ADVENT THERAPEUTICS INC — Department of Health and Human Services SBIR Phase I: NHLBI

Description

Advent Therapeutics IncAdventis a biotech company focusing on the developmentreformulation and optimized delivery of legacy drugs to address serious unmet medical needs in underserved patient populationsAdvent is developing an aerosol formulation of its proprietary optimizedwater miscible vitamin AvitApalmitate for non invasiveinhaleddelivery of the drug to preterm infantsOur innovative inhaled vitA formulationavoids the drawbacks of invasive intramuscularIMinjectionsthe current dosing modalityandprovides both direct to target organ delivery to prevent bronchopulmonary dysplasiaBPDknown also as chronic lung diseaseCLDof prematurityand systemic delivery for treating vitA deficiencyVADin premature neonatesOur preliminary in vitro testing shows that our vitA formulation can be efficiently aerosolized by a commercial nebulizerAerogen Aeroneb Proproducing optimally sized particles for efficient inhalation dosingEarly in vivo studies with our collaboratorDrVirender Rehan at Harbor UCLA Medical Centerin a pre weaned rat modelshow that inhaled vitA leads to a rise in serum vitA levelsindicating systemic deliveryAdditionallyin the lunglevels of protein and mRNA of genes involved in lung maturation are upregulatedproviding direct evidence that inhaled vitA stimulates the developing lungAll metrics showed significant improvements in these early studiesOur proposal describes an expanded collaborationwith in vivo work in DrRehan s lab and shared efforts on assays analysisThe consequences of VAD including BPDretinopathy of prematurityand sepsis are all costly complications of prematuritywith significant risk of poor clinical outcomesCurrently available vitA therapies either require invasive IM injectionor are generally inadequate for premature neonatesenteral or IV routesInhalation dosing overcomes all of these hurdlesenabling higher vitA utilizationreducing risk and cost for BPD CLDOur goals in Phase I are to demonstrate in a well characterized pre weaned rat model thatour vitA formulation delivered by non invasive inhalation is at least as effective as invasive IM injectionandthat inhaled vitA can attenuate hyperoxic lung injurythereby reducing the risk for development of BPDTo achieve thisour specific Aimwill measure the effectiveness of inhalation of our proprietary vitA formulationaerosolized by the Aeroneb Proon raising serum vitA and stimulating lung maturation in pre weaned ratscomparing to effects of IM vitA dosing as a baselineAnalysis of lung and liver tissue will be by Western blotRT PCRand immunohistochemistryVitamin A and retinol binding protein will by assayed by using ELISAOur measure of success will be direct demonstration of at least similar effects with aerosolized vitA vstypical IM dosingin comparison to untreated control groupsIn specific Aimwe will evaluate the effect of inhaled vitA on attenuating hyperoxia induced neonatal lung injury as compared to IM deliveryOur measure of success will be efficacy in reducing hyperoxic lung damage equal to or better than IM dosing and relevant controls NarrativeThe consequences of inadequately treated vitamin A deficiencyVADin premature neonates including increased risk for bronchopulmonary dysplasiaBPDretinopathy of prematurityROPand sepsisare associated with poor clinical outcomes in these fragile patients and require costly long term treatmentAdvent Therapeutics is developing an aerosol formulation of its proprietary optimizedwater miscible vitamin A palmitate for non invasive delivery of the drug to preterm infantsThe aerosol formulation obviates the need for invasive intramuscularIMinjectionand allows potential increased effectiveness by delivery directly to the lunga directto target organ treatment for BPDwhile simultaneously providing systemic vitamin A availability important for treating VAD and the other related complicationsDosing vitamin A by inhalation should overcome current hurdles limiting vitamin A supplementation use in the NICUenabling much higher vitamin A utilizationthereby reducing risk and cost of BPD and ROP in preterm infants