On April 28, 2025 Plexium, Inc. (Plexium), a leading next-generation targeted protein degradation company, reported multiple presentations with the Company’s selective monovalent degrader programs for SMARCA2, IKZF2 and CDK2 at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 25-30, 2025, in Chicago, IL (Press release, Plexium, APR 28, 2025, View Source [SID1234652243]).

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"These data highlight the clinical and preclinical progress we’ve made across our portfolio, including the use of a novel E3 ligase DCAF16, in our SMARCA2 program—an industry first that reinforces the differentiated potential of our monovalent degrader platform," said Jorge F. DiMartino, MD, PhD, Chief Medical Officer at Plexium. "We are also excited to share initial clinical data from PLX-4545, which demonstrated clinical proof of mechanism and intended pharmacological immunophenotypic effects."

Oral Presentation Details:

Title: "Discovery and characterization of novel, potent and selective CDK2 molecular glue degrader against CCNE1-amplified tumors"
Session: MS.ET09.01 – Degraders and Glues
Abstract Number: 6375
Date and Time: April 29, 2:55 PM – 3:10 PM
Presenting Author: Leenus Martin, PhD

Title: "PLX-4545, a selective IKZF2 degrader, reprograms suppressive Tregs leading to tumor growth inhibition and combination benefit with immune checkpoint therapy"
Session: MS.ET09.01 – Degraders and Glues
Abstract Number: 6380
Date and Time: April 29, 4:10 PM – 4:25 PM
Presenting Author: Peggy Thompson, PhD

Poster Presentation Highlights:

Title: "Mechanistic characterization of selective monovalent direct degraders of SMARCA2″
Session: PO.ET09.04 – Degraders and Glues 1
Abstract Number: 404
Section: 18
Date and Time: April 27, 2025, 2:00 PM – 5:00 PM
Presenting Author: Julia Toth, PhD

Plexium’s SMARCA2 degraders function by bromodomain binding and covalent modification
A CRISPR knockout screen identified DCAF16 as being required for PLX-61639 mediated SMARCA2 degradation
MOA studies demonstrate PLX-61639-mediated SMARCA2:DCAF16 protein interactions and the requirement of covalent binding to a specific DCAF16 cysteine to support a stable ternary complex and subsequent SMARCA2 degradation
Title: "Preclinical characterization of PLX-61639, a potent and orally bioavailable SMARCA2-selective monovalent direct degrader"
Session: PO.ET09.10 – Degraders and Glues 2
Abstract Number: 1653
Section: 18
Date and Time: April 28, 2025, 9:00 AM – 12:00 PM
Presenting Author: Gregory Parker, PhD

Plexium has designed PLX-61639, a potent and selective direct degrader of SMARCA2, and nominated it as a development candidate
Daily oral dosing of PLX-61639 results in deep and sustained SMARCA2 degradation, eliciting robust tumor growth inhibition and regression in SM4mut CDX and PDX models, no tumor growth inhibition is observed in a control SM4wt CDX model
PLX-61639 is currently advancing through IND-enabling studies
Title: "A first in human trial of PLX-4545, a molecular glue degrader of IKZF2, in healthy volunteers, shows pharmacologic modulation of Tregs at well-tolerated doses"
Session Title: PO.CT01.02. First-in-Human Phase I Clinical Trials 2
Abstract Number: CT150
Section: 48
Date and Time: April 29, 2025, 9:00 AM – 12 PM
Presenting Author: Jorge DiMartino, MD, PhD

PLX-4545 an oral, CRBN molecular glue degrader of IKZF2, a lineage-defining transcription factor for Tregs was tested in healthy adult volunteers
With repeated daily dosing for 14 days, all dose levels achieved complete degradation of IKZF2 in PBMCs by Day 2 leading to conversion of Tregs into effector-like T cells and an increase in activated T effector cells
TEAEs were mostly Grade 1 or 2 (mild or moderate) in severity and no Dose Limiting Toxicities were encountered. All AEs were reversible with discontinuation of dosing
The AACR (Free AACR Whitepaper) 2025 posters will be made available on the Plexium website.