You are here

Targeting lipid rafts for treatment of asthma

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AI147879-01
Agency Tracking Number: R41AI147879
Amount: $599,929.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA18-575
Solicitation Year: 2018
Award Year: 2019
Award Start Date (Proposal Award Date): 2019-06-20
Award End Date (Contract End Date): 2021-05-31
Small Business Information
San Diego, CA 92121-2734
United States
DUNS: 081343492
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (858) 531-5766
Business Contact
Phone: (858) 531-5766
Research Institution
9500 Gilman Drive, Mail Code 0934
LA JOLLA, CA 92093-0934
United States

 Nonprofit College or University

Asthma, characterized by airways obstruction with symptoms of wheezing, shortness of breath, chest tightness
and consequently cough, remains a significant health problem. While advances in bronchodilator, corticosteroid
and Th2-targeting therapy allow for well-controlled asthma in a large population of patients, subjects with severe,
corticosteroid resistant asthma require frequent hospitalizations and emergency care for life-threatening
conditions. In these patients, strong neutrophilic, Th1 and Th17 inflammatory responses, often to bacterial or
fungal pathogens, result in exacerbation of disease and steroid resistance. Importantly, many cellular immune
and inflammatory responses are initiated by receptors localized to lipid rafts, membrane microdomains
characterized by increased content of cholesterol and sphingolipids. In this proposal, a collaboration initiated
between Raft Pharmaceuticals LLC and the University of California San Diego (UCSD) seeks to fully evaluate
RFT001, a biologic that selectively interferes with lipid rafts in activated cells. Preliminary studies indicate that
inhaled RFT001 reduces lung inflammation and the number of mucus-producting cells in mice challenged with
house dust mite (HDM) allergen, as well as acute lung injury by bacterial lipopolysaccharide. We propose that
administration of RFT001 can inhibit the pathogenesis of both corticosteroid sensitive Th2 dependent asthma
(effects on lipid rafts in mast cells, B cells regulating IgE, Th2 cells, and epithelial cells expressing eosinophil
chemoattractants), as well as inhibit corticosteroid resistant severe asthma in a mouse model (by effects on lipid
rafts in Th1, Th17, and epithelial cells expressing neutrophil chemoattractants). In both preclinical models, the
UCSD team will examine efficacy of RFT001 in reducing airway hyperresponsiveness and immune and
inflammatory responses in bronchoalveolar lavage and the lungs. Raft Pharmaceuticals will determine exposure
margins for the described efficacy studies and will examine whether RFT001 demonstrates a reasonable safety
margin in a repeat dose safety study. Collective data from this proposal will determine utility and feasibility of
RFT001 for development as an asthma therapeutic.PROJECT NARRATIVE
Asthma remains a significant health problem, particularly in patients with the severe, corticosteroid resistant form
of diseases. Raft Pharmaceuticals will test the efficacy, exposure and preliminary safety of RFT001 representing
a novel class of inhaled biologics targeting lung inflammation.

* Information listed above is at the time of submission. *

US Flag An Official Website of the United States Government