Inspired by the concept of using genes as drugs and fueled bya research collaboration with Genentech Inc., a newbiotechnology company, GenVec, entered the world onWednesday, with up to $25.5 million in backing.
In vivo gene therapy pioneer Ronald Crystal, an 18-yearveteran of the National Heart, Lung and Blood Institutes ofHealth, is a founder and will be chief scientific adviser of thecompany, which will be located in Maryland.
Hal Broderson, acting chief executive officer, announced thenew company, incubated since last December, to quellspeculation surrounding its well-known scientific adviser.
Broderson is a general partner of Hillman Medical VenturesInc., which is leading an $8.5 million initial financing, alongwith Sierra Ventures of Menlo Park, Calif., and Prince Venturesof Stamford, Conn.
However, GenVec already has a collaboration with Genentech(NYSE:GNE) of South San Francisco, Calif., that will provide up to$17 million in research support, milestone payments andfuture equity investments. Genentech will retain worldwidemarketing rights to any gene therapy product developed forcystic fibrosis (CF).
Crystal was one of the first investigators to receive approvallast December from the National Institutes of Health'sRecombinant Advisory Committee (RAC) to begin human genetherapy experiments on patients with CF.
CF is the most common deadly genetic disease amongCaucasians, affecting about 30,000 people in the U.S., 3,000 inCanada and 20,000 in Europe. The disease is caused by a faultyprotein that triggers abnormally thick mucus in the lungs,which impairs breathing and leads to early death.
Crystal is stepping down as chief of the Pulmonary Branch ofthe NIH and will become professor of medicine and chief of thedivision of pulmonary and critical care medicine at the NewYork Hospital-Cornell Medical Center.
He will continue as a guest worker at NIH, overseeing the trialof 10 CF patients who will be given the cystic fibrosistransmembrane conductance regulator gene in a modifiedcommon cold virus, or adenovirus. The virus has been renderedunable to replicate, and will not induce cold symptoms inpatients.
Results from this ascending-dose feasibility study will be in thepublic domain, as is all work conducted by the NIH, Crystalsaid. The new company will try to create proprietary, second-generation adenovirus gene therapy products with improvedusefulness in specific diseases.
Crystal, who published one of the first papers in the field inJanuary 1992, said other conditions might also be treated withadenovirus vectors, which are capable of infecting cells in thelung, brain, liver and blood vessels. GenVec expects to enterclinical trials next year with a potential cancer gene therapy.
William Young, Genentech's senior vice president, said hiscompany expects to file for regulatory approval of the CFtreatment DNAse by the end of March, and may gain approvalby the fall. DNAse relieves CF symptoms by thinning the mucussecreted in the lungs.
Attempting to cure cystic fibrosis or other conditions with anadenovirus vector is attractive, Crystal said, because the virusenters the nucleus but does not integrate its genetic materialinto the chromosome, and would likely not cause permanentproblems. And the dose can be readily adjusted.
The first trials use a bronchoscope to introduce a virus solutionto the lungs under local anesthesia, but later therapies mightuse aerosols, tablets or injections.
Crystal turned to adenoviruses because retroviruses used inother gene therapy research will not infect epithelial cellslining the lungs. This in vivo approach to gene therapycontrasts with more involved ex vivo methods, in which apatient's gene is removed, modified and returned.
Gene therapy skips the drug-delivery problems inherent inusing a gene to create a protein therapeutic, which usuallycannot withstand the harsh environment of the stomach and isunsuited to be taken as a tablet. Also, the compound does nothave to be produced in a test tube and scaled up to commercialquantities, Crystal said. Instead, the body will manufacture theprotein itself.
Genzyme Corp. (NASDAQ:GENZ) of Cambridge, Mass., is alsoworking on CF gene therapy with the transmembraneconductance regulator gene, and has RAC approval to study itsadenovirus vector in three patients.
James Wilson, formerly of the University of Michigan and nowat the University of Pennsylvania, received RAC approval forhis cystic fibrosis gene therapy protocol at the same meetingwhere Crystal's study was approved.
The University of North Carolina also has a program in thisfield, as does Genetic Therapy Inc. of Gaithersburg, Md., whichreceived RAC approval of its CF trial Wednesday.
-- Nancy Garcia Associate Editor
(c) 1997 American Health Consultants. All rights reserved.