# Aerosolized Vitamin A: Impact on Neonatal Lung Maturation, Hyperoxic Lung Injury and Bronchopulmonary Dysplasia

> **NIH NIH R44** · ADVENT THERAPEUTICS, INC. · 2021 · $1,270,686

## Abstract

Advent Therapeutics Inc. (Advent) is a biotech company focusing on the development, reformulation and
optimized delivery of legacy drugs to address serious unmet medical needs in the underserved neonatal and
pediatric patient populations. Advent is developing an aerosol formulation of its proprietary, optimized water
miscible vitamin A (vitA) palmitate for non-invasive (inhaled) delivery to preterm infants to address vitA deficiency
(VAD) and associated serious complications such as bronchopulmonary dysplasia (BPD, the focus of our Phase
I SBIR and this Phase II application), retinopathy of prematurity (ROP), and neonatal sepsis – all costly
complications with significant morbidity/mortality. Our innovative inhaled (non-invasively dosed) vitA formulation
1) avoids the drawbacks of invasive intramuscular (IM) injections and absorption limitations of current oral forms,
overcoming significant hurdles to more frequent NICU utilization, and 2) provides direct-to-target-organ delivery
for increased efficacy, with our Phase I in vivo data showing significant benefit over IM dosing in mitigating
hyperoxic lung damage (our BPD animal model), while providing adequate systemic delivery to also treat VAD.
 In collaboration with Dr. Virender Rehan at Harbor-UCLA Medical Center, we have accomplished our Phase
I Specific Aims, demonstrating that: 1) inhaled vitA stimulates lung maturation as demonstrated via assay of lung
biomarkers showing upregulation of retinol receptors, surfactant protein and phospholipid synthesis, and
maturation biomarkers while simultaneously raising serum vitA levels similar to IM dosing; and 2) inhaled vitA
dramatically (vs IM) reduces hyperoxic lung tissue damage via examination of lung tissue histomorphometry and
reduction of lung-injury biomarkers.
 In Phase II, we will further refine the inhaled vitA dosing strategy for mitigating hyperoxic lung damage in a
step-wise approach by studying the well characterized pre-weaned rat model as in Phase I and then expanding
our studies to a pre-term rabbit model, with lung maturation status more closely mimicking human preterm infant
lung to allow for translation of our findings into the clinical. Phase II Specific Aims are: 1: Optimize the dosing
regimen of aerosolized vitA for mitigating hyperoxic lung damage in our rat model for the “neonatal” timeframe
(acute phase) and long term sequalae into adulthood (chronic phase) using similar biomarkers and morphologic
evaluation as per Phase I. Aim 2: Extend acute and chronic phase benefits of inhaled vitA to the premature
rabbit model. Aim 1 & 2 measures of success will be demonstration of improved lung maturation and mitigation
of lung injury vs IM-dosed controls, with an ideal outcome of showing lung status similar to healthy normal
controls. Aim 3: Optimize aerosol characterization/delivery (initial in vitro experiments done concurrent with Aim
1), and subsequently conduct in vivo IND-enabling toxicology/PK studies. Aim 3 measures of success...

## Key facts

- **NIH application ID:** 10238056
- **Project number:** 5R44HL142353-03
- **Recipient organization:** ADVENT THERAPEUTICS, INC.
- **Principal Investigator:** Craig Gelfand
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,270,686
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-03-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10238056

## Citation

> US National Institutes of Health, RePORTER application 10238056, Aerosolized Vitamin A: Impact on Neonatal Lung Maturation, Hyperoxic Lung Injury and Bronchopulmonary Dysplasia (5R44HL142353-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10238056. Licensed CC0.

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