PIC Therapeutics, Inc., a biotechnology company pioneering the discovery and development of first-in-mechanism, first-in-class allosteric small molecule therapies targeting eIF4E, is presenting pre-clinical data today on the company’s advancing eIF4E program for breast cancer in a poster at the American Association for Cancer Research (AACR) Annual Meeting 2023, taking place in Orlando, FL.
Advanced or metastatic breast cancers represent a large patient population with limited long-term solutions that address both the heterogenous nature of resistant tumors and the aggressiveness of their proliferation. The aim of our therapies is to drive strong mechanistic responses, in a majority of breast cancer tumor subtypes, that induce a rapid commitment to cell death. To accomplish this, our approach addresses a key fundamental mechanism in protein translation at the convergence of many oncogenic signaling pathways through which resistance arises.
eIF4E is a key component of protein translation that often becomes dysregulated in breast cancer, supporting cell survival and metastasis alongside therapeutic resistance. PIC compound regulation of eIF4E induces rapid commitment to apoptosis and selective proteomic shifts that are consistent with canonical eIF4E regulation including cell cycle impacts, e.g. effects on cyclin family members and CDKs, DNA repair regulation and metabolic proteins. PIC Compounds also potently impact multiple clinical drivers for ER+ and Triple Negative Breast Cancers, which are evidenced by mRNA signatures that include changes consistent with proteomic impacts to key transcription factors.
Previous communications revealed our eIF4E regulators potently cause cell death in primary breast cancer organoid models, but spared models derived from healthy tissue. Expanding our efforts in this domain, the impact on normal immune cells was evaluated by exposing PBMCs, CD4+ T cells, and bone marrow mononuclear cells to our compounds. Our eIF4E regulators did not impair survival of these cells up to a maximum tested dose of 25 micromolar. Primary CD4+ T cells were also found to be functional in the presence of eIF4E regulators up to 5 micromolar, which included assessments of CD3/CD28 stimulated cytokine production and proliferative responses, highlighting its remarkable differentiated impact on normal cells compared to tumor cells.
“We continue to uncover interesting and distinctive preclinical data sets that underscore the potential for unique therapeutic advantages of allosterically regulating eIF4E, as a promising strategy for patients with various subtypes of breast cancer,” said Kathy Bowdish, Ph.D., President and Chief Executive Officer of PIC Therapeutics.
Our findings suggest that allosteric regulation of eIF4E provides a unique and efficient way to address multiple resistance mechanisms while sparing normal immune cellular function. Our eIF4E regulators represent a potential beneficial therapeutic approach to address multiple resistant cancer patient populations and fulfill the promise of this elusive target.
Title: eIF4E allosteric regulators cause rapid commitment to apoptosis in cancer cells while sparing immune cells
Session Category: Experimental and Molecular Therapeutics
Session Title: Novel Antitumor Agents 3
Session Date and Time: Monday April 17, 9:00 AM – 12:30 PM
Location: Section 17
Poster Board Number: 14
Abstract Number: 1624
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 regulate protein translation in a context dependent manner. 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 regulates 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