April 29, 2002 — By compressing genes to under 25 nanometers, Cleveland-based Copernicus Therapeutics (CT) has advanced delivery of gene-therapy drugs that may one day help thousands of cystic fibrosis sufferers live longer, healthier lives.
Its CF therapy is currently in Phase-I human trials at the University Hospitals of Cleveland, but CT has actually developed three core technologies that work in concert to deliver genes into cell nuclei without the threat of attack by the body’s immune system — a common problem with viral delivery methods. CT’s methods seem to clear this hurdle and, along with it, a major stumbling block on the way to better treatments for genetic-based diseases such as cancer or even skin disorders like psoriasis.
“This is certainly a major step forward,” said Robert Beall, president and chief executive of the Cystic Fibrosis Foundation (CFF). “Up to this point (viruses) clearly were thought to be the most efficient way to deliver genes.” CFF has invested $1.5 million to date in CT’s development efforts. CFF’s total 2002 budget for such investments is $59 million.
If CT’s treatments make it through the U.S. Food and Drug Administration’s arduous approval process, CF patients could receive the aerosol form of this therapy within four years. In the long term, CT is working on an injectable form of the treatment for CF and this same technology could be used to develop treatments for any number of genetically based afflictions.
According to CT, the overall market for genetic therapies will be $12 billion by 2007. The CF market alone is $2.5 billion and, although it is still only spending venture capital dollars at the moment, CT’s take of this market could be substantial.
“If you’re asking me to speculate on what our potential is, say five years from now, I wouldn’t be surprise if we have a market cap of $3-5 billion,” said Dr. Mark Cooper, a clinical oncologist and senior vice president of science and medical affairs for CT.
By compressing healthy DNA strands — which would normally measure around 200 nanometers — to less than 25 nanometers, the company can slip healthy genes through the membrane surrounding a targeted cell’s nucleus.
Introducing healthy genes into a cell forces the cell to perform normally. In the case of CF, this means metabolizing salt properly. Without treatment, CF sufferers tend to live short lives plagued by a buildup of mucus in the lungs and other problems caused by an improperly functioning pancreas.
CT’s compression and delivery bypasses the need to use viruses, which have long been the only gene delivery vehicles available. Viruses have been used because they reproduce by injecting their DNA into a cell, forcing it to make new virus. But, because viruses are invaders and usually considered harmful by the body, therapies can be compromised by a patient’s own immune system.
“The genetic compression technology, that’s certainly unique because nobody’s been able to deliver DNA in that sense before,” said Dr. William McCulloch, executive vice president and medical director at the venture capital advisory firm A.M. Pappas & Associates, and former CT board member.
CT has also developed two complementary technologies, a cell targeting technology that allows doctors to pick out which cells receive treatment and which do not, and a replicating technology that overrides a cell’s normal math and causes introduced genes to replicate en masse. This can be used to either kill a cell directly, say in the case of cancer, or cause it to stand out like a beacon for other cells to do the killing.
This technology can also be used to simply force the expression of some desired characteristic or function instead of killing the cells.
By combining the three technologies, CT can develop drug therapies that target specific cells and cause them to behave in a predetermined fashion. This has a number of benefits but perhaps the most important is a reduced risk of treatment toxicity. Often, as in the case of cancer, it has been said the treatment is worse than the disease because the massive doses of cancer drugs that are delivered kill as many healthy cancer cells. This is why cancer patients often loose their hair and appear gaunt and drawn after a series of chemotherapy treatments.
If successful, CT’s delivery methods could eliminate this problem by targeting just the cancer cells for treatment and leaving healthy cells unharmed.
To exploit its research, CT intends to emerge from the startup world as a full-fledged pharmaceutical company designing and manufacturing drugs. To distribute its product, the company will use outside contractors so it can focus on drug development activities.
Although McCulloch does not see CT becoming a huge, multinational drug company, there is still a substantial market for their therapies once they get past these first clinical trials and prove the efficacy of their treatment methodologies.
“If CT could really crack something with as big a market as CF has then I think they could become one of the leading companies in gene therapy,” he said. “They could really rise to the top if this stuff works.”
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