# Advancing a novel potent double anti-HCV nucleoside analog combination treatment for the OUD population to the clinic

> **NIH NIH R44** · RIBOSCIENCE, LLC · 2020 · $995,102

## Abstract

Our goal is to develop an ultra short curative regimen for hepatitis C virus (HCV) infection in OUD patients.
HCV is a major co-morbidity of many OUD patients. Treating their HCV reduces their subsequent IV drug use.
While currently available regimens can cure HCV in most patients in 8-12 weeks, longer in patients with
advanced liver disease or drug resistance mutations that are more frequent in OUD patients, when these same
regimens are used for just 4 weeks, most patients fail and they develop drug resistance mutations. Ultra short
treatment regimens with high cure rates are not currently achievable, nor can they be anticipated with any of
the drugs on the market or in development. We now seek to leverage our exciting “SBIR Phase 1 equivalent”
research results into a novel double nucleoside-based treatment for HCV in OUD patients. Our overall
hypothesis is that Riboscience’s unique and highly synergistic double nucleoside (nuc) regimen (RBS1154, a
uridine monophosphate prodrug that is more potent than Gilead’s sofosbuvir + RBS1502, an equally superior
cytidine mono-phosphate prodrug) will cure patients with just one prescription in 4 weeks or less (most
probably in 1-2 weeks, but those who don’t get cured can simply be treated a bit longer—as their is no risk of
resistance with an all nucleoside regimen). Such a double nuc combo will have a major impact with respect to
the supportive care of a large segment of the OUD population--accelerating time to cure of a frequent major
comorbidity, reducing the risk of HCV spread to other OUD patients, and decreasing IV drug use. To test
our hypothesis, and enable clinical studies of our double nucleoside combo in OUD patients, we seek to
accomplish the following specific aims: 1) complete critical chemistry and manufacturing (CMC) and virology
activities by: a) finishing RBS1502’s process chemistry and synthesize 1 Kg non-GMP of each nuc for non-
GLP tox studies; b) complete primary pharmacology package (virology); 2) enable IND-enabling GLP toxicity
studies by: a) synthesizing 15 Kg of GMP API of each nucleoside to support GLP tox and Phase 1 studies; b)
develop analytical methods to support ADME and toxicity studies; 3) Perform in vitro and in vivo
characterizations to enable GLP toxicity studies by: a) completing primary and secondary pharmacology
characterizations for the U and C analogs in line with FDA guidances, including PK and in vitro and in vivo
ADME studies; b) performing dose-range finding non-GLP toxicity studies for the U and C analogs; 4) complete
data package to support IND filing by performing: a) 8-wk GLP toxicity studies for U and C and 4-wk U+C
combination toxicity study; b) GLP safety pharmacology (respiratory, CV, CNS) and genotoxicity studies.
Successful accomplishment of our aims will have a major impact on the supportive care of OUD patients.
Our novel double nucleoside approach can yield the most convenient, safest, ultra short treatment option for
HCV-infected OUD patients. Th...

## Key facts

- **NIH application ID:** 10013182
- **Project number:** 5R44DA050368-02
- **Recipient organization:** RIBOSCIENCE, LLC
- **Principal Investigator:** Klaus Klumpp
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $995,102
- **Award type:** 5
- **Project period:** 2019-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10013182

## Citation

> US National Institutes of Health, RePORTER application 10013182, Advancing a novel potent double anti-HCV nucleoside analog combination treatment for the OUD population to the clinic (5R44DA050368-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10013182. Licensed CC0.

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