# IND enabling development of LGM2605 as adjuvant treatment for asthma

> **NIH NIH R42** · LIGNAMED, LLC · 2020 · $1,000,000

## Abstract

Project summary
IND enabling development of LGM2605 as adjuvant treatment for asthma
Glucocorticoid resistance is a major treatment problem in asthma. Our recent studies in mice, non-human
primates and severe asthma patients, along with reports by others suggest that glucocorticoid receptor (GR)
expression was impaired by psychosocial stress, in association with enhanced NF-kB activation and
glucocorticoid non-responsiveness of immune cells. This Phase II STTR proposal was developed jointly between
LignaMed (Dr. Sielecki), UPenn (Dr. Christofidou-Solomidou and UC Davis (Dr. Haczku) based on our results
generated by the Phase I STTR project. Our study strongly suggested that LGM2605, a racemic synthetic form
of a novel, natural, non-toxic, anti-inflammatory component of flaxseed, secoisolariciresinol diglucoside (SDG)
may be effective to treat severe asthma exacerbation induced by inhalation of ozone. LGM2605 is a racemate
which has proven free radical scavenging activities in vitro and in vivo and it induces activation of nuclear factor
erythroid 2-related factor 2 (NRF2) a major anti-oxidant transcription regulator and inhibitor of NF-kB. As part of
assembling an IND package we will complete a pivotal proof of concept study using rhesus macaques, because
of their phylogenetic proximity to humans with a high degree of immune crossreactivity and a predisposition to
spontaneously develop both asthma and psychosocial stress. Our exciting preliminary results from stressed
asthmatic macaques treated with LignaMed’s LGM2605 demonstrated a significant suppression of airway
inflammation and it abolished airway hyperresponsiveness (AHR) in response to ozone exposure. We
hypothesize that LGM2605 alleviates asthma symptoms by interfering with activation of immune and airway
structural (epithelial and smooth muscle) cells and improving glucocorticoid responsiveness through activation
of NRF2 gene expression and downstream anti-oxidant pathways. Aim 1. Assess the mechanism of action
and dose-dependent effects of LGM2605 treatment on regulation of the GR, NF-kB and NRF2 expression
and glucocorticoid responsiveness in vitro. Aim 2. A. Scale up and definition of release specifications
of the single isomer of LGM2605; B. Pharmacokinetic evaluation of the single isomer of LGM2605 in non-
human primates (rhesus macaques). Aim 3. Study the dose-dependent effects of single isomer LGM2605
on preventing AHR, immune cell activation and improving glucocorticoid responsiveness in ozone-
exposed rhesus macaques. Our translational approach using rhesus macaques (in vivo clinical testing) and
cells from severe asthma patients (in vitro mechanistic studies on cell types relevant to asthma) will establish
how LGM2605 affects glucocorticoid responsiveness and will lay the groundwork for subsequent human clinical
trials.

## Key facts

- **NIH application ID:** 9983557
- **Project number:** 5R42AI132012-03
- **Recipient organization:** LIGNAMED, LLC
- **Principal Investigator:** ANGELA HACZKU
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,000,000
- **Award type:** 5
- **Project period:** 2017-07-18 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983557

## Citation

> US National Institutes of Health, RePORTER application 9983557, IND enabling development of LGM2605 as adjuvant treatment for asthma (5R42AI132012-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9983557. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*