PIC Therapeutics to Present Pre-Clinical Data on eIF4E Program to Address Breast Cancer Drug Resistance at AACR Annual Meeting 2022

“The preclinical results highlighted in this poster underscore the unique therapeutic advantages of allosterically modulating eIF4E and further demonstrate its potential as a promising strategy for patients with ER+ breast cancer,” said Kathy Bowdish, Ph.D., president and chief executive officer of PIC Therapeutics.

PIC Therapeutics is targeting a fundamental mechanism at the convergence of many oncogenic signaling pathways, and results in cancer cell death while sparing normal cells. Allosteric modulation of eIF4E offers many advantages to previous approaches, and simultaneously addresses multiple drivers of pharmacology, allowing our small molecules to truly drive differential CAP dependent translation in target cells.

Importantly, preclinical studies show that PIC compounds modulate, but do not block protein translation. Consistently, our data demonstrate that as many proteins are upregulated as are downregulated as we alter protein complex membership. In ER+ breast cancer lines, PIC compounds upregulate a number of proteins responsible for apoptosis induction, including increases in caspase 3/7 activity along with demonstrated Annexin V binding, while simultaneously downregulating proteins involved in DNA repair. PIC compounds mechanistically modulate cellular proteomes, leading to rapid and significant reduction in cancer cell viability via apoptosis. Inducing apoptosis rather than senescence is an important distinguishing feature of PIC’s approach to this elusive target.

In ER+ breast cancer models, we observe evidence of mechanistic impacts in specific protein biomarkers with PICRN1024, PIC’s lead compound. Specifically aligned with patient data, we observe significant negative impacts on ERα expression, Cyclin D1 expression, CDK4 protein expression and decreases in the level of phospho-Rb. This mechanistic pharmacology helps us understand our impact on cell cycle transitions and correlates with decreases in ER+ breast cancer cell viability. Importantly, we also see simultaneous impacts on multiple mechanisms of breast cancer drug resistance including loss of PTEN, loss of Rb, CDK2, cyclin E, among others. Each of these impacts represent anticipated molecular profiles of ER+ Advanced Metastatic Breast Cancer patient tumors that have developed resistance to CDK4/6 inhibitors.

PIC Therapeutics is therefore uniquely positioned to therapeutically address eIF4E as one of the key drivers of cancer cell survival, uncovering unique mechanisms that may be harnessed for ER+ breast cancer patient benefit, with potential to expand more broadly across other oncology indications.

Presentation details are as follows:

Title: eIF4E modulators to address breast cancer resistance
Session Category: Experimental and Molecular Therapeutics
Session Title: Cell Cycle, Replication Inhibitors, and Immunotherapy Agents
Session Date and Time: April 12, 2022, 9:00 AM – 12:30 PM CT
Location: New Orleans Convention Center, Exhibit Hall D-H, Poster Section 21
Abstract Number: 2562

About PIC Therapeutics, Inc.

PIC Therapeutics is a preclinical stage biotechnology company pioneering the discovery and development of first-in mechanism, first-in-class small molecule medicines focused on fundamentally changing how we treat cancer by developing therapeutics that modulate protein translation. PIC Therapeutics targets a “master switch” of cancer signaling pathways, selectively impacting oncogene protein production by altering the Pre-Initiation Complex (PIC) that drives their mRNA translation. PIC Therapeutics’ selective approach modulates cancer cell proteomes, impacting multiple dysregulated oncogenic drivers leading to a powerful new generation of cancer-treating therapeutics. Our agents offer the opportunity to address both drug resistance and tumor heterogeneity, issues that plague many existing treatments. For more information visit www.pictherapeutics.com. PIC is guided by a dedication to improving cancer patient outcomes and to realizing the potential of our programs to their benefit.

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