Sunnyvale, CA, December 7, 2022 /PRNewswire/ -- Riboscience, LLC, a private clinical-stage biotechnology company leveraging a proprietary library of nucleoside and non-nucleoside analogues to rationally design drug candidates that are highly efficacious and highly selective for essential targets in the virology and oncology spaces, today announced the publication of two abstracts that will be presented  at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) Congress 2022,  taking place  virtually and on-site in Geneva, Switzerland from December 7-9, 2022.

Abstract #195TiP outlines the trial design for the Phase 1 clinical evaluation of orally administered RBS2418, a potent and selective ENPP1 inhibitor.  ENPP1 inhibition results in the protection of immune-activating cGAMP and ATP from hydrolysis in the TME and in the reduced production of immune-suppressive adenosine. The ongoing study is a Phase 1a/b, open-label, non-randomized study in patients (pts) (≥18 years) with advanced, unresectable, recurrent or metastatic solid tumors, who have progressed on, or are ineligible for standard therapies. The study begins with dose-escalation where in a 3+3 fashion pts will receive in one cohort RBS2418 starting at 100mg bid as monotherapy and in a second cohort RBS2418 in combination with Pembrolizumab (200 mg IV q3w). The study will enroll up to 64 pts at 10 sites in the US. The primary objectives of the study are safety, tolerability, ENPP1 inhibition and cGAMP protection of RBS2418 as monotherapy and in the combination setting. Immune biomarkers predictive of anti-tumor responses will be explored as well as translational analyses will be done to explore the depth and breadth of immune activation both in tumor tissue and blood. This study is being funded by Riboscience, LLC.

Abstract#169P summarizes the PK, PD and immunomodulatory profile of RBS2418, which is also the first-in-human experience with an ENPP1 inhibitor.  This was an expanded access study in a patient with advanced adrenal cancer, who had previously progressed on a treatment with pembrolizumab and cabozantinib. The results showed that weekly intra-patient escalation of doses from 100 mg BID to 400 mg BID in combination with pembrolizumab was safe, well tolerated with no DLTs. RBS2418 PK data showed oral bioavailability with plasma levels leading to complete serum ENPP1 inhibition at all time points already at the 100 mg starting dose level. The treatment induced increases in peripheral cDCs, proliferation of CD4 and CD8 T cells and hyperexpansion of TCR clonotypes in peripheral blood as well as upregulation of T cell cytotoxic granule protein gene expression, consistent with a treatment-induced immune activation from a baseline cold tumor phenotype.  These results support further clinical development of this novel first-in-class immunotherapy agent in the  on-going Phase1a/b clinical trial described above (NCT05270213).

December 8th/ 12.30pm/ Foyer ABC Palexpo exhibition center, Geneva: #195TiP

A First-In-Human, Phase 1 a/b Dose Escalation and Expansion Study to Evaluate RBS2418 as Monotherapy and in Combination with Pembrolizumab in Subjects with Advanced Unresectable, Recurrent or Metastatic Tumors (NCT05270213)

December 8th/12.30pm/ Foyer ABC Palexpo exhibition center, Geneva: #169P

Immunomodulatory effects of RBS2418, an oral ENPP1 inhibitor in combination with pembrolizumab in checkpoint-refractory metastatic adrenal cancer 

About Riboscience, LLC.
Riboscience applies specialized chemistry and biology to create novel treatments for human diseases. We particularly focus on building ribose-based molecules, and we use structure-guided design to generate highly selective and efficacious drug candidates.

Nucleoside analogs are examples of ribose-based molecules that have become important drugs for the treatment of a number of viral diseases and cancers.  The Riboscience library of nucleoside and non-nucleoside molecules is rationally designed to deliver drug candidates that are highly efficacious and highly selective for essential targets in the virology and oncology spaces.

About RBS2418.

RBS2418 is a nucleoside-derived small molecule that has been optimized for potent (picomolar binding affinity) and selective binding to the active site of ENPP1. ENPP1 is the only enzyme known in human to hydrolyze the immune-activating messenger molecule cGAMP that is generated in tumor cells in the context of replication errors, DNA damage and a variety of replication defects.  ENPP1 also hydrolyzes ATP and contributes to the generation of increased immune-suppressive adenosine levels in the TME. ENPP1 upregulation is commonly observed in tumors and is associated with immune evasion, cold tumor phenotype, disease progression and non-response to checkpoint inhibitors.  RBS2418 is the first clinical stage ENPP1 inhibitor and is being investigated in a Phase 1a/b dose escalation  and expansion study as  monotherapy and in combination with Pembrolizumab.  Refer to the clinicaltrials.gov overview for more information:  RBS2418 Evaluation in Subjects With Unresectable or Metastatic Tumors - Full Text View - ClinicalTrials.gov For additional information, please visit Https://www.Riboscience.com

Forward-Looking Statements
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified using words such as "anticipate," "believe," "forecast," "estimated" and "intend" or other similar terms or expressions that concern Riboscience expectations, strategy, plans or intentions. These forward-looking statements are based on Riboscinece current expectations and actual results could differ materially. There are several factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, clinical trials involve a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results; our clinical trials may be suspended or discontinued due to unexpected side effects or other safety risks that could preclude approval of our product candidates; risks related to business interruptions, including the outbreak of COVID-19 coronavirus, which could seriously harm our financial condition and increase our costs and expenses; uncertainties of government or third party payer reimbursement; dependence on key personnel; limited experience in marketing and sales; substantial competition; uncertainties of patent protection and litigation; dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. There are no guarantees that our product candidate will be utilized or prove to be commercially successful. Additionally, there are no guarantees that future clinical trials will be completed or successful or that any precision medicine therapeutics will receive regulatory approval for any indication or prove to be commercially successful. While the list of factors presented here is considered representative, no such list should be considered to be a complete statement of all potential risks and uncertainties. Unlisted factors may present significant additional obstacles to the realization of forward-looking statements. Forward-looking statements included herein are made as of the date hereof, and Riboscience, LLC does not undertake any obligation to update publicly such statements to reflect subsequent events or circumstances.

Riboscience Contact:

Jill Jene, PhD, MBA

Chief Business Officer

jjene@riboscience.com