# Targeting lipid rafts for treatment of asthma

> **NIH NIH R44** · RAFT PHARMACEUTICALS, LLC · 2023 · $999,991

## Abstract

PROJECT SUMMARY
Patients with severe asthma who display persistent bronchoconstriction and/or reduced lung function despite
available bronchodilator, corticosteroid and Th2-targeting therapy develop significant morbidity, which severely
impacts their quality of life owing to persistent symptoms, as well as frequent and life-threatening exacerbations.
Aspects of severe asthma currently not managed by available therapies may display a strong inflammatory
component driven by the innate and adaptive immune systems, particularly following viral exacerbations.
Development of new therapeutic strategies targeting a wide range of inflammatory mechanisms, not only Th2
and Th1/Th17 responses, is needed to control severe asthma. Raft Pharmaceuticals proposes a new target for
treatment of severe asthma – overabundant and clustered, pathological lipid rafts in bronchial epithelial and
immune cells in asthmatics. Cholesterol-rich lipid rafts provide ordered plasma membrane domains, where
receptors, ion channels and adaptor molecules can associate to form functional complexes. Large lipid rafts are
required as the landing pad for microbes on host cells and for initiation of many inflammatory processes in
bronchial epithelial and immune cells. We discovered apoA-I binding protein (AIBP) as a molecule that selectively
targets the cholesterol depletion machinery to pathologic lipid rafts in inflammatory cells, without affecting
homeostatic cellular function. The latter explains an exceptional safety profile of AIBP in mice and rats. In the
Phase I of this grant, using mouse models of asthma, we demonstrated that administration of a biologic derived
from the AIBP protein, was effective in an acute HDM model of asthma in mice, reducing airway
hyperresponsiveness, airway eosinophilia, and expression of Th2 cytokines and epithelial alarmins. In a model
of severe asthma, AIBP significantly reduced pulmonary neutrophilia. For Phase II proposal, a team of experts
in biologic drug development and in preclinical assessment and clinical trials of therapeutic agents in asthma
has been assembled to further the characterization of an improved AIBP sequence, RFT1124, as a development
candidate for severe asthma. Specifically, we plan to manufacture and release RFT1124 drug product for efficacy
and toxicology studies using cGMP-compatible processes and analytical assays. The efficacy of RFT1124 as
an add-on therapy to standard-of-care inhaled corticosteroids and long-acting beta-agonists (ICS+LABA) will be
tested in mouse models of asthma exacerbated by rhinovirus (RV) infection. In addition, we will use precision
cut lung slices from asthmatics and non-asthmatics postmortem lung tissue to test the efficacy of add-on
RFT1124 in ICS+LABA treatment in RV infected human airways. RNAseq studies will establish whether
RFT1124 inhibits corticosteroid insensitive anti-inflammatory pathways and/or enhances corticosteroid sensitive
pathways in RV infected human bronchial epithelial cells....

## Key facts

- **NIH application ID:** 10697410
- **Project number:** 2R44AI147879-03A1
- **Recipient organization:** RAFT PHARMACEUTICALS, LLC
- **Principal Investigator:** DAVID H BROIDE
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $999,991
- **Award type:** 2
- **Project period:** 2019-06-20 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10697410

## Citation

> US National Institutes of Health, RePORTER application 10697410, Targeting lipid rafts for treatment of asthma (2R44AI147879-03A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10697410. Licensed CC0.

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