NANO BIOTHERAPEUTICS INC — Department of Health and Human Services STTR Phase II: NHLBI

Description

Sepsis induced ALI ARDS is a devastating syndrome of acute respiratory failure in critically ill patients that accounts for among the highest admission rates in ICU and mortalityDuring STTR Phasewe at Cell Biologics Incdemonstrated that piceatannola naturally occurring anti inflammatory that selectively inhibits Syk tyrosine kinasewhen entrapped in innm albumin nanoparticlesPANPswas therapeutically effective in treating experimental ALI and significantly reduced mortality indifferent mouse sepsis induced ALI ARDS models such as endotoxemiacecal ligation punctureCLPinduced polymicrobial sepsisand pneumonia induced by Pseudomonas aeruginosaThis protection was ascribed directly to PANP mediated delivery of the drug into phagocytic cells and could not be reproduced by injecting the inhibitor aloneMoreoveralbumin nanoparticlesANPwithout the drug entrappedhad no therapeutic effectThe nanoparticles were preferentially taken up by cell surface Fc RIIIa expressed in activated phagocytic cells such as neutrophils and monocytes macrophagesTreatment with PANPs suppressed the IL Iand TNFinflammatory cytokine stormImportantlyPANP treatment however did not adversely affect the host defense response in the circulating non adherent phagocytic cellsIn normal micePANPs were mainly internalized by liver cells whereas they were preferentially in lung microvascular entrapped activated phagocytic cells in endotoxemic mice model substantiating our hypothesis that PANPs target activated phagocytic cells mediating ALI ARDSThe overreaching goal in STTR Phase II is to generate supporting data to seek FDAINDstatus for PANP therapy of ALI ARDSFor Phase IIwe chose Pig and ex vivo human lung models of sepsis induced ALI ARDSas tese are the closest to humansIn specific aimwe will undertake the scaling up of PANPs to meet demands of pig sepsis induced ALI ARDS and ex vivo human lung studiesWe will ensure stabilitypotency and storage capabilities of the nanoparticlesSpecific aimwill determine pharmacokinetic parametersdrug metabolism and early toxicological studies using the pig modelThe goal of specific aimwill be to establish the efficacy of PANPs in treatment of sepsis induced ALI ARDSAs the disease has multiple etiologiesstudies in pigs will be made using LPSendotoxemiaEcoliinduced peritonitisand polymicrobial sepsis induced by CLPStudies in the ex vivo human lung model will be made by challenging lungs with bacterial pneumoniaEcolidelivered by the intra tracheal routeWe will concomitantly implement the detailed commercialization plan we have developed with the help of bio pharma industryFDA and clinical consultantsWe have established clear time lines of goals to be achieved for submission of IND package to FDAIn additionwe have outlined the necessary regulatory pathwayWe have also proposed a PANP based patient intervention plan that will aid us in pursuing future PANP clinical trialsAs we make progress validating the efficacy of PANP in pig and ex vivo human lung models of ALIwe will make aggressive efforts to seek commitments from biopharma and investment firms Acute lung injuryALIand its more aggressive form Acute Respiratory distress syndromeARDSare extremely devastating diseases and the associated unacceptably high mortality rates and associated health care costs at about $billion dollarsWe still have no effective therapies to combat sepsis and the ever increasing aging population is likely to exacerbate the already severe problemBased on the scientific data gathered so farPicetannol entrapped in albumin nano particlesPANPappears to be very effective in suppressing sepsis induced ALI ARDS in mouse models