Company: ARVN
Filing Date: 2025-02-11
Form Type: 10-K
Source: 0001655759-25-000016
Chunk: 95

Company: ARVINAS, INC.
Filing Date: 2025-02-11
Form: 10-K
Item: Item 1
Chunk 95
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 to treat cells, both BCR-Abl and C-Abl are effectively degraded. The figure below shows western blots of cells treated by increasing concentrations of our PROTAC targeted protein degrader and shows decreasing presence of each of BCR-Abl and C-Abl protein (depicted by a lighter shade of the BCR/Abl and C-Abl band in the western blot). Downstream signaling, as denoted by reduction of phosphorylated Stat5 (pStat5), is subsequently inhibited.

1Tubulin is a protein the GNF-2 PROTAC targeted protein degrader is not targeted to degrade, and is included as a control to ensure total protein is equivalent in each lane.

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PROTAC-induced degradation may offer a solution for historically undruggable proteins because only binders, not functional inhibitors, are needed to facilitate E3 ligase recruitment and initiation of the degradation process. The probability of finding a suitable ligand using binding-site-agnostic screening is increased because the function of the ligand itself is not required. As a result, there is the potential for PROTAC targeted protein degraders to generate therapeutics from poorly selective ligands, weak-affinity ligands, or ligands that may not be intrinsically biologically active. 

Our Clinical Stage Programs

Oncology Programs

Estrogen Receptor Program: Vepdegestrant for the Treatment of Patients with Locally Advanced or Metastatic ER+/HER2- Breast Cancer 

We are developing vepdegestrant, an investigational orally bioavailable PROTAC ER degrader designed to specifically target and degrade the ER for the treatment of patients with ER+/HER2- breast cancer. Vepdegestrant is being developed as a potential monotherapy and as part of a combination therapy across multiple treatment settings for ER+/HER2- metastatic breast cancer, as an alternative to, and potentially more potent degrader than, the intramuscular injection fulvestrant and other selective ER degraders, or SERDs, currently approved or in development for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer. We chose ER degradation as a therapeutic focus given the well-documented biology of ER signaling as a principal driver in a high percentage of breast cancers. In July 2021, we announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant.

Vepdegestrant has demonstrated activity in ER+ breast cancer preclinical models and