Plexium's Pipeline
A Targeted Therapy-Based Portfolio Strategy
Programs
- Discovery
- Lead Optimization
- IND-Enabling
- Phase 1
Indication
I-O Combo with CPIs
Rights
Wholly Owned
Overview
PLX-4545 targets an “undruggable” transcription factor, IKZF2, using a molecular glue strategy. IKZF2 is a marker of highly suppressive regulatory T cells (Tregs), and its degradation results in conversion of Tregs into effector-like T cells. We have demonstrated that selective degradation of IKZF2 reverses tumor immune evasion resulting in anti-tumor activity. IKZF2 degradation has the potential to improve clinical responses to immune checkpoint inhibitor therapy across multiple solid tumor types.
Indication
SMARCA4-Deficient solid tumors
Rights
Wholly Owned
Overview
SMARCA2 and SMARCA4 are mutually exclusive components of the chromatin remodeling BAF complex, which regulates gene expression. Functional genomic screens in cancer cell lines have shown a synthetic lethal relationship between SMARCA2 and SMARCA4. SMARCA4 loss of function (LOF) mutations occur in 5-7% of all human cancers. SMARCA4-deficient cancer cells are highly dependent on SMARCA2 for survival. We have designed novel, selective, orally bioavailable monovalent direct degraders of SMARCA2 that utilize a tissue-restricted E3 ligase and demonstrate synthetic lethality in SMARCA4 LOF cancer cell lines.
Indication
ER+, Her2- Breast Cancer; CCNE1amp tumor types
Rights
Wholly Owned
Overview
Cyclin E regulates cell cycle progression by binding and activating CDK2. Amplification or overexpression of cyclin E is associated with poor survival in select solid tumors and as a resistance mechanism to CDK4/6 inhibitors in HR positive breast cancer patients. As a result, CDK2 is an attractive target for treating patients with tumors driven by CCNE1-amplification or overexpression. We have applied our knowledge of redirecting the E3 ligase substrate receptor cereblon to design potent, highly selective and orally bioavailable CDK2 molecular glue degraders.
Indication
RAS driven tumors
Rights
Wholly Owned
Overview
The MAPK pathway is activated in >30% of human cancers, primarily via mutations in KRAS, NRAS and BRAF. The majority of patients have no effective treatment options. The scaffolding function of CRAF is essential for KRAS-driven tumorigenesis. This highlights the opportunity to develop selective degraders of CRAF to provide treatment options for patients with RAS mutant tumors. We have applied SBDD and computational modeling to discover selective monovalent direct degraders of CRAF that demonstrate antiproliferative activity in pan-RASmut cancer cell lines.
Indication
Undisclosed
Rights
Wholly Owned
Overview
Indication
Undisclosed
Rights
Wholly Owned
Overview
Indication
Undisclosed
Rights
Partnered
Overview
We use our platform approach and know-how to generate bespoke on-bead libraries and screen in cell-based assays to discover monovalent degraders of proteins of interest. We are currently partnering with AbbVie to discover new monovalent degraders for neurological conditions.
