DISCOVERY LABORATORIES, INC. — Department of Health and Human Services SBIR Phase II: NIAID

Description

DESCRIPTION provided by applicant Exposure to ionizing radiation from a nuclear reactor accident or deliberate terrorist actions including the detonation of andquot dirty bombsandquot is a significant public health concern The lung is particularly susceptible to ionizing radiation injury from external sources or inhalation of radioactive particles from radioactive fall out Radiation pneumonopathy can manifest with an acute radiation pneumonitis ARS and or delayed effects of acute radiation exposure DEARE leading to progressive often fatal pulmonary fibrosis As prior warning of exposure is unlikely medical countermeasures MCMs to mitigate radiation pneumonopathy that can be given in mass casualty situations many hours days and even months post exposure are needed Data from our proof of principle approach Phase I SBIR study using a well established targeted thoracic radiation mouse model C BL provided robust evidence supporting the effectiveness of KL surfactant a proprietary peptide based synthetic surfactant in mitigating both ARS and DEARE In these experiments KL surfactant was delivered intranasally twice daily for weeks beginning hrs post irradiation Preservation of lung function and reduced inflammation was observed in KL surfactant treated mice at and wks post irradiation i e mitigation of ARS and importantly reduction in subacute inflammation and pulmonary fibrosis DEARE at months post exposure Discovery Laboratories Inc a biotechnology company small business concern continues to evaluate KL surfactant lucinactant as a broad spectrum multi use MCM against chemical biological radiological and nuclear threat agents targeting the lung Given KL surfactantandapos s lung protective and immune modulatory properties ability to be delivered as an aerosol to spontaneously breathing subjects and its robustness resistance to inactivation by plasma proteins and oxidants present in the inflamed lung the drug is an ideal MCM test candidate to treat radiation pneumonopathy Moreover the extensive preclinical and clinical safety efficacy experience with KL surfactant andgt treated patients and recent approval by the FDA for prevention of neonatal RDS should facilitate the regulatory approval of the drug as a MCM Exogenous surfactants have never been evaluated for treating radiation pneumonopathy thus our approach is novel This SBIR Phase II proposalandapos s Specific Aims are to conduct an in depth evaluation of KL surfactant as a mitigator of radiation pneumonopathy using a more clinically relevant scenario than that used in Phase I Utilizing the same C BL thoracic irradiation mouse model in collaboration with Dr Melpo Christofidou Solomidou at the Univ of Pennsylvania as in Phase I we will now deliver KL surfactant in an aerosol formulation in addition to evaluating three different treatment regimens that could be clinically relevant a andquot earlyandquot treatment b andquot earlyandquot plus andquot lateandquot and c andquot lateandquot only treatment Aim evaluates whether aerosolized KL surfactant delivered as in a can prevent ARS and Aim whether delivery of KL surfactant as in b and c can mitigate DEARE The long term objective is to obtain FDA approval of KL surfactant as a MCM for radiation pneumonopathy PUBLIC HEALTH RELEVANCE Exposure to ionizing radiation and inhalation of radioactive particles from nuclear reactor accidents or deliberate terrorist actions is a significant health concern since acute lung damage or delayed often fatal lung scaring can occur in exposed individuals and unprotected rescue workers Discovery Laboratories Inc a biotechnology company is testing its proprietary synthetic KL surfactant technology as a medical countermeasure MCM to treat radiation induced lung injury KL surfactantandapos s lung protective and anti inflammatory properties suggest its potential as a broad spectrum multi use MCM candidate The proposed follow on animal experiments should establish whether KL surfactant in an inhalation formulation should be further developed to protect the human lung and if successful ultimately be approved as a MCM and be included in the Strategic National Stockpile for treating radiation exposure an important goal of Project Bioshield