On November 6, 2023 Ribometrix, a biotechnology company developing small molecule therapeutics that modulate RNA biology, reported its lead wholly-owned development program targeting the protein eIF4E, and announced it will present initial preclinical data demonstrating the anti-tumor benefit of eIF4E inhibition at the 20th International Congress of the Society for Melanoma Research (SMR), held November 6-9, 2023, in Philadelphia, PA (Press release, Ribometrix, NOV 6, 2023, View Source [SID1234637085]).
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"As a leader in the emerging field of small molecule modulation of RNA biology, we’re thrilled to debut our eIF4E program, which we see as a high-value target for addressing a significant unmet need in melanoma with potential applicability in a wider range of tumor types"
Ribometrix is developing therapeutics that target eIF4E to treat cancer by inhibiting tumor cell growth. eIF4E is a potent oncogene that promotes cell growth by regulating the synthesis of oncoproteins known to drive abnormal cell proliferation and tumorigenesis. Common cancer drivers, such as mutant versions of BRAF/MEK and PI3K/AKT, are reliant on activation of eIF4E for the production of oncoproteins that lead to uncontrolled cell proliferation.
"As a leader in the emerging field of small molecule modulation of RNA biology, we’re thrilled to debut our eIF4E program, which we see as a high-value target for addressing a significant unmet need in melanoma with potential applicability in a wider range of tumor types," said Michael Solomon, Ph.D., Chief Executive Officer of Ribometrix. "eIF4E has long been known as a regulator of mRNA translation, but its potential as a therapeutic target has been underexplored due to the historical challenges in modulating RNA biology with small molecules. The preclinical dataset we’re building for this program as a potential first- and second-line treatment for melanoma is a testament to Ribometrix’s expertise and internal capabilities in addressing the new world of targeting RNA biology for the benefit of patients in need."
Ribometrix will present data at SMR showing its eIF4E-targeted small molecule inhibitors:
Reduce the production of eIF4E-regulated oncoproteins and inhibit the growth of several cancer cell lines, including BRAF mutant melanoma.
Demonstrate strong anti-tumor monotherapy efficacy in a xenograft mouse model with no overt signs of toxicity after daily oral dosing.
Potentiate the effects of BRAF and MEK inhibitors (BRAFi/MEKi) in treatment naïve BRAF mutant melanoma cell lines.
Re-sensitize BRAFi/MEKi resistant BRAF mutant melanoma cell lines to treatment, a significant outcome as more than half of patients that receive BRAFi/MEKi will develop resistance within the first year of therapy.
Ribometrix is evaluating its portfolio of eIF4E inhibitors in preclinical studies and plans to select a development candidate in 2024. Additional preclinical data in other indications will be presented at upcoming medical conferences, including the San Antonio Breast Cancer Symposium in December 2023.
At SMR, data will be presented as a poster by Matthew Friedersdorf, Ph.D. and on display beginning today, November 6, 2023, at 4:00pm EDT, at which time it will become available on the Ribometrix website.
About eIF4E
Eukaryotic translation initiation factor 4E (eIF4E), the main regulator for cap-dependent mRNA translation and pro-oncogenic protein synthesis, is a critical node of multiple tumor signaling pathways. Targeting eIF4E has the potential to enhance anti-cancer activity of targeted therapies and overcome drug resistance. Specifically, known oncogenic drivers including BRAF, MEK, PI3K, AKT and CDK4/6 converge on eIF4E leading to hyper-translation of oncogenic proteins. Furthermore, while targeted therapies inhibiting a specific pathway are highly efficacious, tumors eventually emerge resistant to the treatments. Due to the innate biology, inhibition of eIF4E can resuppress that pathway leading to efficacy in the treatment resistant setting. Ribometrix is developing eIF4E inhibitors as a promising therapeutic strategy to inhibit oncogene expression and overcome resistance to targeted anti-cancer therapies.