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Oxidation-resistant Anti-protease Therapy

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R42HL140670-01
Agency Tracking Number: R42HL140670
Amount: $224,967.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NHLBI
Solicitation Number: PA16-303
Timeline
Solicitation Year: 2016
Award Year: 2018
Award Start Date (Proposal Award Date): 2018-02-01
Award End Date (Contract End Date): 2019-01-31
Small Business Information
106 W 117TH ST
New York, NY 10026-2256
United States
DUNS: 080561393
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 RONALD CRYSTAL
 (212) 746-2258
 rgcryst@med.cornell.edu
Business Contact
 RONALD CRYSTAL
Phone: (347) 915-4363
Email: lexeotherapeutics@gmail.com
Research Institution
 WEILL MEDICAL COLL OF CORNELL UNIV
 
1300 YORK AVENUE, BOX 89
NEW YORK, NY 10065-4805
United States

 Nonprofit College or University
Abstract

AbstractLEXEO TherapeuticsLLCis an early stage biotechnology company focused on using gene
therapy technologies to protect vulnerable organs from oxidant stressLEXthest LEXEO productis ast in classnext generation gene therapy treatment for alphaantitrypsinAATdeficiencyan autosomal
recessive hereditary disorder associated with low serum levels of AATAATSERPINAakDa serine
antiprotease produced by the liverprotects the lung from proteolytic enzymes released by inflammatory
cellsIn AAT deficiencythe lung is vulnerable to destruction by proteolytic enzymes released by inflammatory cells that degrade the lungresulting in emphysemaAAT deficiency is currently treated with
weekly infusions of AAT purified from pooled human plasmaGene therapy for AAT deficiency holds the
promise that a single administration will generate sufficient amounts of AAT to protect the lung on a persistent basisobviating weekly AAT protein therapyFirst generation gene therapy strategies are under development to treat AAT deficiency using adenoassociated virusAAVgene transfer vectors to deliver the
human AAT coding sequence in vivo by various routesThe Achilles heel of these strategies is the sensitivity of the AAT molecule to oxidantsThe active site of human AAT includes Metwith acontribution by MetWhen oxidizede gby cigarette smokeinflammatory cell productsambient pollutionAAT is rendered ineffective and cannot inhibit neutrophil elastaseits primary targetLEXdesigned as
an AAV vector coding for an elastase inhibitingoxidation resistant human AATsolves this problem with substitution at Metand or Metwith Val or Leu to render the AAT molecule oxidation resistantyet maintaining its function as an anti elastaseThis is a Fast Track application with the goal of being clinical trial ready withinyrSuccessful completion of these aims will make LEXEO attractive for
biotechpharma and or venture investmentPhase IAimUsing the normal MAAAT coding
sequence as a baseassess combinations of MetLeu and Val at positionsandto determine the
optimal neutrophil elastase inhibitingoxidation resistant form of AAT to use in LEXPhase IAimDetermine that intrapleural administration of LEXto experimental animals results in persistenthigh levels of oxidation resistant human AAT in serum and lung epithelial lining fluidPhase IAimHave a preIND meeting with the FDA regarding the LEXdevelopment planPhase IIAimProduce and validate
GMP clinical grade LEXand demonstrate in experimental animals it is safe to use in a human trialPhase IIAimDevelop and validate the assays to be used in the clinical studySubmit to the FDA an
IND permitting initiation of a phase I clinical study of LEXfor AAT deficiency NarrativeLEXEO Therapeutics is developing ast in classnext generationgene therapy strategy to
treat alphaantitrypsinAATdeficiencya hereditary disorder associated with early development of
emphysemaThe deliverable of this Fast Track application is an FDA approved investigational new
drug application permitting initiation of a phase I clinical trial to treat AAT deficiency with a single administration of LEXan adeno associated gene transfer vector coding for a non oxidizable form of
AAT

* Information listed above is at the time of submission. *

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