RIBOSCIENCE ESMO PRESENTATION HIGHLIGHTS SAFETY, PK, PD AND EFFICACY DATA FROM THE FIRST 19 PATIENTS OF THE ENPP1 INHIBITOR RBS2418 PHASE 1 STUDY

SUNNYVALE, Calif., Oct. 20, 2023 /PRNewswire/ -- Riboscience, LLC, today announced the first presentation of data from the ongoing Phase 1 clinical trial of the ENPP1 inhibitor RBS2418 that will be delivered by Dr. Thomas U. Marron, MD, PhD, from Mount Sinai, New York at the European Society for Medical Oncology (ESMO) Congress 2023 on October 21, 2023. RBS2418 is the first ENPP1 inhibitor in clinical development.

Clinical study RBS2418-1001 (NCT05270213) is a Phase 1, open-label, non-randomized study in adult patients with advanced, unresectable, recurrent or metastatic solid tumors, who have progressed on, or are ineligible for standard therapies. The dose escalation phase of the study follows a 3+3 design with increasing doses of RBS2418 given orally as monotherapy or in combination with Pembrolizumab.

The ESMO presentation #1025MO summarizes the safety, PK and PD results and clinical outcomes of treatment with RBS2418 from the first 19 patients in the dose escalation phase of the study. There are 11 different cancer types represented and 84% of patients had failed 3 or more lines of prior treatment. The concentration of RBS2418 in plasma and in tumor samples exceeded the human serum EC90 of ENPP1 inhibition in all patients at all dose levels (100, 200, 400 mg) and at all time points tested. Median plasma Cmax and Ctrough levels of RBS2418 increased dose proportionally. No DLTs, no treatment-related SAEs or treatment-related AEs above grade 2 were observed for treatment durations up to 1 year. Immune activation and tumor infiltration of CD4 and CD8 cells was observed in patients who expressed ENPP1 and cGAS protein in baseline tumor samples, EG(+) phenotype. The EG(+) phenotype was present in 53% of the patients at baseline.

This phenotype predicted outcome with RBS2418 treatment, as 60% of treated EG(+) patients experienced stable disease as compared to 0% of patients who did not express ENPP1 or cGAS in the baseline tumor sample, EG(-) phenotype. Progression-free survival (PFS) was significantly increased in EG(+) vs EG(-) phenotypes (p=0.0013). Clinical benefit from RBS2418 was dependent on the presence of the drug target (ENPP1), indicating target-inhibition dependent clinical benefit with RBS2418 treatment, consistent with the PK/PD results that demonstrated full ENPP1 inhibition and cGAMP stabilization at all dose levels.

These results show a target-inhibition-dependent immune activation and significant clinical benefit of a well-tolerated oral RBS2418 treatment and support further clinical development of this novel first-in-class immunotherapy agent. The clinical study is proceeding into a dose-expansion phase.

About Riboscience, LLC

Riboscience is a private clinical-stage biotechnology company leveraging a proprietary library of nucleoside and non-nucleoside analogs to rationally design drug candidates that are highly selective for essential targets in the virology and oncology spaces.

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 humans 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, metastasis, and non-response to checkpoint inhibitors. The orally administered 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

Previously, RBS2418 was evaluated in an expanded access study RBS2418-EA-001, the results of which have been presented at the ESMO-IO conference 2022 (#169P). This was an expanded access study in a patient with advanced adrenal cancer, who had previously progressed on multiple treatments, including 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 are consistent with the preliminary results from the Phase 1 a/b study presented at ESMO 2023.

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:
Klaus Klumpp, PhD
President
klaus.klumpp@riboscience.com

SOURCE Riboscience LLC