Ribometrix, Inc.

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.

The deal leaves Ascidian free to go after other targets within neurology. Roche has added to its flotilla of RNA alliances, handing Ascidian Therapeutics $42 million upfront to use an alternative to gene editing to treat neurological diseases. The agreement includes up to $1.8 billion in milestones. Ascidian is at the forefront of efforts to treat disease by rewriting mRNA. Rather than change DNA, as happens in gene editing, Ascidian edits RNA exons. During the transcription of DNA into RNA, exons are spliced together to form mRNA that is then translated into protein. Mutations in the exons can result in malformed, disease-driving proteins. Ascidian wants to replace mutated exons to treat disease. The Boston-based biotech delivers DNA constructs, using a range of vehicles, which are transcribed into exon RNA, driving the production of full length, healthy proteins. Like gene therapy, the approach could enable the one-time treatment of disease. Robert Bell, Ph.D., head of research at Ascidian, explained to Fierce Biotech in an interview why a drug developer may want to take that approach rather than edit the gene at the root of a disease.  “Number one is we can edit at the kilobase scale, thousands of bases of RNA, with one therapeutic modality. When you think about genes that are very large, and genes that are large and have very high mutational variance, one exon editor construct could be applicable to a very broad patient population,” Bell said. The second core advantage is the platform can make edits without using foreign bacterial or engineered enzymes. Rather, Ascidian relies on existing molecular machinery. Bell said the approach “takes away some of the complexities” inherent in certain gene-editing technologies, which can require multiple vectors and multiple pieces of editing machinery to come together in a target cell.  Ascidian’s lead candidate is a retinal disease program targeting the genetic cause of Stargardt disease but the biotech has also applied the platform to neurological conditions in earlier-stage tests. The broader potential of the platform informed talks with potential partners including Roche, which stepped up its interest in a deal after seeing Ascidian navigate an important early regulatory test.  “The scientific discussion really accelerated after we got FDA feedback and opened our IND for Stargardt disease. Now, RNA exon editors have a path to the clinic,” Dan Rosan, chief financial and business officer at Ascidian, told Fierce. “We settled on a really discrete set of targets with very, very high unmet need, where Roche can bring excellent delivery capabilities, disease biology capabilities, and we can combine that with the RNA exon editing platform to make a drug.”  Roche is making an initial payment of $42 million and committing to up to $1.8 billion in research, clinical and commercial milestone payments to secure exclusive rights to Ascidian’s technology for undisclosed neurological targets. Ascidian will work with Roche on discovery and certain preclinical activities, before handing full control to the Swiss drugmaker for further preclinical work and beyond.  The deal leaves Ascidian free to go after other targets within neurology, something that was important to the biotech as its researchers continue to explore the potential of the platform. Ascidian is working on its next set of development candidates, which it plans to take into early clinical trials itself, and still has the appetite and capacity for further deals. Interested? Then Ascidian wants you to bring more than money. “We want folks with a deep commitment to gene editing and genetic disease as a core of their strategy, folks who bring things like manufacturing expertise, delivery expertise, disease biology expertise,” Rosan said. “It's not going to be the same answer for each genetic target. But, in all cases, we will be guided by who we think is the most likely to improve the probability of converting that idea into a drug.” Roche’s commitment to the RNA space is clear. The Big Pharma teamed up with Arrakis Therapeutics and Ribometrix to develop RNA-targeting small molecules in 2020 and 2021, respectively. Later in 2021, Roche partnered with Shape Therapeutics on RNA editing. The series continued in 2024, when the Swiss drugmaker hooked up with Remix Therapeutics.