When you talk to Paul Dorman these days, he’s all excited about nanotechnology and the possible implications of using that to treat cancer and other diseases.
On Sept. 12, DFB Pharmaceuticals announced a cooperative venture with CritiTech and US Biotest to form a new company called NanOlogy to develop an advanced form of cancer treatment using nanoparticles injected directly into tumors.
Dorman and others believe this will be a more efficient and safer way to use chemotherapy to treat cancer and other serious illnesses. They believe cancer treatment drugs delivered this way will reduce the toxicity of traditional chemotherapy, which in itself can make the patient very ill, and increase the exposure time the drugs have to work on killing the cancer cells.
Airplane pilots will tell you that a crash is seldom caused by a single incident but by a series of incidents stacked one on another that build to a critical mass. That’s sort of what happened here. Except that researchers hope the result is positive.
In 2003, Dorman bought a company called Phyton Biotech, which manufactured paclitaxel, the active ingredient in one of the leading breast cancer drugs initially called Taxol, owned by Bristol Myers. Paclitaxel was made from the bark of the yew tree and it took about three trees to make enough paclitaxel to treat a single patient.
Because of the potential environmental damage from killing so many yew trees, goverment agencies created incentives for someone to develop a way to make paclitaxel without killing the trees.
It turned out there was a Biology 101 answer, developed by a group of scientists at Cornell University in Ithaca, NewDor York.
The researchers found a way to take cells from a yew tree and cultivate them in a laboratory and then cryopreserve them.
“Even today, I still have something like eight to 10 years of cells cryopreserved. You take them out and thaw them, then you put them in a reactor and do the fermentation. You don’t have to sacrifice any more trees,” Dorman said.
“They obtained patents on the process and I bought the company, which had a contract with Bristol Myers to make all of their paclitaxel for their drug Taxol,” he said. “The reason they sold it to me is that contract was coming to an end in three or four years. I gave them three years of revenue and picked up the value after the fourth year.”
He thought there was a way to expand that technology. He kept the Phyton business when he sold the other companies. “I thought I’d keep a few people and we’d continue to expand that technology,” he said. Phyton has a manufacturing plant in Germany and one in Canada.
When he sold Healthpoint to Smith & Nephew, he kept the office building. He reserved the fourth floor for Phyton and other investments and leases the remaining three floors to Smith & Nephew.
“The plant in Germany made the upstream process. The downstream process was made in Canada and we’d ship it to Bristol Myers and other companies to make the finished product, which was basically taking the paclitaxel and putting it in a solvent, sterilizing it and shipping it off to the physician to use in the patient,” Dorman said.
“It was a very stable process managed by a group of engineers in Germany and a group of scientists and technicians in Canada,” Dorman said. “It didn’t require a lot of management time, so I designated three or four people in Fort Worth for management of the business.”
For about a year, he talked to other companies to see whether that cryopreservation technology could be used for other drugs. That’s when he became aware of a group of engineers at the University of Kansas who had developed a proprietary process for making nanoparticles.
The initial discussions were about putting their equipment into his Canadian plant. The discussions evolved into a joint venture to use this technology for the treatment of cancer.
In traditional cancer treatment, both the paclitaxel and the solvent used to make it injectable into the bloodstream are toxic to the human body, so there is a careful balance between killing the cancer cells and minimizing the side effects to the patient. In some cases, the amount of paclitaxel that can be injected is limited by the toxicity of the solvent more than the drug.
Because of the toxicity, chemotherapy can only be administered every week or so, and the therapeutic dose — the level necessary to kill the cancer cells — only lasts about eight hours. The body immediately begins to rid itself of the toxic mixture through the natural body processes.
But in the new process, the drugs can be made into nanoparticles suspended in saline solution and injected directly into the tumor. They are solid particles of uncoated paclitaxel that become entrapped in the tumor and dissolve over about four weeks.
“In essence, currently a drug is injected once a week into the vein and some of it goes into the tumor and resides there for about eight hours, killing those cells that are dividing in that eight-hour period. With our technology, we go directly into the tumor. All the injected drug resides in the tumor for 24 hours a day for over 30 days, constantly killing cancer cells as they divide,” Dorman said.
The U.S. Food and Drug Administration requires drugs to go through three phases of testing. The first phase is to show that the drug is safe, which is one of the first principles of medicine — first do no harm.
“If a new treatment is found to be reasonably safe in phase I clinical trials, it can then be tested in a phase II clinical trial to find out if it works,” says the American Cancer Society. “Phase III clinical trials compare the safety and effectiveness of the new treatment against the current standard treatment.” The FDA wants to see clinical trials in a number of hospitals to show that it is not just one group of oncologists showing positive results.
“We’re in phase II now for about five or six different cancers: ovarian, prostatic, pancreatic cancers, pancreatic cysts, cutaneous metastases, and active in pre-clinical work for lung cancer, breast cancer and bladder cancer,” Dorman said.
He’s committed. “It was a major decision for me, because I was ready to enjoy the good life in retirement, resulting from the success that we’ve had when we sold all the businesses,” he said.
“When I realized the potential of this technology, I made a decision that I just couldn’t live with myself if I had something that had the potential to make a major impact on cancer, and I didn’t do it,” Dorman said.
“I don’t have a desire to start up a sales organization like I did in dermatology, wound care, and the development of the DPT business. I’ll let other people who already have an existing sales forces take it and make it available to the cancer patients around the world. But it’s just something I just have to explore,” he said.
“I really feel we’ve been given the opportunity to make a real serious impact here. You don’t have that kind of opportunity very often in life to make that kind of impact on other people’s lives. If we are wrong, then the potential impact was worth the effort.”
The announcement of NanOlogy is a major step on the path to finding out.