Problem: Pneumonia is the leading cause of death worldwide. Even in developed countries, it continues to be the leading cause of death from infection and a serious complication for patients being treated for other diseases. The threat of lung infections is elevated when there is a decreased level of host resistance (e.g. immunocompromised cancer patients) and when there is an increased level of pathogen exposure (e.g. pandemics, bioterror, and biowarfare). Acute leukemia patients are currently some of the most at-risk patients, as they are faced with significant immunocompromise resulting from their cancer treatments. Many times these risks prevent the full cancer treatment plan from being completed. As a result, each year an estimated 44,700 leukemia patients spend more than one-half billion dollars on a range of treatments in an effort to prevent pneumonia. Pulmotect's Solution: Pulmotect has identified and is developing a novel technology to address the risks of inhaled microbes. Our therapeutic (PUL-042) is a combination of two TLR ligands that stimulate the lung's own innate defense mechanisms to create a hostile environment for pathogens and reduce or prevent infection. Both in vitro and in vivo experiments have been completed to validate this technology. Importantly, because of the low cell-turnover rate, the lung epithelium is resistant to chemotherapy drugs so the innate immune response remains intact. It is in these most at-risk patients where proof-of-concept can be captured for additional markets. The focus of this proposal is to accomplish key milestones that will validate this technology for commercialization. This SBIR application is focused on addressing important preclinical important issues. The three Aims included are designed to validate and expand upon the proof-of-concept data already obtained. The Aims are focused for transitioning this technology into the clinic. Achieving these milestones would provide significant data for an IND application for a product that is safe and efficacious. Positive results from this phase I proposal would potentially lead to a phase II SBIR application to perform an in-depth study of the therapy in a second animal model, including FDA approved safety and toxicity studies. Additionally, by demonstrating subsequent discoveries in Pulmotect's pipeline, additional outside funds from investors can better be pursued to transition this technology into the clinic and market place. Overall, the outlined milestones of this proposal would build upon previous work, add to the foundation of this platform technology, and help bring this technology to the clinic. )
Public Health Relevance: Pulmotect, Inc is developing novel therapeutics that stimulates the innate immune system to protect against infectious diseases, even in cases of severely compromised immunity. Proof-of-concept data has shown that this technology effectively protects against a broad range of inhaled pathogens. This project will provide significant data to help transition this technology from the lab to the clinic, where physicians are asking to use the technology to benefit their patients.
Thesaurus Terms: 1-.Beta.-D-Arabinofuranosyl-4-Amino-2(1h)Pyrimidinone;1.Beta.-D-Arabinofuranosylcytosine;Ara-Cell;Active Follow-Up;Acute Leukemia;Address;After Care;After-Treatment;Aftercare;Airway Hyper-Responsiveness;Alexan;Animal Model;Animal Models And Related Studies;Arabine;Arabinofuranosylcytosine;Arabinosylcytosine;Aracytidine;Aracytin;Aracytine;Aspiration, Respiratory;Biologic Warfare;Biological Warfare;Blood;Blood (Leukemia);Breathing;Bronchial Lavage Fluid;Cancer Patient;Cancer Treatment;Cause Of Death;Cells;Clinic;Comment;Comment (Pt);Comment [publication Type];Commentary;Commentary (Pt);Communicable Diseases;Complication;Consultations;Cytarabine;Cytarabinum;Cytarbel;Cytosar;Cytosar-U;Cytosaru;Cytosine Arabinoside;Cytosine-.Beta.-Arabinoside;Data;Data Set;Dataset;Defense Mechanisms;Developed Countries;Developed Nations;Development;Disease;Disorder;Dose;Douching, Other Than Vaginal;Drugs;Editorial Comment;Editorial Comment (Pt);Environment;Epithelial;Epithelium;Erpalfa;Fda Approved;Foundations;Funding;Host Resistance;Inflm;Immune Response;Immune System;Immunity;Immunity, Innate;Immunity, Native;Immunity, Natural;Immunity, Non-Specific;Immunocompetent;Immunocompromised;Immunocompromised Host;Immunocompromised Patient;Immunosuppressed Host;In Vitro;Industrialized Countries;Industrialized Nations;Infection;Infection Prevention;Infectious Disease Pathway;Infectious Diseases;Infectious Diseases And Manifestations;Infectious Disorder;Inflammation;Inhalation;Inhaling;Inspiration, Respiratory;Irrigation;Irrigation, Other Than Vaginal;Lavage;Lavage Fluids, Alveolar;Lead;Leukemias, General;Ligands;Liquid Substance;Lung;Lung Inflammation;Lung Lavage Fluid;Malignant Neoplasm Therapy;Malignant Neoplasm Treatment;Mammals, Mice;Marketing;Measures;Medication;Mice;Microbe;Murine;Mus;Natural Immunity;Nonvaginal Irrigation;Nonvaginal Lavage;Patients;Pb Element;Permeability;Pharmaceutic Preparations;Pharmaceutical Preparations;Phase;Physicians;Pneumonia;Pneumonitis;Preparation;Prevent Infection;Published Comment;Pulmonary Inflammation;Resistance;Respiratory System, Lung;Respiratory Physiology;Reticuloendothelial System, Blood;Risk;Sbir;Sbirs (R43/44);Safety;Small Business Innovation Research;Small Business Innovation Research Grant;Solutions;Sputum;Tarabine Pfs;Technology;Therapeutic;Time;Toxic Effect;Toxicities;Udicil;Viewpoint;Viewpoint (Pt);Work;Aerosolized;Airway Hyper-Reactivity;Airway Hyperreactivity;Airway Hyperresponsiveness;Anticancer Therapy;Biomarker;Biowarfare;Body System, Allergic/Immunologic;Cancer Therapy;Chemotherapeutic Agent;Chemotherapy;Commercialization;Cytokine;Design;Designing;Disease /Disorder;Disease/Disorder;Drug /Agent;Drug/Agent;Experiment;Experimental Research;Experimental Study;Fluid;Follow-Up;Heavy Metal Pb;Heavy Metal Lead;Host Response;Immunoresponse;Immunosuppressed Patient;In Vivo;Inspiration;Irrigation Therapy;Lavage Therapy;Leukemia;Liquid;Lung Function;Meetings;Microbial;Model Organism;New Technology;New Therapeutics;Next Generation Therapeutics;Novel Therapeutics;Organ System, Allergic/Immunologic;Pandemic;Pandemic Disease;Pathogen;Pathogen Exposure;Pre-Clinical;Preclinical;Prevent;Preventing;Psychological Defense Mechanism;Pulmonary;Research Study;Resistant;Respiratory Function;Treatment Planning
