Riboscience Presents Phase 1a/b Overall Survival Data for ENPP1 Inhibitor RBS2418 as Monotherapy and in Combination Therapy in Advanced Solid Tumors and Late-Line CRC

• Median overall survival of 12 months with RBS2418 monotherapy in subjects with heavily pretreated tumors that express ENPP1 and cGAS proteins (TME-EG+ phenotype), versus 4.2 months in subjects whose tumors do not (median 3 prior systemic therapies; p=0.0022)
• Median overall survival of 14 months in heavily pretreated TME-EG+ late-line metastatic colorectal cancer (mCRC, median 4 prior systemic therapies), including subjects with liver metastases
• Well tolerated, with no treatment-related serious adverse events or discontinuations

PALO ALTO, Calif., Oct. 26, 2026 /PRNewswire/ -- Riboscience, LLC, a privately held, clinical-stage biotechnology company developing first-in-class immunotherapies, today announced the presentation of initial overall survival (OS) and immune activation data from the Phase 1a/b clinical trial of RBS2418, its oral inhibitor of ENPP1, at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain.

Poster 1977P presented on October 24 reports safety, pharmacokinetic, pharmacodynamic, immune activation and overall survival data from 81 subjects with heavily pretreated advanced, metastatic solid tumors who received RBS2418 as monotherapy (n=49) or in combination with pembrolizumab (n=27) or other treatments (n=5). Data are also presented from 19 subjects with heavily pretreated mCRC, including 17 with microsatellite-stable / proficient in mismatch repair (MSS/pMMR) disease, who received RBS2418 as monotherapy (n=13), in combination with pembrolizumab (n=5) or FOLFIRI (n=1).

Median OS (mOS) was 12 months in subjects receiving RBS2418 monotherapy whose tumors had the TME-EG+ phenotype at baseline, defined by ENPP1 and cGAS expression in cancer cells or stroma, compared with 4.2 months in subjects with TME-EG− tumors (median 3 prior systemic therapies; p=0.0022). The observed difference is particularly notable because higher ENPP1 and cGAS expression was associated with poorer overall survival across the six tumor types most represented in the study in an analysis of The Cancer Genome Atlas data (p=0.002).

Median OS was 14 months in the late-line TME-EG+ mCRC population (n=15; median 4 prior systemic therapies). Among 19 subjects with mCRC, 17 had MSS/pMMR disease, 74% had liver metastasis at baseline, and 68% received RBS2418 monotherapy. Prolonged mOS in this population has been particularly difficult to achieve to date.

Longer OS was associated with intratumoral immune activation during RBS2418 treatment, including increased tumor infiltration by activated CD4+ and CD8+ T cells and cell-killing CD8+ cells. Pharmacodynamic analyses showed full protection of serum cGAMP and normalization of elevated baseline pyrophosphate levels, findings consistent with ENPP1 inhibition. Because ENPP1 hydrolyzes extracellular cGAMP, preservation of cGAMP is consistent with the proposed mechanism of immune activation by RBS2418. Together, these findings support further evaluation of the relationship between TME-EG status, immune activation, and clinical outcomes with RBS2418.

"These are the first overall survival data from our Phase 1a/b study, and they show an association with target protein expression in the tumor and intratumoral immune activation. It is very exciting to observe longer than expected survivals for these heavily pretreated patients" said Dr. Thomas U. Marron, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and presenting author of this RBS2418 Phase 1a/b abstract at ESMO.

Study Design

RBS2418-1001 (NCT05270213) is a Phase 1a/b, open-label, non-randomized study in adults with advanced, unresectable, recurrent, or metastatic solid tumors that had progressed following, or were ineligible for, standard therapies. RBS2418 is administered orally as monotherapy or in combination with pembrolizumab or other approved cancer therapies. The study is currently ongoing in Phase 1b, with open cohorts in selected tumor types.

Safety and Tolerability

RBS2418 was safe and well tolerated in the safety population of 89 treated subjects. No treatment-related serious adverse events or treatment discontinuations were reported. Treatment-related adverse events were predominantly low grade: Grade 1, 2 and 3 events occurred in 19%, 15% and 2.2% of subjects, respectively, while 64% of subjects had none.

Pharmacokinetics and Target Engagement

At all dose levels evaluated, RBS2418 concentrations in plasma and tumor exceeded EC₉₀ for ENPP1 inhibition in human serum. Pharmacodynamic findings were consistent with target engagement: RBS2418 fully protected serum cGAMP and normalized elevated baseline pyrophosphate levels. cGAMP is an endogenous immune activator and substrate of ENPP1, while pyrophosphate is generated through ENPP1-mediated hydrolysis of ATP.

Survival and Biomarker Results

Longer overall survival and intratumoral immune activation during RBS2418 treatment were associated with the baseline TME-EG+ phenotype. In the TME-EG+ RBS2418 monotherapy population (n=37), median overall survival (OS) was 12 months, consistent with the mOS observed in the overall TME-EG+ study population (n=68, 12 months).

Late-Line metastatic Colorectal Cancer

In subjects with heavily pretreated TME-EG+ late-line mCRC (n=15), mOS was 14 months. Of note, mOS was 12 months among the 12 subjects with liver metastases at baseline, a clinically challenging feature in mCRC.

Next Steps

These results support continued development of RBS2418. RBS2418 is being evaluated in two ongoing Phase 2 studies: as monotherapy in late-line mCRC (NCT06824064), and in combination with the STRIDE regimen (tremelimumab plus durvalumab) as first-line treatment for hepatocellular carcinoma (NCT07175441).

About RBS2418

RBS2418 is oral, small-molecule inhibitor of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and the first ENPP1 inhibitor to enter clinical trials. It binds ENPP1 with picomolar affinity and high selectivity. ENPP1 is an innate immune checkpoint that regulates cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), an immune signaling molecule produced by cyclic GMP-AMP synthase (cGAS). ENPP1 upregulation is common in solid tumors and is associated with immune evasion, an immunologically cold tumor phenotype, disease progression, metastasis and non-response to checkpoint inhibitors. By inhibiting ENPP1, RBS2418 is designed to protect extracellular cGAMP and restore antitumor immune activation.

RBS2418 is being evaluated in a Phase 1a/b trial in advanced solid tumors (NCT05270213); as monotherapy in a Phase 2 trial in late-line mCRC (NCT06824064); and in combination with the STRIDE regimen (tremelimumab with durvalumab), in a Phase 2 trial as first-line treatment for hepatocellular carcinoma (NCT07175441).

About Riboscience

Riboscience is a privately held, clinical-stage biotechnology company based in Palo Alto, California. The company applies structure-guided design and carbohydrate chemistry to develop selective drug candidates for cancer, joint and infectious diseases. Riboscience has brought the first ENPP1 inhibitors into clinical development. For more information, visit www.riboscience.com.

Contact

Klaus Klumpp, Co-Founder and President, Riboscience
[email protected]

SOURCE Riboscience LLC