On December 7, 2018 Arvinas Inc. (Nasdaq: ARVN), a biotechnology company creating a new class of drugs based on targeted protein degradation, reported its positive preclinical data on the company’s lead clinical candidate, ARV-471, for advanced or metastatic ER-positive/HER2-negative breast cancer at the 2018 San Antonio Breast Cancer Symposium (SABCS), taking place December 4-8 in San Antonio, Texas (Poster P5-04-18; Session 5: Tumor Cell and Molecular Biology: Endocrine Therapy and Resistance) (Press release, Arvinas, DEC 7, 2018, View Source [SID1234531969]). In this study, orally administered ARV-471 demonstrated improved potency and anti-tumor activity both as a monotherapy and in combination with a CDK4/6 inhibitor, compared to current standard of care treatment regimens.
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"We believe that ARV-471 has the potential to be the first oral protein degrader for the treatment of patients with metastatic ER-positive/HER2-negative breast cancer, when used either as a single-agent or in combination with other routinely used anti-cancer agents," said John Houston, Ph.D., President and CEO of Arvinas. "This data reinforces our growing confidence that our PROTAC protein degraders have the potential to provide distinct advantages over existing approaches across a broad range of disease targets and to improve clinical outcomes over current standard of care. We continue to expect to initiate our Phase 1 clinical trial of ARV-471 in mid-2019."
Key highlights from the poster "ARV-471, an oral estrogen receptor PROTAC degrader for breast cancer":
Orally bioavailable ARV-471 demonstrated potent ERa degradation in wild-type and mutant ERa-expressing cell lines.
Oral administration of ARV-471 caused near-complete ERa degradation and resulted in tumor shrinkage in an orthotopic MCF7/estradiol breast cancer preclinical model; ARV-471 demonstrated superior tumor growth inhibition and ERa degradation compared to standard-of-care agent, fulvestrant.
Combination of ARV-471 and a CDK4/6 inhibitor demonstrated superior tumor growth inhibition when compared to the combination of fulvestrant and a CDK4/6 inhibitor.
ARV-471 inhibited growth of tamoxifen-resistant and ERa gene (ESR1) mutant tumors while also reducing tumor ERa levels.
ARV-471 displayed no ER agonist activity.