Company: ARVN
Filing Date: 2025-02-11
Form Type: 10-K
Source: 0001655759-25-000016
Chunk: 296

Company: ARVINAS, INC.
Filing Date: 2025-02-11
Form: 10-K
Item: Item 7
Chunk 296
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 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 provides an advantage versus inhibition in vitro and in vivo. Our degrader is designed to eliminate, rather than inhibit, KRAS G12D, and preclinically it was 30-fold more potent than an inhibitor in vitro and provided 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 Investigational New Drug 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

We have conducted preclinical studies to establish the potential of our PROTAC Discovery Engine in the central nervous system, or CNS, for the treatment of neurodegenerative diseases, including tauopathies, the largest of which is Alzheimer’s disease. We have demonstrated that tau PROTAC protein degrader molecules could be dosed peripherally and degrade pathogenic tau in the brain of mouse tauopathy models. 

In preclinical studies, we have demonstrated that PROTAC alpha-synuclein degraders can specifically degrade aggregated forms of the protein. We have conducted in vitro experiments in cells expressing the A53T mutant form of alpha-synuclein, a mutation that causes aggregation of alpha-synuclein and early-onset PD in patients. We treated these cells with alpha-synuclein targeting PROTAC degraders at 1 μM