Ribociclib Succinate

In the largest study to date of bone and soft tissue tumors, OGM detected 100% of the variants found by multiple standard techniques, including karyotyping, fluorescent in-situ hybridization (FISH) & gene fusion assays OGM was also more sensitive, including detection of diagnostic or pathogenic variants missed by karyotype in 74% (14/19) of cases that failed or were negative by karyotyping When OGM results and next-generation sequencing (NGS) results were combined, diagnostic and pathogenic structural variants (SVs), copy number variants (CNVs), and/or single nucleotide variants (SNVs) were found in ~98% of cases, a substantially greater rate than when karyotyping, FISH and NGS are used Dec. 23, 2024 -- Bionano Genomics, Inc. (Nasdaq: BNGO) today announced a publication in Modern Pathology by a group of researchers at the Johns Hopkins University School of Medicine, showing that optical genome mapping (OGM) can outperform traditional techniques in analysis of bone and soft tissue tumors. Several prior publications have shown the utility of OGM compared to traditional cytogenetics in studies of hematologic malignancies, however, data on the application of OGM in solid tumors has been relatively sparse. This study provides compelling support for extending the utility of OGM in cancer beyond hematologic malignancies to solid tumors. OGM detected all variants revealed by conventional cytogenetics: OGM showed 100% concordance, identifying all pathogenic variants detected by standard of care cytogenetic methods. The specificity of OGM was assessed to be 100%, i.e. OGM correctly identified the same pathogenic SVs and CNVs detected by standard of care/routine cytogenetics (karyotyping and FISH). OGM detected pathogenic variants missed by karyotyping: In 74% of cases with normal or failed karyotype, OGM detected diagnostic or pathogenic SVs that were missed by karyotyping. Further, in 6 cases that failed to yield any karyotyping results due to culture failure, OGM detected pathogenic SVs in all of them. Variants found by OGM but missed by standard of care included the EWSR1::ETV1 fusion, which is a key molecular hallmark of clear cell sarcoma and helps to differentiate it from other soft tissue sarcomas and melanomas. OGM resolved complex cancer genomes: Study authors found that OGM data could re-characterized and better defined complex structural rearrangements including chromoanagenesis in 27% of cases and complex 3-6-way translocations in 15% of cases when compared to traditional cytogenetic methods. OGM combined with NGS found pathogenic variants in 98% of cases, a substantially greater rate than when karyotyping, FISH and NGS are used: The integrated approach of the combination of OGM and NGS resulted in the detection of pathogenic SVs and sequence variants in ~98% of cases. OGM was 100% concordant with NGS for aneuploidy detection. OGM findings have the potential to qualify subjects for targeted therapies that otherwise would not have been possible: The authors state that several of the OGM findings could result in the potential for these cases to qualify for either targeted treatments or clinical trials. For example, cases with potential to be treated by CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib), TRK inhibitors (larotrectinib, entrectinib), pan-FGFR inhibitors (erdafitinib or futibatinib) were highlighted. Erik Holmlin, president and chief executive officer of Bionano commented, “Approximately 50% of bone and soft tissue tumor samples fail to reveal actionable information for proper classification of disease, prognosis and therapeutic management because they either fail to culture or because traditional techniques in cytogenetics lack adequate sensitivity and specificity to reliably detect relevant variants. We have seen increasing evidence for OGM as a valuable alternative to cytogenetic methods in blood cancers, and we are thrilled to see researchers at Johns Hopkins publishing this compelling case for extending OGM’s utility to bone and soft tissue tumors.” The full research publication is available at: https://doi.org/10.1016/j.modpat.2024.100684 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 optical genome mapping (OGM) solutions, diagnostic services and software. The Company offers OGM solutions for applications across basic, translational and clinical research. The Company also offers an industry-leading, platform-agnostic genome analysis software solution, and nucleic acid extraction and purification solutions using proprietary isotachophoresis (ITP) technology. Through its Lineagen, Inc. d/b/a Bionano Laboratories business, the Company also offers OGM-based diagnostic testing services. The content above comes from the network. if any infringement, please contact us to modify.

CDK2-directed MGD drove deep tumor regression in preclinical models of HR-positive/HER2-negative breast cancer when combined with either a CDK4/6 inhibitor or a CDK4/6 inhibitor and endocrine therapy Potential to provide more sustained responses in a difficult-to-treat patient population, while avoiding toxicities typically associated with limited selectivity of CDK2 inhibitors BOSTON, Dec. 11, 2024 (GLOBE NEWSWIRE) -- Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, today announced the company will present preclinical data on the potential of its highly selective cyclin-dependent kinase 2 (CDK2)-directed molecular glue degrader to treat HR-positive/HER2-negative breast cancer at the 2024 San Antonio Breast Cancer Symposium, held December 10-13 in San Antonio, Texas. The data demonstrate that the company’s CDK2-directed MGD, MRT-9643, has superior selectivity compared to clinical-stage CDK2 inhibitors and induced robust downstream CDK2 pathway suppression. When combined with current standard of care therapies, MRT-9643 drove deep tumor regression in preclinical models of HR-positive/HER2-negative breast cancer. “Degrading CDK2 in conjunction with CDK4/6 inhibition has the potential to provide more sustained responses in patients with HR-positive/HER2-negative breast cancer. While currently approved CDK4/6 inhibitors offer clinical benefit, patients often relapse as tumors become reliant on the CDK2 pathway. However, attempts to inhibit CDK2 with conventional modalities have led to substantial toxicities, likely due to inadequate target specificity,” said Sharon Townson, Ph.D., Chief Scientific Officer of Monte Rosa Therapeutics. “Our results demonstrate that MRT-9643 is a highly selective oral CDK2 degrader that could potentially avoid many of the dose-limiting toxicities associated with less selective CDK2 inhibitors. Additionally, in preclinical models of HR-positive/HER2-negative breast cancer, the combination of our CDK2-targeted MGD with either a CDK4/6 inhibitor or a CDK4/6 inhibitor plus an endocrine therapy drove deep tumor regression. We look forward to advancing our CDK2 MGD program towards a development candidate nomination in H1 2025.” The poster, entitled, “Selective Targeting of CDK2 Using Molecular Glue Degraders for the Treatment of HR-Positive/HER2-Negative Breast Cancer” (Poster Number P5-01-26), will be displayed on Friday, December 13, from 12:30 to 2:00 p.m. CST in Poster Session 5: Developmental Therapeutics Translational Science Tumor Biology. The poster will be presented by William Tahaney, Scientist II, Biology, and Nina Ilic-Widlund, Director, Biology, Monte Rosa Therapeutics. Summary of findings: In cellular assays, MRT-9643 induced deep CDK2 degradation, resulting in CDK2-dependent cancer cell growth inhibition.MRT-9643 engages CDK2 through a novel binding mode that does not utilize the catalytic site typically engaged by catalytic-site inhibitors, enabling superior selectivity over conserved CDKs and other kinases.MRT-9643 demonstrated superior selectivity as compared to several clinical-stage small molecule CDK2 inhibitors evaluated.The combination of MRT-9643 and ribociclib, an FDA-approved CDK4/6 inhibitor, delayed resistance to CDK4/6 inhibition both in vitro and in vivo.When dosed orally in preclinical models of HR-positive/HER2-negative breast cancer, MRT-9643 drove deep tumor regression in combination with a CDK4/6 inhibitor or triple combination with a CDK4/6 inhibitor and endocrine therapy (fulvestrant), resulting in enhanced downstream pathway suppression as compared to a CDK4/6 inhibitor alone. About CDK2 MGDs and MRT-9643Cyclin-dependent kinase 2 (CDK2) is a key driver of cell cycle progression in cancer, acting in coordination with CDK4 and CDK6 to drive cell proliferation. CDK4/6 inhibitors, in combination with endocrine therapy, are FDA-approved agents for the treatment of HR-positive/HER2-negative breast cancer, however many patients become resistant because their tumors become reliant on CDK2. Targeting CDK2 in conjunction with CDK4/6 inhibition has the potential to provide more sustained clinical responses. In preclinical studies, Monte Rosa’s CDK2-targeted MGD, MRT-9643, has demonstrated highly selective degradation of CDK2, with no detectable off-target activity. MRT-9643 induced robust downstream CDK2 pathway suppression and drove deep tumor regression in preclinical models of HR-positive/HER2-negative breast cancer when combined with either a CDK4/6 inhibitor or a CDK4/6 inhibitor plus an endocrine therapy. Targeting CDK2 with MRT-9643 represents a potentially novel approach to treating HR-positive/HER2-negative breast cancer in combination with current standard of care therapies. About Monte RosaMonte Rosa Therapeutics is a clinical-stage biotechnology company developing highly selective molecular glue degrader (MGD) medicines for patients living with serious diseases in the areas of oncology, autoimmune and inflammatory diseases, and more. MGDs are small molecule protein degraders that have the potential to treat many diseases that other modalities, including other degraders, cannot. Monte Rosa’s QuEEN™ (Quantitative and Engineered Elimination of Neosubstrates) discovery engine combines AI-guided chemistry, diverse chemical libraries, structural biology, and proteomics to identify degradable protein targets and rationally design MGDs with unprecedented selectivity. The QuEEN discovery engine enables access to a wide-ranging and differentiated target space of well-validated biology across multiple therapeutic areas. Monte Rosa has developed the industry’s leading pipeline of MGDs, which spans oncology, autoimmune and inflammatory disease and beyond. Monte Rosa has a global license agreement with Novartis to advance VAV1-directed molecular glue degraders and a strategic collaboration with Roche to discover and develop MGDs against targets in cancer and neurological diseases previously considered impossible to drug. For more information, visit www.monterosatx.com. Forward-Looking StatementsThis communication includes express and implied “forward-looking statements,” including forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements that are not historical facts and in some cases, can be identified by terms such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. Forward-looking statements contained herein include, but are not limited to, statements about the therapeutic potential of CDK2 degradation, including using the company’s CDK2-directed MGD, MRT-9643, that degrading CDK2 in conjunction with CDK4/6 inhibition has the potential to provide more sustained responses in patients with HR-positive/HER2-negative breast cancer, about preclinical data presented at the 2024 San Antonio Breast Cancer Symposium, held December 10-13 in San Antonio, Texas supporting the potential of its highly selective cyclin dependent kinase 2 (CDK2)-directed molecular glue degrader to treat HR-positive/HER2-negative breast cancer, and about the Potential of CDK2-directed MGDs, including MRT-9643, to provide more sustained responses in a difficult-to-treat patient population while avoiding toxicities typically associated with limited selectivity of CDK2 inhibitors, among others. By their nature, these statements are subject to numerous risks and uncertainties, including those risks and uncertainties set forth in our most recent Annual Report on Form 10-K for the year ended December 31, 2023, filed with the U.S. Securities and Exchange Commission on March 14, 2024, and any subsequent filings, that could cause actual results, performance or achievement to differ materially and adversely from those anticipated or implied in the statements. You should not rely upon forward-looking statements as predictions of future events. Although our management believes that the expectations reflected in our statements are reasonable, we cannot guarantee that the future results, performance, or events and circumstances described in the forward-looking statements will be achieved or occur. Recipients are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date such statements are made and should not be construed as statements of fact. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, any future presentations, or otherwise, except as required by applicable law. Certain information contained in these materials and any statements made orally during any presentation of these materials that relate to the materials or are based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party studies, publications, surveys and other data to be reliable as of the date of these materials, we have not independently verified, and make no representations as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of our internal estimates or research and no reliance should be made on any information or statements made in these materials relating to or based on such internal estimates and research. Investors Andrew Funderburkir@monterosatx.com Media Cory Tromblee, Scient PRmedia@monterosatx.com