Company: ARVN
Filing Date: 2025-02-11
Form Type: 10-K
Source: 0001655759-25-000016
Chunk: 116

Company: ARVINAS, INC.
Filing Date: 2025-02-11
Form: 10-K
Item: Item 1
Chunk 116
---
 sites other than enzymatic active sites and the ability to initiate the degradation process using only weak binders, offer us opportunities to degrade those targets. 

Oncology

KRAS is a driver oncogene in several major tumor types and is associated with poor prognosis and resistance to standards of care. Preclinically, our degrader is a highly selective and potent molecule that demonstrates dose-responsive degradation of KRAS G12D, leading to robust antitumor activity in KRAS G12D mutated cancers including pancreatic and colorectal cancers. In the second quarter of 2023, we presented in vivo and in vitro data at the AACR - Targeting RAS Special Conference that demonstrated that our PROTAC KRAS G12D degraders were potent, selective and led to tumor stasis in a mouse xenograft model with intermittent dosing and degradation of KRAS G12D that provides an advantage versus inhibition in vitro and in vivo. Our degrader is designed to eliminate, rather than inhibit, KRAS G12D and, in preclinical studies, it was 30-fold more potent than an inhibitor in vitro and provides additional aspects of differential biology contributing to its potent and broad antitumor effect in vivo. Our KRAS G12D program is currently in preclinical development and we anticipate filing an IND application for our PROTAC KRAS G12D degrader in 2025. 

Our exploratory and research activities in oncology include programs directed to degrade KRAS, as noted above; Myc, an oncogenic transcription factor driving tumor cell proliferation; and hematopoietic progenitor kinase 1, a suppressor of T cell activation. 

Neurologic Diseases

Neurologic diseases, in particular, neurodegenerative diseases, are generally progressive in nature and result in the degeneration and often death of neurons in the brain, leading to cognitive decline, functional impairment and eventually death. These diseases affect a rapidly growing patient population and represent one of the largest unmet medical needs of our time. Alzheimer’s and PD encompass the largest patient populations among the neurodegenerative diseases. The Alzheimer’s Association estimated that 6.9 million Americans aged 65 and older, about one in nine individuals, were living with Alzheimer’s dementia in 2024, with 73% aged 75 or older, and the Parkinson’s Foundation estimated that nearly one million Americans are living with PD. Alzheimer’s disease is marked by the progressive accumulation of aggregated tau protein, while aggregation of alpha-synuclein