# Development of a first-in-class antiviral to address CMV drug resistance in immunocompromised patients

> **NIH NIH R42** · VXBIOSCIENCES, INC. · 2023 · $300,000

## Abstract

ABSTRACT
Human cytomegalovirus (CMV) infects a majority of the world’s population and is a leading cause of disease in
transplant patients and newborns, accounting for more congenital birth defects than Down’s syndrome, spina
bifida, or fetal alcohol syndrome. There is no approved vaccine and all current antiviral therapies for CMV
prevention or treatment suffer from toxicity and a low barrier to the evolution of resistance. Consequently, there
is an urgent unmet medical need for effective CMV antivirals that have a high barrier to the evolution of drug
resistance. The mission of VxBiosciences is to develop escape-resistant or resistance-proof therapeutics. The
long-term goal of this work is to develop and clinically translate a first-in-class antiviral that effectively overcomes
CMV antiviral resistance. The specific objectives of this proposal are: (i) to establish in vivo efficacy and dosing
of a first-in-class ‘escape-resistant’ nucleic-acid lipid nanoparticle (LNP) that targets viral transcriptional circuitry
via use of an animal-specific analog (i.e., ‘surrogate’); and (ii) to develop a GMP-grade formulation of the drug
product to enable collection of IND-enabling GLP-toxicology data. The proposed antiviral builds off our studies
mapping an essential transcriptional feedback circuit in CMV (Teng et al. 2012; Vardi et al. 2018; Chaturvedi et
al. 2020), our work isolating feedback disruptors (FD) molecules that inhibit CMV (Chaturvedi et al. 2022), and
recent data showing the systemic delivery of the drug product inhibits CMV in multiple organs in mice, and halts
systemic disease to dramatically increase survival of infected immunocompromised mice. These extensive
preliminary data establish proof-of-concept that the FD drug substance displays strong CMV antiviral efficacy in
vitro and in vivo and have a very high genetic barrier to the evolution of resistance. The rationale for the LNP-
FD drug product approach rests upon FDA-approval and safety profiles of LNP nanomedicines (e.g., Onpattro)
and our successful development of LNP-based drug products for other viruses. Based on our extensive
preliminary data, our central hypothesis is that LNP-FDs will constitute a safe, effective antiviral strategy with a
high barrier to the evolution of resistance. The proposal’s rigor rests upon our published studies, our GMP-
production expertise, and our experience shepherding first-in-class antivirals through the FDA to clinical trials.
The Phase-I specific aims will evaluate efficacy and safety in vivo using a surrogate molecule (based on existing
FDA precedent for use of surrogates) and the expected outcome is reduced CMV disease and improved survival
in this physiologically-relevant model. Phase-II specific aims will establish of GMP-grade production of the
antiviral and collect IND-enabling data. The payoff of these studies will be to establish feasibility of a first-in-
class nanomedicine targeting transcriptional circuitry and demonstrate that such ...

## Key facts

- **NIH application ID:** 10766598
- **Project number:** 1R42AI174554-01A1
- **Recipient organization:** VXBIOSCIENCES, INC.
- **Principal Investigator:** Robert Rodick
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2023-09-12 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10766598

## Citation

> US National Institutes of Health, RePORTER application 10766598, Development of a first-in-class antiviral to address CMV drug resistance in immunocompromised patients (1R42AI174554-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10766598. Licensed CC0.

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