# Optimization of LGM2605 for use as a device in lung transplant

> **NIH NIH R44** · LIGNAMED, LLC · 2020 · $1,440,044

## Abstract

LignaMed, LLC is developing a novel small molecule device, LGM2605, that will be utilized and administered
via FDA approved ex vivo lung perfusion (EVLP), to improve lung function parameters of ex vivo donor lungs in
advance of transplant surgery. Per FDA device regulations LGM2605 will be fully cleared from the donor lung
prior to transplant. This work supports the efforts of the NHLBI to promote the prevention and treatment of
lung diseases and enhance the health of individuals to live longer and more fulfilling lives, and also addresses
an NHLBI stated goal of expanding the donor lung pool. Chronic lung diseases affect 35 million Americans and
result in almost 400,000 deaths annually. Lung transplantation is the only life-saving therapy for patients with
certain types of end-stage lung disease. However, the procedure has limited availability because not all donor
lungs are safe for transplantation. This shortage of donor lungs results in the death of 20 percent of lung
transplant candidates awaiting transplant. This shortage arises in part from damage to donor lungs prior to and
during preservation due to generation of reactive oxygen species (ROS) and subsequent oxidative lung tissue
damage. This damage is also linked to eventual primary graft dysfunction (PGD) after transplantation. PGD
arises from ischemia/reperfusion (I/R) Injury associated with storage and transplant maneuvers. Allograft
quality combined with ROS and other oxidants produced with I/R lead to direct damage that decreases the
pool of transplantable lungs. Thus, blocking ROS is a critical step in reducing ROS-induced damage.
LignaMed's novel device works through a unique three-prong mode of action to impact reactive ROS via a)
direct free radical scavenging, b) activation of the Nrf2/antioxidant response element (ARE) pathway and c)
decrease of ROS production via inhibition of inflammasome and inflammatory cell influx (neutrophils /
macrophages) . LGM2605 has excellent drug-like properties including desirable physiochemical properties and
oral bioavailable. PK/PD studies in mouse and non-human primates have shown good oral, intravenous and
subcutaneous distribution while studies in the EVLP model show excellent exposure to lung tissue with
aerosolized drug. When administered to mice, LGM2605 prevented radiation-induced lung inflammation and
fibrosis and improved lung function parameters and arterial blood oxygenation. Moreover when administered
via EVLP in pilot studies run in collaboration with Dr. Christie's group at the University of Pennsylvania,
LGM2605 significantly improved/rehabilitated lung function parameters in donor lungs that previously failed to
meet “transplant viable” acceptance criteria. In this Fast-track SBIR proposal, our Phase I aims will focus to
characterize the kinetics of inhaled LGM2605. In Phase II we will validate the magnitude of the effect and
determine safety in an expanded patient population. LignaMed has submitted a background and meeting
requ...

## Key facts

- **NIH application ID:** 9764840
- **Project number:** 4R44HL140680-02
- **Recipient organization:** LIGNAMED, LLC
- **Principal Investigator:** Jason D Christie
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,440,044
- **Award type:** 4N
- **Project period:** 2018-09-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9764840

## Citation

> US National Institutes of Health, RePORTER application 9764840, Optimization of LGM2605 for use as a device in lung transplant (4R44HL140680-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9764840. Licensed CC0.

---

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