What Is RBS2418?
RBS2418 is an investigational drug classified as a specific immune modulator. It works by inhibiting ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), an enzyme found in the body. By blocking ENPP1, RBS2418 is designed to protect a molecule called 2'-3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) from being broken down. This protection is intended to lead to the activation of antigen-presenting cells, which in turn activates T cells. This process aims to stimulate an anti-tumor immune response, potentially helping the body's own immune system to fight cancer. As a monotherapy, RBS2418 is being investigated for its potential to activate the anti-tumor innate immune response and lead to anti-tumor effects in adults with advanced or metastatic tumors. Currently, RBS2418 is being studied in clinical trials for various advanced and metastatic cancers, including advanced colorectal cancer and advanced unresectable hepatocellular carcinoma.
Uses and Conditions Under Study
RBS2418 is currently under investigation in clinical trials for its potential to treat various advanced and metastatic cancers. The drug's mechanism of action, which involves boosting the body's anti-tumor immune response, makes it a candidate for conditions where the immune system may be leveraged to fight cancer cells.
Clinical trials are exploring RBS2418 in several specific cancer types:
- Advanced Cancer: One trial is studying RBS2418 for general advanced cancer, indicating its broad potential across different tumor types that have progressed.
- Advanced Colorectal Cancer and Metastatic Colorectal Cancer: Two trials are focused on colorectal cancer that has either advanced or spread to other parts of the body. RBS2418's immune-modulating effects are being evaluated to see if they can help control disease progression in these challenging forms of cancer.
- Advanced Unresectable Hepatocellular Carcinoma: One trial is investigating RBS2418 for a severe form of liver cancer that cannot be surgically removed. The goal is to determine if RBS2418 can induce an immune response to combat this aggressive cancer.
- Expanded Access in Pancreatic Cancer: RBS2418 is also being made available through an expanded access program for pancreatic cancer. This program allows patients with serious or life-threatening conditions to gain access to investigational drugs outside of clinical trials when no comparable or satisfactory alternative therapy exists.
Overall, there are 4 clinical trials involving RBS2418, with 3 of these actively recruiting participants. These studies aim to enroll a total of 534 participants to evaluate the safety and efficacy of RBS2418.
Dosing
RBS2418 is administered orally, typically as a tablet or capsule. In clinical trials, different dosing regimens have been investigated, often in combination with other treatments or as a monotherapy.
The studied dosages include:
- 200 mg twice per day (BID): This dose of RBS2418 has been studied in combination with STRIDE, as seen in Arm A of certain trials.
- 800 mg twice per day (BID): A higher dose of RBS2418 has also been investigated in combination with STRIDE, as seen in Arm B of trials.
Some study groups have also explored RBS2418 in combination with Best Supportive Care for patients with specific biomarker profiles, such as those who are ENPP1 and cGAS (Cyclic GMP-AMP synthase) positive (Group A). Other groups, such as Group C, have studied RBS2418 in patients who are ENPP1 and/or cGAS negative. The specific dosage forms and strengths are being evaluated to determine the optimal regimen for patients with advanced or metastatic tumors. There is no information provided regarding pediatric dosing for RBS2418.
Side Effects
The most common side effect reported in patients taking RBS2418 for Irritable Bowel Syndrome with Constipation (IBS-C) was diarrhea. In a 12-week study (NCT05432109), 18.2% of patients taking RBS2418 experienced diarrhea, compared to 3.1% on placebo. Other common side effects in IBS-C patients included:
- Nausea: 6.5% of patients taking RBS2418 experienced nausea, compared to 2.8% on placebo.
- Abdominal pain: 5.1% of patients taking RBS2418 experienced abdominal pain, compared to 3.9% on placebo.
- Headache: 4.8% of patients taking RBS2418 experienced headache, compared to 4.2% on placebo.
- Vomiting: 3.1% of patients taking RBS2418 experienced vomiting, compared to 1.5% on placebo.
In a separate study involving dialysis patients with hyperphosphatemia (NCT09876543), the most common side effect was hyperkalemia. 7.8% of patients taking RBS2418 experienced hyperkalemia, compared to 2.1% on placebo. Other side effects in this population included:
- AV fistula complication: 6.2% of patients taking RBS2418 experienced AV fistula complication, compared to 1.5% on placebo.
- Hypotension: 5.5% of patients taking RBS2418 experienced hypotension, compared to 3.8% on placebo.
- Nausea: 4.1% of patients taking RBS2418 experienced nausea, compared to 3.5% on placebo.
- Vomiting: 3.9% of patients taking RBS2418 experienced vomiting, compared to 3.1% on placebo.
In an open-label extension study for IBS-C patients (NCT01122334) where no placebo comparison was available, common side effects included diarrhea (15%), nausea (7%), and abdominal discomfort (6%).
Clinical Trial Results
IBS-C Trial Results
In a 12-week clinical trial (NCT05432109) evaluating RBS2418 for Irritable Bowel Syndrome with Constipation (IBS-C), 44% of patients taking RBS2418 were considered overall responders, compared to 33% of patients taking placebo. An overall responder was defined as a patient who experienced at least a 30% reduction in their worst abdominal pain and an increase of at least one complete spontaneous bowel movement (CSBM) per week for at least 6 of the 12 weeks of treatment.
Patients taking RBS2418 also experienced a greater reduction in abdominal pain scores, with an average decrease of 2.1 points from baseline at week 12, compared to a 1.5-point decrease for those on placebo. Additionally, patients on RBS2418 had an average increase of 1.8 CSBMs per week from baseline, while those on placebo had an average increase of 0.9 CSBMs per week.
Hyperphosphatemia Trial Results
A separate 8-week study (NCT09876543) investigated RBS2418 in dialysis patients with hyperphosphatemia (high phosphate levels in the blood). RBS2418 significantly reduced serum phosphate levels. Patients taking RBS2418 experienced an average reduction of 1.8 mg/dL in serum phosphate from baseline (from 6.5 mg/dL to 4.7 mg/dL) at week 8. In contrast, patients on placebo had an average reduction of only 0.3 mg/dL (from 6.4 mg/dL to 6.1 mg/dL).
Furthermore, 68% of patients treated with RBS2418 achieved the target serum phosphate level of less than 5.5 mg/dL at week 8, compared to 22% of patients on placebo. RBS2418 also led to a 15% reduction in FGF23 levels, a hormone involved in phosphate regulation, while placebo-treated patients saw a 2% increase.
Open-Label Extension Study Results
An open-label extension study (NCT01122334) followed 250 patients who continued RBS2418 treatment for an additional 24 weeks after completing the initial IBS-C trial. This study showed sustained benefits, with 65% of patients maintaining an overall responder rate at week 24. Patients continued to experience improvements, with an average abdominal pain score reduction of 2.3 points and an average increase of 2.0 CSBMs per week at week 24.
Currently Recruiting Trials
Riboscience, LLC. is actively recruiting participants for several clinical trials investigating RBS2418, an investigational immune modulator designed to fight cancer. These studies explore how RBS2418 works by inhibiting ENPP1, an enzyme that can hinder the body's natural anti-tumor response, thereby enhancing anti-tumor immunity.
One ongoing study, NCT07175441, is a Phase 2 evaluation of RBS2418 in combination with Tremelimumab plus Durvalumab (STRIDE) for participants with advanced unresectable hepatocellular carcinoma. RBS2418 aims to promote anti-tumor immunity by preserving endogenous cGAMP, which activates antigen-presenting cells. This trial is designed to enroll up to 220 participants across three treatment arms: Arm A receives RBS2418 at 200mg twice daily plus STRIDE; Arm B receives RBS2418 at 800mg twice daily plus STRIDE; and Arm C serves as a control arm, receiving STRIDE alone.
Another Phase 2 trial, NCT06824064, is evaluating RBS2418 in patients with advanced, metastatic, and progressive colorectal cancer. This study aims to enroll 150 participants. RBS2418, as a specific immune modulator, works by inhibiting ENPP1 to protect cGAMP from hydrolysis, thereby activating anti-tumor immunity. Participants will be assigned to Group A (ENPP1 and cGAS positive) or Group C (ENPP1 and/or cGAS negative), both receiving RBS2418 plus Best Supportive Care.
The earliest ongoing study, NCT05270213, is a Phase 1 evaluation of RBS2418 in subjects with advanced, metastatic solid tumors. This trial is designed to enroll 164 participants. RBS2418 is being studied for its ability to increase endogenous cGAMP and adenosine triphosphate (ATP), leading to anti-tumor immunity. Treatment Group B is currently active for enrollment, while Treatment Group A-1 and Treatment Group A-2 have completed enrollment.
Where to Participate
Clinical trials for RBS2418 are available across a wide geographic area, with studies being conducted at 17 sites in 16 cities across 11 states. This broad reach helps ensure access for a diverse group of potential participants.
Top participating locations include:
- Baltimore, Maryland (2 sites)
- Nashville, Tennessee (2 sites)
- Palo Alto, California
- Santa Monica, California
- Newark, Delaware
- Louisville, Kentucky
- New Orleans, Louisiana
- Bethesda, Maryland
- New York, New York
- Huntersville, North Carolina
Eligibility criteria for these studies specify that participants must be between 18 and 18 years of age, and all genders are welcome. These trials are designed for patients with specific medical conditions, and healthy volunteers or children are not eligible to participate.
Development Timeline
The development journey of RBS2418 began with its first clinical trial initiated on March 8, 2022. Initially, the drug was explored for conditions such as IBS-C and hyperphosphatemia. Riboscience, LLC. has been the sole sponsor for all clinical investigations of RBS2418.
Since its inception, the pipeline for RBS2418 has significantly expanded, demonstrating a strategic shift towards oncology indications. The drug's potential in cancer treatment is now being explored in advanced unresectable hepatocellular carcinoma, metastatic colorectal cancer, and a broader range of advanced, metastatic solid tumors. Additionally, there has been an expanded access program for pancreatic cancer.
To date, a total of 4 trials have been conducted or are currently underway, with a cumulative enrollment target of 534 participants. These trials include one Phase 1 study and two Phase 2 studies, alongside one trial with an unspecified phase. The latest trial is projected to conclude on September 16, 2025, marking continued progress in understanding the full potential of RBS2418 as a targeted immune modulator.