Plexium Initiates Dosing in Phase 1 Study of PLX-4545, a Potent and Selective Degrader of the Tran­scrip­tion Factor IKZF2

SAN DIEGO, Dec. 12, 2023 /PRNewswire/ — Plexium, Inc. (Plexium), a leading next-generation targeted protein degradation company, today 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.

“We are very pleased to have dosed the first subjects in the Phase 1 study with PLX-4545, advancing Plexium into a clinical stage company,” said Mike Grey, Executive Chairman of Plexium. ​“Initiation of this study represents an important milestone for Plexium, as PLX-4545 is our first small molecule degrader program stemming from our proprietary drug discovery platform to enter human studies. In addition, we continue to discover potent and selective protein degraders of important cancer targets, such as SMARCA2, CDK2 and CRaf, and we look forward to progressing one or more of these programs into development in 2024.”

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.

“While checkpoint inhibitors have demon­strated broad clinical activity in several tumor types, many cancer patients are unre­spon­sive to therapy, often due to immune suppression within the tumor stroma,” said Simon Bailey, Ph.D., Executive Vice President, Drug Discovery at Plexium. ​“The immune tran­scrip­tion factor IKZF2 is a marker of highly suppressive regulatory T cells, and we have shown that potent and selective degradation of IKZF2 results in the conversion of Tregs into effector-like T cells. We have also shown that oral admin­is­tra­tion of PLX-4545 in preclinical in vivo cancer models has demon­strated promising efficacy, an effect that is even more pronounced when PLX-4545 is co-admin­is­tered with a checkpoint inhibitor.”

“Data from this initial study will provide a strong foundation for subsequent clinical studies to evaluate PLX-4545 in cancer patients with tumors that are refractory to checkpoint inhibitors, both as a single agent and in combination with a checkpoint inhibitor, an area of high unmet need,” continued Dr. Bailey.

Plexium expects to announce results from the PLX-4545 Phase 1 study in the second half of 2024.

About PLX-4545

PLX-4545 is a potent, selective and orally bioavail­able molecular glue degrader of IKZF2, designed to destabilize highly suppressive regulatory T cells (Tregs). PLX-4545 delivers rapid, deep and selective degradation of IKZF2 resulting in desta­bi­liza­tion of Tregs in vitro and in vivo. In preclinical studies, PLX-4545 has demon­strated single agent anti-tumor activity in vivo comparable to pembrolizumab and increased efficacy in combination. 

To learn more about the PLX-4545 clinical trial, visit https://www.australianclinicaltrials.gov.au/ (Trial regis­tra­tion #ACTRN12623001265662).

About Plexium Inc.

Plexium Inc. is the premier, next-generation Targeted Protein Degradation (TPD) company seeking to discover monovalent direct degraders and molecular glues that will address difficult to drug targets for the treatment of cancer. The company’s proprietary drug discovery platform is designed to identify novel small molecules that induce selective degradation of pathogenic proteins through E3 ligase mediated proteasomal degradation. Plexium is advancing a pipeline of novel targeted monovalent direct degraders and molecular glues for the treatment of cancer, and has also entered into a strategic collab­o­ra­tion with AbbVie to expand the potential of TPD to neurodegenerative diseases.

For more information, visit https://plexium.com/ and engage with us on LinkedIn.