Company: ARVN
Filing Date: 2025-02-11
Form Type: 10-K
Source: 0001655759-25-000016
Chunk: 98

Company: ARVINAS, INC.
Filing Date: 2025-02-11
Form: 10-K
Item: Item 1
Chunk 98
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 control tumors. 

We have also conducted preclinical studies to test vepdegestrant in a tumor line derived directly from a patient, referred to as a patient derived xenograft, or PDX, model. This model is derived from a tumor with an ESR1 mutation (Y537S), which is a mutation in the ER that occurs in patients who have been treated with standard-of-care agents such as tamoxifen or an aromatase inhibitor, such as letrozole, and has been cited as a mechanism of resistance to those drugs. These studies included a comparison with fulvestrant. In this 28-day dosing study, oral vepdegestrant inhibited tumor growth by 99% at the 10 mpk dosing level and by 106% at the 30 mpk dosing level which was observed to be superior at both dosing levels to a clinically relevant dose of 200 mpk of fulvestrant. Further, vepdegestrant was shown to reduce ER by 79% and 88% at the 10 mpk and 30 mpk dosing levels, respectively, compared with 63% at the 200 mpk of fulvestrant dosing level. 

We have also conducted preclinical studies of vepdegestrant in combination with abemaciclib, a CDK4/6 inhibitor that is standard of care when used together with endocrine therapy. In these studies, we have achieved significant tumor shrinkage with vepdegestrant in ER+/HER2- MCF-7 xenograft models. As shown in the figure below, in a 28-day dosing study in MCF-7 xenografts, vepdegestrant at 30 mpk daily in combination with abemaciclib was superior in shrinking tumors, as compared to either abemaciclib as a single agent at 50 

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mpk daily, or the standard-of-care combination of abemaciclib at 50 mpk daily plus fulvestrant at 200 mpk twice per week for two weeks and then once per week for two weeks. 

We conducted similar studies for vepdegestrant in combination with palbociclib or ribociclib in the MCF-7 xenograft model, which demonstrated similar results for improved tumor growth inhibition for vepdegestrant in combination with palbociclib or vepdegestrant in combination with ribociclib relative to single agents or