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May 09, 2024 -- Arvinas, Inc. (Nasdaq: ARVN) today announced that two posters, including updated clinical trial data, for vepdegestrant will be presented at the 2024 European Society for Medical Oncology (ESMO) Breast Cancer Annual Congress held from May 15-17, 2024, in Berlin, Germany. Vepdegestrant is a novel investigational PROTAC® estrogen receptor (ER) degrader that is being jointly developed by Arvinas and Pfizer for the treatment of patients with early and locally advanced or metastatic ER positive/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer. Poster session details are as follows: Date: Thursday, May 16, 2024 Time: 12:00 – 1:00 p.m. CET/ 6:00 – 7:00 a.m. ET Category: Metastatic Breast Cancer Poster Title and Number: Vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, plus palbociclib (palbo) in ER+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer: updated phase 1b cohort results, Poster 218P Presentation Type and Abstract Number: Abstract, 453 Poster Title and Number: TACTIVE-K: phase 1b/2 study of vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, in combination with PF-07220060, a cyclin-dependent kinase (CDK)4 inhibitor, in ER+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer, Poster 264 Presentation Type and Abstract Number: Trial-in-Progress (TiP), 488 Abstracts are now available via the official ESMO Breast Cancer Annual Congress website here. Vepdegestrant is an investigational, orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with ER positive (ER+)/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer. Vepdegestrant is being developed as a potential monotherapy and as part of combination therapy across multiple treatment settings for ER+/HER2- metastatic breast cancer. In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will share worldwide development costs, commercialization expenses, and profits. The U.S. Food and Drug Administration (FDA) has granted vepdegestrant Fast Track designation as a monotherapy in the treatment of adults with ER+/HER2- locally advanced or metastatic breast cancer previously treated with endocrine-based therapy. Arvinas is a clinical-stage biotechnology company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases through the discovery, development, and commercialization of therapies that degrade disease-causing proteins. Arvinas uses its proprietary PROTAC® Discovery Engine platform to engineer proteolysis targeting chimeras, or PROTAC® targeted protein degraders, that are designed to harness the body’s own natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. In addition to its robust preclinical pipeline of PROTAC protein degraders against validated and “undruggable” targets, the company has four investigational clinical-stage programs: vepdegestrant for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer; ARV-766 and bavdegalutamide for the treatment of men with metastatic castration-resistant prostate cancer; and ARV-102 for the treatment of patients with neurodegenerative disorders. For more information, visit www.arvinas.com. The content above comes from the network. if any infringement, please contact us to modify.

NORTHFIELD, Ill.--(BUSINESS WIRE)-- The College of American Pathologists (CAP) updated the “Principles of Analytic Validation of Immunohistochemical Assays” guideline to provide increased precision and accuracy of clinical immunohistochemical assays. This update assesses evidence published since the release of the original guideline in 2014 and provides new recommendations on how to analytically validate/verify immunohistochemical assays used for diagnostic and predictive purposes. “This updated guideline provides new and revised recommendations for analytic validation/verification of immunohistochemical assays, which often guide therapeutic decision making for cancer treatment,” explains guideline chair, Jeffrey D. Goldsmith, MD, FCAP. “This guideline update serves to revise validation guidelines for all immunohistochemistry assays with particular focus on predictive markers; major changes to validation of immunohistochemistry assays performed on cytology specimens are also included.” Validation Recommendations While many of the original guideline statements remain similar, there are several new recommendations which provide guidance for validation/verification of IHC assays performed on cytology specimens and predictive marker assays that have distinct scoring systems, such as programmed death receptor-1 (PD-L1). For initial analytic validation/verification of every assay used clinically, laboratories should achieve at least 90% overall concordance between the new assay and the comparator assay or expected results. This guideline revision also applies to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor 2 (HER2) IHC performed on breast carcinoma, also reset at 90% concordance, superseding the previously different concordance thresholds. This recommendation harmonizes validation requirements for all immunohistochemical markers. “Although the systematic review did not identify substantive new literature, the numerical considerations and modeling discussed in the initial guideline document remains relevant,” states Dr. Goldsmith. “If validation/verification yields unexpected results, the causes should be investigated by the immunohistochemistry medical director.” Another strong recommendation pertains to predictive marker assays, such as HER2 and PD-L1, in which more than one scoring system is used. The recommendation stipulates separate validation/verifications based on antibody clone/scoring system combination. Additional specific guidance is offered for validating immunohistochemistry performed on cytology specimens. These updated recommendations, now available in an early online release in the Archives of Pathology & Laboratory Medicine, were established through the assessment of evidence published since the release of the original guideline in 2014. Current tools, resources, and information for the Principles of Analytic Validation of Immunohistochemical Assays: Guideline Update can be found on the guideline webpage on cap.org. About the College of American Pathologists As the world’s largest organization of board-certified pathologists and leading provider of laboratory accreditation and proficiency testing programs, the College of American Pathologists (CAP) serves patients, pathologists, and the public by fostering and advocating excellence in the practice of pathology and laboratory medicine worldwide. For more information, visit the CAP Newsroom, CAP.org and yourpathologist.org to watch pathologists at work and see the stories of the patients who trust them with their care.

Researchers have discovered that estrogen receptor (ER), expressed in the lateral septum of the limbic system, plays a crucial role in suppressing anxiety-like behavior exhibited by male mice in social situations. They also discovered that the distribution and expression region of ER differs from that of ER. Researchers from the University of Tsukuba have discovered that estrogen receptor (ER) β, expressed in the lateral septum of the limbic system, plays a crucial role in suppressing anxiety-like behavior exhibited by male mice in social situations. They also discovered that the distribution and expression region of ERβ differs from that of ERα. Estradiol (E2), a sex steroid hormone, plays an essential role in social behavior, including regulating social anxiety, which is anxiety experienced when unknown individuals are encountered. In males, testosterone secreted by the testes is converted to E2 in the brain, and the E2 binds to two types of estrogen receptors (ERs), ERα and ERβ, to regulate social behavior. However, its neuroendocrine basis has not been understood. In this study, the role of ERα and ERβ expressed in the lateral septum (LS), which regulates social anxiety, was investigated using male mice. The researchers first investigated the expression of ERα and ERβ in LS using genetically modified male mice. ERβ-expressing cells in the mice were labeled with red fluorescent protein, which revealed that the distributions of ERα and ERβ are different. Furthermore, the researchers investigated the knockdown effects of ERα or ERβ gene expression in the LS of male mice during situations of social and nonsocial anxiety. The results show that social anxiety increases with the inhibition of ERβ expression. Additionally, ERα- and ERβ-positive cells in the LS projected into different regions of the hypothalamus. Thus, the researchers concluded that ERα- and ERβ-expressing cells in LS are distinct cell populations with different localizations and neuronal projections, and the ERβ population plays a crucial role in neural circuitry that regulates anxiety-like behavior in social situations. This work was supported by grant-in-aid for Scientific Research 15H05724, 21K18547, and 22H02941 to SO.