# Advancing a broad-spectrum anti-influenza A virus RNA packaging inhibitor to an IND

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $745,482

## Abstract

Our goal is to leverage our collective academic and industry experience in antiviral research and
development to advance an exciting novel inhibitor with broad-spectrum activity against the influenza A virus
(IAV) Priority Pathogen—towards an IND. Our lead molecule, LNA9, is a short 15 base locked nucleic acid
(LNA) “gapmer” that specifically targets an essential IAV packaging signal composed of a unique RNA second-
ary structure that we recently discovered and found to be conserved across all examined subtypes of IAV,
including 1918 pandemic flu, high path avian (H5N1) and 2009 `swine' (H1N1). LNA9 has a nuclease-resistant
phosphorothioate backbone and an internal RNAse H activating sequence that is designed to catalytically
disrupt and degrade its target IAV packaging signal. In vitro, LNA9 dramatically inhibits IAV packaging at nM
concentrations when added before or after infection, and in vivo, intranasal (IN) administration of LNA9 at -12,
8, and 36 hours post infection completely prevents IAV lethality in mice. We now seek to develop LNA9 into a
clinical stage drug by: 1) Further expanding the virology data package by a) demonstrating activity against
additional highly pathogenic and drug resistant strains of IAV; b) providing additional evidence for LNA9's high
barrier to the development of resistance compared to other direct-acting antivirals in vitro and in vivo; c)
determining the minimum in vivo effective dose, and number of days before or after infection that LNA9
administration can rescue from influenza mortality; and d) demonstrating LNA9's efficacy in second validated
ferret model, including prevention of transmission: 2) Enabling the optimal delivery and monitoring methods for
in vivo preclinical studies by: a) demonstrating the in vivo efficacy of IV delivery to complement the currently
proven IN route; b) establishing the analytical methods to monitor the distribution and clearance kinetics of
LNA9 following in vivo administration; and c) performing mouse, rat, and dog single dose PK studies via IN and
IV routes; 3) Manufacturing LNA9 to support the requisite IND-enabling and initial clinical studies by a)
synthesizing 5g of non-GMP LNA9, and 10g of GMP LNA9; and b) performing the final release/stability studies
of the product (API); 4) Performing initial in vitro ADME-Tox and preclinical animal safety testing; and 5)
Completing the IND-enabling GLP safety pharmacology and multiple dose 14-day escalation rodent and non-
rodent toxicity studies, a clinical development plan, and pre-IND meeting package.
 Our multidisciplinary team--including academics and industry partners with demonstrated expertise in
virology, influenza biology, oligonucleotide chemistry, pulmonary formulation and delivery, regulatory affairs,
and successful early drug development—is ideally suited for this proposal. Successful accomplishment of our
specific aims will yield an exciting novel drug capable of conferring protection against this key Priority
Pathog...

## Key facts

- **NIH application ID:** 10165884
- **Project number:** 3R01AI132191-04S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** JEFFREY S GLENN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $745,482
- **Award type:** 3
- **Project period:** 2020-05-05 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165884

## Citation

> US National Institutes of Health, RePORTER application 10165884, Advancing a broad-spectrum anti-influenza A virus RNA packaging inhibitor to an IND (3R01AI132191-04S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10165884. Licensed CC0.

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