Company: ARVN
Filing Date: 2025-02-11
Form Type: 10-K
Source: 0001655759-25-000016
Chunk: 121

Company: ARVINAS, INC.
Filing Date: 2025-02-11
Form: 10-K
Item: Item 1
Chunk 121
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 to guiding treatment decisions, reduction in PSA is often an indicator of the effectiveness of treatment in clinical trials, however, it is not recognized as a surrogate endpoint for purposes of regulatory approval. For example, bavdegalutamide demonstrated equivalent reduction in PSA to enzalutamide at ten-fold lower concentration levels in an in vitro inhibition study of PSA synthesis in Lymph Node Cancer of the prostate cells, which are androgen-sensitive human prostate adenocarcinoma cells, that have been engineered to overexpress AR. 

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In in vivo mouse models, bavdegalutamide has inhibited AR-dependent tumor growth in a statistically significant manner. Bavdegalutamide exhibited superior tumor growth inhibition compared to enzalutamide in both castrated and intact (non-castrated) xenograft models derived from VCaP cell lines. 

To assess the ability of bavdegalutamide to treat enzalutamide-resistant cancers, we conducted in vivo studies of bavdegalutamide in an enzalutamide-resistant VCaP xenograft model. These VCaP tumors acquired resistance to enzalutamide after being continuously propagated in castrated, enzalutamide treated mice for approximately three years. We observed that tumors in mice dosed with enzalutamide grew at nearly the same rate as tumors in mice dosed only with the drug vehicle - a control similar to dosing a placebo. Orally delivered bavdegalutamide significantly inhibited tumor growth, described as tumor growth inhibition, or TGI, in these enzalutamide-resistant VCaP tumors. 

We have also conducted preclinical studies of bavdegalutamide for enzalutamide-insensitive tumors. We conducted an in vivo study in a PDX model that is derived from a tumor from a patient not treated with enzalutamide but that is insensitive to enzalutamide and showed that tumors in mice dosed with enzalutamide grew at only a slightly slower rate than tumors in mice dosed only with the drug vehicle. In contrast, orally delivered bavdegalutamide significantly inhibited tumor growth in these enzalutamide-insensitive tumors, achieving a TGI value of 100%. Further, PSA levels in the plasma of mice following 20 days of bavdegalutamide dosing significantly decreased in comparison to those dosed with only the drug vehicle or enzalutamide. We believe the