Company: ARVN
Filing Date: 2025-02-11
Form Type: 10-K
Source: 0001655759-25-000016
Chunk: 118

Company: ARVINAS, INC.
Filing Date: 2025-02-11
Form: 10-K
Item: Item 1
Chunk 118
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 of mouse tauopathy models. 

In preclinical studies, we have demonstrated that alpha-synuclein PROTAC 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 for 48 hours.

In addition to our tau and alpha-synuclein programs, our neuroscience pipeline includes a program directed to mutant huntingtin, or mHTT, a key protein target for Huntington’s disease. We have identified ligands that bind to mutant mHTT protein without binding to wild-type HTT protein in preclinical studies. This selectivity differentiates these ligands from other small molecule splice modulators that reduce both mHTT and wild-type HTT protein. We believe that our discovery of selective mHTT PROTAC degraders has the potential to eliminate the toxic mHTT protein that causes this devastating disease. In our preclinical neurology research efforts, we have expanded our focus into additional mechanisms that contribute to the pathologic dysfunction in the brain including those that contribute to neuroinflammation and aging.

Other Programs: Luxdegalutamide (ARV-766) and bavdegalutamide (ARV-110)

We had been developing luxdegalutamide (ARV-766) and bavdegalutamide (ARV-110), each an investigational, orally bioavailable, AR degrading PROTAC targeted protein degrader, for the treatment of men with mCRPC. Both luxdegalutamide (ARV-766) and bavdegalutamide (ARV-110) demonstrated activity in preclinical models of AR overexpression and AR mutations, both common mechanisms of resistance to current standard-of-care agents in men with prostate cancer. We believe that the differentiated PROTAC pharmacology of luxdegalutamtide (ARV-766) and bavdegalutamide (ARV-110), including their iterative activity, has the potential to translate into significantly improved clinical outcomes over current standard-of-care agents. However, our clinical data showed signals of improved tolerability and efficacy with luxdegalutamide (ARV-766) as compared to bavdegalutamide. In addition, luxdegalutamide (ARV-766