SBIR-STTR Award

Throughout the world, lower respiratory infections cause significant death and mortality. Seasonal influenza pneumonia alone causes more than 40,000 deaths a year in the U.S. Pandemic influenzas have even more impacts, with at least 50 million influenza-related deaths in 1918-9. Further, the anticipated avian- origin H5N1 influenza in human populations with its associated high mortality is of great concern with no immediate solution currently available. Pulmotect's Solution: Pulmotect has identified and is developing a novel technology to prevent respiratory infections. The lead drug (PUL-042) is a combination of two TLR ligands that stimulates the lung's own innate defense mechanisms to create a hostile environment for pathogens and prevent or attenuate respiratory infections. Both in vitro and in vivo experiments have been completed to validate this technology and the drug is progressing through the regulatory process for a treatment to benefit cancer patients during periods of immunocompromise. The focus of this proposal is to accomplish key milestones that will further transition this technology for commercialization against viral infections. The project is organized into three measurable Specific Aims: 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 Statement:


Public Health Relevance:
Pulmotect, Inc is developing novel therapeutics that stimulate 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 for viral infections. This work will leverage ongoing activities currently underway developing the technology for cancer patients.

Project Terms:
Address; Animal Model; Attenuated; base; Birds; Breathing; California; Cancer Patient; Cessation of life; Clinic; commercialization; Communicable Diseases; Consultations; Data; Data Set; Defense Mechanisms; design; Dose; Environment; FDA approved; Foundations; Funding; Human; Immune system; Immunity; Immunocompromised Host; In Vitro; in vivo; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype; interest; Lead; Ligands; Lung; Marketing; Measurable; Measures; Modeling; Mortality Vital Statistics; new technology; novel therapeutics; Oseltamivir; pandemic disease; pathogen; Pharmaceutical Preparations; Phase; phase 1 study; Phase I Clinical Trials; Pneumonia; Population; pre-clinical; prevent; Prevention; Process; public health relevance; research study; respiratory; Respiratory Tract Infections; Risk; Safety; seasonal influenza; Small Business Innovation Research Grant; Solutions; Technology; Texas; Time; Toxic effect; treatment duration; Viral; Virus; Virus Diseases; Work

Pulmotect, Inc. was founded in 2007 to translate discoveries that induce innate immune resistance in the lung into therapeutics that will provide protection from inhaled pathogens. Our technology platform is a direct result of basic research by our founders on the mechanisms of microbial resistance in the lung epithelium. We have developed an inhaled therapeutic, PUL-042, that provides immediate protection against a broad spectrum of respiratory pathogens. PUL-042 is a clinical stage, specific combination of two well-characterized synthetic molecules, a lipopeptide (Pam2CSK4) and an oligodeoxynucleotide (ODN M362) that act as agonists of the Toll-like Receptors TLR2/6 and TLR9, respectively. This unique, proprietary combination of molecules synergizes to rapidly and powerfully stimulate the body's natural defenses. The response is localized and specific to the site of administration. In mice, treatment before and after exposure with aerosolized PUL-042 results in increased survival rates to pathogens including multiple Gram+ and Gram- bacteria (three of which are Class A bioterror agents), the fungus Aspergillus fumigatus, and the Sendai and influenza viruses. In each case, increased survival is associated with a reduction of lung pathogen burden, not simply increased tolerance to the pathogen by the host, which indicates a resistance mechanism of action. Pulmotect's long-term strategy is to leverage its technology across a wide array of important threats from inhaled pathogens by limiting the pathogen burden and transmission of disease. The range of applications for PUL-042 currently in development includes use in immunosuppressed patients, pandemic influenza, asthma exacerbations associated with viral infections and manmade bioterror threats as well as naturally emerging viruses. While this broad spectrum technology is not envisioned to replace traditional vaccine approaches, its value and differentiation reside in the ability to confer immediate host-based protection that is not limited by the identity of the pathogen. The potential indications that lie outside the scope of this proposal are synergistic, building on experimental methods that we established since our earliest research in this field. The scientific basis of boosting the innate immune system in the lungs is rapidly expanding as we better understand the underlying mechanism of action. The primary goal of this proposal is to complete a Phase II clinical trial in immunosuppressed cancer patients. This will be a multi-center randomized double-blind trial that will compare PUL-042 against placebo on the overall incidence and severity of pneumonia, specifically on those who have been screened to have a parainfluenza infection prior to enrollment. The three objectives of the trial are described below. • Primary objective: to determine the safety and tolerability of PUL-042 inhalation solution in patients with documented parainfluenza infection. • Secondary objective: to determine the efficacy of PUL-042 inhalation solution to prevent the progression of documented parainfluenza infection to clinically documented lower respiratory tract infection. • Exploratory objectives: 1 evaluate the effect of PUL-042 on parainfluenza viral titers and neutralizing antibodies; 2) evaluate the effect of PUL-042 over time on the microbiome and virome in nasal washes in the study population; and 3) determine whether PUL-042 induces neutralizing antibodies against PUL-042 components. The successful achievement of these objectives will demonstrate proof-of-concept in man and further validate the technology for market use. With secured matching funds already in place, this NIH proposal is designed to help move the project to the end goal, rather than provide the initial seed funds to start the process. The Company would be well positioned to advance existing collaborations, partnerships and discussions with leading large pharma and biotechnology organizations, accelerating the path to the market to address the serious unmet needs that many patients are currently facing.

Project narrative:
Pulmotect, Inc. is developing novel therapeutics that stimulate 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, including viral challenges that often cause asthma exacerbations. Early clinical studies have shown the drug to safe in humans up to the expected therapeutic dose. This project aims to further advance the clinical development of this technology by completing a proof-of-concept Phase II clinical trial in immunosuppressed cancer patients.

Project Terms:
Achievement; Address; aerosolized; Agonist; Agreement; Aspergillus fumigatus; Asthma; Bacteria; base; Basic Science; Biotechnology; Breathing; Cancer Patient; cancer therapy; Clinical; Clinical Research; clinical research site; Clinical Trials; Collaborations; Communicable Diseases; Cyclic GMP; Data; design; Development; disease transmission; Dose; Enrollment; Epithelium; Evaluation; follow-up; Funding; fungus; Goals; Health; healthy volunteer; Hematologic Neoplasms; Hematology; Human; Immune; immune resistance; Immune system; Immunity; Immunocompromised Host; immunosuppressed; Incidence; Individual; Infection; influenzavirus; Lead; Lower Respiratory Tract Infection; Lung; man; Marketing; Methods; microbial; microbiome; Mus; Myeloablative Chemotherapy; Nasal Lavage Fluid; neutralizing antibody; novel therapeutics; oncology; outreach; pandemic influenza; Parainfluenza; pathogen; Patients; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Placebos; Pneumonia; Population Study; Positioning Attribute; prevent; Prevention; Process; Pulmonary Disease (Specialty); Randomized; Recruitment Activity; Research; Resistance; resistance mechanism; respiratory; response; Safety; Secure; Seeds; Sendai virus; Severities; Site; Solutions; Staging; success; Survival Rate; Technology; technology development; Testing; Therapeutic; Time; TLR2 gene; Toll-like receptors; Translating; United States National Institutes of Health; University of Texas M D Anderson Cancer Center; Vaccines; Viral; virome; Virus; Virus Dis