Sheryl M. Gough*, Dan Sherman, Lynn DeCarr, Sarah Eaton, Maja Milanovic, Mark Bookbinder, Jennifer Pizzano, Martha Altieri, John Corradi, Hong Xiao, Felipe Gallego, Leofal Soto, Ram Lingamaneni, Xin Chen, Wei Zhang, Gan Wang, Hanqing Dong, Deborah Chirnomas, Michael Berlin, Keith Hornberger, John Houston, Lawrence Snyder and Ian Taylor.
ASH 2021 Poster #2272 Atlanta GA, USA
Session 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster II
Disclosures
All authors are current employees of Arvinas and equity holders. SMG, DS, LD, JC, FG, XC, WZ, JH, LS and IT have divested Arvinas equity in the past 24 months.
Session 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster II, #2272
2
BCL6 is a driver of B-cell malignancies and a therapeutic target in
regulates the transcription of numerous target genes as a transcriptional repressor and master regulator of germinal center formation, B-cell development, and other cellular processes such as cell cycle and DNA damage response
has been shown to be a key molecular driver of diffuse large B-cell lymphoma (DLBCL) via somatic mutation resulting in overexpression or the deregulated expression of BCL6
facilitates a permissive environment for mutation acquisition and aberrant cell proliferation
We have developed specific, potent and orally bioavailable BCL6 PROteolysis
TArgeting Chimera (PROTAC®) degraders that are efficacious in multiple pre-
clinical DLBCL models.
Session 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster II, #2272
3
PROTAC® protein degraders harness the ubiquitin-proteasome system to induce the degradation of disease-causing proteins
Session 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster II, #2272
4
PROTAC ® degraders demonstrate potent, on-mechanism degradation of BCL6 in-vitro
BCL6 levels / % vehicle (GAPDH norm.)
BCL6 ELISA
OCI-Ly1in-vitro 24 hr
140
120
100 80 60
40
20
0
0.01 0.1 1 10 100
Compound Log10 (nM)
ARVN-71228 DC50 0.7 nM
ARVN-129441
(E3-inactiveARVN-71228)
ARVN-71228
+ 30 μM E3-ligand (competition)
BCL6 levels following 24 hr ARVN-71228 treatment and blocked with E3-ligand competition
Session 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster II, #2272
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Arvinas Inc. published this content on 12 December 2021 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 15 December 2021 22:28:10 UTC.
Arvinas, Inc. is a clinical-stage biotechnology company focused on improving the lives of patients suffering from debilitating and life-threatening diseases through the discovery, development, and commercialization of therapies that degrade disease-causing proteins. The Company uses its PROTAC Discovery Engine platform to engineer proteolysis targeting chimeras, or PROTAC targeted protein degraders, that are designed to harness the body's own natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. It has four investigational clinical-stage programs: vepdegestrant (ARV-471) for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer; ARV-766 and bavdegalutamide for the treatment of men with metastatic castration-resistant prostate cancer, and ARV-102 for the treatment of patients with neurodegenerative disorders. Its product candidate, ARV-393, is designed to target the B-cell lymphoma 6, or BCL6 protein.
ARVINAS, INC. 
