Company: ARVN
Filing Date: 2025-08-06
Form Type: 10-Q
Source: 0001655759-25-000139
Chunk: 169

Company: ARVINAS, INC.
Filing Date: 2025-08-06
Form: 10-Q
Item: Part I, Item 8
Chunk 169
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 and provide a compelling rationale for considering combination strategies including chemotherapy-free approaches. Key findings from these preclinical studies included:

•Single-agent ARV-393 significantly reduced tumor burden in peripheral blood, bone marrow and spleen in a systemic PDX model of nTFHL-AI derived from a patient who relapsed post chemotherapy.

•ARV-393 monotherapy treatment resulted in robust (≥95%) tumor growth inhibition, or TGI, in two PDX models of tFL.

•ARV-393 in combination with five classes of SMIs targeting potentially cooperative oncogenic drivers (tazemetostat, palbociclib, everolimus, acalabrutinib, or venetoclax) demonstrated increased TGI in CDX models of HGBCL and aggressive DLBCL compared with the respective monotherapy treatments. Tumor regressions were observed when ARV-393 was combined with tazemetostat, palbociclib, acalabrutinib, or venetoclax.

•RNA sequencing studies carried out to further characterize downstream mechanism of action suggested that ARV-393 inhibits tumor cell cycle progression and promotes differentiation, driving antitumor activity and broad combinability in preclinical models.

We plan to share preclinical data for ARV-393 in combination with glofitamab, an emerging SOC option, in models of aggressive high grade DLBCL in the second half of 2025.

Neuroscience Program: ARV-102 

ARV-102 is our first oral PROTAC protein degrader in development to treat neurodegenerative diseases. In preclinical studies, ARV-102 has been shown to cross the blood-brain barrier and degrade LRRK2, which is a large, multidomain scaffolding kinase that plays a critical role in effective endolysosomal trafficking.  Unlike traditional SMIs that only block LRRK2’s kinase activity, LRRK2 degraders eliminate pathologic scaffolding function, GTPase activity and the kinase activity of LRRK2 implicated in disease.  We believe our LRRK2 degraders are particularly well positioned to be evaluated in two diseases where there are no disease modifying therapies available:  

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•Parkinson’s Disease, or PD, where increased LRRK2 expression and activity contributes to neurodegeneration and pathogenesis of PD, and; 

•Progressive Supranuclear Palsy, or PSP, where genetic variations in LRRK2