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Principal Investigator: JEFF T HUTCHINS
Organization: INHALON BIOPHARMA, INC.
Fiscal Year: 2024
Award: $1,024,942
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary
Human metapneumovirus (MPV) is the second leading cause of lower respiratory tract infections
(LRTI) in infants and young children, and a major cause of respiratory illness among the immunocompromised
and the elderly. Unfortunately, there is currently no effective therapy or vaccine for MPV. A pathogen-specific,
safe and effective antiviral would undoubtedly address the current gap in pharmacological interventions.
MPV, like many common respiratory viruses, spreads in the respiratory tract by shedding progeny (i.e.
daughter) virions back into airway mucus (AM); viruses must then diffuse through AM to reach and infect the
next cell. Thus, the infection remains restricted to the apical side of the airways as it spreads from the upper
respiratory tract to the lower respiratory tract, making it difficult to target by systemically dosed antivirals.
Indeed, while neutralizing monoclonal antibodies (mAbs) offer a safe and likely effective antiviral
intervention, their use is greatly limited by inconvenient dosing and limited distribution into the respiratory tract.
Inhalon has been advancing a platform of inhaled mAb treatments capable of achieving very high
concentrations of mAb directly in the respiratory tract (i.e. the site of infection) nearly instantly. Specifically, we
have developed methods that enable stable and efficient delivery of mAbs via handheld vibrating mesh
nebulizers, with dosing completed within minutes per day in the comfort of a patient’s own home. Inhalon has
also developed a platform of muco-trapping mAbs, based on tuning sugars on the Fc domain of mAbs that
enable effective crosslinking of virion/mAb complexes to mucins. Muco-trapping mAbs can directly block
progeny viruses from diffusing through AM, and can quickly remove them from the airways by harnessing
natural mucus clearance mechanisms. We have validated our topical mAb therapy approach in hamsters
infected with MPV, as well as in lambs infected with RSV (another virus that, like MPV, propagates exclusively
by apical shedding). Recently, we completed a Phase 1 human clinical study of the safety, tolerability, and
pharmacokinetics of an inhaled mAb against SARS-CoV-2, and found excellent safety and high concentrations
of drug in the airways in humans, despite using a far lower dose compared to typical IV doses.
Inhalon is advancing IN-003, comprised of a pair of potent neutralizing mAbs against MPV F protein, as
an inhaled mAb therapy against hMPV. By delivering IN-003 directly to the airways, we expect to enable
efficacious and cost-effective treatment for MPV, with limited risk of adverse side effects. In this project, we
seek to produce a GLP tox lot batch of IN-003, and conduct the key GLP IND-enabling studies required by the
FDA before advancing to the clinic. The proposed work, based on our recent regulatory experience advancing
inhaled mAbs for SARS-CoV-2 and RSV, represents the critical path to advance IN-003 into the clinic.
Successful completion of this work will put us in a position to quickly file an IND following GMP manufacturing
of clinical trial materials, leading to the first clinical study of an inhaled mAb therapy for MPV.
Terms: <0-11 years old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Accounting><Address><Age><Agreement><Animals><Anti-viral Agents><Antibody Therapy><Apical><Back><Blood><Blood Reticuloendothelial System><Body Tissues><Bronchiolitis><CD183><CHO Cells><CKR-L2><CMKAR3><COVID-19 antibody><COVID-19 virus><COVID19 virus><CRG-2><CXCL10><CXCL10 gene><CXCR3><CXCR3 gene><Cell Body><Cell Line><CellLine><Cells><Characteristics><Chemokine (C-X-C Motif) Receptor 3><Child><Child Youth><Children (0-21)><Chinese Hamster Ovary Cell><Clinic><Clinical Research><Clinical Study><Clinical Treatment Moab><Clinical Trials><CoV-2><CoV2><Common Rat Strains><Complex><Contracting Opportunities><Contracts><Cotton Rats><Coupled><Cricetinae><Critical Paths><Critical Pathways><Cyclic GMP><Data><Daughter><Development><Diffuse><Diffusion><Dorsum><Dose><Drug Kinetics><Drugs><Elderly><Engineering><Ensure><Fc domain><Formulation><G Protein-Coupled Receptor 9><GPR9><Guanosine Cyclic Monophosphate><Hamsters><Hamsters Mammals><Home><Hospital Admission><Hospitalization><Hu-mABs><Human><Human Metapneumovirus><IFI10><INP10><IP-10><IP10><IP10 Receptor><IP10-Mig receptor><IP10-R><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunosuppressed Host><Infant><Infection><Inflammation Mediators><Inhalation><Inhalation Toxicology><Inhaling><Intervention><Intervention Strategies><Lower Respiratory Tract Infection><Lower respiratory infection><Lower respiratory tract structure><Lung><Lung Respiratory System><MOB-1><Medication><Metapneumovirus><Methods><Mice><Mice Mammals><Mig Receptor><Mig-R><MigR><Modern Man><Monoclonal Antibodies><Monoclonal Antibody Therapy><Morbidity><Morbidity - disease rate><Mucins><Mucous body substance><Mucus><Mucus Glycoprotein><Murine><Mus><Nasal><Nasal Passages Nose><Nebulizer><Neutrophil Infiltration><Neutrophil Recruitment><Neutrophilic Infiltrate><Nose><Patients><Pharmaceutical Preparations><Pharmacokinetics><Phase><Phase I Study><Pilot Projects><Pneumonia><Position><Positioning Attribute><Production><Proliferating><Prophylactic treatment><Prophylaxis><Proteins><Pulmonary Body System><Pulmonary Organ System><Pulmonary Pathology><Rat><Rats Mammals><Rattus><Reporting><Respiratory System><Respiratory System, Nose, Nasal Passages><Respiratory Tracts><Respiratory tract structure><Risk><Running><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 antibody><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SBIR><SCYB10><Safety><Serious Adverse Event><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe Adverse Event><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Side><Site><Small Business Innovation Research><Small Business Innovation Research Grant><Specific qualifier value><Specified><Strains Cell Lines><Supportive Therapy><Supportive care><Therapeutic><Tissues><Upper respiratory tract><Vaccines><Viral><Viral Burden><Viral Load><Viral Load result><Viral Respiratory Tract Infection><Virion><Virus><Virus Particle><Work><Wuhan coronavirus><access to vaccination><access to vaccines><advanced age><ages><anti-viral compound><anti-viral drugs><anti-viral medication><anti-viral therapeutic><anti-virals><antibody against COVID-19><antibody against SARS-CoV-2><antibody against coronavirus disease 2019><antibody against severe acute respiratory syndrome coronavirus 2><antibody based therapies><antibody to COVID-19><antibody to SARS-CoV-2><antibody to coronavirus disease 2019><antibody to severe acute respiratory syndrome coronavirus 2><antibody treatment><antibody-based therapeutics><antibody-based treatment><cGMP><clinical development><coronavirus disease 2019 antibody><coronavirus disease 2019 virus><coronavirus disease-19 virus><cost><cost effective therapy><cost effective treatment><cross reactivity><crosslink><cultured cell line><design><designing><developmental><diffused><diffuses><diffusing><diffusions><drug/agent><effective therapy><effective treatment><experience><first in man><first-in-human><gIP-10><geriatric><hCoV19><homes><humAbs><human mAbs><human monoclonal antibodies><human monoclonals><human study><immunosuppressed patient><inflammatory mediator><interventional strategy><kids><lower respiratory tract><lung pathology><mAB-based therapy><mAb therapy><mAb-based therapeutics><mAbs><manufacture><monoclonal Abs><mortality><mucous><mucus clearance><nCoV2><nebulization><nebulize><neutralizing mAb><neutralizing monoclonal antibodies><pathogen><pharmacologic><phase 1 study><pilot study><portability><pre-clinical><pre-clinical study><preclinical><preclinical study><prevent><preventing><pulmonary><respiratory><respiratory virus><safety study><senior citizen><serious adverse experience><serious adverse reaction><severe acute respiratory syndrome coronavirus 2 antibody><side effect><sugar><upper airway tract><vaccination access><vaccination availability><vaccine access><vaccine availability><vibration><viral respiratory infection><youngster>