— First data disclosure from Ribometrix's RNA-targeted drug discovery platform identifies small molecules targeting c-MYC, a validated but historically untreatable cancer driver —
— Data show small molecule binds directly to c-MYC RNA and reduces associated protein levels – a long-standing goal for RNA therapeutic development —
— Demonstrated RNA-binding protein inhibitor program targeting eIF4E in vivo Tumor regression combination, in vitro data support efficacy in drug-resistant tumors —
Durham, North Carolina, April 7, 2024–(BUSINESS WIRE)–Ribometrix, a biotechnology company developing small molecule therapeutics that modulate RNA biology, today announced that it will be attending the 2024 American Association for Cancer Research (AACR) Annual Meeting. We have shared the full data for two posters highlighting advances across two different treatments presented at . , held in San Diego, California from April 5th to 10th.
The poster includes the company's first public release of data validating its RNA targeting platform for designing small molecules that bind directly to RNA. The ability of these small molecules to selectively bind to mRNA encoding c-MYC, an important cancer driver, and reduce c-MYC protein expression. It includes data supporting the multi-tumor therapeutic potential of the company's program, which targets the RNA-binding protein eukaryotic translation initiation factor 4E (eIF4E).
Ribometrix's RNA targeting platform identifies small molecules that bind to cancer gene mRNA. Proof of concept delivered through the c-MYC program
These data support Ribometrix's world-leading expertise in RNA structural analysis to help identify novel small molecule binders of RNA aimed at interfering with downstream protein translation.
The data in the first poster shows how Ribometrix does it.
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We identified druggable RNA structural motifs and used them to screen for RNA binders with properties comparable to approved protein-targeted drugs. This suggests that established small molecule development processes can be leveraged for future developments.
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Generate RNA targeting compounds that directly engage c-MYC mRNA.
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Selectively reduced c-MYC protein and downstream effectors in c-MYC-expressing cell lines.
“For the first time, we share data demonstrating the ability to directly target RNA with small molecules and simultaneously reduce associated proteins and downstream targets, a long-standing scientific goal for our field.” said Dr. Michael Solomon. , Chief Executive Officer of Ribometrics. “Our ability to bind to c-MYC mRNA and demonstrate functional consequences validates our platform and opens the door to using this approach to target other high-value targets that are currently difficult to reach with traditional small molecule approaches. We are demonstrating the potential to deal with it.”
Novel eIF4E inhibitor potently and selectively suppresses tumor growth
These preclinical data are the most advanced demonstration to date that inhibition of the RNA binding protein (RBP) eIF4E serves as a potential anticancer therapy. These data are based on presentations at last year's Melanoma Research Association and San Antonio Breast Cancer Symposium. eIF4E is a major regulator and rate-limiting factor of protein synthesis and is elevated in many tumor types. These properties make it a promising target for multiple difficult-to-treat cancers, both as an effector of several targeted therapy pathways and as an important part of many resistance mechanisms. These roles create an opportunity to combine eIF4E inhibition with standard of care (SOC) to improve efficacy and duration of response in treatment-naïve patients, as well as restore susceptibility to resistant patients.
The data in the second poster shows how Ribometrix does it.
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synergistically strengthen in vivo In combination with eIF4E inhibitors, SOC exerts antitumor effects across many tumor types, including non-small cell lung cancer, breast cancer, and melanoma.
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Combination treatment with SOC caused tumor regression in mouse models of advanced melanoma, ER+ breast cancer, and non-small cell lung cancer.
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Sensitivity to SOC restored in multiple resistant cell lines in vitro Combination with eIF4E inhibitors provides a potential mechanism to resensitize resistant patient populations to initial therapy.
“The ability to target RNA-binding proteins that regulate cancer genes is a powerful therapy with the potential to address cancer indications with high unmet need. “We demonstrate broad applicability to amplify the benefits of current treatments by enhancing anti-tumor efficacy and reversing resistance,” said Jessica Soren, senior vice president of translational medicine. Dr. Tino said. “We are making excellent progress toward our goal of filing an IND in the first half of 2025. Together with our c-MYC data, we are leveraging our deep RNA expertise to target currently refractory targets with new We demonstrate multiple unique and innovative strategies to address RNA-directed modalities. ”
Posters can be viewed on the 'Publications' page of the Ribometrix website.
About eIF4E
Eukaryotic translation initiation factor 4E (eIF4E) is a key regulatory element of mRNA translation and a well-documented driver of oncogenesis. Clinically, eIF4E activity is elevated in many tumor indications and is usually associated with poor prognosis. Targeting eIF4E may enhance anticancer activity when administered in combination with standard treatments. Furthermore, eIF4E inhibition may overcome drug resistance and resensitize tumors to anticancer therapy. Based on substantial external and internal data, Ribometrics is developing eIF4E inhibitors as a promising combination therapy approach and treatment for treatment-resistant tumors.
About c-MYC
c-MYC is a well-validated oncogene with broad anti-cancer effects, as its expression is dysregulated in over 70% of cancers and it is a key regulator in nearly all aspects of carcinogenesis. is. c-MYC has remained recalcitrant for traditional small molecule drug discovery, primarily due to the lack of a defined small molecule binding pocket. By targeting c-MYC mRNA with small molecules, Ribometrics circumvents the “undruggable” challenge and successfully reduces c-MYC protein levels, thereby preventing cancer caused by c-MYC. We are developing new anti-cancer treatments.
About Ribometrics
Ribometrix is a biotechnology company pioneering an entirely new class of small molecule therapeutics that modulate RNA biology to treat human diseases. Ribometrix leverages its world-leading expertise in 3D RNA structure analysis to identify novel small molecules that inhibit the production of disease-associated proteins. Ribometrics is pursuing multiple in-house programs, including one targeting the oncogenic RNA-binding protein eIF4E and one directly targeting the oncogenic c-MYC mRNA, and is currently working with Roche Group companies Genentech and Vertex. We have established collaborations with Pharmaceuticals and leverage Ribometrics' discovery platform. Ribometrics is headquartered in Durham, North Carolina.
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contact address
Ribometrics contact information:
Chris Reilly
tenbridge communications
chris@tenbridgeecommunications.com
+1 617-834-0936