例AR-LBD突变阴性患者，两组分别有53%和33.8%的患者接受过醋酸阿比特龙或恩扎卢胺治疗，63.6%和55.9%的患者接受过卡巴他赛治疗。结果显示，MK-5684可深度抑制雄激素合成，导致有AR-LBD突变和没有AR-LBD突变的患者中分别有55.6%和16.7%的患者出现PSA50（前列腺特异性抗原PSA减少≥50%）应答，69.8%和30.0%的患者出现PSA30应答。MK-5684耐受性良好，最常见的治疗相关不良事件与肾上腺抑制有关。 根据研究人员得出的结论，MK-5684用于重度预处理的mCRPC患者显示出良好的抗肿瘤活性，PSA50反应在携带AR-LBD激活突变的患者中尤为常见。 参考资料： [1]中国药物临床试验登记与信息公示平台官网.Retrieved Feb 26，2024, From http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml [2]MK-5684 (ODM-208), a CYP11A1 inhibitor, in patients with metastatic castration-resistant prostate cancer (mCRPC) with and without AR-LBD mutations: CYPIDES phase 2 results. Retrieved Jan 29，2024, From https://ascopubs-org.libproxy1.nus.edu.sg/doi/10.1200/JCO.2024.42.4_suppl.159 内容来源于网络，如有侵权，请联系删除。

SAN DIEGO, Jan. 25, 2024 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO) today announced a peer-reviewed publication in Cancers from a team of cancer researchers primarily at the NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute and Scripps MD Anderson in La Jolla, California. The publication describes what could be the first study to use optical genome mapping (OGM) for the discovery of structural variants (SVs) that drive drug resistance and sensitivity in cancer. Study Design Patient Samples. The study analyzed 26 leukemia samples from 23 subjects, including 3 samples from subjects after relapse. Genome Variation Signatures. The study compared genome variation signatures obtained from the leukemia samples by OGM and by classical cytogenetic methods including karyotyping (KT) and fluorescence in situ hybridization (FISH). Drug Library. The study used a broad collection of 120 cancer drugs based on the Oncology Drug Library (ODL, ODL2 and ODL3) and the FDA-approved oncology collection drugs from the NCI’s Developmental Therapeutics Program, including some experimental agents and those in phase II/III trials. Drug Resistance & Sensitivity Assay. The study used a cell viability and drug screening assay based on growing leukemia-enriched cell collections in the presence of different concentrations of drug agents to measure cell viability. Cells that grew well in the presence of drugs were determined to be resistant and those that didn’t were determined to be sensitive. Key Findings Overall, the study shows that OGM for SV detection combined with drug sensitivity data for the same samples is a useful approach to identifying potentially pathogenic SVs that may be drivers of drug sensitivity or resistance. Key findings are as follows: OGM detected all SVs that had been observed using classical cytogenetic methods as well as multiple additional variants that were not previously reportedBCR-ABL1 translocated leukemia samples are sensitive to the tyrosine kinase inhibitor Nilotinib, as expected, but exhibit resistance to proteasome inhibitorsDrug sensitivities associated with previously unreported genomic rearrangements were revealed Leukemia samples with KMT2A translocations are associated with drug sensitivities to the microtubule disruptors Paclitaxel and Cabazitaxel and resistance to Bcl-2 family inhibitorsChemosensitivity associations with SVs detected by OGM are able to reveal several potential new treatment strategies for leukemia “This paper represents incredibly well-done research that demonstrates the potential biological and clinical significance of structural variants and the ability of OGM to detect SVs in a reliable and efficient sample to answer workflow. SVs are historically underrepresented in genomics studies due to limitations associated with classical cytogenetic methods and sequencing. We are pleased to see this type of biomarker discovery research and hope it will lead others to conduct more studies, which we believe will help pharmaceutical companies develop better drugs and clinicians provide the right drugs to the right patients,” commented Erik Holmlin, PhD, president and chief executive officer of Bionano. The paper is available at: https://www.mdpi.com/2072-6694/16/2/418. About Bionano Bionano is a provider of genome analysis solutions that can enable researchers and clinicians to reveal answers to challenging questions in biology and medicine. The Company’s mission is to transform the way the world sees the genome through OGM solutions, diagnostic services and software. The Company offers OGM solutions for applications across basic, translational and clinical research. Through its Lineagen, Inc. d/b/a Bionano Laboratories business, the Company also provides diagnostic testing for patients with clinical presentations consistent with autism spectrum disorder and other neurodevelopmental disabilities. The Company also offers an industry-leading, platform-agnostic software solution, which integrates next-generation sequencing and microarray data designed to provide analysis, visualization, interpretation and reporting of copy number variants, single-nucleotide variants and absence of heterozygosity across the genome in one consolidated view. The Company additionally offers nucleic acid extraction and purification solutions using proprietary isotachophoresis (ITP) technology. For more information, visit www.bionano.com, www.bionanolaboratories.com or www.purigenbio.com. Bionano’s OGM products are for research use only and not for use in diagnostic procedures. Forward-Looking Statements of Bionano This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “believe,” “could,” “potential,” “will” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the ability and utility of OGM to detect SVs in leukemia samples; the ability and utility of OGM to detect SVs that drive drug resistance and sensitivity in cancer; the ability and utility of OGM to detect SVs compared to classical cytogenetic methods, including FISH and KT; the ability and utility of OGM to detect SVs in a reliable and efficient sample to answer workflow; the ability and utility of OGM to detect novel causative or pathogenic SVs associated with drug efficacy and resistance; and execution of our stated strategies and plans. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the risks and uncertainties associated with: the impact of geopolitical and macroeconomic developments, such as recent and potential future bank failures, supply chain disruptions, global pandemics, inflation and the ongoing conflicts between Ukraine and Russian and Israel and Hamas, on our business and the global economy; general market conditions; the failure of OGM to detect SVs in leukemia samples; the failure of OGM to detect SVs that drive drug resistance and sensitivity in cancer; the failure of OGM to detect SVs compared to classical cytogenetic methods, including FISH and KT; the failure of OGM to detect SVs in a reliable and efficient sample to answer workflow; the failure of OGM to detect novel causative or pathogenic SVs associated with drug efficacy and resistance; study results that differ or contradict the results reported in the study referenced in this press release; changes in the competitive landscape and the introduction of competitive technologies or improvements to existing technologies; changes in our strategic and commercial plans; our need and ability to obtain sufficient financing to fund our strategic plans and commercialization efforts, our ability to effectively manage our uses of cash, and our ability to continue as a “going concern”; the ability of medical and research institutions to obtain funding to support adoption or continued use of our technologies; and the risks and uncertainties associated with our business and financial condition in general, including the risks and uncertainties described in our filings with the Securities and Exchange Commission, including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2022 and in other filings subsequently made by us with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise. CONTACTSCompany Contact:Erik Holmlin, CEOBionano Genomics, Inc.+1 (858) 888-7610eholmlin@bionano.com Investor Relations:David HolmesGilmartin Group+1 (858) 888-7625IR@bionano.com