PLX-4545 / Plexium - LARVOL DELTA

Plexium Announces Multiple Presentations at AACR 2025 with Selective Monovalent Degrader Programs Targeting…IKZF2… (PRNewswire) - P1 | N=96 | ACTRN12623001265662 | Sponsor: Plexium Australia Pty Ltd | "Plexium...announced today multiple presentations with the Company's selective monovalent degrader programs for...IKZF2...at the 2025 American Association for Cancer Research (AACR) Annual Meeting....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."

P1 data • Oncology

A first in humans trial of PLX-4545, a molecular glue degrader of IKZF2, in healthy volunteers, shows pharmacologic modulation of Tregs at well-tolerated doses (AACR 2025) - "PLX-4545 demonstrated dose-proportional increases in AUC0-∞ and slightly greater than proportional increases in Cmaxand AUC0-last in the SAD study from 10 mg to 200 mg. Tmax was similar across doses, ranging from 0.75 - 1.0 hours. In the MAD study, AUC0-∞ also increased dose-proportionally, while Cmax increased slightly less than proportionally."

Clinical • IO biomarker • P1 data • Oncology • CRBN • FOXP3 • IKZF2

PLX-4545, a selective IKZF2 degrader, reprograms suppressive Tregs leading to tumor growth inhibition and combination benefit with immune checkpoint therapy (AACR 2025) - "PLX-4545, a selective IKZF2 degrader, preferentially converts tumor Tregs into effector-like T-cells, enhances CD8 T-cell response and shifts Teff:Treg balance in favor of anti-tumor activity, resulting in single agent activity and combination benefit with CPI. IKZF2 expression is elevated in cancer patient subsets, particularly in tumor Tregs and dysregulated CD8 TILs. PLX-4545 provides the potential to overcome immune resistance and broaden clinical response to CPI."

IO biomarker • Oncology • CD4 • CD8 • FOXP3 • GZMB • IFNG • IKZF2 • IL2 • IL2RA • TIGIT

Plexium Announces Two Oral Presentations and Multiple Posters at the American Association for Cancer Research (AACR) Annual Meeting 2025 (PRNewswire) - "Plexium...announced that initial Phase 1 clinical results with PLX-4545, a selective IKZF2 molecular glue degrader, and preclinical results from the Company's SMARCA2 monovalent direct degrader and CDK2 molecular glue degrader programs will be presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting..."

P1 data • Preclinical • Oncology

A Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of PLX-4545 in Healthy Volunteers (ANZCTR) - P1 | N=96 | Completed | Sponsor: Plexium Australia Pty Ltd | Recruiting ➔ Completed

Trial completion • Oncology • Solid Tumor • IKZF2

Preclinical activity of PLX-4545, an IKZF2 degrader, shows single agent anti-tumor activity and combination benefit with anti-PD1 therapy in solid tumors (SITC 2024) - "PLX-4545 provides the potential to overcome immune resistance and broaden clinical response to CPI. PLX-4545 is currently in a Phase I clinical trial to evaluate safety, exposure and pharmacodynamic response."

IO biomarker • Preclinical • Oncology • Solid Tumor • CD4 • CD8 • IFNG • IKZF2 • IL2 • IL2RA

Discovery of PLX-4545, a molecular glue degrader of IKZF2 (ACS-Fall 2024) - "PLX-4545 reverses Treg suppression, increases proliferation and infiltration of effector T cells, and shifts the Teff:Treg balance in favor of anti-tumor activity. PLX-4545 is currently being evaluated in an ongoing Phase 1 trial of healthy volunteers."

Oncology • Targeted Protein Degradation • CD4 • IKZF2

Plexium Initiates Dosing in Phase 1 Study of PLX-4545, a Potent and Selective Degrader of the Transcription Factor IKZF2 (PRNewswire) - "Plexium...reported that the first subjects have been dosed in a Phase 1 clinical study of orally administered PLX-4545, a potent and selective molecular glue degrader of IKZF2, a classically undruggable transcription factor also known as Helios....The randomized, double-blind, placebo-controlled, single- and multiple-ascending dose Phase 1 clinical study is designed to primarily assess the safety and tolerability profile of orally administered PLX-4545, as well as measure pharmacokinetics and pharmacodynamics to identify a pharmacologically effective dose....Plexium expects to announce results from the PLX-4545 Phase 1 study in the second half of 2024."

P1 data • Trial status • Oncology • Solid Tumor