RBS2418 / Riboscience - LARVOL DELTA

Phase 2a, Randomized, Open-Label Study of RBS2418 in Combination With Tremelimumab Plus Durvalumab in Advanced Unresectable Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=220 | Not yet recruiting | Sponsor: Riboscience, LLC.

New P2 trial • Hepatocellular Cancer • Oncology • Solid Tumor

Evaluation of RBS2418 in Subjects With Advanced, Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=164 | Recruiting | Sponsor: Riboscience, LLC. | N=64 ➔ 164 | Trial completion date: Oct 2025 ➔ Dec 2027 | Trial primary completion date: Sep 2025 ➔ Apr 2027

Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Completed phase 1a dose escalation study of the first oral ENPP1 inhibitor RBS2418 immunotherapy in subjects with metastatic solid tumors. (ASCO 2025) - P1 | "The Ph1a dose escalation study with oral RBS2418 alone, and with pembrolizumab has been completed. All doses were safe and well tolerated with no grade 3 TRAEs, SAEs or DLTs. RBS2418 plasma concentrations enabling full cGAMP protection was observed in all patients at all dose levels."

Clinical • IO biomarker • Metastases • P1 data • Colorectal Cancer • Fatigue • Oncology • Solid Tumor • CGAS • ENPP1

VISTA-1: Evaluation of RBS2418 in Patients with Advanced, Metastatic, and Progressive Colorectal Cancer (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Riboscience, LLC.

New P2 trial • Colorectal Cancer • Oncology • Solid Tumor

Safety, PK, immune activation, and clinical outcomes with RBS2418 treatment, an oral ENPP1 inhibitor, alone or in combination with pembrolizumab in advanced solid tumors (ESMO 2024) - P1 | "Oral RBS2418 alone or with pembrolizumab is safe and well tolerated in pts with a wide range of advanced solid tumors at exposures consistent with >90% target inhibition in tumors and plasma. Immune activation and treatment benefit correlated with baseline EG+ phenotype in tumors, and occurred in pts with cold tumor phenotype at baseline."

Clinical • Clinical data • Combination therapy • IO biomarker • Metastases • Oncology • Solid Tumor • CD8 • CGAS • ENPP1

Evaluation of RBS2418 in Subjects With Advanced, Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Riboscience, LLC. | Trial completion date: Jul 2025 ➔ Oct 2025 | Trial primary completion date: Jun 2025 ➔ Sep 2025

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Correlation of baseline ENPP1 and cGAS expression in advanced solid tumors with intratumoral immune activation and clinical outcomes after treatment with the first-in-class oral ENPP1 inhibitor RBS2418, alone or in combination with pembrolizumab. (ASCO 2024) - P1 | "Oral RBS2418 alone or with pembrolizumab has been safe, well tolerated with no DLTs at all dose levels evaluated to date in the ongoing Ph1 dose escalation and expansion study. The robust PK profile shows plasma levels enabling complete ENPP1 inhibition at all time points. Immune activation and observed clinical benefit of treatment in late line treatment of refractory metastatic solid tumors such as CRC and HCC was associated with baseline ENPP1 and cGAS protein expression in tumors."

Clinical • Clinical data • Combination therapy • IO biomarker • Metastases • Oncology • Solid Tumor • CGAS • ENPP1

Evaluation of RBS2418 in Subjects With Advanced, Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Riboscience, LLC. | Trial completion date: Mar 2025 ➔ Jul 2025 | Trial primary completion date: Feb 2025 ➔ Jun 2025

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Inhibition of ENPP1 catalyzed ATP and cGAMP hydrolysis and in vivo antitumor efficacy of RBS2418 in the Hepa1-6 and GL261-luc syngeneic liver and glioblastoma mouse models (AACR 2024) - "RBS2418 inhibited ATP and cGAMP hydrolysis by ENPP1 with similar high potency. The pharmacology profile was optimized to achieve low serum protein binding and oral bioavailability in humans. RBS2418 treatment was well tolerated in mice under conditions where tumor and plasma levels exceeding ENPP1 serum EC90 levels were achieved."

Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • ENPP1

RBS2418 Evaluation in Subjects With Unresectable or Metastatic Tumors (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Riboscience, LLC. | Trial completion date: Jan 2024 ➔ Feb 2025 | Trial primary completion date: Jan 2023 ➔ Jan 2025

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Oncology

Preliminary safety, pharmacokinetics and immunomodulatory activity of RBS2418, an oral ENPP1 inhibitor, alone and in combination with pembrolizumab in patients with solid tumors (ESMO 2023) - P1 | "The PK profile showed plasma levels enabling complete ENPP1 inhibition. Preliminary analyses support the hypothesis that ENPP1 and cGAS co-expression in tumors correlates with RBS2418 treatment associated immune activation and prolonged disease stabilization suggestive of clinical benefit in multiple patients with refractory malignancies including MSS CRC and HCC (NCT05270213)."

Clinical • Combination therapy • Immunomodulating • PK/PD data • Oncology • Solid Tumor • CGAS

RIBOSCIENCE ESMO PRESENTATION HIGHLIGHTS SAFETY, PK, PD AND EFFICACY DATA FROM THE FIRST 19 PATIENTS OF THE ENPP1 INHIBITOR RBS2418 PHASE 1 STUDY (PRNewswire) - P1a/b | N=64 | NCT05270213 | Sponsor: Riboscience, LLC. | "Riboscience, LLC, today announced the first presentation of data from the ongoing Phase 1 clinical trial of the ENPP1 inhibitor RBS2418...at the European Society for Medical Oncology (ESMO) Congress 2023....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....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."

P1 data • PK/PD data • Solid Tumor

Immunomodulatory effects of RBS2418, an oral ENPP1 inhibitor in combination with pembrolizumab in checkpoint-refractory metastatic adrenal cancer (ESMO-IO 2022) - P1 | "RBS2418 PK data showed excellent oral bioavailability with plasma levels leading to complete ENPP1 inhibition. RBS2418 induced increases in peripheral cDCs, proliferation of CD4 and CD8 T cells and expansion of TCR clonotypes as well as upregulation of T cell cytotoxic granule protein gene expression supporting clinical development of this novel first-in-class immunotherapy agent in an ongoing clinical trial (NCT05270213)."

Combination therapy • IO biomarker • Adrenal Cortex Carcinoma • Endocrine Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CD4 • CD8 • GZMB • PRF1

First-in-human experience using RBS2418, an oral ENPP1 inhibitor within an expanded access protocol in combination with pembrolizumab in a patient with metastatic adrenal cancer. (ASCO 2022) - "RBS2418 with pembrolizumab was safe and well tolerated and no drug-related safety concerns were reported. The pharmacokinetics of RBS2418 showed excellent oral bioavailability, with plasma levels of RBS2418 > 17-fold and > 40-fold above serum EC90 of ENPP1 at the 100 and 200 mg BID dose levels, respectively. Dose levels are further studied in the current Phase 1 trial."

Clinical • Combination therapy • IO biomarker • P1 data • Adrenal Cortex Carcinoma • Endocrine Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

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) (ESMO-IO 2022) - P1 | "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."

Clinical • Combination therapy • Monotherapy • P1 data • Adrenal Cortex Carcinoma • Endocrine Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Expanded Access to RBS2418 (clinicaltrials.gov) - P=N/A | N=N/A | Available | Sponsor: Riboscience, LLC.

New trial • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Riboscience ESMO I/O Presentations Highlight RBS2418 Phase 1 Study Design and the First Human Data From the Evaluation of an ENPP1 Inhibitor for Immune Activation (Newswire) - P1 | N=64 | NCT05270213 | Sponsor: Riboscience, LLC. | "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."

P1 data • Oncology • Solid Tumor

Riboscience ESMO I/O Presentations Highlight RBS2418 Phase 1 Study Design and the First Human Data From the Evaluation of an ENPP1 Inhibitor for Immune Activation (Newswire) - "Abstract #195TiP outlines the trial design for the Phase 1 clinical evaluation of orally administered RBS2418, a potent and selective ENPP1 inhibitor. 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."

Clinical protocol • Oncology • Solid Tumor

RBS2418 Evaluation in Subjects With Unresectable or Metastatic Tumors (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Riboscience, LLC. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Monotherapy • Immune Modulation • Oncology