EIF4E

DURHAM, N.C.--( BUSINESS WIRE )-- Ribometrix , a biotechnology company developing small molecule therapeutics that modulate RNA biology, presented the latest data from its eIF4E program at the European Society for Medical Oncology (ESMO) Congress, taking place in Barcelona, Spain, September 13-17. The poster presentation reviews in vitro and in vivo studies of a small molecule eIF4E inhibitor, RBX-6610, as a potential treatment for KRAS G12C mutant non-small cell lung cancer (NSCLC). Acquired resistance is observed in most patients treated with the two approved therapies for KRAS G12C mutant NSCLC, creating a significant opportunity for a therapy that re-sensitizes tumors to KRAS inhibition. Ribometrix’s data supports RBX-6610’s ability to deliver this mechanism in combination with the approved therapies. “ In less than three years, Ribometrix has advanced its eIF4E program from concept to a lead molecule that has just completed non-GLP toxicology studies,” stated Michael Solomon, CEO of Ribometrix, Inc. “ The program is a testament to Ribometrix drug discovery capabilities, and the commitment and professionalism of the Ribometrix team. We look forward to moving this program forward into the clinic in collaboration with a partner who shares our vision of its potential to benefit patients, via its novel mechanism of action.” “ These data further evidence the broad potential of eIF4E inhibition in multiple tumor types, particularly in combination as a re-sensitizing agent. We have further validated the mechanism of action and characterized the synergistic benefit of RBX-6610, our most advanced eIF4E inhibitor,” said Jessica Sorrentino, Ph.D., SVP of Translational Medicine. “ RBX-6610 is progressing towards the clinic and we see significant promise for its inclusion with the standard-of-care for both naïve and treatment resistant NSCLC patients, especially whose tumors have KRAS mutations.” Key highlights: RBX-6610 demonstrated consistent anti-proliferative effects in KRAS G12C mutant tumor cell lines, in both treatment-naïve lines and those with acquired resistance. Additionally, the combined in vitro effects of co-treatment of RBX-6610 with KRAS inhibitors were synergistic, such that the proliferative inhibitory effects were greater than the sum of either treatment alone. Mechanistically, this was due to an induction of apoptosis, specific to co-treatment in treatment-naïve tumor cells as well as cells resistant to KRAS inhibitors. This synergistic phenotype was observed with both approved KRAS inhibitors, as well as investigational RAS inhibitors. Daily oral RBX-6610 monotherapy led to substantial tumor growth inhibition in both treatment naïve and resistant KRAS G12C NSCLC xenograft model (75% vs 71% TGI, respectively), corroborating the anti-proliferative effects seen in vitro . In combination with sotorasib, an approved KRAS inhibitor, daily oral treatment with RBX-6610 led to significant tumor regression and improved survival in both the treatment-naïve and sotorasib resistant setting (34% and 49% mean tumor regression respectively). No toxicity was observed in up to 35 days of daily oral treatment across all cohorts. In vitro data demonstrated improved selectivity of cap dependent translation inhibition by RBX-6610 relative to other translation inhibitors including zotatifin, an eIF4A inhibitor. Ribometrix continues to generate data demonstrating the multi-tumor therapeutic potential of eIF4E inhibition. Studies in melanoma and breast cancer were presented at the Society for Melanoma Research and the San Antonio Breast Cancer Symposium in 2023, and data across melanoma, colorectal, breast, and non-small cell lung cancer were presented at the American Association for Cancer Research Annual Meeting in 2024. Data have repeatedly included support for both monotherapy and combination regimens as well as the potential to re-sensitize to standard-of-care treatments. The ESMO poster is now available to view on the “ Publications ” page of Ribometrix’s website. About eIF4E Eukaryotic translation initiation factor 4E (eIF4E) is a crucial regulatory component of mRNA translation and well-documented driver of oncogenesis. Clinically, eIF4E activity is elevated in many tumor indications and it is typically associated with poor prognosis. Targeting eIF4E has the potential to enhance anti-cancer activity when given in combination with standard-of-care. Additionally, eIF4E inhibition has the potential to overcome drug resistance and re-sensitize tumors to anti-cancer therapies. Based on substantial external and in-house data, Ribometrix is developing eIF4E inhibitors as a promising combination therapy approach and treatment for treatment-resistant tumors. About Ribometrix Ribometrix is a biotechnology company pioneering a completely new class of small molecule therapeutics that modulate RNA biology to treat human diseases. Ribometrix leverages its world-leading expertise in three-dimensional RNA structural analysis to identify 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 one directly targeting oncogenic c-MYC mRNA, and has established collaborations with Genentech, a member of the Roche Group, and Vertex Pharmaceuticals, which leverage Ribometrix’s discovery platform. Ribometrix is headquartered in Durham, North Carolina.

DURHAM, N.C.--( BUSINESS WIRE )-- Ribometrix , a biotechnology company developing small molecule therapeutics that modulate RNA biology, today announced the latest data from its eIF4E program will be presented at the European Society for Medical Oncology (ESMO) Congress, taking place in Barcelona, Spain, September 13-17. A poster presentation will review in vitro and in vivo studies of a small molecule eIF4E inhibitor, RBX-6610, as a potential treatment for non-small cell lung cancer (NSCLC), specifically NSCLC with KRAS G12C , a common mutation. Acquired resistance is observed in the majority of patients treated with the two approved therapies for KRAS G12C mutant NSCLC, creating a significant opportunity for a therapy that resensitizes tumors to these treatments. Ribometrix’s data supports RBX-6610’s ability to deliver this mechanism in combination with the approved therapies. “ The close relationship of eIF4E and KRAS signaling suggested the potential for eIF4E inhibition to restore tumor sensitivity to KRAS inhibition, and it is exciting to see this thesis borne out given the important medical need among patients with NSCLC,” said Jessica Sorrentino, Ph.D., SVP of Translational Medicine. “ We look forward to sharing our full dataset at ESMO 2024.” In vitro outcomes in the poster include: RBX-6610 monotherapy demonstrated consistent anti-proliferative effects in KRAS G12C mutant tumor cell lines, in both treatment-naïve lines and those with acquired resistance RBX-6610 combined with KRAS inhibitors resulted in a synergistic apoptotic induction in treatment-naïve tumor cells and re-sensitized resistant tumor cells to KRAS inhibitors. In vivo outcomes in the poster include: RBX-6610 monotherapy caused significant tumor growth inhibition RBX-6610 combined with a KRAS inhibitor resulted in significant tumor regression in a treatment-naïve model A further in vivo study reviewing RBX-6610’s ability to re-sensitize tumor cells to KRAS inhibition will be included in the final poster presentation. The presentation details are: 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 The ESMO poster will be available to view on the “ Publications ” page of Ribometrix’s website following the presentation. About eIF4E Eukaryotic translation initiation factor 4E (eIF4E) is a crucial regulatory component of mRNA translation and well-documented driver of oncogenesis. Clinically, eIF4E activity is elevated in many tumor indications and it is typically associated with poor prognosis. Targeting eIF4E has the potential to enhance anti-cancer activity when given in combination with standard-of-care. Additionally, eIF4E inhibition has the potential to overcome drug resistance and re-sensitize tumors to anti-cancer therapies. Based on substantial external and in-house data, Ribometrix is developing eIF4E inhibitors as a promising combination therapy approach and treatment for treatment-resistant tumors. About Ribometrix Ribometrix is a biotechnology company pioneering a completely new class of small molecule therapeutics that modulate RNA biology to treat human diseases. Ribometrix leverages its world-leading expertise in three-dimensional RNA structural analysis to identify 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 one directly targeting oncogenic c-MYC mRNA, and has established collaborations with Genentech, a member of the Roche Group, and Vertex Pharmaceuticals, which leverage Ribometrix’s discovery platform. Ribometrix is headquartered in Durham, North Carolina.

Part of the next steps include looking for strategic alternatives for eFFECTOR’s development programs. It’s the end of an era—eFFECTOR Therapeutics’ era to be exact. The oncology biotech has laid off staff as it plans to wind down, according to a June 24 company release. This includes eFFECTOR CEO Stephen Worland, Ph.D.; Chief Financial Officer Michael Byrnes; and Chief Medical Officer Douglas Warner, M.D., who all stopped serving in their positions at the end of last week. The company expects to spend about $600,000 by June 30 in one-time charges and cash expenditures tied to the workforce reduction, according to Securities and Exchange Commission documents. In the meantime, the board of directors has tapped Craig Jalbert to lead as eFFECTOR’s CEO, president, treasurer, secretary and sole board member. Jalbert is a principal from the accounting firm Verdolino & Lowey, P.C., and has more than three decades of experience helping companies wind down.  Part of the next steps include looking for strategic alternatives for eFFECTOR’s development programs. The biotech’s lead asset is zotatifin, a selective eIF4A inhibitor being tested out in several mid-stage trials for solid tumors. In April, the company's other wholly-owned asset, tomivosertib, failed to improve progression-free survival in a phase 2b trial of patients with non-small cell lung cancer (NSCLC). Based on all the data available in the primary analysis, the company said it didn't see an obvious path forward for continuing development of the asset in frontline NSCLC. eFFECTOR also had a partnership with Big Pharma Pfizer for a preclinical asset dubbed eIF4Ei, which is also designed to tackle solid tumors. The $507 million biobucks deal was struck back in 2019 when Pfizer paid out $15 million up front in an exclusive licensing agreement to develop small-molecule inhibitors of eukaryotic initiation factor 4E (eIF4E) with eFFECTOR. The biotech was founded in 2012 based on research from the University of California, San Francisco labs of Davide Ruggero, Ph.D., and Kevan Shokat, Ph.D. eFFECTOR plans to ask to be delisted from the Nasdaq. Since announcing the planned shuttering, the biotech’s stock plummeted 77% from $1.17 per share at market close Friday to 29 cents this morning at opening.