# Extracellular NAMPT is a Novel Therapeutic Target in Chorioamnionitis-Related Prematurity (ChorP)

> **NIH NIH R41** · AQUALUNG THERAPEUTICS CORP. · 2020 · $265,096

## Abstract

ABSTRACT:
Intrauterine infection and chorioamnionitis are common complications of pregnancy associated with significant
maternal, perinatal, and long-term adverse outcomes. Adverse maternal outcomes include postpartum
infections and sepsis while adverse infant outcomes include stillbirth, premature birth, neonatal sepsis, chronic
lung disease and brain injury leading to cerebral palsy and other neurodevelopmental disabilities. There is a
desperate need to identify novel therapies to reduce the perinatal mortality and long-term morbidity of
chorioamnionitis-related prematurity (ChorP). The mechanisms responsible for chorioamnionitis-induced
preterm birth remain poorly understood but involve chorioamnionitis-induced development of the fetal
inflammatory response syndrome (FIRS) defined by increased systemic inflammatory cytokine
concentrations, inflammation of the umbilical cord, and fetal vasculitis. FIRS leads to poor cardiorespiratory,
neurological, retinal, and renal outcomes in the newborn infants. Given that over 400,000 premature births
occur each year in the US, there is an unmet need to address the complications of chorioamnionitis-related
prematurity (ChorP) beyond the current therapy of antibiotic administration. Aqualung Therapeutics, Corp. has
identified a novel therapeutic ChorP target, nicotinamide phosphoribosyltransferase (NAMPT), an upstream
highly inflammatory cytozyme that binds Toll-like receptor 4 (TLR4) and, we speculate, contributes to FIRS
development. We have recently demonstrated that NAMPT expression in placentas from women with
chorioamnionitis is dramatically increased and that women with ChorP have elevated eNAMPT levels in their
plasma. Of further critical importance, the IV delivery of a polyclonal eNAMPT-neutralizing antibody (pAb) in
the preclinical pregnant mouse model of ChorP, attenuates the development of FIRS, premature delivery, and
bronchopulmonary dysplasia. We speculate eNAMPT to significantly contribute to ChorP and FIRS
development. Given the lack of currently approved therapies for ChorP, Specific Aim #1 of this STTR Phase I
application is designed to validate eNAMPT as a ChorP biomarker and link plasma eNAMPT levels in high risk
pregnant mothers (utilizing a highly specific ELISA assay) to the risk of developing ChorP. In preclinical ChorP
studies, Specific Aim #2 will assess whether our lead eNAMPT-neutralizing humanized mAb, eNamptorTM
(currently in stable cell line development) is an effective therapeutic intervention for pregnant murine dams with
ChorP to ameliorate ChorP mortality and lung injury (bronchopulmonary dysplasia) utilizing wild type and
NAMPT-/- heterozygous mice. This academic-private biotech partnership (University of Arizona-Aqualung
Therapeutics) will leverage substantial clinical and translational expertise to address a serious unmet medical
need and improve preterm morbidity and mortality in this vexing disorder by ameliorating novel signaling
pathways not previously targeted in...

## Key facts

- **NIH application ID:** 10081144
- **Project number:** 1R41HD101202-01A1
- **Recipient organization:** AQUALUNG THERAPEUTICS CORP.
- **Principal Investigator:** Mohamed Ahmed
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $265,096
- **Award type:** 1
- **Project period:** 2020-09-18 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10081144

## Citation

> US National Institutes of Health, RePORTER application 10081144, Extracellular NAMPT is a Novel Therapeutic Target in Chorioamnionitis-Related Prematurity (ChorP) (1R41HD101202-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10081144. Licensed CC0.

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