On December 8, 2023 Ribometrix, a biotechnology company developing small molecule therapeutics that modulate RNA biology, reported preclinical data supporting the potential of its eIF4E inhibitors in Estrogen Receptor-positive (ER+) breast cancer at the annual San Antonio Breast Cancer Symposium (SABCS), held December 5-9, 2023, in San Antonio, TX. This builds on analogous data announced last month in melanoma, providing further depth to the data supporting this target and Ribometrix’s portfolio of eIF4E-targeted small molecule inhibitors (Press release, Ribometrix, DEC 8, 2023, View Source [SID1234638333]).

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Ribometrix’s preclinical studies in ER+ breast cancer include evaluation of eIF4E inhibition via both monotherapy and in combination with standard-of-care (SoC) CDK4/6 inhibitors, which target key pro-oncogenic signaling pathways shared with eIF4E. Furthermore, eIF4E controls parts of the pathway that complement those targeted by CDK4/6 inhibition, suggesting additive benefit from combined therapy. All patients eventually develop resistance to CDK4/6 inhibitors, leaving a large unmet need and opportunity to restore tumor sensitivity to treatment and improve outcomes. Ribometrix expects to present additional data and select a development candidate in 2024.

"The data presented at SABCS reflect Ribometrix’s ability to efficiently translate the well-supported eIF4E target hypothesis into an RNA-modulating small molecule drug that has now achieved preclinical in vivo proof-of-concept in an additional tumor indication," said Michael Solomon, Ph.D., Chief Executive Officer of Ribometrix. "We are encouraged to see the added validation of eIF4E as an important mediator of pro-oncogenic signaling, this time in ER+ breast cancer, and the excellent emerging profiles of our eIF4E inhibitors. These data provide a strong foundation on which to build and refine the clinical development strategy for which eIF4E inhibition can ultimately have the greatest impact for patients."

Key takeaways from the presentation at SABCS include:

• Daily oral dosing of single agent Ribometrix eIF4E inhibitors shows anti-tumor efficacy in vivo with no signs of overt toxicity in an ER+ breast cancer tumor model

• Targeting ER+ breast cancer resistant to CDK4/6 inhibitors with a Ribometrix eIF4E inhibitor has the potential to mitigate drug resistance and restore sensitivity to standard of care (SoC) in a second line setting

• eIF4E inhibition with Ribometrix compounds potentiates cancer cell sensitivity to CDK4/6 inhibition, supporting a combination approach to improve SoC response durability in ER+ breast cancer

The data will be presented as a poster by Matthew Friedersdorf, Ph.D. and on display beginning today, December 8, 2023, at 12pm CT, at which time it will become available on the Ribometrix website.

About eIF4E
Eukaryotic translation initiation factor 4E (eIF4E), the main regulatory component of cap-dependent mRNA translation, selectively promotes pro-oncogenic protein synthesis in response to activation of multiple tumor signaling pathways. Interestingly, many pro-oncogenic signaling pathways require eIF4E activity to promote tumor growth. Clinically, eIF4E activity is elevated in many tumor indications and is typically associated with poor prognosis. Thus, targeting eIF4E has the potential to enhance anti-cancer activity when given in combination with standard-of-care (SoC). Additionally, eIF4E is also central to many resistance mechanisms, therefore eIF4E inhibition has the potential to overcome drug resistance and re-sensitize tumors to anti-cancer therapies. Ribometrix is developing eIF4E inhibitors as a promising therapeutic strategy to inhibit oncogene expression to enhance efficacy in combination with SoC and overcome resistance to targeted anti-cancer therapies.