Ribometrix to Present eIF4E Program Data for KRAS Mutant NSCLC at ESMO 2024

Ribometrix, a biotechnology company based in Durham, North Carolina, is developing small molecule therapeutics aimed at modulating RNA biology. Recently, the company announced that it will present new data from its eIF4E program at the European Society for Medical Oncology (ESMO) Congress, scheduled to take place in Barcelona, Spain, from September 13-17, 2024. The presentation will feature a poster detailing both in vitro and in vivo studies of an eIF4E inhibitor, RBX-6610, which is being evaluated as a potential treatment for non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation—a common and challenging mutation in this type of cancer.

The current standard treatments for KRAS G12C mutant NSCLC often lead to acquired resistance in most patients, opening the door for innovative therapies that can re-sensitize tumors to these existing treatments. Ribometrix's data supports the efficacy of RBX-6610 in achieving this goal when used in combination with approved KRAS inhibitors.

Dr. Jessica Sorrentino, Senior Vice President of Translational Medicine at Ribometrix, highlighted the significance of the relationship between eIF4E and KRAS signaling. She emphasized that inhibiting eIF4E could potentially restore tumor sensitivity to KRAS inhibition, addressing an unmet medical need for patients with NSCLC. Dr. Sorrentino expressed excitement about these findings and looked forward to sharing the full dataset at ESMO in 2024.

The poster presentation will cover the following key findings:

In vitro results:
- RBX-6610 monotherapy showed consistent anti-proliferative effects in KRAS G12C mutant tumor cell lines, both in treatment-naïve lines and those with acquired resistance.
- When combined with KRAS inhibitors, RBX-6610 induced a synergistic apoptotic response in treatment-naïve tumor cells and re-sensitized resistant tumor cells to KRAS inhibitors.

In vivo results:
- RBX-6610 monotherapy led to significant tumor growth inhibition.
- The combination of RBX-6610 with a KRAS inhibitor resulted in notable tumor regression in a treatment-naïve model.
- An additional in vivo study will explore RBX-6610's capability to re-sensitize tumor cells to KRAS inhibition, with these findings to be included in the final poster presentation.

The presentation details are as follows:
- Date: Sunday, September 15, 2024
- Location: Dedicated poster area of Hall 6
- Presentation number: 202P
- Title: “eIF4E inhibition exhibits anti-tumor activity and re-sensitizes acquired resistant KRAS G12C NSCLC to KRAS inhibitors”

eIF4E, or eukaryotic translation initiation factor 4E, is a key regulatory component in mRNA translation and a well-documented driver of oncogenesis. Elevated eIF4E activity is clinically observed in numerous tumor types and is often linked to poor prognosis. Targeting eIF4E holds promise for enhancing anti-cancer activity when combined with standard-of-care treatments. Moreover, eIF4E inhibition has the potential to overcome drug resistance and re-sensitize tumors to anti-cancer therapies. Ribometrix is leveraging substantial external and in-house data to develop eIF4E inhibitors as part of a promising combination therapy approach and as a treatment for resistant tumors.

Ribometrix is pioneering a new class of small molecule therapeutics that modulate RNA biology. Utilizing its expertise in three-dimensional RNA structural analysis, the company identifies novel small molecules that inhibit the production of disease-associated proteins. Ribometrix is advancing multiple internal programs, including one targeting the oncogenic RNA-binding protein eIF4E and another targeting oncogenic c-MYC mRNA. Additionally, Ribometrix has established collaborations with Genentech and Vertex Pharmaceuticals, leveraging its discovery platform to advance RNA-targeted therapies.

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