Ribometrix Presents eIF4E Program Data for KRAS Mutant NSCLC at ESMO 2024

Ribometrix, a biotechnology firm focused on developing small molecule therapeutics that modulate RNA biology, recently presented compelling data from its eIF4E program at the European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain. The company highlighted its progress in developing RBX-6610, an eIF4E inhibitor, as a potential treatment for KRAS G12C mutant non-small cell lung cancer (NSCLC).

The poster presentation detailed the results from both in vitro and in vivo studies of RBX-6610. This small molecule demonstrated significant anti-proliferative effects in KRAS G12C mutant tumor cell lines, including those that had developed resistance to existing therapies. The data suggested that RBX-6610, when used in combination with KRAS inhibitors, could re-sensitize tumors to KRAS inhibition, offering a potential breakthrough for patients who have developed resistance to current treatments.

Within three years, Ribometrix transitioned from the conceptual phase of its eIF4E program to developing a lead molecule, RBX-6610, which has successfully completed non-GLP toxicology studies. Michael Solomon, CEO of Ribometrix, emphasized the company's swift progress and expressed optimism about moving the program into clinical trials in partnership with a like-minded collaborator.

Jessica Sorrentino, Ph.D., SVP of Translational Medicine, elaborated on the broad potential of eIF4E inhibition across various tumor types, highlighting RBX-6610’s ability to act as a re-sensitizing agent. The company is optimistic about the inclusion of RBX-6610 in standard treatments for both treatment-naïve and resistant NSCLC patients, especially those with KRAS mutations.

Key findings from the studies included:
- RBX-6610 consistently inhibited cell proliferation in KRAS G12C mutant tumor lines, both in treatment-naïve and resistant contexts.
- The combination of RBX-6610 with KRAS inhibitors produced synergistic effects, resulting in greater anti-proliferative activity than either treatment alone. This synergy was attributed to the induction of apoptosis specifically in both naïve and KRAS inhibitor-resistant cells.
- In vivo, daily oral administration of RBX-6610 led to significant tumor growth inhibition in KRAS G12C NSCLC models, both in treatment-naïve and resistant settings.
- When combined with sotorasib, an approved KRAS inhibitor, RBX-6610 resulted in notable tumor regression and improved survival rates in both treatment-naïve and resistant models. Importantly, no toxicity was observed during the 35-day study period.
- The in vitro data demonstrated that RBX-6610 had enhanced selectivity for cap-dependent translation inhibition compared to other translation inhibitors, such as zotatifin.

Ribometrix is also exploring the therapeutic potential of eIF4E inhibition in other cancers. Studies presented at the Society for Melanoma Research and the San Antonio Breast Cancer Symposium in 2023, as well as the American Association for Cancer Research Annual Meeting in 2024, showcased data across various cancers, including melanoma, colorectal, breast, and NSCLC. These studies supported the potential of eIF4E inhibitors both as monotherapies and in combination with other treatments to re-sensitize tumors to standard therapies.

The ESMO poster is available on the Ribometrix website.

eIF4E is a critical regulator of mRNA translation and has been linked to oncogenesis. Its activity is elevated in several tumor types and is often associated with poor prognosis. Inhibiting eIF4E offers a promising approach to amplify anti-cancer activity when used alongside standard treatments and to overcome drug resistance in tumors.

Ribometrix, headquartered in Durham, North Carolina, is at the forefront of pioneering small molecule therapeutics that modulate RNA biology. The company utilizes advanced three-dimensional RNA structural analysis to discover novel inhibitors targeting disease-associated proteins. Alongside its internal programs targeting eIF4E and c-MYC mRNA, Ribometrix has collaborations with Genentech and Vertex Pharmaceuticals, leveraging its discovery platform to develop innovative treatments.